case study of child with meningitis

Case-based learning: meningitis

Causes, diagnosis and initial management options for adults and children with meningitis.

JL / The Pharmaceutical Journal

Meningitis is the second leading infection-related cause of death in children in the world, second only to pneumonia [1] . It is responsible for more deaths than malaria, AIDS, measles and tetanus combined [1] . The disease is more prevalent in children under the age of four years and in teenagers. In England, there has been a decline in confirmed cases of invasive meningococcal disease over the past two decades, from 2,595 cases in 1999/2000 to 755 cases in 2017/2018, which is a small increase from the 748 cases reported in 2016 and 2017 [2] .

Pharmacists have a vital role in raising awareness of the signs and symptoms of meningitis, while also maximising the benefit of the national immunisation programme to reduce the incidence of the disease. This article will cover initial management options, with a focus on children and neonates.

Meningitis — inflammation of the membranes covering the brain and spinal cord (meninges) — can be caused by viruses, bacteria or fungi.

Meningococcal disease encompasses meningococcal septicaemia (25% of cases), meningococcal meningitis (15% of cases) or a combination of the two (60% of cases) [3] . Up to 95% of meningitis in the UK is aseptic, where there is no growth on cerebrospinal fluid (CSF) culture, usually with a viral aetiology (e.g. enteroviruses) [3] .

Bacterial meningitis is most commonly caused by Neisseria meningitidis (also known as meningococcus), although the main pathogens alter with age. As such, N. meningitidis , Streptococcus pneumoniae (also known as pneumococcus) and Haemophilus influenzae type b are the leading causes of meningitis in children older than three months; however, Streptococcus agalactiae , Escherichia coli , S. pneumoniae and Listeria monocytogenes are more common in children younger than three months [3] .

The bacteria that cause meningitis are very common — they are present in the nasopharynx in around one in ten people who may not ever show any symptoms of disease. The reasons why some people develop meningitis while others do not are not yet fully understood. However, it is thought that genetic variations in the genes for Factor H and Factor H-related proteins may have a role to play [4] . These proteins regulate a part of the body’s immune system called the complement system, which recognises and kills invading bacteria.

Risk factors

In general, young children are at the highest risk of bacterial meningitis and septicaemia, but other age groups, including older people, can also be vulnerable to specific types. One study found that meningococcal meningitis was less frequent in older patients, whereas pneumococcal, listerial and meningitis of unknown origin were more frequent [3], [5] . People with low immunity, for example, those with HIV or those having chemotherapy treatment for cancer, may also be at an increased risk.

Individual countries show seasonal patterns of bacterial meningitis. For instance, increased cases have been observed between the months of December and March in the United States, France and the UK [6] . There is also evidence that mass gatherings and exposure to cigarette and wood smoke can make people more susceptible to certain causes of meningitis and septicaemia, potentially from interference with mucosal immunity [7] .

Depending on the cause, cases of meningitis may be isolated. However, those who have been in close contact with someone with bacterial meningitis may be at increased risk of disease.

Pathophysiology

Infection occurs through transmission of contaminated respiratory droplets or saliva. Pili on the bacterial surface are thought to disrupt endothelial cell junctions in the blood–brain barrier, allowing the pathogens to penetrate it [8] . Once they have entered the subarachnoid space (the area of the brain between the arachnoid membrane and the pia mater), the pathogens replicate rapidly. This causes the production of several inflammatory mediators, including lymphocytes and inflammatory cytokines, as well as local immunoglobulin production by plasma cells. This enhances the influx of leukocytes into the CSF, which releases toxic substances that contribute to the production of cyctotoxic oedema and increased intracranial pressure. It is this process that can contribute to neurological damage and even death [9] , [10] .

Signs, symptoms and immediate management

Symptoms typically occur within 3–7 days after transmission [3] . Early, non-­specific symptoms of meningitis include:

• Irritability;
• Ill appearance;
• Refusing food/drink;
• Other aches and respiratory symptoms;
• Vomiting/nausea;

Healthcare professionals should be aware that classic signs of meningitis that include neck stiffness, bulging fontanelle and high-pitched cry are often absent in infants with bacterial meningitis [3] , [11] . Less common early symptoms include shivering, diarrhoea, abdominal pain and distention, coryza and other ear, nose and throat symptoms [3] .

General features of meningitis include a non­-blanching rash that can appear anywhere on the body, altered mental state, shock, unconsciousness and toxic or moribund state. If a patient presents with these symptoms, the glass test (also known as the ‘Tumbler test’; see Figure 1) may be used to aid diagnosis, where the side of a clear glass should be firmly pressed against the rash; if it does not fade under pressure, the patient may have septicaemia and needs urgent medical attention (see Figure 2) [3] , [12] . However, it should be noted that the National Institute for Health and Care Excellence’s Clinical Knowledge Summary states that the glass test should not be used solely for diagnosing bacterial meningitis and meningococcal septicaemia [13] .

Figure 1: Glass or ‘tumbler’ test

Source: Alamy Stock Photo / Mediscan

A rash that does not fade under pressure is a sign of meningococcal septicaemeia. However, this test should not be used solely in diagnosis.

The classic rash associated with meningitis usually looks like small, red pin pricks that spreads quickly over the body and turns into red or purple blotches. However, a rash is not always present with meningitis and may be less visible in darker skin tones. It is, therefore, important to also check the soles of the feet, palms of the hands and eyelids in the patient with suspected meningitis [3] .

Furthermore, if the patient is a child or young person, it is important for healthcare professionals to consider other non-specific features of their presentation, such as the level of parental or carer concern (particularly compared with previous illness in the child or young person or their family), how quickly the illness is progressing, and clinical judgement of the overall severity of the illness [3] .

Figure 2: Immediate management of suspected meningitis in children and neonates

Source: National Institute for Health and Care Excellence [3]

CRP: C-reactive protein; CSF: cerebrospinal fluid; CT: computerised tomography; EDTA: ethylenedianinetetraacetic acid; FBC: full blood count; GCS: Glasgow coma scale; HSV: herpes simplex virus; ICP: intracranial pressure; IV: intravenous; LFT’s: liver function tests; LP: lumbar puncture; Mg: magnesium test; PCR: polymerase chain reaction; TB: tuberculosis; U+E’s: urea and electrolytes; WBC: white blood cell.

Prevention and vaccination

As meningitis can be caused by several different pathogens, there are several vaccinations available that can offer some protection against the disease (see Table) [10] .

Case studies

Several case studies show how assessment and treatment of meningitis varies by patient. All patients, events and incidents in these case studies are fictitious and should only be used as examples in the clinical setting.

Case study 1: a toddler with mild meningitis

Eva is a three-year-old girl who is on holiday with her grandparents. Eva is unusually tired and is complaining that her legs are aching. This morning, Eva’s grandparents noticed a very small purple rash on her leg, and so they have to come to the pharmacy for advice. Eva has no fever or any other symptoms, but her grandmother has a cold sore.

Assessment and diagnosis

The rash does not fade under pressure when a glass is pressed against it.

Petechiae and purpura are significantly more common with invasive meningococcal infection than with pneumococcal meningitis, which rarely presents with a rash [13] . However, although the glass test is widely promoted in patient information leaflets, the National Institute for Health and Care Excellence (NICE) has found no evidence on its use. The test is not promoted in the NICE guidelines. Consequently, the glass test should not be used as the only test for diagnosing the condition [12] . Public Health England is also informed that Eva may have meningitis, and 999 is called.

Treatment options

On arrival at hospital, Eva is showing signs of shock — she is tachycardic with increased drowsiness and cold peripheries. After having initial tests, she is treated for shock with a fluid bolus of 20mL/kg sodium chloride 0.9% over 10 minutes. A lumbar puncture is contraindicated in shock and, therefore, Eva is empirically started on intravenous (IV) ceftriaxone and steroids. She is also started on IV aciclovir, owing to her history of contact with the herpes simplex virus.

Advice and recommendations

Eva is treated with antibiotics for ten days and her grandparents are both prescribed rifampicin as chemoprophylaxis. Antibiotic prophylaxis should be given as soon as possible (ideally within 24 hours) after the diagnosis of the index case [12] .

Case study 2: a baby with meningitis

Katherine is a mother of two young children who comes into the pharmacy and asks for advice. She has a young baby, Jacob, who is six weeks old and Esmé who is four years old. Jacob has a blocked nose and fever. Katherine explains that Esmé had gastroenteritis with cold symptoms and fever last week, but no rash. Katherine is worried about Jacob and asks for advice.

Katherine brings her children into the consultation room for further assessment. Jacob has been more unsettled than usual and does not want to feed as much as normal. Upon examination, Jacob has a rash on his stomach and back, which his mother says was not present this morning. His rash looks like red blotches and does not fade with the glass test. Owing to his age, Jacob is too young to have received any vaccinations.

It is important to remain calm and inform Katherine that you think Jacob may have meningitis, as he has the characteristic rash, as well as other known symptoms. Jacob needs to be taken to hospital for emergency assessment and an ambulance is called.

On arrival at the hospital, Jacob has blood tests taken and a lumbar puncture. He is started on intravenous (IV) cefotaxime with amoxicillin (if he was three months or older, IV ceftriaxone would be administered) with full-volume maintenance fluids and enteral feeds as tolerated [3] . Corticosteroids must not be used in children aged younger than three months with suspected or confirmed bacterial meningitis.

Jacob has hourly observations initially for heart rate, blood pressure, respiratory rate, oxygen saturation, fluid balance and Glasgow Coma Scale (GCS). The GCS is a neurological scale used to describe the level of consciousness in a person following a traumatic brain injury — the lower the number, the more severe the brain injury. Public Health England is also informed that Jacob may have meningitis.

In children younger than three months, ceftriaxone may be used as an alternative to cefotaxime (with or without ampicillin or amoxicillin); however, it should not be used in premature babies or in babies with jaundice, hypoalbuminaemia or acidosis, as it may exacerbate hyperbilirubinaemia [3] .

The microbiology consultant calls the ward to confirm that Jacob has Group B streptococcal meningitis. As per the National Institute for Health and Care Excellence’s guidelines, Jacob will need treating with IV cefotaxime for at least 14 days [3] .

Before discharge, Katherine is given the contact details of several patient support organisations, including meningitis charities that can offer support and written information to signpost her to further help. Jacob has an audiology appointment booked in two weeks and will be seen by a paediatrician after this. At this appointment, the following morbidities will be considered:

• Hearing loss;
• Orthopaedic complications;
• Skin complications (including scarring from necrosis);
• Psychosocial problems;
• Neurological and developmental problems;
• Kidney failure.

Outcome of the advice

Jacob makes a full recovery from his meningitis with no lasting effects. 

Case study 3: an adult with suspected meningitis

Jane is a paediatric haematology nurse who comes into the pharmacy asking to buy paracetamol. She says she has a terrible headache and upset stomach. She seems confused and disorientated; talking to her further highlights that something is not right.

Jane explains that she has not felt well since last night and has spent most of the day in bed, as she feels like she has no energy. However, some of what Jane also says does not make sense, and she is finding it hard to follow the conversation. She has no fever or rash.

Vomiting, severe headache and confusion are all symptoms of meningitis. Using a symptoms checker, such as the one by the Meningitis Research Foundation , to help with decision making.

Upon further questioning, it is clear that Jane must go to a hospital immediately and an ambulance is called. Jane presented with confusion and disorientation, which might indicate a stroke; however, bacterial meningitis can cause stroke.

When the paramedics arrive at the pharmacy, they find Jane has a Glasgow Coma Scale of 4/15. Once Jane arrives in hospital, they follow the stroke pathway, but she is now also febrile. Jane has a lumbar puncture and the results show she has bacterial meningitis. She also has a CT scan that shows an infarct on her right temporal lobe. Jane is treated in hospital with antibiotics and steroids, and eventually discharged to go home after three weeks.

Jane was working in the paediatric intensive care unit the week preceding the symptoms. She was looking after a child with Haemophilus influenzae type b (Hib). The patient was in a neutral pressure side room with a positive pressure lobby — this is an infection control measure to prevent the spread of microbial contaminants outside the patient’s side room. The lobby had been used to store an apheresis machine; however, the door between the side room and lobby had been left open, inadvertently leading to the exposure of Hib.

Although Jane has now fully recovered, she has to wear glasses owing to damage to her optical nerve. She also has tinnitus and occasionally suffers from severe headaches.

Recovering from meningitis/complications

Some of the most common complications associated with meningitis are [10] :

• Hearing loss, which may be partial or total — people who have had meningitis will usually have a hearing test after a few weeks to check for any problems;
• Recurrent seizures;
• Problems with memory and concentration;
• Problems with coordination, movement and balance;
• Learning difficulties and behavioural problems;
• Vision loss, which may be partial or total;
• Loss of limbs — amputation is sometimes necessary to stop the infection spreading through the body and remove damaged tissue;
• Bone and joint problems, such as arthritis;
• Kidney problems.

Overall, it is estimated that up to one in every ten cases of bacterial meningitis is fatal.

Useful resources

• Meningitis Research Foundation
• Meningitis Now
• National Institute for Health and Care Excellence clinical guideline [CG102]

[1] UNICEF, WHO, World Bank Group & United Nations. Levels and Trends in Child Mortality Report. 2017. Available at: https://www.unicef.org/publications/index_101071.html (accessed June 2019)

[2] Public Health England. Invasive meningococcal disease in England: annual laboratory confirmed reports for epidemiological year 2017 to 2018. 2018. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/751821/hpr3818_IMD.pdf (accessed June 2019)

[3] National Institute for Health and Care Excellence. Meningitis (bacterial) and meningococcal septicaemia in under 16s: recognition, diagnosis and management. Clinical guideline [CG102]. 2015. Available at: https://www.nice.org.uk/guidance/cg102 (accessed June 2019)

[4] Davila S, Wright VJ, Khor CC et al . Genome-wide association study identifies variants in the CFH region associated with host susceptibility to meningococcal disease. Nat Genet 2010;42(9):772–776. doi: 10.1038/ng.640

[5] Domingo P, Pomar V, de Benito N & Coll P. The spectrum of acute bacterial meningitis in elderly patients.  BMC Infect Dis 2013;13:108. doi: 10.1186/1471-2334-13-108

[6] Paireau J, Chen A, Broutin H et al . Seasonal dynamics of bacterial meningitis: a time-series analysis. Lancet Glob Health 2016;4(6):e370–e377. doi: 10.1016/S2214-109X(16)30064-X

[7] Cooper LV, Robson A, Trotter CL et al . Risk factors for acquisition of mening ococcal carriage in the African meningitis belt. Trop Med Int Health 2019;24(4):392–400. doi: 10.1111/tmi.13203

[8] Kolappan S, Coureuil M, Yu X et al . Structure of the Neisseria meningitidis type IV pilus.  Nat Commun 2016;7:13015. doi: 10.1038/ncomms13015

[9] Tunkel AR & Scheld WM. Pathogenesis and pathophysiology of bacterial meningitis. Clin Microbiol Rev 1993;6(2):118–136. doi: 10.1128/CMR.6.2.118

[10] Sáez-Llorens X & McCracken GH Jr. Bacterial meningitis in children. Lancet 2003;361(9375):2139–2148. doi: 10.1016/S0140-6736(03)13693-8

[11] NHS Choices. Meningitis. 2019. Available at: https://www.nhs.uk/conditions/meningitis (accessed June 2019)

[12] Baines P, Reilly N & Gill A. Paediatric meningitis: clinical features and diagnosis. Clin Pharm 2009;1:307–310. URI: 10971150

[13] The National Institute for Health and Care Excellence. Clinical Knowledge Summaries: meningitis — bacterial meningitis and meningococcal disease. 2019. Available at: https://cks.nice.org.uk/meningitis-bacterial-meningitis-and-meningococcal-disease (accessed June 2019)

[14] NHS Choices. Pneumococcal vaccination. 2019. https://www.nhs.uk/conditions/vaccinations/pneumococcal-vaccination (accessed June 2019)

[15] Cooper LV, Robson A, Trotter C et al. Risk factors for acquisition of meningococcal carriage in the African meningitis belt. Trop Med Int Health 2019;24(4):392–400. doi: 10.1111/tmi.13203

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Acute Bacterial Meningitis Case Study

Bacterial meningitis is a life-threatening infection of the linings or meninges of the brain and spinal cord. Survivors may experience hearing loss or deafness, brain damage, seizures, and/or the retention of fluid on the brain. Symptoms may be mistaken for the flu. Find out what happens to a 14-year-old when bacteria invade his central nervous system.

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• Second Opinion

Meningitis in Children

What is meningitis in children?

Meningitis is a swelling (inflammation) of the thin membranes that cover the brain and the spinal cord. These membranes are called the meninges.

What causes meningitis in a child?

Meningitis is most often caused by a bacterial or viral infection that moves into the cerebral spinal fluid (CSF). CSF is the fluid that protects and cushions the brain and spinal cord. A fungus or parasite may also cause meningitis. This is more common only in children with a weak immune system.

Meningitis caused by a virus is more common and usually less severe. Bacterial meningitis is usually more severe and may lead to long-term complications or death.

Viruses that can cause meningitis include polioviruses, the mumps virus (paramyxovirus), the flu virus, and West Nile virus.

Bacteria that can cause meningitis include group B streptococcus, E. coli, Haemophilus influenzae type b (Hib), and a strep bacteria that causes pneumonia. Syphilis, tuberculosis, and Lyme disease bacteria can also cause meningitis. The bacteria, viruses, and fungi that cause meningitis usually grow in a person’s respiratory tract. A child may have no symptoms at all, but may carry the organism in his or her nose and throat. They may be spread by:

Close contact with someone carrying the infection

Touching infected objects, such as doorknobs, hard surfaces, or toys, and then touching nose, mouth, or eyes

Droplets from a sneeze, close conversation, or kissing

An infection usually starts in the respiratory tract. In a child, it may first cause a cold, sinus infection, or ear infection. It can then go into the bloodstream and reach the brain and spinal cord.

Which children are at risk for meningitis?

A child is more at risk for meningitis if he or she has an infection caused by a number of viruses, bacteria, or fungi. Children with a weakened immune system are at great risk.

What are the symptoms of meningitis in a child?

The symptoms of meningitis vary depending on what causes the infection. The symptoms may start several days after your child has had a cold and runny nose, or diarrhea and vomiting. Symptoms can occur a bit differently in each child. Symptoms may appear suddenly. Or they may develop over several days.                                                                                                                                         

In babies, symptoms may include:

Irritability

Sleeping more than usual

Poor feeding

Crying that can’t be soothed

High-pitched cry

Arching back

Bulging soft spots on the head (fontanelles)

Changed temperament

Purple-red splotchy rash

In children age 1 or older, symptoms may include:

Refusing to eat

Reduced level of consciousness

Eyes sensitive to light (photophobia)

Nausea and vomiting

Neck stiffness

A purple-red splotchy rash

The symptoms of meningitis can be like other health conditions. Make sure your child sees his or her healthcare provider for a diagnosis.

How is meningitis diagnosed in a child?

The healthcare provider will ask about your child’s symptoms and health history. He or she may also ask about your family’s health history. He or she will give your child a physical exam. Your child may also have tests, such as:

Lumbar puncture (spinal tap).  This is the only test that diagnoses meningitis. A needle is placed into the lower back, into the spinal canal. This is the area around the spinal cord. The pressure in the spinal canal and brain is measured. A small amount of cerebral spinal fluid (CSF) is removed and sent for testing to see if there is an infection or other problems.

Blood tests. These can help diagnose infections that cause meningitis. 

CT scan or MRI.  These are tests that show images of the brain. A CT scan is sometimes done to look for other conditions that may cause similar symptoms as meningitis. An MRI may show inflammatory changes in the meninges. These tests give more information. But meningitis can’t be diagnosed using these tests alone.

Nasal, throat, or rectal swabs. These tests help diagnose viral infections that cause meningitis.

How is meningitis treated in a child?

Treatment will depend on your child’s symptoms, age, and general health. It will also depend on how severe the condition is.                                         

Treatment varies by type of meningitis. The treatments by type include:

Bacterial meningitis.  Treatment is started as quickly as possible. The healthcare provider will give your child IV (intravenous) antibiotics, which kill bacteria. Your child will also get a corticosteroid medicine. The steroid works by decreasing the swelling (inflammation) and reducing pressure that can build up in the brain. Steroids also reduce the risk for hearing loss and brain damage. 

Viral meningitis.  Most children get better on their own without treatment. In some cases, treatment may be done to help ease symptoms. There are no medicines to treat the viruses that cause viral meningitis. The only exception is herpes simplex virus, which is treated with IV antiviral medicine. Babies and children with a weakened immune system may need to stay in the hospital.

Fungal meningitis.  Your child may get IV antifungal medicine.

Tuberculous (TB) meningitis.  Your child will be treated with a course of medicines over 1 year. Treatment is done with several medicines for the first few months. This is followed by other medicines for the remaining time.

While your child is recovering from meningitis, he or she may also need:

Increased fluid intake by mouth or IV fluids in the hospital

Medicines to reduce fever and headache. Don’t give aspirin or medicine that contains aspirin to a child younger than age 19 unless directed by your child’s provider. Taking aspirin can put your child at risk for Reye syndrome. This is a rare but very serious disorder. It most often affects the brain and the liver.

Supplemental oxygen or breathing machine (respirator) if your child has trouble breathing

Talk with your child’s healthcare providers about the risks, benefits, and possible side effects of all treatments.

What are the possible complications of meningitis in a child?

Bacterial meningitis is usually more severe and may lead to long-term complications. Some children may have long-term problems with seizures, brain damage, hearing loss, and disability. Bacterial meningitis can also cause death.

How can I help prevent meningitis in my child?

Several vaccines are available to prevent some of the bacterial infections that can cause meningitis. These include:

H. influenzae type b vaccine (Hib). This is given as a 3- or 4-part series during your child's routine vaccines starting at 2 months old.

PCV13 pneumococcal vaccine. The American Academy of Pediatrics recommends this vaccine for all healthy children younger than age 2. PCV13 can be given along with other childhood vaccines. It is recommended at ages 2 months, 4 months, 6 months, and 12 to 15 months. One dose is also advised for older children who did not get the 4-dose series, and for those at high risk for pneumococcal disease.

PPSV23 pneumococcal vaccine . This vaccine is also recommended for older children at high risk for pneumococcal disease.

Meningococcal vaccine. This vaccine is part of the routine vaccine schedule. It is given to children ages 11 to 12, with a booster given at age 16. It is given to teens entering high school if they were not vaccinated at age 11 or 12. A booster is also given at age 16 to 18, or up to 5 years later. Babies and young children at increased risk may also have this vaccine. Ask your child's healthcare provider about the number of doses and when they should be given.

Vaccines that protect against viruses such as measles, mumps, chickenpox, and the flu can prevent viral meningitis.                                                    

Talk with your child’s healthcare provider if you have questions about the vaccines. 

You and your child can do other things to prevent the spread of infections. Proper handwashing and staying away from people who are sick can help prevent meningitis.

When should I call my child’s healthcare provider?

Call the healthcare provider if your child has:

Not received vaccines

Contact with someone who has meningitis

Symptoms that don’t get better, or get worse

New symptoms

Key points about meningitis in children

Meningitis is an inflammation of the thin membranes that cover the brain and the spinal cord.

It is most often caused by a bacterial or viral infection that moves into the cerebral spinal fluid. A fungus or parasite may also cause meningitis.

A lumbar puncture (spinal tap) is the only test that diagnoses meningitis. A needle is placed into the lower back, into the spinal canal.

Several vaccines are available to prevent some of the bacterial and viral infections that can cause meningitis.

Tips to help you get the most from a visit to your child’s healthcare provider:

Know the reason for the visit and what you want to happen.

Before your visit, write down questions you want answered.

At the visit, write down the name of a new diagnosis, and any new medicines, treatments, or tests. Also write down any new instructions your provider gives you for your child.

Know why a new medicine or treatment is prescribed and how it will help your child. Also know what the side effects are.

Ask if your child’s condition can be treated in other ways.

Know why a test or procedure is recommended and what the results could mean.

Know what to expect if your child does not take the medicine or have the test or procedure.

If your child has a follow-up appointment, write down the date, time, and purpose for that visit.

Know how you can contact your child’s provider after office hours. This is important if your child becomes ill and you have questions or need advice.

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• Research article
• Open access
• Published: 04 June 2021

Clinical features of bacterial meningitis among hospitalised children in Kenya

• Christina W. Obiero 1 , 2 ,
• Neema Mturi 1 ,
• Salim Mwarumba 3 ,
• Moses Ngari 1 , 4 ,
• Charles R. Newton 1 , 5 ,
• Michaël Boele van Hensbroek 2 &
• James A. Berkley 1 , 4 , 6  

BMC Medicine volume  19 , Article number:  122 ( 2021 ) Cite this article

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Diagnosing bacterial meningitis is essential to optimise the type and duration of antimicrobial therapy to limit mortality and sequelae. In sub-Saharan Africa, many public hospitals lack laboratory capacity, relying on clinical features to empirically treat or not treat meningitis. We investigated whether clinical features of bacterial meningitis identified prior to the introduction of conjugate vaccines still discriminate meningitis in children aged ≥60 days.

We conducted a retrospective cohort study to validate seven clinical features identified in 2002 ( KCH-2002 ): bulging fontanel, neck stiffness, cyanosis, seizures outside the febrile convulsion age range, focal seizures, impaired consciousness, or fever without malaria parasitaemia and Integrated Management of Childhood Illness (IMCI) signs: neck stiffness, lethargy, impaired consciousness or seizures, and assessed at admission in discriminating bacterial meningitis after the introduction of conjugate vaccines. Children aged ≥60 days hospitalised between 2012 and 2016 at Kilifi County Hospital were included in this analysis. Meningitis was defined as positive cerebrospinal fluid (CSF) culture, organism observed on CSF microscopy, positive CSF antigen test, leukocytes ≥50/μL, or CSF to blood glucose ratio <0.1.

Among 12,837 admissions, 98 (0.8%) had meningitis. The presence of KCH-2002 signs had a sensitivity of 86% (95% CI 77–92) and specificity of 38% (95% CI 37–38). Exclusion of ‘fever without malaria parasitaemia’ reduced sensitivity to 58% (95% CI 48–68) and increased specificity to 80% (95% CI 79–80). IMCI signs had a sensitivity of 80% (95% CI 70–87) and specificity of 62% (95% CI 61–63).

Conclusions

A lower prevalence of bacterial meningitis and less typical signs than in 2002 meant the lower performance of KCH-2002 signs. Clinicians and policymakers should be aware of the number of lumbar punctures (LPs) or empirical treatments needed for each case of meningitis. Establishing basic capacity for CSF analysis is essential to exclude bacterial meningitis in children with potential signs.

Peer Review reports

Childhood bacterial meningitis is associated with significant mortality and neurocognitive sequelae [ 1 , 2 ]. The disease burden is highest in low- and middle-income countries (LMICs) where a quarter of children who survive vaccine-preventable meningitis develop post-discharge complications [ 2 , 3 ]. Prompt recognition and antimicrobial treatment with cerebrospinal fluid (CSF) penetration for an adequate duration are critical.

CSF culture is the gold standard for bacterial meningitis but has limited sensitivity [ 4 ] as it may be compromised by prior administration of antimicrobials [ 5 ] and is usually unavailable or unreliable in public hospitals in sub-Saharan Africa. Public hospitals also often lack adequate CSF microscopy capacity, and lumbar puncture (LP) may be commonly ordered but not done [ 6 , 7 ]. Thus, antimicrobial management decisions are often based on clinical features only.

The World Health Organization (WHO) advises suspecting bacterial meningitis if one or more of the following are present: convulsions, inability to drink, irritability, lethargy, impaired consciousness, a bulging fontanel, or neck stiffness [ 8 ]. However, this recommendation is based on limited evidence collected prior to the introduction of Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae conjugate vaccines targeting the leading causes of bacterial meningitis.

In the Gambia ~20 years ago, a set of Integrated Management of Childhood Illness (IMCI) signs (lethargy, impaired consciousness, convulsions, or a stiff neck) [ 9 ] had 98% sensitivity and 72% specificity in predicting bacterial meningitis [ 10 ]. Concurrently, among children aged ≥60 days at Kilifi County Hospital (KCH), Kenya, a bulging fontanel, neck stiffness, cyanosis, seizures outside the febrile convulsions age range, focal seizures, and impaired consciousness were identified as indicators of bacterial meningitis ( KCH-2002 ) [ 11 ]. These findings were incorporated into Kenyan national paediatric guidelines [ 12 ].

Hib and 10-valent pneumococcal conjugate vaccines at 6, 10, and 14 weeks of age without booster were introduced in Kenya in 2001 and 2011, respectively, resulting in a markedly reduced incidence and mortality from bacterial meningitis [ 13 , 14 , 15 , 16 , 17 ]. Since the early 2000’s severe malaria, which may mimic bacterial meningitis [ 18 ], has declined, with changes in age and disease profile reported at several centres in Africa [ 19 , 20 , 21 ].

Changes in epidemiology, patient profile and differential diagnoses may have altered associations between clinical features and bacterial meningitis. We therefore performed a revalidation study of the KCH-2002 and IMCI signs among children aged ≥60 days.

Location and participants

KCH is a public hospital serving a mostly rural population. Paediatric care is supported by the KEMRI/Wellcome Trust Research Programme. Children aged 60 days to 13 years hospitalised at KCH between January 1, 2012, and December 31, 2016, were included in this analysis.

All children admitted were systematically assessed using standardised demographic and clinical proforma by trained clinicians at admission, and data were entered on a database in real-time. All admissions had a complete blood count, malaria slide, and blood culture. LP was performed at admission if suggestive signs were present, or if a child developed new clinical features of meningitis according to the WHO [ 8 ] and Kenyan guidelines [ 12 ] detected through daily clinical reviews until discharge. LP was deferred in children with cardiorespiratory compromise or suspicion of raised intracranial pressure [ 22 ]. Children with suspected meningitis were treated empirically with penicillin plus chloramphenicol or ceftriaxone (as per national and WHO guidelines [ 8 , 12 ]) while awaiting LP results. Once available, treatment was modified based on culture and susceptibility profile as needed. Data collection (SSC1433) and this analysis (SSC3001) were approved by the KEMRI Scientific and Ethics Review Unit.

Laboratory analysis

CSF examination included leukocyte and red blood cell (RBC) count using the Neubauer counting chamber method, and if leukocyte count >10 cells/μl, differential leukocyte count, Gram and Indian ink staining, latex antigen agglutination tests (Wellcogen™ Bacterial Antigen kit for S. pneumoniae , H. influenzae , N. meningitidis, and CrAg Lateral Flow Assay kit Ref CR2003 for Cryptococcus neoformans ) were done. CSF and blood samples were cultured, and pathogens identified using standard methods as previously described [ 11 , 18 ]. Coagulase-negative S taphylococci were considered non-significant [ 23 ]. CSF protein, glucose, and concurrent blood glucose were measured on an ILab Aries analyser (Werfen, Germany). External quality assurance was by the United Kingdom External Quality Assessment Service, and Good Clinical Laboratory Practice was accredited by Qualogy, UK [ 11 ].

Definitions

For this analysis, we used the KCH-2002 [ 11 ] definition of bacterial meningitis: (i) positive CSF culture for a known pathogen, (ii) positive CSF antigen test, (iii) an organism observed on CSF microscopy (Gram stain or Indian Ink), (iv) CSF leucocyte count ≥50 cells/μL, or (v) CSF to blood glucose ratio <0.1. We also defined possible meningitis as CSF leucocyte count >10–49 cells/μL in the absence of the above criteria.

Statistical analysis

For the primary analysis, children who underwent LP not meeting meningitis criteria or without an LP were classified as not having meningitis, as was assumed in KCH-2002 . We initially excluded children with possible meningitis [ 11 ] and calculated the highest criterion for meningitis in the order given above.

We examined the performance of KCH-2002 [ 11 ] and IMCI signs (neck stiffness, lethargy, impaired consciousness, or seizures) [ 9 ] at admission by calculating their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for meningitis diagnosed by LP either at admission or at any time during hospitalisation versus no meningitis, defined as negative CSF analysis or no clinical suspicion of meningitis until discharge from hospital. We calculated the number of LPs needed to identify one case of meningitis as the inverse of the risk difference obtained by subtracting the prevalence of meningitis in each group from that in the group without the indicators of interest. As sensitivity analyses, we (i) included possible meningitis cases, (ii) excluded those who died before LP, and (iii) used a narrow microbiological definition of meningitis (positive CSF culture for a known pathogen, positive CSF antigen test, an organism observed on CSF microscopy (Gram stain or Indian Ink), or CSF leucocyte count >10 cells/μL plus a positive blood culture).

Proportions were compared using the chi-squared test or Fisher’s exact test. Continuous variables were compared using Wilcoxon rank-sum test. All analyses used Stata version 15 (Stata Corp, USA).

There were 12,986 admissions aged 60 days to 13 years: 2975 (23%) <1 year, 6248 (48%) 1–4 years, and 3763 (29%) ≥5 years old; 463 (3.6%) were HIV antibody positive. Two thousand six hundred-two (20%) children had an LP, of which 409 (16%) were aged <1 year. LPs were more commonly done among children aged 1–5 years [1484/6248 (24%)] than in children aged >5 years [709/3,763 (19%)] or <1 year [409/2975 (14%)], P<0.001 . A positive malaria smear was present in 1189 (46%) children who had an LP. Of 10,384 children who did not have an LP, 565 died before an LP (193 (34%) <1 year, 230 (41%) 1–5 years and 142 (25%) ≥5 years) while 9819 survived (2373 (24%) <1 year, 4534 (46%) 1–5 years, and 2912 (30%) ≥5 years) ( P<0.001 ). Median [interquartile range (IQR)] age of 565 children who died before an LP was 21 months (8.0–60) compared to 20 months (9.5–59) in 88 children who died after an LP ( P=0.874 ).

Meningitis cases

Ninety-eight children had meningitis (Fig. 1 , Group C): 0.8% of 12,986 admissions and 3.8% of 2602 children with an LP. Fifty-one (0.4%) children had possible meningitis (Group D) and were excluded from the primary analysis. Median (IQR) ages of children with meningitis, possible meningitis, or no meningitis were 25 (7.4–77), 40 (11–83), and 29 (12–67) months, respectively (P=0.167) . Fifteen (15%) meningitis cases died during hospitalisation; 2.3% (15/653) of all inpatient deaths.

Flow chart of study participants. Abbreviation: LP, lumbar puncture

Leading CSF pathogens were S. pneumoniae (16 culture-positive and 4 antigen-positive) and H. influenzae (5 culture-positive and 3 antigen-positive) (Table 1 ). Fifty (51%) meningitis cases had CSF leukocyte count ≥50/μl only. One hundred twenty (4.8%) of 2521 children had differential leukocyte count done of which 118 (98%) had polymorphonuclear cell predominance (≥60%) and 77 had meningitis. Five (2.0%) of 249 children with CSF RBC count ≥500 cells/μL had positive CSF cultures while 4 (1.6%) children missed leukocyte counting due to grossly blood-stained CSF. Thirty-three (34%) children with meningitis had positive blood culture; 23 matched CSF isolates (13 S. pneumoniae , 4 H. influenzae , 2 Salmonella spp., and 1 each of E. coli , K. pneumoniae , P. aeruginosa , and C. neoformans ). Forty-one (42%) meningitis cases had turbid CSF.

Admission clinical features

Two thousand three hundred thirty (79%), 3762 (60%), and 2007 (54%) children aged <1, 1–5, and ≥5 years, respectively, presented with KCH-2002 signs ( P<0.001 ), while 899 (30%), 2661 (43%), and 1391 (37%) had IMCI signs ( P<0.001 ). Bulging fontanel, neck stiffness, impaired consciousness, seizures outside the febrile convulsion age range, focal seizures, history of fever, and axillary temperature ≥39°C were more common among children with meningitis than without, and malaria was less common (Table 2 ). Of 8099 children with KCH-2002 signs, 485 (6.0%) died before LP (277 (57%) within 24 h of admission). Of 4951 children with IMCI signs, 359 (7.3%) died before LP (240 (67%) within 24 h of admission).

Performance of clinical features

One or more KCH-2002 signs were present in 8099 children, of whom 84 (1.0%) had meningitis compared with 14/4836 (0.3%) without KCH-2002 signs: sensitivity 86% (95% CI 77–92), specificity 38% (95% CI 37–38), PPV 1.0% (95% CI 0.8–1.3), and NPV 100% (95% CI 99–100). One hundred thirty-four children (95% CI 99–208) presenting with ≥1 KCH-2002 signs would need to undergo an LP for each case of meningitis identified (Table 3 ).

One or more IMCI signs were present in 4951 children, of whom 78 (1.6%) had meningitis compared with 20/7984 (0.3%) without IMCI signs: sensitivity 80% (95% CI 70–87), specificity 62% (95% CI 61–63), PPV 1.6% (95% CI 1.3–2.0), and NPV 100% (99%CI 99–100). Seventy-six children (95% CI 59–104) presenting with ≥1 IMCI signs would need to undergo an LP for each case of meningitis identified (Table 3 ).

Admission versus later LP

Thirty-three (34%) meningitis cases had their LP after admission, of which 6/33 (18%) and 8/33 (24%) were not identified by KCH-2002 signs and IMCI signs, respectively, at admission. Seven (7.1%) meningitis cases were not identified by either KCH-2002 signs or IMCI signs at admission (Fig. 2 ).

Clinical features of meningitis in 98 children with definite meningitis. Abbreviations: KCH-2002, previously identified signs at Kilifi Country Hospital; IMCI, Integrated Management of Childhood Illness. a History of fever with positive malaria smear ( n =1), history of diarrhoea ( n =2), history of vomiting ( n =2), oedema ( n =1), palmar pallor ( n =1), severe acute malnutrition ( n =2), died ( n =2)

Sensitivity analysis

Excluding 565 who died before an LP (Group G) and including 51 cases with possible meningitis (Group D) as ‘meningitis’ gave similar results for KCH-2002 and IMCI signs (Table S 2 ). Fifty children with microbiologically confirmed meningitis fulfilled criteria as follows: 31 positive CSF cultures only (of which 23 had positive blood culture), 7 positive antigen tests only (of which 2 had positive blood culture), 5 positive microscopies (of which 2 had CSF leukocyte count >10), and 7 CSF leukocyte counts >10 cells/μL plus positive blood culture. For microbiologically confirmed meningitis, KCH- 2002 signs had a sensitivity of 90% (95% CI 78–97) and specificity of 39% (95% CI 38–39). IMCI signs had a sensitivity of 76% (95% CI 62–87) and specificity of 63% (95% CI 62–64).

Misdiagnosis of bacterial meningitis based on clinical signs only may result in overtreatment with prolonged courses of antimicrobials, or undertreatment of missed cases [ 24 ], both contributing to mortality and selection of resistant organisms.

We studied a large cohort of hospitalised children to validate the clinical features of bacterial meningitis. Using the same definitions and inclusion criteria as in 2002, we observed a reduction in the prevalence of bacterial meningitis among paediatric admissions at our centre from 2% in 2001–2002 [ 11 ] to 0.8% in 2012–2016. There was also a decline in annual paediatric admissions and number of LPs done. However, we observed an increase in the prevalence of KCH-2002 signs (55% in 2001–2002 vs 63% in 2012–2016, P<0.001 ) and a decrease in the prevalence of IMCI signs (42% in 2001–2002 vs 38% in 2012–2016, P<0.001 ) [ 11 ]. Although S. pneumoniae and H. influenzae remained the leading causes of bacterial meningitis, cases arising from these organisms declined over time (57 vs 20 pneumococcal, and 66 vs 8 H. influenzae cases, comparing 1994–1998 [ 25 ] to 2012-2016). These changes may be attributed to conjugate vaccination and herd immunity in older children. Our study excluded infants aged <60 days who typically have bacterial meningitis due to different pathogens [ 17 ], different clinical presentation [ 26 ], and alternative diagnoses such as birth asphyxia [ 27 ], and associated higher risk of neurological disability and mortality [ 17 ].

Clinical guidelines for limited-resource settings should comprise straightforward features, easily identifiable by clinicians [ 28 ]. Overall, we found that the clinical signs at admission had lower sensitivity and PPV in discriminating children with bacterial meningitis than in 2002 [ 11 ]. KCH-2002 and IMCI signs did not statistically significantly differ in the proportions of meningitis cases missed (14% vs 20%, P=0.258 ), although numbers were limited for this comparison. Results did not appear to be altered by the exclusion of children who died before LP or using a narrower microbiological case definition.

History of fever was common with (90%) or without meningitis (68%) and nearly half of the LPs were done in children with malaria since signs overlap. The previous KCH-2002 analysis found that exclusion of fever without malaria parasitaemia from the screening rule had lower sensitivity but higher specificity (sensitivity 79%, specificity 80%, PPV 8.0%) than when it was included (sensitivity 97%, specificity 44%, PPV 3.5%) [ 11 ]. The present analysis also shows that although the specificity of KCH-2002 signs excluding fever without malaria parasitaemia has not changed, sensitivity was again markedly reduced (to 58% from 86%). Malaria parasitaemia has been shown to augment predictive models for bacterial meningitis [ 11 , 29 ]; however, the significant morbidity and mortality associated with meningitis means a screening rule with higher sensitivity may be favourable despite lower specificity.

Although conjugate vaccination has resulted in a reduction in bacterial meningitis cases, antimicrobial resistance to penicillin [ 30 ] and chloramphenicol [ 31 , 32 ] is reported. Ceftriaxone as a first-line treatment for bacterial meningitis has been associated with lower resistance rates, and reduction in mortality and neurological complications compared to chloramphenicol [ 32 , 33 ]. Thus, clinical decision rules with optimal performance in predicting bacterial meningitis contribute to antimicrobial stewardship by guiding initiation of treatment and minimising selection of resistant microorganisms.

Limitations

An inescapable limitation is that a selective group of children underwent an LP based on clinical suspicion at admission or later during admission. It is possible that a number of bacterial meningitis cases may have been missed due to apparent recovery and discharge. However, we believe that the higher than usual clinical staffing, training oversight, and availability of laboratory resources due to the presence of the research programme helped limit the chances of missed meningitis cases. Although performing LPs in all children is diagnostically optimal and would provide an understanding of the true prevalence of meningitis, this is not possible due to the risks involved and would not be ethically justified [ 22 ]. Our dataset may not be perfect, but it addresses research gaps in similar settings. Of 2602 LPs done, 1026 (39%) were performed after admission; 33/98 (34%) meningitis cases were diagnosed after admission, underscoring the importance of daily clinical reviews following standard guidelines. Our assumption of true negatives in children who did not develop signs suggestive of meningitis during hospitalisation and were discharged home alive is valid. The highest proportion of children having an LP was in those aged 1–5 years. KCH-2002 signs were most frequent among children aged <1 year, fewer LPs done in this age group may be attributed to early deaths or more LPs being deferred due to contraindications since most deaths occurred in young infants (7.4%, 4.3%, and 4.4% deaths in children aged <1, 1–5, and ≥5 years, respectively, P<0.001 ). However, age bias in LPs may have affected our findings. Importantly, our aim was to inform clinical guidelines for empiric treatment and indications for LP rather than describe the epidemiology of meningitis for which post-mortem LPs would have been necessary.

Molecular tests for bacterial and viral causes were not routinely done, potentially missing true bacterial meningitis cases and falsely including viral meningitis cases. Although differential leukocyte count was done in some CSF samples, it was not included in our standard definition of meningitis. Polymorphonuclear cell predominance can occur in both bacterial and aseptic meningitis [ 34 ]. We lacked data on pre-hospital antibiotic exposure which may be common and has been shown to alter CSF leukocyte count and biochemical profile and impede detection of bacterial pathogens [ 5 , 35 ]. Diagnostic delay may decrease survival [ 36 ] and increase neurological sequelae in Hib meningitis [ 37 ] and may be more of a problem in settings without advanced diagnostic resources such as CSF polymerase chain reaction (PCR) [ 38 ].

Low LP rates reported in settings like ours have raised concerns regarding missing meningitis cases [ 6 , 7 ]. Knowing that a large number of LPs is needed in order to diagnose each case of bacterial meningitis is important in this regard. The KCH-2002 or IMCI signs at admission suggest an LP may be needed in ~40 to 60% of children presenting to the hospital with these signs to achieve >80% sensitivity. There are no studies evaluating the additional discriminatory value of a structured repeated evaluation of signs that develop later during admission, or of biomarkers in this context. Although traumatic LPs are common and may complicate CSF leukocyte interpretation, adjustment of CSF leukocyte count has been shown to lack additional value in predicting meningitis [ 39 ]. In our study, only 5 children with CSF RBC ≥500 cells/μL met our laboratory meningitis criteria. Our results provided important guidance for performing LPs in LMICs settings where there is a paucity of comprehensive data on this important question.

Bacterial meningitis is an uncommon but important diagnosis in children. Declining incidence is welcome but identifying children with meningitis has become more difficult. Clinicians and policymakers should be aware of the number of LPs or empirical treatments needed for each case of bacterial meningitis to be identified, and this may vary with malaria endemicity. The IMCI criteria offer a balance between the more specific KCH-2002 signs (impaired consciousness or any one of bulging fontanel, neck stiffness, cyanosis, seizures outside 6 months to 6 years, or focal seizures) and non-malarial fever. While the IMCI criteria will continue to be used, the number of LPs needed to identify a single case of bacterial meningitis has increased 3-fold from 24 to 76. Clinicians should continue to have a high index of suspicion while assessing children during daily reviews. Support to establish accurate CSF cell counting, Gram stain, and glucose measurement as a minimum in resource-poor settings to optimise antimicrobial treatment is essential to providing effective inpatient paediatric services.

Availability of data and materials

The dataset used and analysed during the current study is available from the KWTRP Data Governance Committee (DGC) on reasonable request ( [email protected] ), ensuring the protection of the privacy, rights and interests of research participants and primary researchers, and upholding transparency and accountability. KWTRP is the custodian of the data used in this analysis, and the KWTRP DGC oversees the internal data repository.

Abbreviations

• Low- and middle-income countries
• Cerebrospinal fluid
• Lumbar puncture

World Health Organization

Haemophilus influenzae type b

Integrated Management of Childhood Illness

Kilifi County Hospital

Positive predictive value

Negative predictive value

Mann K, Jackson MA. Meningitis. Pediatrics Review. 2008;29(12):417–30. https://doi.org/10.1542/pir.29-12-417 .

Article   Google Scholar  

Edmond K, Clark A, Korczak VS, Sanderson C, Griffiths UK, Rudan I. Global and regional risk of disabling sequelae from bacterial meningitis: a systematic review and meta-analysis. Lancet Infect Dis. 2010;10(5):317–28. https://doi.org/10.1016/S1473-3099(10)70048-7 .

Article   PubMed   Google Scholar  

Ramakrishnan M, Ulland AJ, Steinhardt LC, Moisi JC, Were F, Levine OS. Sequelae due to bacterial meningitis among African children: a systematic literature review. BMC Med. 2009;7(1):47. https://doi.org/10.1186/1741-7015-7-47 .

Article   PubMed   PubMed Central   Google Scholar  

Manning L, Laman M, Mare T, Hwaiwhanje I, Siba P, Davis TM. Accuracy of cerebrospinal leucocyte count, protein and culture for the diagnosis of acute bacterial meningitis: a comparative study using Bayesian latent class analysis. Trop Med Int Health. 2014;19(12):1520–4.

Article   CAS   Google Scholar  

Kanegaye JT, Soliemanzadeh P, Bradley JS. Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment. Pediatrics. 2001;108(5):1169–74.

CAS   PubMed   Google Scholar  

Ayieko P, Ogero M, Makone B, Julius T, Mbevi G, Nyachiro W, et al. Characteristics of admissions and variations in the use of basic investigations, treatments and outcomes in Kenyan hospitals within a new Clinical Information Network. Arch Dis Childhood. 2016;101(3):223–9. https://doi.org/10.1136/archdischild-2015-309269 .

Herbert G, Ndiritu M, Idro R, Makani JB, Kitundu J. Analysis of the indications for routine lumbar puncture and results of cerebrospinal fluid examination in children admitted to the paediatric wards of two hospitals in East Africa. Tanzania J Health Res. 2006;8(1):7–10.

WHO. Pocket book of hospital care for children: WHO Press; 2013. Available from: http://www.who.int/maternal_child_adolescent/documents/child_hospital_care/en/ .

WHO IMCI. Integrated Management of Childhood Illness (IMCI) Chart Booklet. Distance Learn Course. 2014;(March):1–76.

Weber MW, Herman J, Jaffar S, Usen S, Oparaugo A, Omosigho C, et al. Clinical predictors of bacterial meningitis in infants and young children in The Gambia. Trop Med Int Health. 2002;7(9):722–31. https://doi.org/10.1046/j.1365-3156.2002.00926.x .

Berkley JA, Versteeg AC, Mwangi I, Lowe BS, Newton CRJC. Indicators of acute bacterial meningitis in children at a rural Kenyan District Hospital. Pediatrics. 2004;114(6):e713–e9. https://doi.org/10.1542/peds.2004-0007 .

MOH. Basic Paediatric Protocols for ages up to 5 years February 2016. Available from: https://www.tropicalmedicine.ox.ac.uk/_asset/file/basic-paediatric-protocols-2016.pdf .

Mwenda JM, Soda E, Weldegebriel G, Katsande R, Biey JN-M, Traore T, et al. Pediatric bacterial meningitis surveillance in the World Health Organization African Region using the invasive bacterial vaccine-preventable disease surveillance network, 2011–2016. Clin Infect Dis. 2019;69(Supplement_2):S49–57.

Cowgill KD, Ndiritu M, Nyiro J, Slack MPE, Chiphatsi S, Ismail A, et al. Effectiveness of haemophilus influenzae type b conjugate vaccine introduction into routine childhood immunization in Kenya. Jama. 2006;296(6):671–8. https://doi.org/10.1001/jama.296.6.671 .

Article   CAS   PubMed   PubMed Central   Google Scholar  

Gessner BD, Adegbola RA. The impact of vaccines on pneumonia: key lessons from Haemophilus influenzae type b conjugate vaccines. Vaccine. 2008;26:B3–8. https://doi.org/10.1016/j.vaccine.2008.04.013 .

Article   CAS   PubMed   Google Scholar  

Wahl B, O'Brien KL, Greenbaum A, Majumder A, Liu L, Chu Y, et al. Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000-15. Lancet Global Health. 2018;6(7):e744–e57. https://doi.org/10.1016/S2214-109X(18)30247-X .

Zunt JR, Kassebaum NJ, Blake N, Glennie L, Wright C, Nichols E, et al. Global, regional, and national burden of meningitis, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17(12):1061–82. https://doi.org/10.1016/S1474-4422(18)30387-9 .

Berkley JA, Mwangi I, Mellington F, Mwarumba S, Marsh K. Cerebral malaria versus bacterial meningitis in children with impaired consciousness. QJM : monthly journal of the Association of Physicians. 1999;92(3):151–7. https://doi.org/10.1093/qjmed/92.3.151 .

Mogeni P, Williams TN, Fegan G, Nyundo C, Bauni E, Mwai K, et al. Age, spatial, and temporal variations in hospital admissions with malaria in Kilifi County, Kenya: a 25-year longitudinal observational study. PLoS Med. 2016;13(6):e1002047. https://doi.org/10.1371/journal.pmed.1002047 .

Nkumama IN, O'Meara WP, Osier FHA. Changes in malaria epidemiology in Africa and new challenges for elimination. Trends Parasitol. 2017;33(2):128–40. https://doi.org/10.1016/j.pt.2016.11.006 .

Njuguna P, Maitland K, Nyaguara A, Mwanga D, Mogeni P, Mturi N, et al. Observational study: 27 years of severe malaria surveillance in Kilifi, Kenya. BMC Med. 2019;17(1):124. https://doi.org/10.1186/s12916-019-1359-9 .

Schulga P, Grattan R, Napier C, Babiker MO. How to use lumbar puncture in children. Arch Dis Child Educ Pract Ed. 2015;100(5):264–71. https://doi.org/10.1136/archdischild-2014-307600 .

Chun S, Kang C-I, Kim Y-J, Lee NY. Clinical Significance of Isolates Known to Be Blood Culture Contaminants in Pediatric Patients. Medicina. 2019;55(10):696. https://doi.org/10.3390/medicina55100696 .

Aipit J, Laman M, Hwaiwhanje I, Bona C, Pomat N, Siba P, et al. Accuracy of initial clinical diagnosis of acute bacterial meningitis in children from a malaria-endemic area of Papua New Guinea. Trans R Soc Trop Med Hyg. 2014;108(7):444–8. https://doi.org/10.1093/trstmh/tru067 .

Mwangi I, Berkley J, Lowe B, Peshu N, Marsh K, Newton CR. Acute bacterial meningitis in children admitted to a rural Kenyan hospital: increasing antibiotic resistance and outcome. Pediatric Infect Dis J. 2002;21(11):1042–8. https://doi.org/10.1097/00006454-200211000-00013 .

Obiero CW, Mturi N, Mwarumba S, Ngari M, Newton C, Boele van Hensbroek M, et al. Clinical features to distinguish meningitis among young infants at a rural Kenyan hospital. Archives of disease in childhood. 2021;106(2):130–6. http://dx.doi.org/10.1136/archdischild-2020-318913 .

Abdul-Mumin A, Cotache-Condor C, Owusu SA, Mahama H, Smith ER. Timing and causes of neonatal mortality in Tamale Teaching Hospital, Ghana: a retrospective study. PLoS One. 2021;16(1):e0245065. https://doi.org/10.1371/journal.pone.0245065 .

Curtis S, Stobart K, Vandermeer B, Simel DL, Klassen T. Clinical features suggestive of meningitis in children: a systematic review of prospective data. Pediatrics. 2010;126(5):952–60. https://doi.org/10.1542/peds.2010-0277 .

Laman M, Manning L, Greenhill AR, Mare T, Michael A, Shem S, et al. Predictors of acute bacterial meningitis in children from a malaria-endemic area of Papua New Guinea. Am J Trop Med Hyg. 2012;86(2):240–5. https://doi.org/10.4269/ajtmh.2012.11-0312 .

Nhantumbo AA, Gudo ES, Caierao J, Munguambe AM, Come CE, Zimba TF, et al. Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae in children with acute bacterial meningitis in Mozambique: implications for a national immunization strategy. BMC Microbiol. 2016;16(1):134. https://doi.org/10.1186/s12866-016-0747-y .

Sanneh B, Okoi C, Grey-Johnson M, Bah-Camara H, Kunta Fofana B, Baldeh I, et al. Declining trends of pneumococcal meningitis in gambian children after the introduction of pneumococcal conjugate vaccines. Clin Infect Dis. 2019;69(Suppl 2):S126–S32. https://doi.org/10.1093/cid/ciz505 .

Manning L, Laman M, Greenhill AR, Michael A, Siba P, Mueller I, et al. Increasing chloramphenicol resistance in Streptococcus pneumoniae isolates from Papua New Guinean children with acute bacterial meningitis. Antimicrob Agents Chemother. 2011;55(9):4454–6. https://doi.org/10.1128/AAC.00526-11 .

Duke T, Michael A, Mokela D, Wal T, Reeder J. Chloramphenicol or ceftriaxone, or both, as treatment for meningitis in developing countries? Arch Disease Childhood. 2003;88(6):536–9. https://doi.org/10.1136/adc.88.6.536 .

Negrini B, Kelleher KJ, Wald ER. Cerebrospinal fluid findings in aseptic versus bacterial meningitis. Pediatrics. 2000;105(2):316–9. https://doi.org/10.1542/peds.105.2.316 .

Nigrovic LE, Malley R, Macias CG, Kanegaye JT, Moro-Sutherland DM, Schremmer RD, et al. Effect of antibiotic pretreatment on cerebrospinal fluid profiles of children with bacterial meningitis. Pediatrics. 2008;122(4):726–30. https://doi.org/10.1542/peds.2007-3275 .

Tadesse BT, Foster BA, Shibeshi MS, Dangiso HT. Empiric treatment of acute meningitis syndrome in a resource-limited setting: clinical outcomes and predictors of survival or death. Ethiop J Health Sci. 2017;27(6):581–8. https://doi.org/10.4314/ejhs.v27i6.3 .

Kaplan SL, OʼBrian Smith E, Wills C, Feigin RD. Association between preadmission oral antibiotic therapy and cerebrospinal fluid findings and sequelae caused by Haemophilus influenzae type b meningitis. Pediatric Infect Dis J. 1986;5(6):626–32. https://doi.org/10.1097/00006454-198611000-00005 .

Khumalo J, Nicol M, Hardie D, Muloiwa R, Mteshana P, Bamford C. Diagnostic accuracy of two multiplex real-time polymerase chain reaction assays for the diagnosis of meningitis in children in a resource-limited setting. PLoS One. 2017;12(3):e0173948. https://doi.org/10.1371/journal.pone.0173948 .

Bonsu BK, Harper MB. Corrections for leukocytes and percent of neutrophils do not match observations in blood-contaminated cerebrospinal fluid and have no value over uncorrected cells for diagnosis. Pediatr Infect Dis J. 2006;25(1):8–11. https://doi.org/10.1097/01.inf.0000195624.34981.36 .

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Acknowledgements

This study is published with the permission of the Director of Kenya Medical Research Institute. Surveillance at KCH was undertaken at the KWTRP by members of the KWTRP medical, nursing, laboratory and computing team who participated in patient care, data collection, and data storage. We thank all KWTRP staff and KCH patients whose data was included in this analysis.

This work was supported by the Wellcome Trust, UK core grant to KEMRI-Wellcome Trust Research Programme (grant 203077/Z/16/Z). CWO is supported by the Drugs for Neglected Diseases initiative (grant OXF-DND02). JAB is supported by the Bill & Melinda Gates Foundation within the Childhood Acute Illness and Nutrition (CHAIN) Network (grant OPP1131320) and by the MRC/DFID/Wellcome Trust Joint Global Health Trials scheme (grant MR/M007367/1). The funders had no role in the design or conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Christina W. Obiero, Neema Mturi, Moses Ngari, Charles R. Newton & James A. Berkley

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CWO, MN, CRN, MBH, and JAB contributed to the conception and design of the study. CWO, NM, and JAB contributed to inpatient care and data collection. SM was responsible for laboratory analysis. CWO, NM, SM, MN, CRN, MBH, and JAB contributed to the analysis and interpretation of the data. CWO, MBH, and JAB contributed to the drafting of the article. The views expressed in this manuscript are those of the authors and not necessarily those of the KEMRI or the Wellcome Trust. The authors read and approved the final manuscript.

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The collection of surveillance data included in this analysis was reviewed and approved by the Kenya Medical Research Institute Scientific Steering Committee (KEMRI SSC 1433). This retrospective analysis was reviewed and approved by the KEMRI SSC (KEMRI SSC 3001).

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Supplementary Information

Additional file 1: table s1..

Comparison of annual admissions, lumbar punctures and meningitis cases during our study period and our previous analysis. Table S2. Sensitivity Analysis of Potential Screening Criteria at Admission for Meningitis.

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Obiero, C.W., Mturi, N., Mwarumba, S. et al. Clinical features of bacterial meningitis among hospitalised children in Kenya. BMC Med 19 , 122 (2021). https://doi.org/10.1186/s12916-021-01998-3

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Data collection, definitions, statistical analysis, demographic domain, clinical domain, other findings, acknowledgments, differences between viral meningitis and abusive head trauma.

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Danielle Horton , Tanya Burrell , Mary E. Moffatt , Henry T. Puls , Rangaraj Selvarangan , Lyndsey Hultman , James D. Anderst; Differences Between Viral Meningitis and Abusive Head Trauma. Pediatrics July 2022; 150 (1): e2021054544. 10.1542/peds.2021-054544

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To evaluate the hypothesis that viral meningitis may mimic abusive head trauma (AHT) by comparing the history of present illness (HPI) and clinical presentation of young children with proven viral meningitis to those with AHT and those with subdural hemorrhage (SDH) only. We hypothesized that significant differences would exist between viral meningitis and the comparison groups.

We performed a 5-year retrospective case-control study of subjects aged <2 years, comparing those with confirmed viral meningitis (controls) to those with SDH evaluated by the hospital child abuse pediatrics team (cases). Cases were classified as SDH with concomitant suspicious injuries (AHT) and without concomitant suspicious injuries (SDH-only). Groups were compared across demographic (5 measures), HPI (11 measures), and clinical (9 measures) domains. Odds ratios were calculated for measures within each domain.

Of 550 subjects, there were 397 viral meningitis, 118 AHT, and 35 SDH-only subjects. Viral meningitis differed significantly from AHT subjects on all demographic measures, and from SDH-only subjects on age. Viral meningitis differed significantly from AHT subjects in all HPI measures with odds ratios ranging from 2.7 to 322.5, and from SDH-only subjects in 9 HPI measures with odds ratios ranging from 4.6 to 485.2. In the clinical domain, viral meningitis differed significantly from AHT subjects in all measures, with odds ratios ranging from 2.5 to 74.0, and from SDH-only subjects in 5 measures with odds ratios ranging from 2.9 to 16.8.

Viral meningitis is not supported as a mimic of AHT.

Intracranial hemorrhage has been reported with viral meningitis, primarily in association with herpes simplex virus. It has been proposed that viral meningitis may mimic the presentation of abusive head trauma (AHT), however this hypothesis has not been tested.

This study demonstrates that young children with AHT and viral meningitis present with distinctly different history of present illness and clinical features. The presence of features predictive of AHT may aid in guiding medical evaluation and improve diagnostic certainty.

Abusive head trauma (AHT), typically including subdural hemorrhage (SDH), is the leading cause of fatal head injury in young children in the United States and is associated with significant morbidity in survivors. 1 – 6   Diagnosing AHT requires consideration of a differential diagnosis, including birth trauma, accidental trauma, and bleeding disorders, among other conditions. 2 , 5 , 7 – 11   Viral meningitis has been proposed as a “mimic” of AHT; 8 , 12 , 13   however, studies comparing the presentations of the two conditions are lacking. Because there is no standard definition of a mimic, for this study, we define it as a condition that has significant and frequent overlap with a different condition, such that the two may be easily confused. Accurately identifying and characterizing potential mimics of AHT are critical given the consequences of a diagnosis of AHT. 2 , 8 , 9  

Although viral meningitis has been proposed as a mimic of AHT, 8 , 12 , 13   most studies reporting intracranial hemorrhage in the setting of meningitis are cases of bacterial meningitis. 14 – 18   Most studies identifying a viral cause of intracranial hemorrhage involve herpes simplex virus (HSV), often associated with diffuse intracranial hemorrhage and coagulopathy. 8 , 10 , 19 – 22   Characterizing the role of viral meningitis as a possible mimic of AHT would facilitate diagnostic confidence and clarity.

Differential diagnoses for AHT can often be evaluated with a thorough assessment of historical and clinical features. 2 , 8 , 9 , 23   If the initial (emergency department and admission) history of present illness (HPI) and clinical presentations differ significantly and clearly between children with viral meningitis and AHT, then viral meningitis should not be considered a mimic of AHT. This hypothesis may be evaluated by comparing these initial presenting characteristics of children with proven viral meningitis to those with SDH and extracranial concomitant suspicious injuries (CSIs) that are not explained by viral meningitis and serve as the “definite AHT” proxy group. This methodology has been used to evaluate other theorized mimics of AHT. 24   Furthermore, children with SDH only (no CSIs) present a more complicated diagnostic challenge. Comparing initial presenting historical and clinical features in children with SDH only to the AHT and viral meningitis subjects may assist diagnosis in this subpopulation.

The primary objective of this study was to compare children with proven viral meningitis to those with AHT across demographic, HPI, and clinical domains. We hypothesized that significant differences would exist in these comparisons. The secondary objective of this study was to compare children with SDH only to those in the viral meningitis and AHT groups across the same domains. We hypothesized that children in the SDH-only group would be more similar to AHT subjects than viral meningitis subjects.

We performed a retrospective case-control study of subjects aged <2 years at the authors’ institution between January 2014 and December 2018. Controls consisted of children with viral meningitis confirmed by nucleic acid amplification test of cerebral spinal fluid from lumbar puncture. Viral infections identified by nucleic acid amplification test were parechovirus, enterovirus, and HSV. Cases were identified through the child abuse pediatrics (CAP) team database and subdivided into 2 groups: subjects with SDH plus CSIs, serving as the AHT group because of the presence of extracranial CSIs not explained by viral meningitis; and subjects with SDH without CSIs (SDH only). The CAP consultation often captures more detailed information than emergency department or admission notes. To allow more equal comparison among study groups, data from the CAP consultation regarding HPI and clinical presentation (the elements under study) were not included in this study because viral meningitis subjects did not have a CAP evaluation. Subjects were excluded from the study if they had preexisting abnormalities of the brain, including hydrocephalus, intracranial hemorrhage, infection, surgery, tumor/cancer, or anatomic/vascular malformations diagnosed before the study encounter. Subjects with an isolated, small SDH underlying an impact site were excluded, as were those hospitalized for >24 hours at an outside institution before transfer to the study hospital.

Demographic information, medical history, physical examination, laboratory and radiologic findings, and neurologic outcomes were obtained through chart review. Presenting HPI and clinical exam features were recorded exclusively from the initial emergency department and inpatient admission notes.

Definitions of CSIs were based on those used by Hansen et al ( Table 1 ). 24 – 29   CSIs were used to categorize subjects with SDH into our 2 case groups, therefore were not features under study. Bruises, petechiae, and burns were included as CSIs if they were identified in the initial emergency department or inpatient admission note only. Other CSIs were included if identified at any time during the subject’s evaluation.

Definitions of CSIs 24  

ED, emergency department; CT, computed tomography.

Study groups were compared across 3 domains.

Demographic Domain (5 measures)

Study authors abstracted subjects’ age, sex, race, and insurance status. Information regarding the relationship of the caretakers residing in the home to the child was obtained from the social history documented in emergency department and admission notes or social work notes when available.

HPI Domain (11 measures)

HPI features were symptoms reported by the caretaker(s) that prompted the medical evaluation as documented in the emergency department and/or inpatient admission notes. Measures included acute neurologic and respiratory symptoms of seizures, decreased tone, difficulty breathing, apnea, acute mental status change and other ill symptoms of measured or subjective fever, vomiting, cough or congestion, poor feeding, and fussiness. Acute symptoms were defined as those with a sudden, immediate/near immediate onset in a previously well child. Mental status change included any reported change from neurologic baseline such as drowsiness, lethargy, unconsciousness, or irritability. If a history of injury related to the current presentation was documented, this was recorded. “No history of injury” was only recorded if specifically stated.

Clinical Domain (9 measures)

Clinical features included initial examination findings, laboratory and radiograph features, requirement of intensive care, and discharge neurologic status. Measures included macrocephaly, fever (based on first set of vitals), cough or congestion, difficulty breathing, intubation, witnessed seizure, hypotonia, and neurologic status, as well as initial white blood cell count (WBC). Neurologic status of the child was categorized as normal, abnormal, death, or unknown. Abnormal was defined as active seizures, pupil abnormalities, focal neurologic abnormalities, depressed mental status, or Glasgow coma score <8. Children with new neurologic deficits, including tone and feeding issues or seizures requiring ongoing medication at discharge, were considered to have abnormal neurologic status. Laboratory data were obtained from the first documented laboratories during the hospital encounter. Features of SDH or other intracranial findings were obtained from the radiology report of the first head computed tomography and/or MRI after presentation to the hospital.

Using χ 2 test, Fisher’s exact test, and Mann-Whitney U test (for age), groups were compared across a total of 25 measures for the 3 domains: the demographics domain (5 measures), HPI domain (11 measures), and clinical domain (9 measures).

Figure 1 depicts study subject identification and classification. Viral meningitis etiologies included enterovirus ( N = 254), parechovirus ( N = 137) and HSV ( N = 6). Table 2 shows details of testing for occult trauma and viral meningitis. By definition, no SDH-only subjects had retinal hemorrhages characteristic of abuse ( Table 1 ); however, 6 did have retinal hemorrhages that were few in number and did not extend to the periphery. Skin findings and oral injury concerning for abuse were documented in 72 (61.0%) and 9 (7.6%) AHT subjects, respectively. A single viral meningitis subject had petechiae documented that was not described as iatrogenic.

Identification of study subjects. NAAT, nucleic acid amplification test; ICH, intracranial hemorrhage.

Number With Testing for Occult Trauma or Infection

NAAT, nucleic acid amplification test. —, not applicable.

Reported number out of those who received screening test.

Table 3 characterizes the demographics domain. Viral meningitis subjects were significantly younger than AHT and SDH-only subjects. AHT subjects differed from viral meningitis subjects in sex, race/ethnicity, and insurance status. AHT subjects were more likely than viral meningitis and SDH-only subjects to have an unrelated caregiver living in the home. This information was unknown for 18 viral meningitis subjects. The percentage of subjects living with an unrelated caregiver was calculated out of the total number of subjects in each group, including those with an unknown caregiver relationship.

Patient Demographics

OR, odds ratio; —, not applicable.

Significant at P < .05.

Table 4 details the HPI domain. Compared with viral meningitis subjects, AHT subjects were >300 times more likely to be afebrile, >150 times more likely to have a mental status change, and nearly 60 times more likely to have at least 1 or more acute symptom. Similar but less pronounced differences were seen when comparing SDH-only and viral meningitis subjects. The AHT and SDH-only groups had fewer other ill symptoms, except vomiting, than the viral meningitis group. Finally, few differences existed between the SDH-only and the AHT subjects.

HPI Domain: Historical Features Reported by Caregiver at Time of Presentation for Medical Care

CI, confidence interval; OR, odds ratio; —, not applicable.

Significant at  P  <.05.

Relative risk calculated for comparison group because of no subjects in viral meningitis group presenting with the feature.

Table 5 details the clinical domain. AHT subjects were more likely to have neurologic and respiratory symptoms and fewer infectious findings when compared with the viral meningitis group. AHT subjects were nearly 20 times more likely than viral meningitis subjects to require intensive care and were less likely to have normal mental status at discharge ( Table 6 ). Though less acutely ill than the AHT group, the SDH-only group was still 12 times more likely to require intubation and nearly 5 times more likely to require intensive care than the viral meningitis group. Fever was significantly less common in the AHT and SDH-only groups than the viral meningitis group. Among subjects with an abnormal WBC, AHT and SDH-only subjects were more likely to have a high WBC than viral meningitis subjects. The presence of combined features of a history of acute mental status change with lack of clinical fever on presentation had a positive predictive value for abuse of 95%.

Clinical Domain: Clinical Features at Time of Emergency Department Visit or Hospital Admission

Relative risk calculated for comparison group because of no subjects in SDH-only group presenting with the feature.

Clinical Outcomes

CI, confidence interval; OR, odds ratio; —, not applicable.

Nineteen viral meningitis subjects received head imaging ( Supplemental Table 7 ). Of these, 2 subjects aged <10 days old with parechovirus meningitis had posteriorly located SDH. Both presented with fevers and acute neurologic or respiratory symptoms. One had additional findings of subarachnoid hemorrhage and cytotoxic edema with no retinal hemorrhage identified on ophthalmologic exam. The other subject had hypoxic ischemic injury and diffuse leptomeningeal enhancement and did not have an ophthalmologic exam. Three subjects with HSV had parenchymal or ventricular hemorrhage without SDH, a known complication of HSV. Of the remaining 14 viral meningitis subjects who received head imaging, 6 had nonhemorrhagic findings that were consistent with infection and 8 had normal head imaging.

The evaluation of an infant with SDH requires careful consideration of potential causes, including trauma and infections. This study identifies clear differentiating factors that may aid in initial clinical decision-making. Additionally, in legal settings involving children with AHT, this diagnosis may be questioned. Extracranial injuries (CSIs) are often attributed to a different theorized cause, whereas the intracranial findings are then discussed separately and may be attributed to a proposed mimic of AHT, such as viral meningitis. Although viral meningitis may rarely cause SDH, to assert that viral meningitis is a mimic of AHT, it would need to be shown that presenting features of children with viral meningitis have significant and consistent overlap with those seen in AHT. Our study identified significant differences in HPI and presenting clinical features between AHT and viral meningitis, the opposite of what would be expected if AHT could be frequently and easily confused with viral meningitis. Awareness of these differences may aid clinicians in their evaluation of the young infant with SDH and contribute to increased confidence in the diagnosis both clinically and in legal settings.

Two HPI features were >150 times more likely to occur in the AHT group than in viral meningitis (mental status change and lack of fever). Four other historical features (seizure, decreased tone, apnea, difficulty breathing) were at least 15 times more likely to be present in AHT. Conversely, infectious symptoms predominated in the viral meningitis group, particularly fever. These patterns again held true in the clinical domain, witnessed at the time of medical care. Simply put, the children with viral meningitis presented with common infectious symptoms such as fever, cough, or congestion by history and exam. The children with AHT presented with more severe illness (mental status changes, respiratory failure requiring intubation, seizures). These presenting features, taken as a group, provide clear differentiation between viral meningitis and AHT. Although leukocytosis is often associated with infection, acute stress responses related to head trauma can result in leukocytosis, as well. 30   Our results show leukocytosis was more likely in AHT and SDH-only subjects than viral meningitis subjects, thus the presence of leukocytosis should not be used as an indicator to rule out trauma. Demographic differences in race/ethnicity and insurance status may be explained by poverty and the historical effects of racism on poverty, given the known correlations between child maltreatment and poverty. 31 – 33  

Our data suggest that an overlap in presenting features of AHT with viral meningitis would be a very rare occurrence, typically with “mild” AHT accompanied by infectious signs/symptoms, or infrequently viral meningitis with more severe features. A careful evaluation may identify discriminating features such as lack of fever or concerning skin injury in cases with mild/nonspecific symptoms. In rare circumstances, evaluations for both AHT and viral meningitis may be required. However, given the frequent and significant differences in presentation between viral meningitis and AHT, differentiation between the two conditions should be readily apparent in nearly all circumstances.

Only 19 viral meningitis subjects had head imaging; however, most findings were consistent with infection and differed from those seen in AHT. This is similar to existing literature, which primarily describes intracranial hemorrhage in children with HSV with diffuse hemorrhage, 10 , 21 , 22   and rare reports of subdural effusions found in children with possible aseptic meningitis. 19   It has been noted that retinal hemorrhage may be seen associated with coagulopathy in the setting of HSV, but to our knowledge has not otherwise been reported in viral meningitis. 8   No retinal hemorrhages were identified in the 4 HSV subjects that received ophthalmologic exams. In our study, SDH confined to the posterior cranium was present in 2 viral meningitis subjects aged <10 days. Posteriorly located SDH, most resolving by 4 weeks of age, is well described in asymptomatic neonates from birth and differs from the typical locations of SDH seen in AHT. 34 – 36   It is likely that the SDH identified in these subjects was birth-related and not a result of viral meningitis.

SDH-only subjects were more similar to AHT than viral meningitis subjects, particularly regarding HPI features. However, SDH-only subjects were generally less acutely ill than AHT subjects. Across the 25 measures comprising the 3 domains studied, the SDH-only group had statistically significant differences from the viral meningitis group in 15 of 25 measures. Mental status change and lack of fever provide clear differentiation with viral meningitis in this group, as well. Statistically significant differences between the SDH-only and AHT groups were found in only 7 of 25 measures. Findings from this study suggest that the SDH-only group is unlikely to represent missed viral meningitis, given the stark differences between the two, but do not support a specific cause of SDH in this population. Given the similarities to our AHT group, it is possible the SDH-only subjects represent children presenting remotely from abusive injury or with less severely symptomatic AHT and lacking CSIs. To identify subjects with isolated SDH, we excluded subjects with CSIs from classification into the SDH-only group. This may select for those children with more “minor” abusive injuries because they lack multisystem trauma. Other possibilities include children who have SDH from a nonabusive mechanism, such as accidental injury or birth. Further study of this specific subpopulation is needed to offer more clarity around the diagnosis.

This study has several limitations. It is retrospective in nature. Evaluation for occult trauma was rare in the viral meningitis group and few SDH-only or AHT patients received lumbar puncture, introducing the possibility that viral meningitis subjects could have unidentified CSIs and SDH-only or AHT subjects could have unidentified viral meningitis. However, given the relatively low prevalence of both conditions, it would be very rare for a subject to have both AHT and viral meningitis at the same time, making misclassification unlikely. Skin findings that could be concerning for or confused with abuse were identified in 1 viral meningitis patient; however, it is possible that there could have been skin findings not documented on the initial exam or that evolved over the patient’s hospitalization. However, skin findings evolving while hospitalized would be less concerning for abuse and more consistent with a viral exanthem. Because viral meningitis subjects rarely had complete evaluation for occult trauma, it is possible that there could be missed occult injury in this group. However, because viral meningitis does not cause extracranial CSIs, an occult injury would require the consideration of abuse in addition to viral meningitis. AHT and SDH-only subjects were derived from hospital CAP team consultations; however, viral meningitis patients did not receive a CAP consultation. To allow for a more equal comparison among groups, features documented in the CAP note were not used for classification of subjects or for comparison across domains. This could have resulted in erroneous classification of AHT subjects as SDH only if an exam finding consistent with a CSI was noted by a CAP but not by the emergency department or inpatient provider, which would result in our AHT and SDH-only groups appearing more similar. Use of CAP team consultations to identify SDH-only subjects allowed for inclusion of those that had evaluation for occult trauma. However, this may have led to selectively capturing SDH-only subjects with more severe symptoms because it is possible that children with SDH only and minor or no symptoms may not have received a CAP consult.

In summary, the hypothesis that viral meningitis mimics AHT is not supported by this study. Subjects with AHT differed significantly from those with viral meningitis with respect to HPI and clinical presenting features, supporting a difference between how these medical conditions manifest. This is the opposite of what would be expected if viral meningitis is a mimic of AHT.

We thank Sommer Rose and Ashley Sherman for data analysis.

Dr Anderst conceptualized the study, designed the data collection instruments, drafted the initial manuscript, and reviewed and revised the manuscript. Dr Horton designed the data collection instruments, collected data, drafted the initial manuscript, and reviewed and revised the manuscript. Drs Burrell, Moffatt, Puls, and Selvarangan conceptualized the study and reviewed and revised the manuscript. Dr Hultman collected data and reviewed the manuscript. All authors contributed to the design of the study, approved the final manuscript as submitted, and agree to be accountable for all aspects of the work.

FUNDING: No external funding.

CONFLICT OF INTEREST DISCLAIMER: The authors have indicated they have no conflicts of interest relevant to this article to disclose.

abusive head trauma

child abuse pediatrics

concomitant suspicious injury

history of present illness

herpes simplex virus

subdural hemorrhage

white blood count

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9:  Bacterial Meningitis

Jonathan C. Cho

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Patient presentation.

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Chief Complaint

“I have severe headaches and fevers.”

History of Present Illness

DJ is a 54-year-old Caucasian female who presents to the emergency department with worsening headache, neck pain, and back pain of 2 days duration. She also complains of low-grade fevers and chills that developed over the past 24 hours. Her son, who is present during her exam, states that she seems more lethargic and has difficulty maintaining her balance. In addition, she reports 3 to 4 episodes of nausea and vomiting.

Past Medical History

CHF, COPD, HTN, epilepsy, stroke, hypothyroidism, anxiety

Surgical History

Hysterectomy, cholecystectomy

Family History

Father had HTN and passed away from a stroke 4 years ago; mother has type II DM and epilepsy; brother has HTN

Social History

Divorced but lives with her two sons who are currently attending college. Smokes ½ ppd × 27 years and drinks alcohol occasionally.

Home Medications

Advair 250 mcg/50 mcg 1 puff BID

Albuterol metered-dose-inhaler 2 puffs q4h PRN shortness of breath

Alprazolam 0.5 mg PO daily

Aspirin 81 mg PO daily

Atorvastatin 20 mg PO daily

Carvedilol 6.25 mg PO BID

Citalopram 20 mg PO daily

Divalproex sodium 500 mg PO BID

Furosemide 20 mg PO daily

Levothyroxine 88 mcg PO daily

Levetiracetam 500 mg PO BID

Lisinopril 20 mg PO daily

Physical Examination

Vital signs.

Temp 101.2°F, P 72, RR 23 breaths per minute, BP 162/87 mm Hg, pO 2 91%, Ht 5′3″, Wt 56.4 kg

Lethargic, female with dizziness and in mild to moderate distress.

Normocephalic, atraumatic, PERRLA, EOMI, pale or dry mucous membranes and conjunctiva, poor dentition

Diminished breath sounds and crackles bilaterally.

Cardiovascular

NSR, no m/r/g

Soft, non-distended, non-tender, bowel sounds hyperactive

Genitourinary

Normal female genitalia, no complaints of dysuria or hematuria

Lethargic, oriented to place and person, (–) Brudzinski’s sign, (+) Kernig’s sign

Extremities

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Diagnostic status and epidemiological characteristics of community-acquired bacterial meningitis in children from 2019 to 2020: a multicenter retrospective study

• Juan-Juan Liu 1 ,
• Zhi-Wei Xu 2 ,
• Hui-Qing Xu 3 ,
• Jia-Jun Zhu 4 ,
• Jie-Ning Zhang 5 ,
• Sheng Fang 6 ,
• Sheng-Fu Yuan 7 ,
• He-Jia Ge 8 ,
• Hai-Jing Li 9 ,
• Wen-Ji Lou 10 ,
• Li-Hua Chen 11 ,
• Feng Gao 12 &
• Ying-Hu Chen 1  

BMC Pediatrics volume  24 , Article number:  11 ( 2024 ) Cite this article

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Community-acquired bacterial meningitis (CABM) is the main cause of morbidity and mortality in children. The epidemiology of CABM is regional and highly dynamic. To clarify the diagnostic status and epidemiological characteristics of children with CABM in this region, and pay attention to the disease burden, so as to provide evidence for the prevention and treatment of CABM. By retrospective case analysis, the clinical data of 918 CABM cases in children aged 0–14 years in Zhejiang Province from January, 2019 to December, 2020 were collected. The etiological diagnosis rate of CABM in children was 23.1%, the annual incidence rate 4.42–6.15/100,000, the annual mortality rate 0.06–0.09/100,000,the cure and improvement rate 94.4%, and the case fatality rate 1.4%. The total incidence of neuroimaging abnormalities was 20.6%. The median length of stay for CABM children was 20(16) days, with an average cost of 21,531(24,835) yuan. In addition, the incidence rate was decreased with age. Escherichia coli(E.coli) and g roup B Streptococcus agalactiae(GBS) were the principal pathogens in CABM infant<3 months(43.3%, 34.1%), and Streptococcus pneumoniae(S. pneumoniae) was the most common pathogen in children ≥ 3 months(33.9%). In conclusion, the annual incidence and mortality of CABM in children aged 0–14 years in Zhejiang Province are at intermediate and low level. The distribution of CABM incidence and pathogen spectrum are different in age; the incidence of abnormal neuroimaging is high; and the economic burden is heavy.

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Introduction

Community-acquired bacterial meningitis (CABM), an inflammation of meningitis influencing the pia, arachnoid, and subarachnoid space induced by bacteria and bacterial products, is a major cause of morbidity and mortality in children [ 1 ]. The epidemiology of CABM is regional and highly dynamic, affected by factors such as vaccines, climate, latitude, population movement, viral infections, and poverty. For example, in well-resourced areas, the incidence of meningitis is decreased to less than 0.5–1.5 per 100,000 population; while in the Sahel region of Africa, epidemic meningitis induced by Neisseria meningitidis and Streptococcus pneumoniae ( S. pneumoniae ) persists, with an incidence of 1000 per 100,000 cases [ 2 ]. In addition to geographical differences in the incidence of CABM, the prognosis also varies with the age of onset, regions, and causative agents [ 1 , 3 ].

Studies have shown that the case fatality rate of CABM in children is 30%, and 50% of survivors suffer neurological complications [ 3 ]. These complications include seizures, focal neurological deficits, subdural effusions, hydrocephalus, hearing loss, cognitive impairment, and epilepsy, among others. Therefore, prompt assessment and immediate empirical treatment of CABM can reduce the likelihood of death outcomes and chronic neurological sequelae [ 3 , 4 ]. Studies showed mortality rates of untreated BM approaching 100% [ 1 ]. An important basis for empirical treatment is the epidemiological characteristics of CABM in the region. At present, there is a relative lack of data from epidemiological studies of CABM in children in Zhejiang Province. Consequently, in this study, we employed a multicenter and large-sample retrospective case analysis to clarify the epidemiological characteristics of CABM children in Zhejiang Province. And this study could not only guide empirical treatment in the early clinical stage, but also provide an etiological basis for the immunization program of meningitis vaccine.

Study design

This study was a multi-center retrospective study with 50 hospitals as participators. The 50 hospitals included in the study covered almost all the hospitals with children’s inpatient departments in Zhejiang province. These hospitals were distributed in 11 prefecture-level cities in Zhejiang province, including 42 tertiary hospitals and 8 secondary hospitals. The clinical data of 918 children aged ≤ 14 years with discharge diagnosis of “bacterial meningitis (BM)”, “purulent meningitis” or “intracranial infection” from January 1, 2019 to April 30, 2021 were collected for retrospectively analysis. By referring to the electronic medical records, the clinical data of cases that met the inclusion criteria were collected, including demographics, length of hospital stay, hospitalization costs, clinical prognosis, blood and cerebrospinal fluid (CSF) sampling results (microbiologic results, CSF routine, CSF biochemistry, etc.), and head imaging results (ultrasound, CT, and magnetic resonance; all included cases completed at least one of the above imaging data). Inclusion criteria: Patients aged ≤ 14 years (including neonates) with “BM”, “purulent meningitis” or “intracranial infection” were discharged from the hospital from January 1, 2019 to April 30, 2021. Exclusion criteria: (1) Cases whose clinical data did not meet the diagnostic criteria for suspected bacterial meningitis. (2) Intracranial infections induced by laboratory-confirmed non-bacterial pathogens, including viral encephalitis, fungal encephalitis, intracranial infections with mycoplasma, rickettsia and parasitic. (3) Nosocomial BM (craniotomy, CSF leakage, intracranial catheter infection, etc.), infection secondary to traumatic brain injury, and secondary intracranial infection such as tumor, transplantation or chemotherapy in patients with impaired immune system. (4) Discharged from hospital in 2019, with the onset of illness in 2018; Cases that started in 2021. (Fig.  1 )

Flow diagram for the selection of subjects in the retrospective cohort study of CABM in children aged 0–14 years in Zhejiang province from 2019 to 2020

Note: 1). Some critical cases died without lumbar puncture. This type of case could be diagnosed by typical clinical manifestations and brain imaging abnormalities, such as subdural effusion/empyema, meningeal thickening, or enhanced echo of the brain ependymal. 2) The first atypical CSF change required dynamic observation of changes in indicators.

Case classification criteria

Grouping criteria were based on the WHO recommended case definition [ 5 ].

Pathogen confirmed (Confirmed) group: Clear pathogens were determined in CSF or blood with one of the following methods: (1) culture; (2) non-culture methods: antigen detection, Gram staining smear, nucleic acid detection. Clinical diagnosis case (Clinical) group: Typical clinical manifestations; typical changes in CSF; no pathogen found in CSF. Probable case (Probable) group: Atypical changes in CSF; no pathogen observed in CSF; and at least one of the following items were met: (1) prodromal suppurative infection lesions; (2) anatomical factors; (3) peripheral white blood cells ≥ 15 × 10 9 /L and/or high sensitive C-reactive protein ≥ 40 mg/L and/or serum procalcitonin ≥ 1 ng/ml. Typical clinical manifestations of children with clinical syndromes of suspected BM were shown as follows: fever (usually > 38.5 ° C rectal or 38.0 ° C axillary), drowsiness, confusion, severe headache, convulsions, projectile vomiting, bulging anterior fontanel, nuchal rigidity, etc. Typical changes in CSF: (A) turbid or rice soup alike appearance, and the pressure was increased (200–500 mm CSF); (B) up-regulated white blood cell count, often ≥ 1000 × 10 6 /L, and the classification was dominated by multinucleated cells (80 -90%); elevated protein concentration (> 100 mg/dl), and low CSF glucose concentration (< 40 mg/dl) [ 6 ]. Atypical changes of CSF (only 1–2 abnormalities in the following 3 items): white blood cell count of CSF was slightly high (tens to hundreds); CSF glucose was mildly low or protein was a little elevated.

Clinical prognostic criteria

Cure: full course of anti-infection, disappearances of clinical symptoms and signs, and normal CSF indicators. Improved: full course of anti-infection, disappearances of clinical manifestations and signs, normal CSF white blood cell count; and only CSF protein and/or glucose concentration did not return to normal level. Not cured: Discharge with insufficient course of anti-infection or sufficient course but accompanied by serious complications (brain abscess, secondary epilepsy, cognitive impairment, etc.). Death.

Statistical analysis

Spss20.0 statistical software was applied in this report. Continuous variables exhibited a skewed distribution and were expressed as M (IQR). And continuous variables between two groups and among three groups were compared through Mann Whitney U test and Kruskal-wallis test respectively. Categorical variables were displayed as number of cases n (%), and Chi-square test or Fisher’s exact test was applied to check the outcomes. P  < 0.05 was considered as significant difference. Incidence rate = the number of new cases of a disease in a population in a certain period/the number of exposed population in the population during the same period *K. K = 100,000/100,000. Number of exposed population: people in the population of a certain area who were likely to develop the observed disease during the observation period. Therefore, individuals with the disease were not included. However, because it was difficult to divide in practical work, the average population of the area during the observation period was used as the denominator. In this study, the average population during the observation period was used as the denominator. Mortality rate = total number of deaths (due to a disease) in a period/average population in the same period ×100%. In this study, the population base of Zhejiang Province aged 0–14 years was based on the data released by the 7th national census in 2020, and the newborn population was collected from the Statistics Bureau of Zhejiang Province. The 95% confidence interval (95% CI) of the rate was calculated using the following formula: \(p\pm 1.96\sqrt{\frac{pq}{n}}\) , q = 1-p. The 95% CI of the rate difference was calculated as follows:

\(\left({p}_{1}-{p}_{2}\right)\pm 1.96\sqrt{\frac{{p}_{1}{q}_{1}}{{n}_{1}}+\frac{{p}_{2}{q}_{2}}{{n}_{2}} };{q}_{1}=1-{p}_{1;}\, {q}_{2}=1-{p}_{2}\) .

Diagnostic status

A total of 918 children with CABM were included in this study, including 212 pathogen confirmed cases, 275 clinically diagnosed cases, and 431 probable cases. In this study, the etiological diagnosis rate was 23.1% (212 cases, 95% CI: 20.4, 25.8). To be specific, the positive rates of blood and CSF culture were (122 cases, 13.3%, 95% CI:11.1, 15.5) and (138 cases, 15.0%, 95%CI: 12.7, 17.3) respectively. In addition, seven pathogens were detected in CSF by metagenomic next-generation sequencing (mNGS). This study also observed that the positive rate of pathogen culture in septic shock children (55.9%, 19 cases) was much higher than that in children without shock (21.0%, 186 cases), the difference was statistically significant ( P < 0.01).

General clinical data

Of the 918 cases, the gender ratio between male and female was 177.9:100. Neonates accounted for the largest proportion of all cases, reaching 44.4%, and only 12.3% were 1–14 years old. The median length of hospital stay of all children was 20 (16) days, with an average cost of 21,531 (24,835) yuan. In comparisons with the clinical and probable groups, confirmed group exhibited longer length of hospital stay and higher average cost. The overall cure and improvement rate (867 cases, 94.4%, 95% CI: 93.0, 95.9) as well as case fatality rate (13 cases, 1.4%, 95% CI: 0.7, 2.2) was observed. The cure and improvement rate of confirmed group (188 cases, 88.7%) was lower than that of clinical (264 cases, 96.0%) and probable groups (415 cases, 96.3%) (Table  1 ).

Clinical distribution and outcome of confirmed cases

There were 212 children in the confirmed group. Among them, 119 cases were detected with Gram-positive bacteria (G +) and 93 with Gram-negative bacteria (G −). The onset was commonest in neonates (G + 62 cases, G − 58 cases). The cure and improvement rates of positive and negative bacteria were (108 cases, 90.8%, 95% CI: 85.5, 96.0) and (80 cases, 86%, 95% CI: 78.8, 93.2) respectively, and the case fatality rates were (1 case, 0.8%, 95% CI: -0.8, 2.5) and (5 cases, 5.4%, 95% CI: 0.7, 10.0) respectively. There was no statistically significant difference in the compositions of clinical cure, improvement, and other outcomes (including death and not healed) between the groups of G + and G- ( P  > 0.05). Besides, statistical differences between the two groups were not observed in the length of hospital stay and average cost (Table  2 ).

Age distribution of incidence and mortality

In 2019, the annual incidence of CABM in children aged 0–14 years in Zhejiang Province was 6.15/100,000 (95% CI; 5.63, 6.67), and the mortality rate was 0.06/100,000 (95% CI: 0.01, 0.11). In 2020, the incidence rate was 4.42/100,000 (95% CI: 3.98, 4.87), and the mortality rate was 0.09/100,000 (95% CI: 0.03, 0.16). The incidence of CABM in children showed a decreasing trend from 2019 to 2020, with a rate difference of 1.73/100,000 (95% CI: 1.04, 2.41). Additionally, the incidence of CABM in children was declined with age, while the morbidity was as high as 30.13–39.12 per 100,000 in the neonatal period (95% CI: 25.43, 34.82; 34.27, 43.97) (Table  3 ).

Pathogen distribution and detection rate

A total of 267 bacterial pathogens were detected from the blood and CSF of all children, including 147 G + and 120 G −. The top four pathogens of 267 strains were E.coli (95 cases, 35.6%), GBS (75 cases, 28.1%), S. pneumoniae (20 cases, 7.5%), and coagulase-negative staphylococci ( CNS ) (14 cases, 5.2%) in turn. While in newborns the top four pathogens were E.coli (64 cases, 43.2%), GBS (44 cases, 29.7%), CNS (11 cases, 7.4%) and Staphylococcus aureus ( S.aureus ) (5 cases, 3.4%) respectively. The main pathogens in children aged 1–2 months were GBS (27 cases, 45%) and E.coli (26 cases, 43.3%); aged 3–12 months were S. pneumoniae (5 cases, 16.6%), E.coli (5 cases, 16.6%), GBS (4 cases, 13.3%) and Salmonella (4 cases, 13.3%) in turn; and for children aged 1–14 years, S. pneumoniae (15 cases, 51.7%) was the common pathogen, followed by Listeria monocytogenes (4 cases, 13.8%). E. coli and GBS were the top two pathogens in infants < 3 months of age, occupying (90 cases, 43.3%) and (71 cases, 34.1%), respectively. The highest detection rate in children ≥ 3 months was S. pneumoniae (20 cases, 33.9%) (Fig.  2 ). Furthermore, the pathogen detection rate in the newborns group accounted for the highest proportion in all age groups, reaching 29.41%. And there was a statistically significant difference in the pathogen detection rate among different age groups ( P  < 0.01) (Table  4 ).

Composition of 267 pathogens detected by CABM in children aged 0–14 years in Zhejiang Province from 2019 to 2020

Neuroimaging findings

The incidence of abnormal head imaging in 918 children was 20.6% (189 cases, 20.6%, 95% CI: 18.0, 23.2) (Table  5 ). The top two changes of the incidence were subdural fluid collection/empyema and hydrocephalus, (73 cases, 8.0%, 95% CI: 6.2, 9.7), (46 cases, 5.0%, 95% CI: 3.6, 6.4), respectively. Encephalomalacia (36 cases, 3.9%), cerebral hemorrhage (16 cases, 1.7%), ependymitis (11 cases, 1.2%), cerebral infarction (9 cases, 0.98%), brain abscess (8 cases, 0.87%) and other abnormalities (33 cases, 3.6%) (such as cerebral edema, meningeal enhancement, frontal subcortical punctate abnormal signal, etc.) were also observed. The incidence of all brain imaging changes was different among the three groups. Specifically, the incidence of abnormalities was markedly higher in the confirmed and clinical groups (35.8%, 26.2%) than that in the probable group (9.5%). And the incidence of subdural fluid collection/empyema in the confirmed group (16%) was much higher than that in the clinical group (8%) and the probable group (3.9%). There was no significant difference in subdural fluid collection/empyema when gram-negative and gram-positive bacteria appeared ( P  > 0.05) (Table  6 ).

The age of patients with subdural fluid collection/empyema consisted of 66 cases (90.4%) under 1 year old, and 41 cases (56.2%) were < 3 months, including 17 cases of newborns (23.3%). The incidence of subdural fluid/empyema was different between age groups, and the incidence in children aged 3–12 months with confirmed pathogen was 36%. For comparisons of hydrocephalus, the incidence in the confirmed group (10.4%) and the clinical group (7.6%) were remarkably superior to that in the probable group (0.7%). There was no significant difference in the incidence of hydrocephalus in both G + and G − groups ( P  > 0.05). The age composition of children with hydrocephalus was less than 1 year of age in 40 cases (87.0%) and < 3 months in 32 cases (69.6%), including newborns in 21 cases (45.7%). The incidence of hydrocephalus varied between 4.8% and 5.3% in different age groups.

Meningitis is an sever infectious disease syndrome in childhood, with a huge disease burden and large regional incidence variations [ 4 , 7 ]. The Global Burden of Disease study in 2016 revealed that the incidence of meningitis was as high as 207.4 per 100,000 in South Sudan and 0.5 per 100,000 in Australia [ 7 ]. Nearly 3% of deaths in children below 5 years of age worldwide are attributed to meningitis [ 7 ]. The global mortality rate of meningitis/encephalitis in children below 5 years old ranges from 21.28/100,000 to 28.1/100,000, and the case fatality rate of BM fluctuates between 3% and 7% [ 8 , 9 ]. From September 2006 to December 2009, the incidence of BM in children under 5 years old ranged from 6.95/100,000 to 22.30/100,000 in four provinces of China (Shandong, Hubei, Hebei, and Guangxi) [ 10 ]. Our study revealed that the incidence of CABM was 4.42/100,000–6.15/100,000 in children aged 0–14 years and 12.33/100,000–16.91/100,000 in children under 5 years in Zhejiang Province from 2019 to 2020. And the incidence in Zhejiang Province is at the middle and low level in China.

As this study demonstrated that, the mortality rate of CABM (0.14/100,000–0.27/100,000) and case fatality rate (1.4%) in children under 5 years of age in Zhejiang Province from 2019 to 2020 were lower than in the foreign level. When it comes to the cost, the confirmed group was the highest, with an average cost of 35,824 yuan per time. The average cost and length of hospital stay of CABM in children in Zhejiang Province from 2019 to 2020 were higher than those of pneumonia in China (5,026.76 yuan; 7.63 days) [ 11 ]. And it has revealed that the disease economic burden of CABM in children is heavy.

The incidence of BM varies according to age group. In this study, the incidence of CABM in newborns in Zhejiang Province was 30.13/100,000–39.12/100,000 from 2019 to 2020, the children aged 1–2 months was 16.72/100,000–18.80/100,000, and aged 5–14 years was decreased to 0.35/100,000–0.61/100,000. Also, USA exhibited the incidence of 81/100,000 in children under two months of age from 2006 to 2007, while 0.4/100,000 in children aged 11–17 years [ 3 ]. Infants aged ≤ 2 months are high risk population with CABM, and newborns incidence is the highest. The immature immune system of infants under 2 months of age may be responsible for the above phenomenon. On the one hand, there is a lack in maternal immunoglobulin that crosses the placenta before 32 weeks of gestation, and on the other hand, phagocytic ability of neutrophils and monocytes is limited [ 12 ]. In addition, it was discovered by our study that the incidence of CABM in children in 2020 in Zhejiang Province was remarkably lower than that in 2019. And this result was considered to be correlated with the measures such as reducing population aggregation, wearing masks, quarantine and isolation after the outbreak of COVID-19. At the same time, some studies had shown that SARS-CoV2 caused a 20–30% reduction in the incidence of meningitis during the COVID-19 pandemic [ 2 ].

Due to the high mortality rate, CABM requires immediate assessment and prompt empirical therapy [ 4 ]. A total of 918 children were included in this study, involving 46.9% probable cases. The clinical manifestations or laboratory data findings were atypical in probable group and there was a great risk of missed diagnosis. However, with the case fatality rate approaching 100% for untreated BM, suspected cases need immediate actions for specific diagnosis and empirical antimicrobial therapy [ 1 ]. Importantly, early recognition and use of appropriate antibiotics are essential to minimize deaths and complications caused by BM [ 2 ]. This study enrolled the children with probable meningitis to increase clinicians’ attention to their diagnosis and treatment. The pathogenic diagnosis rate of this study was 23.1%, while the positive rate of CSF culture was only 15%. The children in this study conducted blood culture in the early stage of the disease and the CSF of a few children received mNGS detection, improving the diagnostic yield of the pathogen. Therefore, early aseptic body fluid culture is recommended for BM children in clinical practice. For another, non-culture tests should also be performed for patients who require early detection of pathogens or have received antibiotic treatment to identify the pathogen to guide treatment as soon as possible [ 1 ].

The distribution of common pathogens of CABM in children varies among age groups. A global META analysis of BM etiology manifested that S. pneumoniae infection was the most common cause of BM in all pediatric groups [ 13 ]. In this study, the top two pathogens in newborns and infants < 3 months in Zhejiang Province were E.coli (43.3%) and GBS (34.1%), and S. pneumoniae was the most common pathogen in children ≥ 3 months (33.9%). A study by Shenzhen Children’s Hospital reported that GBS and E.coli were the main pathogens in newborns, and S. pneumoniae was mainly observed in older children [ 14 ]. The similar results of the two studies indicated a descending trend in the incidence of E.coli and GBS , and an ascending trend in S. pneumoniae with the increase of the age.

In this study, subdural fluid collections/empyema and hydrocephalus were common brain imaging changes in children with CABM. The incidence of subdural fluid collections/empyema was 8% and didn’t appear obvious differences in G + and G- infections; but the incidence in the confirmed group (16%) was much higher than that in the clinical group (8%) and the probable group (3.9%). The above findings suggested that the children with positive pathogen culture at early stage suffered higher pathogen loading, more severe host inflammatory response, and were prone to subdural fluid collections/empyema, while had little correlation with the G + or G- pathogen. Compared with older children, subdural fluid collections are most commonly observed in infants (< 1 year of age) [ 15 ]. In this paper, 90.4% children with subdural fluid collections/empyema were younger than 1 year old, and the incidence of subdural fluid collections/empyema was the highest among children aged 3–12 months in the confirmed group. In addition, the incidence of hydrocephalus in CABM patients was 5%, which is significantly lower than the results of other studies (15 – 18.8%) [ 16 , 17 ]. And this difference was mainly caused by the inclusion of children with probable BM in this study. The incidence of hydrocephalus in the probable group was only 0.7%, much lower than 10.4% and 7.6% in the confirmed and clinical groups. There was no significant difference in the incidence of hydrocephalus between different age groups in this study, but some study showed that hydrocephalus is more common in neonates and infants (the incidence in patients aged < 3 months reaches 14 – 27%) [ 17 , 18 ]. Zhou Wei et al. revealed a higher incidence of hydrocephalus in meningitis newborns with G- [ 19 ], while the incidence was not significantly different between G + and G- in children aged 0–14 years in this study.

In this article, the overall cure and improvement rate of CABM in children in Zhejiang Province from 2019 to 2020 was 94.4%. The prognosis of the confirmed group was worse than that of the clinical group and the probable group, suggesting that the prognosis of CABM in children was related to the bacterial loading. The main experimental method to confirm the diagnosis in our study was bacterial culture and its positive rate was correlated with bacterial loading [ 6 ]. Children with negative blood culture had lower level of bacterial loading in their blood compared to infants with positive one [ 20 ]. Bacterial loading is associated with the outcome of severe infection in the host [ 21 ]. In this study, the positive rate of bacterial culture in children with septic shock was much higher than that in those without shock, indicating that children with positive bacterial culture were more likely to suffer severe infections. Besides, the overall prognosis of CABM in children in the confirmed group was not significantly different between G + and G-. This conclusion was consistent with the results of a domestic study based on the prognosis of newborns with BM [ 19 ]. In summary, the prognosis of CABM in children is linked to bacterial loading, with little correlation with the G + and G-.

Limitations

There were some limitations in this study. First, it lacked a long follow-up, and further improvement in the evaluation and follow-up of long-term neurological complications was needed. Furthermore, the non-culture detection method of bacterium-free fluids in the early stage of the disease should be pay more attention. Finally, in calculating the annual incidence, the local population during the observation period was used as the denominator. The inclusion of individuals with preexisting conditions in the denominator may have led to an underestimation of incidence.

Conclusions

To sum up, our study assessed the annual incidence and mortality of CABM in children aged 0–14 years in Zhejiang Province. In this study, children with CABM were classified according to their laboratory data and clinical manifestations, including pathogen confirmed group, clinical diagnosis group and probable case group. Neuroimaging abnormalities were more common in the confirmed group, and the clinical prognosis of these children was poor. In addition, our study demonstrated that infants, especially newborns, were at high risk of CABM in children. E.coli , GBS and S. pneumoniae are the top three pathogens of CABM in children in Zhejiang Province. Subdural fluid collections/empyema and hydrocephalus are the most common brain imaging complications. Clarifying the epidemiological characteristics of CABM in children in the region can not only guide early clinical empirical treatment, but also provide an etiological basis for the immunization program of BM.

Data Availability

The datasets used and/or analyzed during the present study are available from the corresponding author upon reasonable request. The data cannot be made public because of privacy or ethical restrictions.

Abbreviations

Bacterial meningitis

Community-acquired bacterial meningitis

Cerebrospinal fluid

Computerized tomography

Escherichia coli

Group B Streptococcus agalactiae

Gram-positive bacteria

Gram-negative bacteria

Streptococcus pneumoniae

Kim KS. Acute bacterial Meningitis in infants and children. Lancet Infect Dis. 2010;10:32–42.

Article   CAS   PubMed   Google Scholar  

Wall EC, et al. Acute bacterial Meningitis. Curr Opin Neurol. 2021;34:386–95.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Zainel A, Mitchell H, Sadarangani M. Bacterial Meningitis in children: neurological Complications, Associated Risk factors, and Prevention. Microorganisms. 2021;9:535.

Article   PubMed   PubMed Central   Google Scholar  

Beaman MH. Community-acquired acute Meningitis and encephalitis: a narrative review. Med J Aust. 2018;209:449–54.

Article   PubMed   Google Scholar  

World Health Organization (Vaccines and Biologicals). WHO-recommended standards for surveillance of selected vaccine-preventable Diseases; 2003. WHO/V&B/03. 01. WHO, Geneva.

Davis LE. Acute bacterial Meningitis. Continuum (Minneap Minn). 2018;24(5):1264–83.

PubMed   Google Scholar  

GBD 2016 Meningitis Collaborators. Global, regional, and national burden of Meningitis, 1990–2016: a systematic a nalysis for the global burden of Disease Study 2016. Lancet Neurol. 2018;17:1061–82.

Article   Google Scholar  

Wright C, et al. The global burden of Meningitis in Children: challenges with Interpreting Global Health estimates. Microorganisms. 2021;9:377.

Svendsen MB, et al. Neurological sequelae remain frequent after bacterial Meningitis in children. Acta Paediatr. 2020;109:361–7.

Li Y, Acute Meningitis and Encephalitis Syndrome Study Group, et al. Population-based surveillance for bacterial Meningitis in China, September 2006-December 2009. Emerg Infect Dis. 2014;20:61–9.

Chinese Preventive Medicine Association, Vaccine and Immunology Branch of the Chinese Preventive Medicine Association. Expert consensus on immunoprophylaxis of pneumococcal Disease (2020 version). Chin J Vaccines Immun. 2021;27:1–47. https://doi.org/10.19914/j.CJVI.2021001

Alamarat Z, Hasbun R. Management of Acute bacterial Meningitis in children. Infect Drug Resist. 2020;13:4077–89.

Oordt-Speets AM, et al. Global etiology of bacterial Meningitis: a systematic review and meta-analysis. PLoS ONE. 2018;13:e0198772.

Shen H, et al. The etiology of acute Meningitis and encephalitis syndromes in a sentinel pediatric hospital, Shenzhen, China. BMC Infect Dis. 2019;19:560.

Namani SA, et al. Early neurologic Complications and long-term sequelae of childhood bacterial Meningitis in a limited-resource country (Kosovo). Childs Nerv Syst. 2013;29:275–80.

Olarte L, et al. Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Meningitis in US children. Clin Infect Dis. 2015;61:767–75.

Hsu MH, et al. Neurological Complications in Young infants with Acute bacterial Meningitis. Front Neurol. 2018;9:903.

Ouchenir L, et al. The Epidemiology, Management, and outcomes of bacterial Meningitis in infants. Pediatrics. 2017;140:e20170476.

Collaborative Study Group for Neonatal Bacterial Meningitis. A multicenter epidemiological study of neonatal bacterial Meningitis in parts of South China. Zhonghua Er Ke Za Zhi. 2018;56:421–8.

Google Scholar  

Stranieri I, et al. Assessment and comparison of bacterial load levels determined by quantitative amplifications in blood culture-positive and negative neonatal sepsis. Rev Inst Med Trop Sao Paulo. 2018;60:e61.

van der Poll T, Opal SM. Host-pathogen interactions in sepsis. Lancet Infect Dis. 2008;8:32–43.

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Acknowledgements

We thank all the members who participated in this study. We are grateful to the hospitals that provided electronic medical records. The list is as follows: Huzhou Maternity and Child Health Care Hospital; Lishui central Hospital; The First People’s Hospital of Xiaoshan District;The First Affiliated Hospital of Wenzhou Medical University; Yiwu Maternity and Child Health Care Hospital; Quzhou Maternity and Child Health Care Hospital; Jinhua Maternity and Child Health Care Hospital; Ruian People’s Hospital; Lanxi People’s Hospital; Taizhou central hospital; Zhejiang Provincial People’s Hospital; Hangzhou Children’s Hospital; Shaoxing Keqiao Women and Children’s Hospital; Lishui People’s Hospital; Dongyang People’s Hospital; Cixi People’s Hospital; Lishui Maternity and Child Health Care Hospital; Quzhou People’s Hospital; Shaoxing Second Hospital; Wenling Maternity and Child Health Care Hospital; Changshan People’s Hospital; The First People’s Hospital of Fuyang Hangzhou; Huzhou central hospital; The First People’s Hospital of Jiashan; The First Hospital of jiaxing affilicated Hospital of Jiaxing University; The First People’s Hospital of Xiangshan; The First People’s Hospital of Yuhang Hangzhou; Zhejiang Xiaoshan Hospital; Zhoushan Women and Children’s Hospital; Zhuji People’s Hospital; Haining People’s Hospital; The Affilicated Hospital of Hangzhou Normal University; The First People’s Hospital of Hangzhou; The First People’s Hospital of Huzhou;Beilun District People’s Hospital; Pan’an People’s Hospital; Shaoxing People’s Hospital; The Fourth Affilicated Hospital Zhejiang University School of Medicine; Changxing People’s Hospital; The First Affilicated Hospital Zhejiang University School of Medicine.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. This work was supported by the National Natural Science Foundation of China (82071812 and 82371829), and a grant from the Key Program of The Independent Design Project of National Clinical Research Center for Child Health (S20A0003).

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Department of Infectious Diseases, National Clinical Research Center for Child Health, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310051, Zhejiang, China

Juan-Juan Liu & Ying-Hu Chen

Department of Pediatric Infectious Disease, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China

Department of Pediatrics, Ningbo Women and Children’s Hospital, Ningbo, 315012, Zhejiang, China

Hui-Qing Xu

Department of Neonatology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China

Jia-Jun Zhu

Department of Pediatrics, Jiaxing Maternity and Child Health Care Hospital, Jiaxing, 314000, China

Jie-Ning Zhang

Taizhou Hospital of Zhejiang Province, Taizhou, 317000, Zhejiang, China

Department of Pediatrics, Yuyao People’s Hospital, Yuyao, 315400, Zhejiang, China

Sheng-Fu Yuan

Department of Pediatrics, The Second Hospital of Jiaxing, Jiaxing, 314000, Zhejiang, China

Department of Neonatal Intensive Care Unit, Shaoxing Maternity and Child Health Care Hospital, Shaoxing, 312000, Zhejiang, China

Hai-Jing Li

Department of Pediatrics, Jinhua Municipal Central Hospital, Jinhua Hospital of Zhejiang University, Jinhua, 321000, China

Department of Neonatology, National Clinical Research Center for Child Health, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310051, Zhejiang, China

Li-Hua Chen

Department of neurology, National Clinical Research Center for Child Health, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310051, Zhejiang, China

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Contributions

Ying-Hu Chen contributed to the study conception and design. Data collection and analysis were performed by Zhi-Wei Xu, Hui-Qing Xu, Jia-Jun Zhu, Jie-Ning Zhang, Sheng Fang, Sheng-Fu Yuan, He-Jia Ge, Hai-Jing Li, Wen-ji Lou, Li-Hua Chen, Feng Gao and Juan-Juan Liu. The first draft of the manuscript was written by Juan-Juan Liu and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ying-Hu Chen .

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Ethical approval and consent to participate.

The study protocol was approved by the Ethics Committee of the Children’s Hospital of Zhejiang University School of Medicine (2019-IRB-094). The requirement for informed consent was waived owing to the retrospective observational nature of the study. The decision not to require informed consent was upheld by the Ethics Committee of the Children’s Hospital of Zhejiang University School of Medicine. All methods were carried out in accordance with relevant guidelines and regulations.

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Liu, JJ., Xu, ZW., Xu, HQ. et al. Diagnostic status and epidemiological characteristics of community-acquired bacterial meningitis in children from 2019 to 2020: a multicenter retrospective study. BMC Pediatr 24 , 11 (2024). https://doi.org/10.1186/s12887-023-04469-1

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• Bacterial Meningitis (BM)
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Determine the factors affecting the time to recovery of children with bacterial meningitis at Jigjiga university referral hospital in the Somali Regional State of Ethiopia: using the parametric shared frailty and AFT models

• Daud Hussein Adawe 1 &
• Dagne Tesfaye Mengistie   ORCID: orcid.org/0000-0003-2282-5946 1  

BMC Research Notes volume  17 , Article number:  85 ( 2024 ) Cite this article

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Neisseria meningitides, Streptococcus pneumonia, and hemophilic influenza type B are frequently linked to bacterial meningitis (BM) in children. It’s an infectious sickness that kills and severely mobilizes children. For a variety of reasons, bacterial meningitis remains a global public health concern; most cases and deaths are found in Sub-Saharan Africa, particularly in Ethiopia. Even though vaccination has made BM more preventable, children worldwide are still severely harmed by this serious illness. Age, sex, and co-morbidity are among the risk variables for BM that have been found. Therefore, the main objective of this study was to identify the variables influencing the time to recovery for children with bacterial meningitis at Jigjiga University referral hospital in the Somali regional state of Ethiopia.

A retrospective cohort of 535 children with bacterial meningitis who received antibiotic treatment was the subject of this study. Parametric Shared Frailty ty and the AFT model were employed with log likelihood, BIC, and AIC methods of model selection. The frailty models all employed the patients' kebele as a clustering factor.

The number of cases of BM declined in young children during the duration of the 2 year, 11 month study period, but not in the elderly. Streptococcus pneumonia (50%), hemophilic influenza (30.5%), and Neisseria meningitides (15%) were the most frequent causes of BM. The time to recovery of patients from bacteria was significantly influenced by the covariates male patients (ϕ = 0.927; 95% CI (0.866, 0.984); p-value = 0.014), patients without a vaccination history (ϕ = 0.898; 95% CI (0.834, 0.965); P value = 0.0037), and patients who were not breastfeeding (ϕ = 0.616; 95% CI (0.404, 0.039); P-value = 0.024). The recovery times for male, non-breastfed children with bacterial patients are 7.9 and 48.4% shorter, respectively. In contrast to children with comorbidity, the recovery time for children without comorbidity increased by 8.7%.

Age group, sex, vaccination status, co-morbidity, breastfeeding, and medication regimen were the main determinant factors for the time to recovery of patients with bacterial meningitis. Patients with co-morbidities require the doctor at Jigjiga University Referral Hospital to pay close attention to them.

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Introduction

Background of the study.

A serious infection of the central nervous system known as bacterial meningitis (BM) can have either a short- or long-term outcome [ 1 , 2 ]. Clinically speaking, meningitis is an inflammation of the meninges that surround the brain and spinal cord [ 3 ]. This inflammation can be caused by a variety of agents, including viruses, fungi, protozoa, bacteria, and encapsulated bacteria. The most well-known and frequent of these are Streptococcus pneumonia, Hemophilic influenza, and Neisseria meningitides [ 4 , 5 ]. Meningitis causes significant neurosensory consequences and a high fatality rate (about 117,000 deaths annually globally). The disease’s median incidence in children under five is 34 cases per 100,000 children annually [ 6 ]. The incidence varies by global region; in the Americas, it is 16.6 per 100,000 children year, whereas in Africa, it is 143.6 per 100,000 children annually. With a range of 31.3% in the Africa region and 3.7% in Southeast Asia, the median case fatality rate is 14.4% [ 2 , 7 ].

The symptoms of fever, altered mental status, headache, and nuchal rigidity are suggestive of bacterial meningitis, though many people with the illness do not exhibit any of these symptom [ 8 ]. A spinal tap is necessary to get cerebrospinal fluid in order to make a conclusive diagnosis of meningitis [ 1 , 5 ]. Meningitis patients frequently have low blood sugar, elevated white blood cell counts, and elevated protein levels in their fluid. It might be possible to determine which bacteria caused the meningitis by analyzing the fluid. By cultivating the CSF sample, bacterial meningitis is diagnosed. After measuring the opening pressure, the fluid should be submitted for microbiology (i.e., Gram stain and cultures), chemistry (i.e., CSF glucose and protein), and cell count (and differential count) [ 1 , 6 ]. The traditional trio of meningitis symptoms fever, stiff neck, and altered mental status occurs in just 41% of cases of bacterial meningitis. The majority of patients who experience the triad are older. At least one of these symptoms will be present in 70% of individuals [ 6 ]. A method carried out in sterile conditions with the goal of preventing the entry of undesired organisms or bacterial pollutants into an environment is known as an aseptic technique. To prevent contamination of lab workers, cultures, and equipment, this is a crucial microbiological lab procedure [ 6 , 9 ]. In the microbiological laboratory, both chemical and physical sterilization techniques are used to guarantee that the materials and equipment are free of germs. Sanitization accomplishes this by lowering contamination to acceptable levels through the use of any cleaning method that mechanically eliminates germs and other debris. While antiseptics are used to disinfect flesh, disinfectants are administered to inanimate surfaces, medical equipment, and other man-made objects [ 1 , 9 ].

Meningitis has been one of the most dreaded infectious diseases throughout the nineteenth and twentieth centuries, and it is now a top priority for public health [ 4 , 6 ]. At least 1.2 million instances of invasive illness are thought to occur annually around the world, and invasive meningococcal disease (IMD) is thought to be responsible for 135,000 of those deaths [ 10 ]. The public health system is severely taxed by the disease burden in nations with high endemicity [ 11 ]. In low-income nations, where the prevalence of bacterial meningitis is highest, there is a higher risk of long-term debilitating sequelae, such as cognitive impairment, bilateral hearing loss, motor impairment, seizures, visual impairment, hydrocephalus, and amputation of limbs owing to tissue necrosis [ 1 , 6 , 12 ].

Streptococcus pneumonia, Hemophilic influenza, and Neisseria meningitides are the primary etiological agents of bacterial meningitis outside of the neonatal period, and it continues to be a significant source of morbidity and mortality [ 2 , 11 ]. These agents are extremely significant in sub-Saharan Africa's meningitis belt, where epidemics of the disease happen every 8–12 years. For instance, there were 42 cases in the Burkina Faso outbreak of 1996, with a 10% case fatality rate (CFR) [ 13 ]. In Ghana, there were 18551 cases in 1997, and 8% of them resulted in death [ 12 ]. The Meningococcal Meningitis Case Fatality Rate (CFR) is estimated by the World Health Organization (WHO) to be 10%, or 500,000 cases, each year, with 27,000 of those cases occurring in African regions [ 14 ]. Bacterial meningitis (BM) alone accounts for roughly 6–8% of all hospital admissions in Ethiopia, and its case fatality rates can reach 22–28%. For the past many decades, Ethiopia’s health has continued to be a major concern [ 15 , 16 ]. Studies on those who have recovered from bacterial meningitis have revealed a wide spectrum of neurological, cognitive, and behavioral consequences [ 17 ].

Systemic infections are predisposed to by malignant illnesses. Important factors include malnourishment, immunosuppressive therapy, and persistent venous catheters. Patients with leukemia, lymphomas, and those who have undergone neurosurgical procedures for brain tumors are more susceptible to meningitis [ 5 , 8 ]. In this demographic group, Streptococcus pneumonia, hemophilic influenza, and Neisseria meningitides are the most prevalent pathogens. An intracranial space-occupying process, thrombocytopenia, or an unusual clinical presentation might occasionally cause a delay in the proper diagnosis and appropriate management [ 18 ].

Recipients of transplant organs are more susceptible to invasive pneumococcal infections, which can cause sepsis and meningitis. Prior to transplantation, pneumococcal vaccination lowers the risk. L. monocytogenes and Nocardia spp. are other culprits that can cause meningitis in this population, particularly in cases where there are several brain abscesses [ 19 ]. Hypo-or asplenia, characterized by splenic dysfunction or absence, puts a person at risk for invasive infections from encapsulated bacteria, including S. pneumonia and H. influenza . Splenectomy is one way to treat acquired hyposplenism. HIV infection, sickle cell anemia, graft-versus-host disease, allogenic bone marrow transplantation, and celiac illness can also cause it to function [ 20 ]. Just 2.5% of community-acquired meningitis cases had asplenia, which is linked to a high death rate of 25% and persistent neurologic sequelae of 58% [ 18 ].

The time to completely recover children from bacterial meningitis (BM) from the day of diagnosis was the event of interest in this study [ 21 ]. The current study identified factors influencing children with bacterial meningitis (BM) recovery time using parametric shared frailty models and an AFT parametric model. The shared frailty model, a variant of the Cox PH model called the frailty model, takes into account any extra heterogeneity in the data [ 22 ].

Data and material

Description of the study area.

The study was carried out at Jigjiga University Referral Hospital, which is located 635 km from Addis Ababa, the capital city of Ethiopia, in the eastern section of the country, in the regional Jigjiga town of the Somali regional state [ 23 ]. The children diagnosed with bacterial meningitis comprise the study population under inquiry.

Study design and population

A retrospective cohort research was conducted at Jigjiga University Referral Hospital in the regional state of Somali. The study's target population consisted of the children less 18 year being treated at Jigjiga University Referral Hospital in Somali Regional State who had bacterial meningitis. The study was conducted between 10th of August 2023 and 30th of August, 2023 among children who were admitted to the hospital with sever bacterial meningitis from September 1, 2019 to July 20, 2023 at Jigjiga University referral hospital in Somali regional state. All children patients who were admitted for this referral hospital due to case of bacterial meningitis during the above stated dates was included the study. There were 535 children bacterial meningitis patients enrolled in this study.

Source of data

The secondary data used in this study was collected from Jigjiga University Referral Hospital in the Somali Regional State of Ethiopia for children less 18 year who had bacterial meningitis (BM).

Inclusion and exclusion criteria

Inclusion criteria.

All instances of bacterial meningitis in children who had a clinical diagnosis and started treatment were included in the study.

Exclusion criteria

The study did not include patients who were admitted but whose bacterial meningitis was not clinically confirmed. After the initial diagnosis, children also developed fungal, viral, or other forms of meningitis.

Data extraction and measurement

Baseline data was being extracted from the department of clinical pediatric registration book on which laboratory findings after investigation and recorded existing patients recorded card in the hospital. The whole patients who admit and diagnosed at Jigjiga university referral hospital. Baseline parameters that was extracted were time, age, sex, drug regimen (antibiotics), pathogen (organism caused the disease), residence place, breastfeeding, co-morbidity, vaccination status and kebele. The patients data about whether cured or not were extracted from daily follow up chart and the time to cure was calculated by subtracted the date of diagnosed from the date of discharge the hospital.

Study variables

Response variable.

The outcome or dependent variable taken into account in this study for children with bacterial meningitis was the length of hospitalization from the first day of the patient's diagnosis at the hospital to the last day of discharge from the hospital.

Independent or explanatory variables

The independent factors included in this study were age, sex, immunization status, nursing practices, organisms or infections, co-morbidity, medication regimen, and place of residence.

Method of data analysis

Several methods were employed in this study to examine the factors affecting the time to recovery of children with bacterial meningitis at Jigjiga University Referral Hospital in the Somali Regional State of Ethiopia by Using the parametric shared frailty and AFT models. Among those for comparing the survival experiences of two or more groups, a nonparametric test was provided. Kaplan–Meier survival function was non-parametric estimation, survival distribution estimation from a sample, and survival distribution were a few of these descriptive statistics. The most common and widely used test was the log-rank test. The Cox proportional hazards model was semi-parametric methods used in multivariable analysis. To further better address the goal of the investigation, AFT and parametric shared frailty models with loglikelhood, the Akaike Information Criterion (AIC), and the Bayesian Information Criterion (BIC) techniques of model selection were applied [ 1 , 24 ]. R and STATA (version 17) were the programs used during this study to analyze statistical data.

A total of 535 children with microbiologically confirmed bacterial meningitis were included in this study. Out of the 535 children with bacterial meningitis, 86 (16.6%) had their cases censored since it was unknown how many of them actually survived; the remaining 449 (83.4%) cases had known outcomes such as recovery from bacteria. Among 221 (41.3%) female children of bacterial patients, 35 (39.3%) of the female patients died, were transferred to other hospitals, lost, or dropped before death, which means they censored or did not recover from bacterial disease, whereas 186 (41.7%) of the female children of bacterial patients recovered from disease or lived. From a total of 314 (58.7%) male patients, 54 (60.7%) male bacterial patients were not recovering from the disease, while 260 (58.3%) male bacterial patients were recovering from the disease. In addition to this, the median recovery times for females and males were 14 and 12 days, respectively.

Out of 158 (29.5%) children with no vaccination status, 61 (68.5%) were censored, but 97 (21.7%) recovered from the disease while Among the 377 (70.5%) of children of bacterial patients that have vaccination status, 28 (31.5%) of children were censored, and 349 (78.3%) of the children of patients recovered from bacterial disease during follow-up. Among a total of 267 (49.9%) children bacterial patients who have comorbidities, 19 (21.3%) were censored, and the rest, 248 (55.6%) of the children with comorbidities, recovered from disease. Patients with co-morbidities spent an average of 13 days in the hospital, of which 73.88% recovered from disease; in contrast, patients without co-morbidities remained an average of 12 days, of which 92.88% recovered.

Among 505 (94.4%) of children who live in urban areas, 82 (92.1%) of the bacterial patients were censored, but 423 (94.8%) recovered from disease. While, out of 30 bacterial patients who lived in rural areas, 7 (7.9%) of the children were censored, and the rest, 23 (5.2%), were removed from bacterial meningitis. In comparison to rural patients, who had a median recovery time of 15 days and a recovery rate of 76.67%, urban patients had a median recovery time of 12 days. Streptococcus pneumonia ( 50 %), hemophilic influenza (30.5%), and Neisseria meningitides (15%) were the most frequent causes of BM. Streptococcus pneumonia and hemophilic influenza were the pathogens or organisms that caused the disease in the patients, and both had a median time to recovery of 12 days, with respective recovery rates of 85.19 and 78.53%. Another pathogen with a median recovery time of 13 days and an overall recovery rate of 83.75% is Neisseria meningitides.

Non‑parametric survival analysis

Plots of the Kaplan-Meir curves for the survival, survival failure, and cumulative hazards experienced for the time to survive of the bacterial patient were used for the non-parametric analysis, as illustrated in Figs. 1 , 2 , 3 , respectively. The outcome showed that the survival plot initially declined at an increasing rate and then occasionally reduced much more. This suggests that the majority of bacterial meningitis patients will get treatment shortly. On the other hand, the hazard plot started out growing faster and kept getting bigger with time.

Survivorship of Bacterial meningitis hospitalization

Survival failure function plot for the time to survive of BM Patient

cumulative Hazard plot for the time to survive of BM Patient

Survival comparison of different groups of BM patients

The age group older than 60 months has a higher survival rate than the age group younger than 1 month, especially in the intermediate stages when everything is essentially the same at the beginning and the end. This suggests that patients older than 60 months have a higher chance of recovering more slowly at a given point in time than patients younger than one month. Table 1 above shows that the group older than 60 months had a substantially different effect from the group younger than 1 month, whereas the other patient age groups did not exhibit a significantly different survival function at 5% level of significance see Fig.  4 .

survival function of age bacterial patient

Male patients have a lower survival rate than female patients, especially at midterm. However, they are all more similar at the beginning and at the bending times depicted in Fig.  5 . This suggests that male patients have a lower probability of recovering at a given time than female patients do.

survival function of sex of bacterial patient

The survival rate for the vaccinated group of patients is lower than that of the non-vaccinated group, especially in the midterms, but everything is the same at the beginning and at the end (see Fig.  6 ). This shows that the probability of the time to recovery for the vaccinated group is lower than when we compare it to the non-vaccinated group, as the probability of curing time for the non-vaccinated group is higher than that of the vaccinated group.

survival function of vaccination by time to recovery bacterial patient

Cox proportional hazard regression model

All covariate Cox proportional hazards models were fitted. The univariate analysis revealed that comorbidities, sex, age, immunization status, breastfeeding status, and comorbidity were all statistically significant factors for the variable of interest. Regarding the other criteria, such as residence and trends in drug use, there was no statistically significant difference.

Model diagnosis for Cox proportional hazards model

Table 2 illustrates how the log-linearity and proportional hazards assumptions of the Cox regression model were examined in the current investigation. The log-linearity test demonstrated that the log hazard, also known as the log cumulative hazard, and the covariate had a linear relationship. The proportional hazard test carried out in this work indicates that the ratio of the hazard function for two persons with different regression covariates does not change over time. The Wald chi-square test statistic was significant, as shown by the global fit test in Table  2 , which disproves the proportional hazards assumption.

Model diagnosis with graphical method

The log (time to recovery) vs. log (-log(s (t))) plots were not parallel to one another. As a result, the proportionate hazards assumption is broken (see Figs. 7 , 8 , 9 ). The smoothed plot, which resembles a straight line with some departure from the horizontal line, indicates that the residuals follow a systematic pattern and are not random, as demonstrated by the plot of the scaled Schoenfeld. Consequently, Fig.  10 ’s proportionate hazards assumption is violated.

log–log plot of survival of pathogen caused disease of time to recovery of bacterial

log–log plot of survival of age group patient of time to recovery of bacterial

log–log plot of survival of comorbidity patient of time to recovery of bacterial

Plot of the scaled schoenfeld for pathogen cause and age group of time to recovery of bacteria

Accelerated failure time model results

Unavailable analysis.

The covariates of breastfeeding, co-morbidity, and vaccination status of the patients are significant in all of the models that were used.

Multivariate AFT analysis

Covariates that were no longer significant in the multivariate analysis were eliminated from the model using the backward elimination approach. As a result, the drug regimen and living address were dropped or omitted. The effect of interaction terms was further investigated at the 10% level of significance and was shown to be statistically insignificant in the multivariable lognormal AFT model. The primary effects of the covariates vaccination status, patient breastfeeding, sex, age, and comorbidity were retained in the final model. All of the AFT models are listed in Table  3 , along with the corresponding log likelihood, BIC, and AIC values.

Table 3 shows that AIC, BIC, and log-likelihood were used to evaluate AFT models like Weibull, exponential, log-logistic, and lognormal distributions to see which one best fit the data. Consequently, the AIC and BIC for the lognormal distribution were the lowest. For this reason, it has been chosen for the current study's univariate and multivariate data analysis.

Univarable analysis for frailty models

The covariates co-morbidity, vaccination status, and breastfeeding are significant in all of the univariable analysis models at the 0.05 level of significance. Age group and sex are also significant at 5% for most of the models except exponential baseline with gamma and inverse Gaussian frailty distribution, where drug regime is significant lognormal at baseline with inverse Gaussian frailty distribution. In all models, the pathogen variables and the residence site are not relevant for the recovery time at the 5% level of significance.

In the univariable analysis, significant covariates were identified and used in the multivariate AFT baseline hazard function with the gamma and the inverse Gaussian frailty distributions. The model with the lowest AIC for the bacterial meningitis data set was lognormal at baseline with an inverse Gaussian frailty distribution. The lognormal inverse Gaussian frailty model, as presented in Table  3 , had the lowest AIC and BIC values of all the parametric frailty models (AIC = 2674.080, BIC = 314.987). This suggests that the model was comparatively the most effective in explaining the children's bacterial meningitis data set.

In the lognormal inverse Gaussian frailty model, the shape parameter was 2.184. This number is more than one unity, indicating that the hazard function’s shape grew initially before eventually decreasing. According to Table  4 , the heterogeneity within clusters is 22.1%, whereas the heterogeneity in the population of clusters estimated for this best model is ϴ = 0.98, which is significant at the 5% level of significance. 13 days was the patients’ overall median recovery period from bacterial meningitis. Table 4 presents the findings of a study using the lognormal inverse Gaussian frailty model. The factors that were shown to be significant at the 5% level of significance were age group, sex, co-morbidity, vaccination status, breastfeeding, and medication regimen.

The age group had a significant effect on the time to recovery for bacterial meningitis patients. Hence, comparing the age group of more than 60 months with those of less than 1 month, the expected time to recovery for more than 60-month-old bacterial patients was increased by 12.8% as compared to less than 1 month-old patients, keeping the other covariates constant (ϕ = 1.623; 95% CI (1.065, 2.4747); p -value = 0.024). This result indicates that more than 60-month-old children with bacterial meningitis had a prolonged time to recovery as compared to less than a month-old child with bacterial meningitis. Although bacterial meningitis can strike anyone at any age, it most commonly strikes infants, young children, and adolescents. Meningitis and septicemia are more common in particular age groups. Because their immune systems are still developing, young children are more vulnerable than older age groups. Vaccines offer this susceptible age group essential protection and enable young children to safely identify dangerous microorganisms.

Vaccination was a significant factor in the time to recovery of children with bacterial meningitis. Comparing vaccinated children patients with not vaccinated, the expected time to recovery for vaccinated children patients was decreased by 10.9% as compared to not vaccinated children patients, keeping the other covariates constant (ϕ = 0.898; 95% CI 0.834, 0.965); p -value < 0.003). This suggests that female children have a better chance of recovering from bacterial meningitis than male children. Because the vaccine does not protect against all strains of the bacteria that can cause the disease. While the vaccine provides very good protection against four of the five most common strains that cause meningococcal disease, it does not provide in all protection from these four strains. Getting the meningococcal vaccine after you've been exposed will not protect you against getting sick from that particular exposure. However, getting the vaccine to protect you against future exposures is a very good idea.

Sex was a significant factor in the time to recovery of children with bacterial meningitis. Comparing male children patients with females, the expected time to recovery for male children patients was decreased by 7.9% as compared to female children bacteria patients, keeping the other covariates constant (ϕ = 0.924; 95% CI 0.866, 0.984); p -value < 0.014). This suggests that female children have a better chance of recovering from bacterial meningitis than male children. Because male patients had higher comorbidities and immunosuppressive diseases than female patients, they were also underinsured. There are notable differences between male and female community-acquired meningitis in terms of comorbidities, presentation symptoms and signs, aberrant laboratory and imaging investigations, and indicators of unfavorable clinical outcomes.

The co-morbidity was also a significant factor in the time to recovery of children with bacterial meningitis. Hence, comparing children patients who haven’t comorbidity with children who have comorbidity, the expected time to recovery for children who haven’t comorbidity was increased by 8.7% as compared to children patients who have comorbidity, keeping the other variable factor remaining constant (ϕ = 1.098; 95% CI 1.022 1.164; P-value < 0.008). This shows that children who don’t have co-morbidity have a prolonged time to recovery as compared to children with co-morbidity. Comorbidity is linked to more complicated clinical management, poorer health outcomes, and higher medical expenses. Comorbidities might make treating a medical issue more difficult. The concept of burden of illness or disease, which is determined by the entire burden of physiological dysfunction or the total burden of all illness kinds that have an effect on a person's physiologic reserve, has also been expressed through the use of comorbidity. The examination of mechanisms such as direct causation, associated risk factors, heterogeneity, and independence that may contribute to the coexistence of many disorders in a patient is necessary, and the consequences for clinical care must be taken into account.

The breastfeeding of children also played a significant effect on the time to recovery of children with bacterial meningitis. Comparing the not-breathing children patient with breastfeeding children patient 1, the expected time to recovery for the no-breathing children patient was decreased by 48.4% as compared to the breastfeeding children bacteria patient, keeping the other covariates constant. (ϕ = 0.616; 95% CI 0.404–0.939; p -value < 0.024). This indicates that breastfeeding children have a greater chance of recovery than non-breathing children caused by bacterial meningitis disease. Human milk offers protection against distinct clinical ailments (such as necrotizing enter apathy, bacteremia, meningitis, respiratory tract infections, diarrheal diseases, and otitis media) as well as against certain pathogens (viruses, bacteria, and parasites). Breast milk is one of the most essential elements in preventing newborns from contracting infectious.

In this study, bacterial meningitis cases were common in 1 month to 1 year of age group (1–12 months) patients, which accounted for 45.42% of bacterial meningitis cases in pediatric departments. Other age groups, such as less than 1 month, between 13 and 36 months, 37–60 months, and greater than 60 months, accounted for 0.56, 20.37, 8.97, and 24.67%, respectively. This study was lower than the study in Swedish and Beverley [ 25 , 26 ].

The age group of children had a significant effect on the time to recovery of children with bacterial meningitis. The median time for improvement was 5 days. The patients whose age is greater than 60 months had a significantly prolonged time of curing as compared to the patients aged less than 1 month. Numerous studies indicate that the following age groups are terminal: The most common age groups to be afflicted by bacterial neuro infections are infants and the elderly. Infants and newborns have a more permeable blood–brain barrier and a developing immune system [ 2 ]. Immune senescence, or the weakening of the immune system in individuals over 65, increases a person’s vulnerability to illnesses and reduces the effectiveness of vaccinations. In contrast, this observation was in line with the previous studies that had already shown that the younger age children patients have prolonged time to recover from the bacterial meningitis [ 1 , 27 ].although, comparable to the research Children under the age of 12 months are the group most impacted by BM in France, Nigeria, Guatemala, and Malaysia1 [ 1 ]. According to Basri in Malaysia, BM increases the risk of death in children under the age of 1 year (OR = 3.13 [1.33–7.24] [ 5 ]. These findings are consistent with our research, which found that children with BM who are younger than 6 months old had a twice-higher chance of dying. Young newborns may need more specialized care because they are a population at risk for BM mortality [ 8 ].

Sex had a significant effect on the time to recovery of children with bacterial meningitis. The female patients had more time to recover as compared to the female patients, and, most similarly to the descriptive type of study that was carried out from May 2012 to April 2013, the male patients had 55.2% [ 28 , 29 ]. According to reports from MacCormick in Malawi [ 30 ], Kuti in Nigeria [ 31 ], and Basri in Malaysia14, most BM impact studies revealed a 50–60% male preponderance. Each nation's sociodemographic composition affects the sex ratio. Sex, however, does not increase the risk of dying from BM.

The vaccinated group of patients had significantly shorter recovery times than the non-vaccinated group; in other words, the non-vaccinated group took longer to heal than the vaccinated group of patients who were successful in getting better. Similar to this, a prospective study on the cause of childhood acute bacterial meningitis was conducted, and this study had already demonstrated that the vaccinated group of patients, who made up 91.3% of the patient population, had better outcomes than the non-vaccinated group in terms of healing time [ 32 ]. Research from many nations’ shows that the PCV vaccination lowers the incidence of pneumonia that is mistakenly diagnosed as a respiratory virus infection as well as the usage of antibiotics. For instance, after PCV7 was made available in the United States in 2000, the number of antibiotic prescriptions for acute otitis media in children under the age of 2 years decreased by 42% between 1997 and 2004 [ 14 ]. An international panel of experts calculated that, across the 75 countries analyzed, universal PCV coverage could prevent up to 11.4 million days of antibiotic therapy for pneumonia caused by S. pneumonia each year in children under the age of five[ 18 ]. This represents a 47% reduction in antibiotic therapy.

The comorbidity of patients had a significant effect on the time to recovery of children with bacterial meningitis. Children who do not have co-morbidity have a prolonged time to recovery as compared to children with co-morbidity. This is also consistent with other research, such as a comparative cohort study that was conducted between 2014 and 2019, in which the co-morbidity of the patients was a significant factor in the patients' outcomes, and another study that was also conducted in Ethiopia, a retrospective chart [ 33 , 34 ]. The presence of comorbidities was associated with the development of acute organ dysfunction (i.e., severe sepsis). Although the presence of comorbidities alters the choice of antibiotic in accordance with scientific societies' guidelines and is linked to an increased likelihood of treatment failure, these indications are primarily based on expert opinion rather than prospective studies [ 18 ]. Therefore, research is required to determine whether the comorbidities have any connection to the microbe that causes AE-COPD and whether this connection could aid in the empirical selection of an antibiotic. In this manner, the likelihood of resistance developing as well as treatment failure could be decreased [ 5 ].

The breastfeeding covariate had a significant effect on the time to recovery of children with bacterial meningitis. The breast feeding of the patient had a positive effect on the time of recovery, and this was consistent with the other study that was conducted in Rebro Country, Sweden, over a 6 year period, 1987–1992. Breastfeeding patients had a shorter curing time than those who were not breastfeeding while using the same covariate [ 35 ]. Also in the study in eastern Ethiopia, the acceleration factor showed that breastfeeding patients had a shorter curing time than those who were not breastfeeding while using the same covariate [ 29 , 36 ].

This study used the parametric shared frailty and AFT models to identify factors influencing the time to recovery of children with bacterial meningitis at Jigjiga University referral hospital in the Somali regional state of Ethiopia. The results of the parametric shared frailty and AFT models revealed that age group, comorbidity, sex, vaccination status, and breastfeeding were significant factors determining the time to recovery of children with bacterial meningitis at Jigjiga University referral hospital. Of these important variables, children with bacterial meningitis recovered more quickly when they were older and if they were non-comorbid. Conversely, there was a negative correlation found between children’s recovery time and sex, vaccinations, and breastfeeding. When compared to female child bacterial patients, the male child patients' anticipated recovery time was 7.9% shorter. Nevertheless, holding the other covariates constant, the number of children without comorbidity increased by 8.7% relative to the number of children with comorbidity, and the number of children without breathing decreased by 48.4% relative to the number of breastfeeding children of bacterial patients.

With esteem to log likelihood, AIC, and BIC values, the BM data set fit better. Consequently, the inverse Gaussian frailty model with the lognormal baseline was better than the lognormal Gamma frailty model, the log logistic Gamma frailty model, the Weibull-Gamma frailty model, the exponential-inverse Gaussian frailty model, and the exponential-Gamma frailty model. The variable of interest was significantly affected by clustering. The time to recovery of patients from the bacterial meningitis dataset is affected by clustering because of differences in the patients' time to recovery distribution among the 20 kebele from which they came.

Recommendations

The study conclusions led to the following recommendations being made: Patients with a co-morbidity of bacterial meningitis should receive extra care from medical staff at the Jigjiga University referral hospital. Patients under 60 months of age must be made aware of the fact that their recovery times are longer than those of other age groups are. To get parents to vaccinate their children against bacterial meningitis, the nation's Ministry of Health and Jigjiga University Referral Hospital must inform the public about the seriousness of the disease. The public should become more aware of the illness and be open to the advice and viewpoints of medical experts.

Limitation of study

The main limitation of the research was the utilization of secondary data, which may have omitted some important patient information such as house rowdiness the residents in a house rooms with two categories a- < 3individual per room and b- > 3individual per room, mother education (elementary, secondary schools and university), malnutrition (anemia), family income, pathogen ( L. monocytogenes and Nocardia spp. ), and high according to local master of living), children's weight, indicators, and symptoms.

Availability of data and materials

This article contains all of the information that was created or examined throughout the investigation.

Abbreviations

Akaike information criteria

• Bacterial meningitis

Case fatality rate

Cerebrospinal fluid

Cerebrospinal meningitis

Ethiopian calendar

Invasive meningococcal disease

Jigjiga University

packed cell volume

Sophisticated intensive care units

Sub-Saharan Africa

World Health Organization

Scheld WM, et al. Pathophysiology of bacterial meningitis: mechanism (s) of neuronal injury. J Infect Dis. 2002;186(2):S225–33.

Article   CAS   PubMed   Google Scholar  

Dias S, et al. Sex-based differences in adults with community-acquired bacterial meningitis: a prospective cohort study. Clin Microbiol Infect. 2017;23(2):121.

Article   Google Scholar  

Yamamoto M, et al. Interferon-γ and tumor necrosis factor-α regulate amyloid-β plaque deposition and β-secretase expression in Swedish mutant APP transgenic mice. Am J Pathol. 2007;170(2):680–92.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Pollard AJ, Perrett KP, Beverley PC. Maintaining protection against invasive bacteria with protein–polysaccharide conjugate vaccines. Nat Rev Immunol. 2009;9(3):213–20.

Gordon SB, et al. Bacterial meningitis in Malawian adults: pneumococcal disease is common, severe, and seasonal. Clin Infect Dis. 2000;31(1):53–7.

Purwanto DS, et al. Isolation and identification of Streptococcus pneumoniae serotype 6B from a patient with bacterial meningitis infection in Jakarta, Indonesia. Access Microbiol. 2020. https://doi.org/10.1099/acmi.0.000123 .

Article   PubMed   PubMed Central   Google Scholar  

Dou Z-Z, et al. Clinical characteristics and outcome analysis of 94 children with brain abscess in Beijing: a single-center retrospective study. Pediatr Infect Dis J. 2021;40(2):109–15.

Article   PubMed   Google Scholar  

Basri R, et al. Burden of bacterial meningitis: a retrospective review on laboratory parameters and factors associated with death in meningitis, Kelantan Malaysia. Nagoya J Med Sci. 2015;77(1–2):59.

PubMed   PubMed Central   Google Scholar  

MacNeil JR, et al. Updated recommendations from the advisory committee on immunization practices for use of the Janssen (Johnson & Johnson) COVID-19 vaccine after reports of thrombosis with thrombocytopenia syndrome among vaccine recipients—United States, April 2021. Morb Mortal Wkly Rep. 2021;70(17):651.

Jafri RZ, et al. Global epidemiology of invasive meningococcal disease. Popul Health Metrics. 2013;11:1–9.

Chaudhuri A, et al. EFNS guideline on the management of community-acquired bacterial meningitis: report of an EFNS task force on acute bacterial meningitis in older children and adults. Eur J Neurol. 2008;15(7):649–59.

Edmond K, et al. Long term sequelae from childhood pneumonia; systematic review and meta-analysis. PLoS ONE. 2012;7(2):e31239.

Zhang X-X, et al. The diagnostic value of metagenomic next-generation sequencing for identifying Streptococcus pneumoniae in paediatric bacterial meningitis. BMC Infect Dis. 2019;19(1):1–8.

Sadeq H, et al. Childhood meningitis in Kuwait in the era of post pneumococcal conjugate vaccination: a multicenter study. J Infect Public Health. 2017;10(6):766–9.

Organization WH. Pocket book of hospital care for children: guidelines for the management of common childhood illnesses. Geneva: World Health Organization; 2013.

Google Scholar  

Christiaensen L, Alderman H. Child malnutrition in Ethiopia: can maternal knowledge augment the role of income? Econ Dev Cult Change. 2004;52(2):287–312.

Salih MMA, et al. Long term sequelae of childhood acute bacterial meningitis in a developing country: a study from the Sudan. Scand J Infect Dis. 1991;23(2):175–82.

Adriani K, et al. Bacterial meningitis in pregnancy: report of six cases and review of the literature. Clin Microbiol Infect. 2012;18(4):345–51.

Rocha AJD, et al. Modern techniques of magnetic resonance in the evaluation of primary central nervous system lymphoma: contributions to the diagnosis and differential diagnosis. Revista Brasileira de Hematologia e Hemoterapia. 2016;38:44–54.

Di Sabatino A, et al. Depletion of immunoglobulin M memory B cells is associated with splenic hypofunction in inflammatory bowel disease. Off J Am College Gastroenterol. 2005;100(8):1788–95.

Keiding N, Andersen PK, Klein JP. The role of frailty models and accelerated failure time models in describing heterogeneity due to omitted covariates. Stat Med. 1997;16(2):215–24.

Mulugeta G, Tesfaye D, Tegegne AS. Predictors for the duration of breastfeeding among ethiopia women of childbearing age with babies; application of accelerate failure time and parametric shared frailty models. BMC nutrition. 2022;8(1):1–10.

de Jonge RC, et al. Predicting sequelae and death after bacterial meningitis in childhood: a systematic review of prognostic studies. BMC Infect Dis. 2010;10(1):1–14.

Economou P, Caroni C. Graphical tests for the assumption of gamma and inverse Gaussian frailty distributions. Lifetime Data Anal. 2005;11:565–82.

Article   MathSciNet   CAS   PubMed   Google Scholar  

Alemu M, et al. Determinants of neonatal sepsis among neonates in the northwest part of Ethiopia: case-control study. Ital J Pediatr. 2019;45(1):1–8.

Article   MathSciNet   Google Scholar  

Indermun S, et al. Current advances in the fabrication of microneedles for transdermal delivery. J Control Release. 2014;185:130–8.

Dätwyler, C. and T. Stucki, Parametric survival models. 2011.

Golding N, et al. Mapping under-5 and neonatal mortality in Africa, 2000–15: a baseline analysis for the sustainable development goals. Lancet. 2017;390(10108):2171–82.

Maes HH, Neale MC, Eaves LJ. Genetic and environmental factors in relative body weight and human adiposity. Behav Genet. 1997;27:325–51.

McCormick DW, et al. Risk factors for death and severe sequelae in Malawian children with bacterial meningitis, 1997–2010. Pediatr Infect Dis J. 2013;32(2):e54.

Article   MathSciNet   PubMed   PubMed Central   Google Scholar  

Kuti BP, et al. Epidemiological, clinical and prognostic profile of childhood acute bacterial meningitis in a resource poor setting. J Neurosci Rural Pract. 2015;6(04):549–57.

Acevedo R, et al. The Global Meningococcal Initiative meeting on prevention of meningococcal disease worldwide: epidemiology, surveillance, hypervirulent strains, antibiotic resistance and high-risk populations. Expert Rev Vaccines. 2019;18(1):15–30.

Xiang Y-T, et al. Timely mental health care for the 2019 novel coronavirus outbreak is urgently needed. Lancet Psychiatry. 2020;7(3):228–9.

Tilahun T, Sinaga M. Knowledge of obstetric danger signs and birth preparedness practices among pregnant women in rural communities of eastern Ethiopia. Int J Nurs Midwifery. 2016;8(1):1–11.

Stewart EJ. Growing unculturable bacteria. J Bacteriol. 2012;194(16):4151–60.

Erdem I, et al. Clinical features, laboratory data, management and the risk factors that affect the mortality in patients with postoperative meningitis. Neurol India. 2008;56(4):433.

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DHA contributed to the design of the analysis, the thorough writing of the article, the critical drafting for significant intellectual interaction. DTM helped with data collection, conceptualization of the article, a paper advice and the submission of the work. The final manuscript was read and approved by all authors.

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Adawe, D.H., Mengistie, D.T. Determine the factors affecting the time to recovery of children with bacterial meningitis at Jigjiga university referral hospital in the Somali Regional State of Ethiopia: using the parametric shared frailty and AFT models. BMC Res Notes 17 , 85 (2024). https://doi.org/10.1186/s13104-024-06740-9

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A case report about a child with drug-resistant tuberculous meningitis

• Jing Tong 1 ,
• Mengqiu Gao 1 ,
• Yu Chen 2 &
• Jie Wang 2  

BMC Infectious Diseases volume  23 , Article number:  83 ( 2023 ) Cite this article

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Hematogenous disseminated tuberculosis predisposes to concurrent tuberculous meningitis (TBM), the most devastating and disabling form of tuberculosis. However, children often have atypical clinical symptoms, difficulty in specimen collection, low specimen content, and an increasing incidence of drug-resistant tuberculosis. Thus, the accurate diagnosis and timely treatment of childhood tuberculosis face monumental challenges.

Case presentation

The 14-year-old female presented to the hospital with intermittent fever, headache, and blurred vision. Her cerebrospinal fluid (CSF) showed a lymphocytic pleocytosis, an elevated protein level, and a decreased chloride level. And her CSF tested positive for TB-RNA. Xpert MTB/RIF detected Mycobacterium tuberculosis in her CSF, but the rifampin resistance test was unknown. Subsequently, her CSF culture was positive for Mycobacterium tuberculosis. The drug sensitivity test (DST) revealed resistance to isoniazid, rifampin, and fluoroquinolones. A computed tomography (CT) of the chest showed diffuse miliary nodules in both lungs. Intracranial enhanced magnetic resonance imaging (MRI) showed “multiple intensified images of the brain parenchyma, cisterns, and part of the meninges.” The final diagnosis is miliary pulmonary tuberculosis and pre-extensive drug-resistant TBM. After 19 months of an oral, individualized antituberculosis treatment, she recovered with no significant neurological sequelae.

For patients with miliary pulmonary tuberculosis, especially children, even if there are no typical clinical symptoms, it is necessary to know whether there is TBM and other conditions. Always look for the relevant aetiological basis to clarify whether it is drug-resistant tuberculosis. Only a rapid and accurate diagnosis and timely and effective treatment can improve the prognosis and reduce mortality and disability rates.

Peer Review reports

Tuberculosis (TB) is one of the world’s most serious diseases that endanger human health, especially among children. According to what the World Health Organization (WHO) reported in 2022, there were about 10.6 million TB patients worldwide in 2021, of whom 1.166 million were children. Globally, the estimated number of deaths from TB was 1.6 million, up from both 2019 and 2020, with about 217,000 children dead [ 1 ]. When Mycobacterium tuberculosis enters the bloodstream, it spreads widely to the lungs and causes lesions that become miliary pulmonary tuberculosis. And in severe cases, it can spread to multiple organs throughout the body. Tuberculous meningitis (TBM) is the most destructive and disabling form of tuberculosis in children and adolescents. However, as a special group, children often have atypical clinical symptoms, difficulty with specimen collection, low specimen content, limited testing conditions, etc. There is an increasing incidence of drug-resistant tuberculosis. According to WHO estimates, the number of drug-resistant tuberculosis patients in 2021 was 450,000, an increase of 3.1% over the 437,000 cases in 2020. The global burden of tuberculosis has further increased, making this population face many difficulties and challenges in diagnosis and treatment [ 2 , 3 ]. In recent years, with the emergence of new technologies for tuberculosis detection and new treatment protocols, more and more patients, especially drug-resistant tuberculosis patients, have been diagnosed and treated promptly and have continuously achieved remarkable results. However, the reported data in the literature on drug-resistant tuberculous meningitis in children is limited. Here, we reported a case of the diagnosis and treatment of a child with miliary pulmonary tuberculosis and drug-resistant TBM.

A 14-year-old girl, presented to the local hospital on July 6, 2019, with 5 days of intermittent fever and a maximum temperature of 38.5℃. She had intermittent right chest pain, without coughing, sputum production, or chest tightness. The local doctor gave her an anti-infective treatment for “pneumonia” for 7 days because of the patchy high-density lung shadow on her chest CT scan, but it did not help her condition. Then she presented to the local TB hospital on July 15, 2019. Here she got a diagnosis of “Mycobacterium tuberculosis-negative pulmonary tuberculosis” based on the chest CT findings, positive interferon-gamma release assay (IGRA) results, and positive tuberculin skin test (TST). The sputum acid-fast bacilli smear was negative. She started anti-tuberculosis medication at a dose of “0.3 g/day of isoniazid, 0.45 g/day of rifampin, 1.0 g/day of pyrazinamide, and 0.75 g/day of ethambutol.” After 2 months of treatment, her fever broke and her chest pain lessened. On October 16, 2019, she went to the hospital, and a chest CT revealed diffuse miliary nodules in both lungs. Her sputum acid-fast bacilli smear was still negative. She was currently receiving high-dose isoniazid (0.6 g/day) and prednisone acetate (30 mg/day) for miliary pulmonary tuberculosis. Prednisone acetate was subsequently tapered and discontinued. However, the youngster experienced a fever again on December 16, 2019, reaching a high of 38.8 °C without chills, a cough, or sputum. She also experienced a paroxysmal headache and blurred vision. Because of the worsening of her headache, she visited the hospital once more on December 30, 2019, and the cranial brain magnetic resonance imaging (MRI) revealed atypical intracranial lesions that were deemed to be TBM. In an emergency, she came to our hospital for further treatment. Prior medical history: no history of hepatitis, tuberculosis, malaria, hypertension, diabetes, cardiovascular disease, psychiatric illness, surgery, trauma, blood transfusion, or allergies. Denial of a history of close contact with active tuberculosis.

When arriving at our hospital, she was febrile (38.6℃). Her vital signs were a heart rate of 112 per minute, a respiratory rate of 24 per minute, blood pressure 109/68 mmHg, and oxygen saturation in room air of 98%. Her physical examination showed slight neck rigidity, positive Kerning's sign, and positive Brudzinski's sign. Her chest CT showed diffuse miliary nodules in both lungs ( Fig.  1 ). The cranial enhancement MRI showed punctiform enhancement in the pontine brain, right cerebellar hemisphere, bilateral frontal, temporal, parietal lobes, nodular enhancement in the local meninges, and linear enhancement in the brain pool ( Fig.  2 ). Considering the possibility of tuberculous meningitis, we immediately obtained a specimen of her CSF. On January 02, 2020, she had her first lumbar puncture. And a culture of Mycobacterium tuberculosis (liquid culture, medium MGIT 960) in the CSF was taken. Her other CSF results showed a lymphocytic pleocytosis, elevated protein level (1.33 g/L, normal value 0.08–0.43 g/L), decreased chloride level (116 mmol/L, normal value 118–132 mmol/L), normal glucose level (2.56 mmol/L, normal value 2.2–3.9 mmol/L), smear-negative for acid-fast bacilli, positive for TB-RNA, Xert MTB/RIF detected Mycobacterium tuberculosis, but rifampin resistance test was unknown. Her sputum acid-fast bacilli smear, TB-RNA, and Xpert were all negative. TBM was confirmed, but the rifampicin resistance was indeterminate. Her first rapid culture of CSF showed positive result on January 28, 2020. We then undertook the traditional-culture based phenotypic testing DST and continued treatment as sensitive TB while waiting for the DST result. The basic treatment regimen is "isoniazid 0.6 g/day, rifampin 0.45 g/day, pyrazinamide 1.0 g/day, and ethambutol 0.75 g/day". Also added "linezolid 0.6 g/day, prothioconazole 0.6 g/day, and prednisone acetate 30 mg/day", in order to enhance the efficacy and ease clinical symptoms. The child’s headache subsided, her body temperature gradually returned to normal, and her vision cleared. However, CSF protein was still higher than 1 g/L. Her chest CT scan revealed a substantial decrease in bilateral lung lesions on March 14, 2020. While her brain enhancement MRI showed punctiform enhancement in the left temporal lobe and right parietal lobe, and nodular-like significant enhancement in the left pontocerebellar horn region, with a slightly larger lesion than before. On March 20, 2020, the DST result showed resistance to “isoniazid, rifampin, streptomycin, levofloxacin, and moxifloxacin”. Finally, we diagnosed her with pre-extensive drug-resistant TBM (pre-XDR TBM).

Representative slices of chest CT images showed diffuse miliary nodules in both lungs

The cranial enhancement MRI showed punctiform enhancement in the pontine brain, right cerebellar hemisphere, bilateral frontal, temporal and parietal lobes, nodular enhancement in the local meninges, and linear enhancement in the brain pool

After considering WHO guidelines for the diagnosis and treatment of drug-resistant TB, drug sensitivity results, the patient’s medication history, and drug penetration in the CSF, we developed an individualized treatment regimen for her. The regimen included linezolid (0.6 g/day), cycloserine (0.5 g/day), clofazimine (0.1 g/day), pyrazinamide (1.0 g/day), ethambutol (0.75 g/day), and prothionamide (0.6 g/day), with vitamin B6 (100 mg/day) and symptomatic supportive therapy. Three months after the therapy regimen changed, her brain MRI showed enlarged upper ocular chiasm, suprasellar cistern, and interpeduncular cistern lesions. Since there were no obvious signs of symptoms, she continued her treatment. In the sixth month of treatment in 2020.09, she developed numbness in both lower legs and feet, which could be tolerated. We confirmed it was “mild peripheral neuropathy” caused by “linezolid”, and advised her to continue to take nutritional neurological drugs such as B vitamins. After 7 months of treatment, the child’s CSF parameters returned to normal. However, she developed joint pain in the lower limbs and a uric acid test of 719 umol/L. We thought it was an adverse reaction to pyrazinamide, excluding other factors. The patient completed the intensive phase of treatment and was recovering well, so we discontinued both ethambutol and pyrazinamide. And the child’s symptoms were significantly relieved after discontinuation of the drug. The child experienced a decrease in visual acuity after 9 months of treatment. After excluding the loss of vision caused by tuberculosis and other factors, we considered it a side effect of linezolid, we discontinued it. After discontinuing linezolid for 1 week, her vision gradually returned to normal. She continued the treatment with the remaining three drugs, with no other significant adverse reactions throughout the treatment period. Throughout the treatment period, all sputum cultures from the patient were negative. Her CSF pressure, protein level, and cell counts continued to be normal after 7 months of treatment. At the completion of 19 months of treatment, the patient’s pulmonary and brain TB lesions had all been absorbed, so we discontinued her treatment. There were no neurological sequelae other than mild peripheral neuropathy.

Discussion and conclusions

Tuberculosis remains one of the infectious diseases that threaten children’s health. Children are often different from adults in terms of onset, clinical manifestations, diagnosis, and treatment. Kids infected with tuberculosis bacteria are prone to involve multiple organs throughout the body, and hematogenous disseminated tuberculosis occurs, of which TBM is a severe and devastating type of tuberculosis that seriously threatens children’s lives [ 4 , 5 ]. The youngster has atypical clinical symptoms, a low etiological positivity rate, difficulty with early diagnosis, and a top case fatality rate. More than half of the TBM survivors have neurological sequelae [ 6 , 7 ]. Drug-resistant tuberculosis is becoming more and more common, making the diagnosis and treatment of drug-resistant TBM in children more torturous.

The WHO suggests the staff can use imaging as an evaluation for the diagnosis of tuberculosis [ 8 ]. When the medical staff has insufficient experience in tuberculosis or encounter diseases that are easily confused with others. It can delay the diagnosis and treatment of tuberculosis, just like in the case presented. Her anti-infective treatment was ineffective. Subsequently, TST and IGRA were positive, but the sputum acid-fast bacilli smear test was negative. No other tests related to sputum, so she started anti-tuberculosis treatment after a clinical diagnosis of pulmonary tuberculosis. The child’s clinical symptoms reduced after 2 months of therapy. Subsequently, the chest CT showed the lesion had progressed to miliary pulmonary tuberculosis. There was no history of exposure to drug-resistant TB patients. The patient’s compliance was good throughout the treatment. The symptoms resolved after the first phase of treatment, followed by a recurrence of the disease. The girl might initially be infected with wild-type resistant bacteria. The broad-spectrum antibacterial effect exerted by rifampicin could relieve clinical symptoms after the application of first-line anti-tuberculosis drugs. In addition, some strains might be effective with ethambutol and pyrazinamide. Another explanation is drug-susceptible and drug-resistant Mycobacterium tuberculosis in the patient. Initially, the sensitive tubercle bacilli was predominant. After conventional anti-tuberculosis treatment, drug-resistant tubercle bacilli gradually became dominant, causing an exacerbation of the disease. Yet, no DST evidence was available for this in the early stages of treatment, so it could not be confirmed.

Mycobacterium tuberculosis reaches the lungs in the bloodstream and becomes miliary pulmonary tuberculosis. Besides the lungs, tuberculosis bacteria can also spread to the lymph nodes, meninges, liver, spleen, and other organs throughout the body. When tuberculosis bacteria invade the nervous system, causing non-purulent bacterial inflammation of the meninges and involving the pia mater, arachnoid membranes, and brain parenchyma, it is called TBM, which is the most deadly type of tuberculosis. TBM is often secondary to tuberculosis foci in other parts of the body, especially hematogenous spread tuberculosis, so patients with miliary pulmonary tuberculosis should be screened in time to determine whether there is TBM and tuberculosis in other parts. In addition, we need to search for pathogenic evidence and get DST results to improve the accuracy of diagnosis. Unfortunately, this child did not carry out these tasks and only adjusted some medication and continued treatment. As a result, it was conceivable that the child developed fever, dizziness, headache, blurred vision, and other neurological symptoms again, at which time TBM was confirmed. The girl’s brain-enhanced MRI showed significant enhancement of the brain parenchyma, brain pools, and meninges, which is consistent with the imaging features of TBM [ 3 , 9 ]. An Xpert MTB/RIF in CSF found Mycobacterium tuberculosis, with unknown drug resistance. Only 3 months later, we got phenotypic susceptibility results from the strains that were culture-positive for CSF, and the child was eventually diagnosed with pre-XDR TBM.

Besides the difficulty of diagnosis, drug-resistant tuberculosis has also been facing enormous challenges in treatment. WHO regularly updates corresponding application guidelines, demonstrating the rapid development of the field of drug-resistant tuberculosis and the importance that society attaches to drug-resistant tuberculosis. Guidelines published by the WHO endorse all-oral regimens to treat drug-resistant TB [ 10 ]. However, anti-TB regimens should be based on susceptibility results and patient-specific susceptibility results with fluoroquinolones, which play an important role in the treatment of drug-resistant TB. After over 40 years of exploration, two new agents (bedaquiline and delamanid) are available to treat MDR/XDR-TB [ 11 , 12 ] and find new uses for older drugs such as linezolid. WHO divided anti-tuberculosis drugs into groups A, B, and C. Groups A and B, being all-oral drugs, from the core drugs of the all-oral chemotherapy regimen and are an essential basis for treatment [ 13 ]. An effective regimen should include at least four potentially effective anti-TB drugs, while the consolidation phase should include at least three potentially effective drugs. The WHO also recommends that treatment regimens for drug-resistant TBM be based on tuberculosis and for childhood tuberculosis in adults [ 14 ]. Several anti-TB drugs have different pharmacokinetics in children compared with adults, and some have poor CSF permeability because of the blood–brain barrier. Therefore, when developing a regimen for drug-resistant TBM, at least four effective drugs, including two or three with moderate CSF permeability, are necessary [ 15 , 16 ]. The chemotherapy drugs selected by this child were all oral, but the DST showed resistance to fluoroquinolones, bedaquiline had poor CSF penetration with the limited data [ 17 ]. And delamanib was not yet available in China. Therefore, we selected drugs with good CSF permeability, such as linezolid, cycloserine, and pyrazinamide. Although adverse drug reactions occurred during treatment, we handled them promptly and without serious consequences, and the eventual outcome was satisfactory.

From the initial pneumonia to the clinical diagnosis of common tuberculosis and finally the diagnosis of drug-resistant TBM, the entire process was tortuous but finally got a good outcome. Throughout the process, we also found some limitations and learned some lessons. Limitations: (1) No repeated screening for bacteriology and DST results when considering tuberculosis. (2) No timely screening for spreading to other areas, especially the cranial area, in the presence of miliary pulmonary tuberculosis. These may cause a delay in the diagnosis and treatment of the disease, resulting in adverse outcomes such as neurological sequelae and life-threatening events.

We have also learned: (1) In the process of diagnosis and treatment of tuberculosis, we should constantly look for the bacteriology, get DST results as much as possible, and achieve an accurate diagnosis. It is in line with the WHO recommendations for TB diagnosis and treatment. (2) Patients with miliary pulmonary tuberculosis should be screened to determine whether there is tuberculosis in other parts, especially TBM, which is extremely fatal. 3) When planning a regime for drug-resistant TBM patients, it is necessary to give preference to drugs that can penetrate the blood–brain barrier and have high cerebrospinal fluid permeability and combine the specific conditions of patients with the DST results. 4) During the anti-tuberculosis treatment, we should closely monitor adverse drug reactions to avoid negative effects on the patient’s body and psychology because of severe adverse reactions.

In conclusion, the most harmful and severe type of TB is drug-resistant TBM, which is the most difficult to identify and cure. More people with drug-resistant TB will benefit from it when new technologies and medications. However, studies related to drug-resistant TBM in children are still limited, and staff in this specialty need to do more studies to provide the best diagnosis and treatment options for children with drug-resistant TBM.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

• Tuberculous meningitis

Cerebrospinal fluid

Drug sensitivity test

Computed tomography

Magnetic resonance imaging

• Tuberculosis

World Health Organization

Interferon-Gamma Release Assay

Tuberculin Skin Test

Pre-extensive drug-resistant

Extensive drug-resistant TB

Multidrug drug-resistant TB

World Health Organization—2022—Global tuberculosis report 2022. pdf. (n.d.).

Basu Roy R, Bakeera-Kitaka S, Chabala C, Gibb DM, Huynh J, Mujuru H, Sankhyan N, Seddon JA, Sharma S, Singh V, Wobudeya E, Anderson ST. Defeating Paediatric Tuberculous Meningitis: Applying the WHO “Defeating Meningitis by 2030: Global Roadmap.” Microorganisms. 2021;9(4):857. https://doi.org/10.3390/microorganisms9040857 .

Article   CAS   Google Scholar  

Schaller MA, Wicke F, Foerch C, Weidauer S. Central nervous system tuberculosis: etiology, clinical manifestations and neuroradiological features. Clin Neuroradiol. 2019;29(1):3–18. https://doi.org/10.1007/s00062-018-0726-9 .

Article   Google Scholar  

Schaaf HS, Seddon JA. Management of tuberculous meningitis in children. Paediatr Int Child Health. 2021. https://doi.org/10.1080/20469047.2021.1952818 .

Leonard JM. Central Nervous System Tuberculosis. Microbiol Spectrum. 2017. https://doi.org/10.1128/microbiolspec.TNMI7-0044-2017 .

Lange C, Dheda K, Chesov D, Mandalakas AM, Udwadia Z, Horsburgh CR. Management of drug-resistant tuberculosis. Lancet. 2019;394(10202):953–66. https://doi.org/10.1016/S0140-6736(19)31882-3 .

Huynh J, Abo Y-N, du Preez K, Solomons R, Dooley KE, Seddon JA. Tuberculous meningitis in children: reducing the burden of death and disability. Pathogens. 2021;11(1):38. https://doi.org/10.3390/pathogens11010038 .

World Health Organization. 2020. WHO consolidated guidelines on tuberculosis modul.pdf.

Dian S, Hermawan R, van Laarhoven A, Immaculata S, Achmad TH, Ruslami R, Anwary F, Soetikno RD, Ganiem AR, van Crevel R. Brain MRI findings in relation to clinical characteristics and outcome of tuberculous meningitis. PLoS ONE. 2020;15(11):e0241974. https://doi.org/10.1371/journal.pone.0241974 .

World Health Organization. WHO consolidated guidelines on tuberculosis: Module 4: Treatment: Drug-susceptible tuberculosis treatment. World Health Organization. 2022. https://apps.who.int/iris/handle/10665/353829

Lange C, Chesov D, Heyckendorf J, Leung CC, Udwadia Z, Dheda K. Drug-resistant tuberculosis: An update on disease burden, diagnosis, and treatment. Respirology. 2018;23(7):656–73. https://doi.org/10.1111/resp.13304 .

Tucker EW, Pieterse L, Zimmerman MD, Udwadia ZF, Peloquin CA, Gler MT, Ganatra S, Tornheim JA, Chawla P, Caoili JC, Ritchie B, Jain SK, Dartois V, Dooley KE. Delamanid central nervous system pharmacokinetics in tuberculous meningitis in rabbits and humans. Antimicrob Agents Chemother. 2019;63(10):e00913-e919. https://doi.org/10.1128/AAC.00913-19 .

Opota O, Mazza-Stalder J, Greub G, Jaton K. The rapid molecular test Xpert MTB/RIF ultra: Towards improved tuberculosis diagnosis and rifampicin resistance detection. Clin Microbiol Infect. 2019;25(11):1370–6. https://doi.org/10.1016/j.cmi.2019.03.021 .

World Health Organization. WHO consolidated guidelines on tuberculosis: Module 5: management of tuberculosis in children and adolescents. World Health Organization. 2022. https://apps.who.int/iris/handle/10665/352522

Garg RK, Rizvi I, Malhotra HS, Uniyal R, Kumar N. Management of complex tuberculosis cases: a focus on drug-resistant tuberculous meningitis. Expert Rev Anti Infect Ther. 2018;16(11):813–31. https://doi.org/10.1080/14787210.2018.1540930 .

Basu Roy R, Seddon JA. Linezolid for children with tuberculous meningitis: more evidence required. Pediatric Infect Dis J. 2017;36(4):439. https://doi.org/10.1097/INF.0000000000001464 .

Akkerman OW, Odish OFF, Bolhuis MS, de Lange WCM, Kremer HPH, Luijckx G-JR, van der Werf TS, Alffenaar J-W. Pharmacokinetics of Bedaquiline in cerebrospinal fluid and serum in multidrug-resistant tuberculous meningitis. Clin Infect Dis. 2015. https://doi.org/10.1093/cid/civ921 .

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Acknowledgements

The study was supported by the Beijing Municipal Science & Technology Commission (Z191100006619077).

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Jing Tong & Mengqiu Gao

Department of Tuberculosis, The Sixth People’s Hospital of Zhengzhou, Zhengzhou, China

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JT integrated data and wrote the manuscript; MQG contributed to the revision of the manuscript; YC provided essential assistance and gave key advice; JW collected relevant information. All authors read and approved the final manuscript.

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Tong, J., Gao, M., Chen, Y. et al. A case report about a child with drug-resistant tuberculous meningitis. BMC Infect Dis 23 , 83 (2023). https://doi.org/10.1186/s12879-023-07990-x

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This disease is spiking in an Ontario city. But there's a vaccine — if you can afford it

Currently, no provinces or territories cover the cost of the meningococcal b vaccine for all children.

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Can you put a price on protecting your children from a potentially deadly meningitis-causing bacterial infection?

Right now, it's about $320 per child, unless you happen to have private insurance, for a two-dose vaccine recommended by public health officials in Kingston, Ont. — one of a handful of regions in Canada seeing a spike in local cases of invasive meningococcal disease (IMD).

IMD is a rare but life-threatening bacterial infection that can infect the brain and spinal cord, causing meningitis, and the bloodstream, causing septicemia.

Up to 10 per cent of people infected with IMD die, according to Health Canada , and complications include deafness, limb amputations and permanent brain damage. There are almost  200 cases  in Canada per year on average.

Most IMD cases are caused by five types of bacteria: A, B, C, Y and W-135, though in Canada, group B causes most illness, according to the health department.

Kingston, Frontenac and Lennox & Addington Public Health (KFL&A) is recommending the meningococcal B   vaccine for people under age 25. It's not a routine vaccine like meningococcal C, typically given to babies at age one, or meningococcal ACYW-135, administered in Grade 7 in Ontario, said the health unit.

Currently, no provinces or territories cover the cost of the meningococcal B vaccine for all children, according to the Canadian Paediatric Society .

• Opposition to vaccination among parents grows, poll suggests
• Routine vaccines for kids slipped during the pandemic. Now provinces are working to catch up

Crystal Harris, 45, plans to vaccinate her two teenagers after getting letters from their schools in Kingston last week recommending the shots. She says she was surprised when she realized how much it would cost, and was grateful she has private insurance that covers it. She also knows she's one of the lucky ones.

"I cannot imagine having to pay that money to keep your children safe and healthy," Harris told CBC News. "It's simply wrong."

People with certain high-risk medical conditions are eligible for a free vaccine, as is anyone who comes in contact with a case. But at this point, the Kingston community at large isn't eligible for publicly funded vaccination, said Dr. Piotr Oglaza, medical officer of health at KFL&A Public Health.

The cost for the general population — about $160 per dose, with two doses required — is "absolutely" a barrier, especially for someone who doesn't have private insurance, Oglaza said.

"I fully understand and appreciate that dilemma and that struggle that individuals may face.

"But really, the best protection against this is the vaccine."

Rare but risky

Last Thursday, KFL&A Public Health  warned of an increase in invasive meningococcal disease type B activity in the region — three cases in recent months, including one pediatric case, according to Oglaza.   Its last case was in 2013, he said.

Kingston isn't the only region seeing an increase. Last month, health officials in the Eastern Townships of Quebec called for vigilance after confirming two cases of invasive meningococcal infection in the region, one of which resulted in a death. The specific type of case isn't yet known.

• Public health urges vigilance after fatal meningococcal infection in Eastern Townships
• Manitoba health officials see spike in infections that can cause meningitis

Manitoba public health officials also recently warned  that the province had seen 11 cases and one death between Dec. 21 and Feb. 29. The serogroup of one of those cases was identified as type B.

Manitoba typically has six cases of IMD reported in a year. 

While IMD cases in Canada are rare, outbreaks do occur across the country, says a 2023 report from the National Advisory Committee on Immunization .

Most cases came from children under age five and adolescents aged 15 to 19, the report said.

"Outbreaks of meningococcal B disease are usually small and localized, and are primarily seen among adolescents and young adults, especially those living in dormitory or other group settings," said Devon Greyson, an assistant professor at the School of Population and Public Health at the University of British Columbia.

University campuses in Atlantic Canada have had outbreaks in the last few years, including student deaths . 

In May 2023, Nova Scotia began  offering the meningococcal B vaccine for free to people aged 25 and under living in group settings, such as university residences. Then in January, Prince Edward Island expanded its free vaccine eligibility to all post-secondary students.

'Multiple tiers of privilege'

There are "multiple tiers of privilege going on" in terms of vaccine accessibility, between the out-of-pocket cost, the potential for coverage by private insurance, and the fact that if you don't have a family doctor, you may not even be having these conversations, said Ian Culbert, the executive director of the Canadian Public Health Association.

"For low-income people, it simply isn't an option."

Funded vaccine programs have much higher uptake rates than unfunded ones, he noted. But even the hesitancy for funded vaccines — such as the measles shot — is increasing post-pandemic, he added.

A new poll released last week by the  Angus Reid Institute  found that a growing number of Canadian parents say they are opposed to vaccinating their children. Among the 1,626 survey respondents, 17 per cent of parents of minors said they were "really against" vaccinating their kids, compared with about four per cent in 2019. 

Given that, there's even less incentive for provincial and territorial governments to fund some of the vaccines for diseases that are less common, Culbert said, even though the outcome of catching IMD can be much more serious than mumps or measles.

"It's this risk-benefit that as individuals we have to think about, but that the governments need to think about, as well."

How to protect yourself against measles

About the author.

Senior writer and editor

Natalie Stechyson is a senior writer and editor at CBC News. She's worked in newsrooms across the country in her 12+ years of journalism experience, including the Globe and Mail, Postmedia News, Calgary Herald and Brunswick News. Before joining CBC News, she was the Parents editor at HuffPost Canada, where she won a silver Canadian Online Publishing Award.

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https://educationhub.blog.gov.uk/2024/03/22/what-to-do-if-you-think-your-child-has-measles-and-when-to-keep-them-off-school/

What to do if you think your child has measles and when to keep them off school

Cases of measles are rising across England, including among children. It’s an infection that spreads very easily and for some people can cause serious problems.

There’s no specific medical treatment for measles, so it’s important to get vaccinated as it’s the best protection against becoming seriously unwell.

The measles, mumps and rubella (MMR) vaccine is one of the  routine childhood vaccinations,  so most children are already vaccinated against measles. If your child has received both doses of the vaccine, they are unlikely to have the virus.

Here, we explain everything you need to know about the rise in measles cases, from getting your child vaccinated to when to keep them off  school .

What are the symptoms of measles?

Measles usually starts with cold-like symptoms (cough, runny nose), a high temperature, and red, sore, watery eyes (conjunctivitis), followed by a rash a few days later. The rash looks brown or red on white skin. It may be harder to see on brown and black skin.

The rash typically starts on the face and behind the ears before spreading to the rest of the body. Some people may also get small white spots (Koplik spots) in their mouth.

Find out more on the  NHS website .

What should you do if you think your child has measles? 

If a child has been vaccinated, it is highly unlikely they have measles.

You should ask for an urgent GP appointment or get help from NHS 111 if you think you or your child may have measles.

Don’t go to the GP or any other healthcare setting without calling ahead first to prevent the further spread of measles.

If your child has been diagnosed with measles by a doctor, they should stay off nursery or school for at least 4 full days from when the rash first appears.

They should also avoid close contact with babies and anyone who is pregnant or has a weakened immune system.

What is the best way to protect against measles?

The best protection against measles for children and adults is to get both doses of the MMR vaccine.

Children are offered a vaccine free on the NHS at 12-months-old and then a second dose when they turn 3-years-and-4-months-old.

But you can catch up at any age – if you or your child haven’t yet been vaccinated, you should contact your GP practice to book a free appointment.

Two doses of the MMR vaccine offer lifelong protection against measles.

In the UK, we have 2 MMR vaccines which work very well. One of them contains porcine gelatine and the other one doesn’t. If anyone would prefer to have the vaccine that does not contain gelatine, they can talk to their practice nurse or GP.

Cold-like symptoms can be an early sign of measles. Should you still send your child to school?

If your child has been vaccinated, it’s very unlikely that they have measles.

School attendance  is vitally important to your child’s learning and health.

According to the NHS, it’s fine to send your child to school with a minor cough or common cold, provided they don’t have a temperature.

When should you keep your child off school or nursery and how long for?

If your child has measles, they should stay off nursery or school for the entire infectious period (4 days before the rash first appears and for at least 4 full days from when the rash first appears where the date the rash appears is day 0). They should avoid close contact with babies and anyone who is pregnant or has a weakened immune system.

Your child can go back to their education or childcare setting once they feel well and following the completion of the 4 day period after the rash first appears.

If your child is unvaccinated against measles and is a close contact of a measles case (for instance a sibling), the health protection team may advise that your child should remain off school or nursery for a number of days to reduce the spread of meases. The number of days will vary on the circumstances. The best way to protect your child from measles and ensure they can continue to attend school is to ensure they have both doses of the MMR vaccine.

If you’re not sure whether your child is due a vaccination or has missed a vaccination, you can check their Red Book or contact your GP practice.

If your child has missed their first or second dose of MMR vaccine, you should contact your GP practice to book an appointment.

Should you keep your child off school if another pupil has been diagnosed with measles?

Your child should continue to attend school if another pupil has been diagnosed with measles as long as they have no symptoms and have not been advised otherwise by the Health Protection Team or GP.

Most children will be protected against measles  if they have had both their MMR vaccinations.

The local Health Protection Team will work with the school or setting to advise on further action.

What should I do if I can’t get a GP appointment and I suspect measles?

Ask for an urgent GP appointment or get help from NHS 111, let them know you suspect measles.

Measles can spread to others easily. Call your GP surgery before you go in. They may suggest talking over the phone.

You can also call 111 or  get help from 111 online .

The child or staff member should not attend the education or childcare setting until they have received advice.

Can I still get my child vaccinated even if they’re older? 

Yes. Anyone who has not had 2 doses of the MMR vaccine should ask their GP surgery for a vaccination appointment.

It’s best to have vaccines on time, but you can still catch up on most vaccines if you miss them. Two doses of the vaccine are needed to ensure full protection.

For schools, nurseries and other education settings

What should education settings do if they have a suspected or confirmed measles case.

If an education setting is told that a child or staff member has seen their doctor in person and been diagnosed with measles, the setting should contact the UKHSA Health Protection Team so that they can investigate and support as required. If measles is suspected by the GP or healthcare professional, they will also notify the UKHSA Health Protection Team, who may then reach out if there is a setting associated with the case.

Education and childcare settings are not expected to diagnose cases, and parents or carers do not need to contact the health protection team. If parents, carers, or staff are concerned that they or a child have symptoms, they should contact their doctor or NHS111. They should alert the surgery or other healthcare setting of symptoms before attending any appointment to prevent the further spread of measles.

How should schools code measles absences?

For confirmed cases, schools should continue to use usual register codes for absence due to illness.

If a child needs to isolate following public health advice, the most appropriate code is likely to be an absence authorised by the school (code C).

As part of its planned changes to the attendance system, the Government is establishing a new register code to cover absences due to public health guidance.

The new code is planned to take effect from September 2024.

Will the Department for Education and Ofsted take measles absences into account when reviewing the attendance statistics for schools?

Schools play a vital role in improving attendance, but not all factors influencing attendance are in their control.

Ofsted will take these factors into account. Schools should demonstrate that they’re doing all they can to achieve the highest possible attendance, even if their attendance numbers are lower than previously.

What advice should special schools follow? Is there any additional advice for pupils who may be more vulnerable to exposure to measles?

Special schools and settings should also follow the  UKHSA guidance .

The Health Protection Team will carry out a risk assessment of the situation based on the information provided.

They will ask the education setting to share information to help them understand the size and nature of the outbreak and the vaccination status of pupils, and advise on any recommended actions.

The MMR vaccine is the safest and most effective way to protect yourself against measles, mumps, and rubella.

What advice is there for staff who might be more vulnerable, for example if they’re pregnant or unvaccinated?

Measles is a viral infection that spreads very easily and can cause severe illness, especially in certain groups including babies, small children, pregnant women, and people with weak immunity.

For adults, it is never too late to catch up on any missed MMR vaccinations. People should contact their GP practice to book an appointment.

Anyone considering getting pregnant should make sure that they are protected by having two doses of the MMR vaccine before they become pregnant.  Unvaccinated pregnant people should make sure they are vaccinated soon after the baby is born, to protect them during future pregnancies. As a precaution, the MMR vaccine is not recommended for pregnant women. This is because it is a live vaccine.

If you’re pregnant and you have been in close contact with someone who has measles, you should ask for an urgent GP appointment or get help from NHS 111.

A staff member isn’t sure if they’ve had the MMR vaccine and their GP doesn’t have their vaccine records. Can they have another dose?

Anyone with an unknown vaccination history should ask their GP for a vaccine appointment. If your vaccine records are not available or do not exist it will not harm you to have the MMR vaccine again. Two doses of the MMR vaccine is the best protection against measles, mumps and rubella.

Are babies who are too young to be vaccinated protected?

Babies who are too young to be vaccinated are not protected from measles. It is still safe for children and babies who are too young to be vaccinated to attend nursery and early years setting, unless they have been advised otherwise by a health protection team or GP.

The best way to protect children under 1, who are more vulnerable, is by ensuring other children and members of the household are fully vaccinated with two doses of MMR. This significantly reduces the risk of them passing the virus onto the young child. Early education settings can help by promoting the importance of the MMR vaccine.

Are staff who aren’t vaccinated and have to stay off work on public health advice entitled to pay for this period?

Unvaccinated staff who have been in contact with measles cases may be asked to stay away from school or childcare settings for a number of days, based on a risk assessment by the Health Protection Team.

The Department for Education has no remit over sick pay, which is at the discretion of the school.

Some useful links to guidance and resources:

The Department for Education hosted a national webinar on the increase in measles cases, with speakers from UK Health Security Agency, the NHS, and school leaders with recent experience of dealing with a measles outbreak. The webinar covered information on measles, current epidemiology, the importance of the MMR vaccine and how to get it, and how to manage cases and outbreaks in educational settings. View this here.

Measles - NHS (www.nhs.uk)

MMR (measles, mumps and rubella) vaccine - NHS (www.nhs.uk)

Supporting immunisation programmes - GOV.UK (www.gov.uk)

Managing outbreaks and incidents - GOV.UK (www.gov.uk)

UKHSA resources for settings:

• Measles: protect yourself, protect others leaflet
• Measles: don’t let your child catch it poster
• Measles: don’t let your child catch it flyer (with translations)
• Thinking of getting pregnant leaflet (German measles or rubella)
• MMR, MenACWY and coronavirus (COVID-19) vaccine comms toolkit for universities  helping to protect students from vaccine preventable infectious diseases.

Copies of printed publications and the full range of digital resources to support the immunisation programmes can be ordered through the  health publications  platform.

You may also be interested in:

• How to protect against measles – vaccines for school pupils
• What are the latest rules around COVID-19 in schools, colleges, nurseries and other education settings?
• Vaccines for students: how to get up to date

Tags: measles , Measles symptoms , mmr , MMR vaccine , UKHSA guidance , Vaccine against measles

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Nearly 130,000 children exposed to lead-tainted drinking water in Chicago

Study says the 19% of kids using unfiltered tap water have about twice as much lead in their blood as they would otherwise

About 129,000 Chicago children under the age of six are exposed to poisonous lead in their household drinking water because of lead pipes, according to a study published on Monday.

The study used artificial intelligence to analyse 38,000 home water tests conducted for the city of Chicago, along with neighborhood demographics, state blood samples and numerous other factors.

It found that Black and Latino residents are more likely to have lead-contaminated water because of lead pipes. And it estimated that the 19% of Chicago children who use unfiltered tap water as their primary drinking source have about twice as much lead in their blood as they would otherwise.

“These findings indicate that childhood lead exposure is widespread in Chicago, and racial inequities are present in both testing rates and exposure levels,” said the study, published by the Johns Hopkins Bloomberg School of Health in Jama Pediatrics. “We estimated that more than two-thirds of children are exposed to lead-contaminated drinking water.”

The federal government has said that there is no safe level of lead in drinking water. Studies have shown that even small amounts of the highly poisonous metal can affect childhood brain development and contribute to preterm births, heart problems and kidney disease. Yet Chicago still has 400,000 homes served by potentially water-contaminating lead service lines – more than any other US city.

“I think residents have reason to be concerned,” said public health professor Benjamin Huynh, who authored the study with Elizabeth Chin and Mathew Kiang. “I think this should be a call to get your water tested for lead, see what the results are, then make your decisions accordingly.”

Huynh said the idea to conduct the research came after seeing the Guardian’s analysis of 24,000 city water tests, which found one-third of home water tests had more lead than the federal limit for bottled drinking water, which is 5 parts per billion (ppb).

The Johns Hopkins study used a more stringent measure, and flagged as concerning any home tests that detected more than 1ppb. Huynh said this was based on the fact that no level of lead consumption is considered safe and lead service lines can often create spikes in lead levels that go undetected, especially after they are disturbed by nearby construction. Similarly, the American Academy of Pediatrics has called for state and local governments to limit the lead in school drinking fountains to no more than 1ppb.

The US Environmental Protection Agency (EPA) has a municipal “action level” of 15ppb, meaning that cities are only required to notify the public when at least 10% of a small sample of homes tested are above that amount.

By this measure, Chicago is in compliance.

“Nothing is more important than the health and safety of Chicago’s residents and, particularly, our children,” city spokesperson Megan Vidis said in an emailed statement. “Chicago’s water continues to meet and exceed all standards set by the US Environmental Protection Agency.”

She said that “the city has introduced five programs to remove Chicago’s 400,000 lead service lines and offers free water testing to any resident”.

While the EPA is proposing to require most cities around the nation to remove all lead service lines within 10 years, it is giving Chicago 40 years to do so because of the large number of unreplaced pipes in the city.

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“If we’re looking at 40 more years of contaminated drinking water, what does that mean for the children?” Huynh said. “What can we do about that in the meantime?”

Chakena Perry, Chicago water advocate for the Natural Resources Defense Council, called for the city to distribute water filters to families with lead service lines and do everything possible to speed up the work to remove them.

“Clean drinking water is something that everyone deserves no matter their zip code or their life circumstances,” said Perry.

The city’s newly elected mayor, Brandon Johnson, has vowed to replace 40,000 lead lines by 2027.

But the study authors and other experts say this is not enough.

“With 400,000 lead service lines, Chicago officials need to be way more aggressive in protecting their children and the population in general,” said water safety engineer Elin Betanzo, who was one of the first to flag Flint’s lead water issues . “There’s really no reason for anybody to be drinking lead in their water.”

• America's dirty divide

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2-year-old with tuberculous meningitis: a case study

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• 1 Sutter Medical Center, Sacramento, CA, USA. [email protected]
• PMID: 15115363
• DOI: 10.1097/01376517-200404000-00006

Tuberculous meningitis (TBM) may occur with tuberculosis infection, and young children are more prone to this disease. The clinical manifestations, time course, and treatment of TBM are unlike those of other types of meningitis, and the disease presents unique challenges for nurses caring for these patients. This case study highlights the typical presentation, course, and management of TBM in a pediatric patient and provides an overview of this devastating disease. Specific nursing issues related to the care of these children are outlined.

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• Tuberculosis, Meningeal / therapy*
• Antitubercular Agents

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Meningitis in College Students: Using a Case Study to Expose Introductory Neuroscience Students to Primary Scientific Literature and Applications of Neuroscience

This case study was based on a popular press news article about Krystle Beauchamp Gridley’s experience with meningitis while in college ( Miller, 2019 ). Students in an introductory neuroscience course read the popular press news article as well as an empirical article that identified risk factors for contracting meningococcal disease in college ( Bruce et al., 2001 ). Students used information from the empirical article to identify Krystle’s risk factors for meningitis. Then, students evaluated their University’s policy on students receiving the meningococcal vaccine based on what they had learned. This case supports two important goals of neuroscience education, 1) exposing students to primary scientific literature early in their undergraduate education and 2) developing an understanding of the broader implications of scientific research for society. Students enjoyed learning about meningitis using the case-study method, reading the primary scientific article, and considering how scientific research can be applied to policy decisions. Further, the case was instrumental in supporting the content and process learning objectives.

BACKGROUND AND CONTEXT

Case studies play an important role in the advancement of science. For example, Scoville and Milner (1957) initially identified the critical role of the hippocampus in their seminal report of patient H.M.’s memory deficits following the resection of the medial temporal lobe. Case studies are also impactful pedagogical tools in the classroom. Case studies personalize course content and foster elaborative encoding, which promotes long-term retention. As noted by Meil (2007) , students may forget the functions of the hippocampus and frontal cortex but be able to remember the names and stories of H.M. and Phineas Gage. Classroom case studies can either be based on published case reports in peer-reviewed journals, such as the Journal of Clinical Neuroscience , or involve the application of course content to a story or scenario.

The current case study was based on a college student’s experience with meningitis that was presented in a popular press news article ( Miller, 2019 ). Students in an introductory neuroscience course learned about the individual’s experience and then identified risk factors for meningitis present in the case after reading an empirical article on risk factors for contracting meningitis in college ( Bruce et al., 2001 ). Exposure to reading and evaluating primary scientific literature during undergraduate education supports scientific literacy and success in graduate school ( Kozeracki et al., 2006 ). However, many faculty do not incorporate primary scientific literature into introductory courses due to the focus on content versus process-based learning objectives ( Coil et al., 2010 ). This lack of exposure subsequently results in students being intimidated by primary scientific literature once they reach upper-level courses ( Smith, 2001 ). As such, there has been a call to begin developing scientific process skills, including reading and interpreting primary literature, early in students’ undergraduate education ( Coil et al., 2010 ).

The last part of the case required students to apply what they had learned about meningococcal disease. Students evaluated their University’s policy on students receiving the meningococcal vaccine. The goal of this component of the case was to expose students to the broader impacts of scientific research for society and policy-based decisions. In addition to understanding the scientific process and quantitative reasoning, the Vision and Change in Undergraduate Biology Education: A Call to Action report by the American Association for the Advancement of Science includes understanding how science intersects society as a core competency of biological sciences, including neuroscience ( Brewer & Smith, 2011 ).

The current case study on meningitis makes multiple contributions to neuroscience education. Whereas most neuroscience case studies have been implemented in upper-level undergraduate courses (e.g., Cook-Snyder, 2017 ; Sawyer & Frenzel, 2018 ; Mitrano, 2019 ; Ogilvie, 2019 ; Watson, 2019 ; cf. Roesch & Frenzel, 2016 ), the current case was implemented in an introductory neuroscience course. Further, students evaluated the case in relation to an empirical report on risk factors for contracting meningococcal disease in college, supporting their knowledge of how an individual case can fit within the context of broader scientific investigation. Lastly, students applied what they learned to evaluate their University’s policy, demonstrating the practical implications of scientific research for society. Student materials and implementation notes are available from the corresponding author or from [email protected] .

LEARNING OBJECTIVES

Content objectives.

At the end of the case, students will be able to:

• Identify the layers of the meninges on the brain and spinal cord.
• Provide symptoms of meningitis.
• Describe tests that can be performed in order to diagnose an individual with meningitis.
• Identify risk and protective factors for meningitis in college students.
• Understand the effectiveness of the meningococcal vaccines for different strains of the bacteria that cause meningitis.
• Apply their knowledge to evaluate their University’s policy on students receiving the meningococcal vaccine.

Process Objectives

• Read and interpret primary scientific literature.
• Begin learning how statistics can be used to evaluate scientific hypotheses.
• Identify real-world implications of neuroscience research.

COURSE OVERVIEW

This case on meningitis was implemented in an introductory neuroscience course that included 30 students. Prerequisites for the course included either introductory psychology or introductory biology. Students completing the course ranged from first-semester freshman to seniors. Students primarily intended to major in Neuroscience (53%), Psychology (23%), and Biology (17%). The case was presented the third week of the semester as we began covering the structure of the nervous system, including cerebrospinal fluid, the meninges, neural development, and gross anatomy. The case was the students’ first exposure to primary scientific literature in the course.

The case was designed to reinforce knowledge of the meninges, expose students to primary scientific literature, and require students to apply knowledge learned in class to a real-world situation. As such, the case included a news article describing the experiences of a college student that contracted meningitis, an empirical article evaluating risk factors for contracting meningitis, and an evaluation of the University’s policy on students receiving the meningococcal vaccine. This case would be appropriate for neuroscience, psychology, or biology courses that include a unit on neuroanatomy. Alternatively, this case could also be used to educate students about the immunological mechanisms of vaccinations or to facilitate a discussion about ethics associated with vaccination.

CLASSROOM IMPLEMENTATION

This case implementation in the classroom involved a modified think-pair-share approach. Students independently completed guided readings prior to class. Then, students discussed responses in small groups during the class meeting prior to the larger class discussion. Before the class period during which the discussion of the case took place, students:

• Read a short textbook passage about the meninges (i.e., dura mater, arachnoid mater, pia mater). The passage identified characteristics of each layer of the meninges as well as their location in relation to the brain and spinal cord.
• Read and answered four questions about a popular press news article about Krystle Beauchamp Gridley’s experience with meningitis ( Miller, 2019 ). Specifically, students were asked to list signs and symptoms of meningitis experienced by Krystle, identify how doctors diagnosed Krystle with meningitis, whether there was anything Krystle could have done to avoid contracting meningitis, and the long-term effects of meningitis experienced by Krystle.
• Read and answered questions about an empirical article from the Journal of the American Medical Association titled, “Risk factors for meningococcal disease in college students” ( Bruce et al., 2001 ). Students were asked to consider how details of Krystle’s case aligned with risk factors identified in the article and assess whether her meningitis could have been avoided if she had received the meningococcal vaccine.

During the 50-minute class meeting, students learned about anatomical directions and the layers of the meninges for the first 25–30 minutes of class. The remainder of the class period was spent on the case study in which there were three pair-and-share opportunities. Students discussed their responses in groups of 3–4 students and then we had a group discussion. During the first pair-and-share, students discussed Krystle’s experience with meningitis. Second, they considered Krystle’s case in relation to risk factors identified in the empirical article after a brief discussion of statistics. I explained that scientists typically use a threshold of.05 for determining whether an effect is statistically significant. Then, together as a class, we identified which risk factors in Tables 2 and 3 from the JAMA article were significant predictors of meningococcal disease and which were not. Based on that discussion, students identified Krystle’s risk factors and spent the most time discussing the fact that Krystle did not receive the meningococcal vaccine. We discussed that the meningococcal vaccine most college students receive protects against some, but not all, of the serogroups that commonly cause meningococcal disease. Additionally, the specific serogroup that caused Krystle’s meningitis was not identified in the news article, so we were unable to definitively state whether the meningococcal vaccine would have protected Krystle from contracting meningitis. Lastly, the students were provided with and asked to evaluate the University’s policy on students receiving the meningococcal vaccine (which can be found on most Universities’ websites).

CASE ASSESSMENT

The questions students answered when completing the case study were not evaluated because I intended for students to perceive the activity as a learning opportunity versus an assessment. The University’s Institutional Review Board approved the case assessment, and students consented to having their data from the exam and evaluation of the case study contribute to the present report. Learning objectives for the case study were included on the list of exam objectives, which students received a week before the exam. Four questions on the first exam (8 points) related to the meninges or meningococcal disease. Two questions were multiple-choice with four response options, and two questions were short answer. The multiple-choice questions required students to 1) provide the order of the layers of the meninges in relation to the brain and 2) identify which medical procedure was most likely used to test for meningitis. Twenty-six of 29 students (89.66%) correctly identified the order of the layers of meninges relative to the brain as well as the procedure used to diagnose meningitis (one student’s performance on the multiple-choice questions is missing because the scantron was not evaluated with the rest of the class). The first short-answer question required students to identify two symptoms of meningitis. Twenty-nine of 30 students (96.6%) received full credit on this question. One student correctly identified only one symptom of meningitis. The second question required students to identify one precaution that can be taken to reduce the probability of contracting meningitis; 100% of students correctly identified that vaccination can protect individuals from contracting meningitis.

After the conclusion of the case study, students completed an anonymous evaluation of the meningitis case. Students responded to eight statements regarding the case using a 5-point Likert-scale (1 = Strongly Disagree, 5 = Strongly Agree; See Table 1 ). Students overall responded favorably to the case study. Another goal of the case study was for students to consider how scientific knowledge can be applied to real-world situations. Students agreed that it is important to consider the broader impacts of scientific knowledge ( M = 4.48 ±.63), and ratings were lower for students indicating that they had previously thought about the way scientific knowledge can affect policies ( M = 3.53 ± 1.14). Most students did not respond to the open-ended question at the end of the questionnaire that asked for other feedback about the case study. However, one student commented, “case studies are a great way for undergraduate student to learn, in a memorable way, about different ailments.”

Presents the mean (± SD) for items on the evaluation questionnaire.

The meningitis case was the first case presented in the semester and the student’s first exposure to primary scientific literature. Self-reported data indicated that the majority of the students enjoyed learning about meningitis using the case-study method, reading the primary scientific article, and considering how scientific research can be applied to policy decisions. Students performed well on the examination questions, and the case provided students with low-stakes exposure to primary scientific literature before they completed four graded empirical article evaluations. As such, the case was effective in promoting the identified content and process objectives.

There are many ways this case can be adapted in the future. Students could independently investigate the meninges or which meningococcal serogroups are targeted by the quadrivalent meningococcal vaccination. The case study could also be adapted for courses in immunology or epidemiology. For example, the case study could be focused on the meningococcal serogroups or involve students comparing data from the JAMA article to recent reports by the CDC (2019 ; ( https://www.cdc.gov/meningococcal/surveillance/index.html ). Further, how the case study is applied could be modified. Rather than evaluate their University’s policy on students receiving the meningococcal vaccine, students could create their own policy, which would challenge them to think at a higher level of Bloom’s taxonomy. Students could also consider the costs versus benefits of the vaccinations given the rarity of meningococcal disease. For example, a relatively recent article in The New York Times discussed concerns related to the cost of the vaccinations in relation to the rarity of meningococcal disease ( Luthra, 2017 ).

Acknowledgements

This case study was supported by the Neuroscience Case Network (NeuroCaseNet; NSF-RCN-UBE Grant #1624104). The author would also like to thank Darlene Mitrano, Ph.D., for providing feedback on the case study and editing the manuscript.

• Brewer CA, Smith D. Vision and change in undergraduate biology education: A call to action. Washington, DC: American Association for the Advancement of Science; 2011. [ Google Scholar ]
• Bruce MH, Rosenstein NE, Caparella JM, Shutt KA, Perkins BA, Collins M. Risk factors for meningococcal disease in college students. JAMA. 2001; 286 (6):688–693. [ PubMed ] [ Google Scholar ]
• Centers for Disease Control and Prevention. Meningococcal Disease. 2019. Available at: https://www.cdc.gov/meningococcal/surveillance/index.html .
• Coil D, Wenderoth MP, Cunningham M, Dirks C. Teaching the process of science: Faculty perceptions and an effective methodology. CBE-Life Sci Educ. 2010; 9 :524–535. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Cook-Snyder DR. Using case studies to promote student engagement in primary literature data analysis and evaluation. J Undergrad Neurosci Educ. 2017; 16 (1):C1–C6. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Kozeracki CA, Carey MF, Colicelli J, Levis-Fitzgerald M. An intensive primary-literature-based teaching program directly benefits undergraduate science majors and facilitates their transition to doctoral programs. CBE-Life Sci Educ. 2006; 5 :340–347. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Luthra S. For Meningitis B vaccines, climbing revenue, and plenty of skepticism. The New York Times. 2017. Sep 7, Available at https://www.nytimes.com/2017/09/07/business/meningitis-b-vaccines.html .
• Meil WM. The use of case studies in teaching undergraduate neuroscience. J Undergrad Neurosci Educ. 2007; 5 :A53–A62. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Miller K. What it’s like to develop meningitis in college: ‘I couldn’t walk” Yahoo Lifestyle. 2019. May 3, Available at https://www.yahoo.com/lifestyle/what-its-like-to-develop-meningitis-in-college-205551620.html?soc_src=social-sh&soc_trk=ma .
• Mitrano DA. Two scientists share Nobel Prize for the first time! A case study developed for exploring the history of neuroanatomy. J Undergrad Neurosci Educ. 2019; 17 (2):C1–C5. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Ogilvie JM. The mysterious case of Patient X: A case study for neuroscience students. J Undergrad Neurosci Educ. 2019; 18 (1):C1–C4. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Roesh LA, Frenzel K. Nora’s medulla: A problem-based learning case for neuroscience fundamentals. J Undergrad Neurosci Educ. 2016; 14 (2):C1–C3. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Sawyer NT, Frenzel KE. Epilepsy and the action potential: Using case based instruction and primary literature in a neurobiology course. J Undergrad Neurosci Educ. 2018; 16 (2):C7–C10. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Scoville WB, Milner B. Loss of recent memory after bilateral hippocampal lesions. J Neurol Neurosurg Psychiatry. 1957; 20 :11–21. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Smith GR. Guided literature explorations. J Coll Sci Teach. 2001; 30 (7):465. [ Google Scholar ]
• Watson TD. ‘Without a key’: A classroom case study. J Undergrad Neurosci Educ. 2019; 18 (1):C5–C7. [ PMC free article ] [ PubMed ] [ Google Scholar ]