Viral meningitis in children: Management, prognosis, and prevention

INTRODUCTION — The management, prognosis, and prevention of viral meningitis in children will be discussed here. The epidemiology, etiology, pathogenesis, clinical manifestations, and diagnosis of viral meningitis in children are discussed separately. (See "Viral meningitis in children: Epidemiology, pathogenesis, and etiology" and "Viral meningitis in children: Clinical features and diagnosis".)

MANAGEMENT

Indications for hospitalization — Indications for hospitalization may include [1,2]:

●Ill appearance or signs of encephalitis (eg, altered or depressed mental status, focal neurologic abnormalities, seizures) (see "Acute viral encephalitis in children: Clinical manifestations and diagnosis", section on 'Clinical features')

●Need for empiric antimicrobial therapy (see 'Empiric antibiotics' below)

●Need for intravenous hydration or aggressive pain control (see 'Supportive care' below)

●Immunocompromised host

●Age younger than one year

Supportive care — Supportive care for children with viral meningitis may include [1]:

●Rest in a quiet, dimly lit room.

●Acetaminophen and/or ibuprofen for headache, pain, and fever; aspirin should be avoided because of its association with Reye syndrome.

●Intravenous fluid therapy if poor oral intake and/or prolonged emesis have resulted in hypovolemia. Careful attention to fluid balance is an important aspect of supportive care. The need for fluid repletion must be balanced against the risk of inappropriate secretion of antidiuretic hormone. (See "Treatment of hypovolemia (dehydration) in children in resource-abundant settings".)

Neonates and immunocompromised hosts may require aggressive supportive care for disseminated disease (eg, myocarditis, pericarditis, hepatitis, coagulopathy), particularly with enterovirus (EV), human parechovirus (HPeV), or herpes simplex virus (HSV) infection [1]. (See "Neonatal herpes simplex virus infection: Management and prevention", section on 'Supportive measures'.)

Initial empiric therapy — Viral meningitis may be suspected based upon epidemiologic data, clinical features, and initial cerebrospinal fluid (CSF) studies (table 1), but the clinical features can overlap with bacterial meningitis (table 2) and it can be difficult to exclude bacterial meningitis with certainty based on initial testing. Ultimately, the definitive diagnosis of viral meningitis requires negative bacterial cultures and detection of a viral pathogen in the CSF. (See "Viral meningitis in children: Clinical features and diagnosis", section on 'Diagnosis'.)

The following sections describe the approach to determining the need for empiric antimicrobial therapy while awaiting bacterial cultures and viral polymerase chain reaction (PCR) studies.

Empiric antibiotics — The results of the initial evaluation can be used to determine the likelihood of bacterial meningitis, which informs the decision of whether to treat with empiric antibiotics pending results of bacterial cultures and PCR studies (algorithm 1).

Assessing risk of bacterial meningitis — Clinical prediction tools can be used in conjunction with clinical judgement to identify patients with a very low risk of bacterial meningitis (algorithm 1).

These tools have more utility for identifying patients with a low risk of bacterial meningitis than they do for identifying patients with bacterial meningitis.

Bacterial meningitis prediction rules should not be used in patients with any of the following:

●Age <3 months

●Ill appearance

●Immune compromise

●Physical examination findings concerning for meningococcal disease (ie, petechiae or purpura)

●CSF shunt or recent neurosurgery

●Pretreatment with antibiotics for another reason (eg, otitis media) within 72 hours prior to lumbar puncture (LP)

●Traumatic LP

The most well studied and most commonly used prediction rule is the Bacterial Meningitis Score (BMS) [3,4]. The Meningitis Score for Emergencies (MSE) is an alternate tool that can be used in conjunction with the BMS, which may improve the sensitivity, specificity, and negative predictive value (NPV) [5]. However, there are fewer available data on the predictive value of the MSE. In addition, the MSE relies on results of laboratory tests (C-reactive protein [CRP] and procalcitonin), which may not be rapidly available in some settings. If it is not possible to determine the MSE (eg, because serum CRP or procalcitonin levels were not measured or not available), the BMS can be used alone.

●The Bacterial Meningitis Score (BMS) – The BMS includes the following variables [3]:

•Positive CSF Gram stain (2 points)

•CSF absolute neutrophil count (ANC) ≥1000 cells/microL (1 point)

•CSF protein ≥80 mg/dL (1 point)

•Peripheral blood ANC ≥10,000 cells/microL (1 point)

•History of seizure before or at the time of presentation (1 point)

A score of 0 indicates "very low risk" of bacterial meningitis. The BMS has been validated in several studies, most of which used retrospective data, though there has been at least one small prospective study [4,6]. In a meta-analysis of eight validation studies (including 5312 patients), BMS ≥1 predicted bacterial meningitis with sensitivity and specificity of 99.3 and 62.1 percent, respectively [4]. Among the 2283 children classified as "very low risk" (BMS 0), 0.4 percent (nine patients) had bacterial meningitis, yielding an NPV of 99.6 percent. However, in six of the nine misclassified patients, use of the BMS was inappropriate due to either age <3 months or concerning examination findings (ie, petechiae or purpura). Excluding these six patients, the estimated NPV was 99.9 percent.

●The Meningitis Score for Emergencies (MSE) – The MSE includes the following variables [5]:

•Serum procalcitonin >1.20 ng/mL – 3 points

•Serum CRP >40 mg/L – 1 point

•CSF ANC >1000/mcL – 1 point

•CSF protein >80 mg/dL – 2 points

A score of 0 indicates very low risk of bacterial meningitis. In a study involving 1009 pediatric patients with CSF pleocytosis, MSE ≥1 predicted bacterial meningitis with a sensitivity of 100 percent, specificity of 83.2 percent, and NPV of 100 percent [5]. In this study, BMS ≥1 had a sensitivity of 96.7 percent, specificity of 51.3 percent, and NPV of 99.4 percent. However, the study included infants as young as 30 days old and, as previously discussed, the BMS is not intended for use in young infants.

Details of interpreting the CSF profile in children who received antibiotics before LP and interpreting traumatic LPs are provided separately. (See "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Interpretation'.)

Risk is very low — For children determined to have very low risk of bacterial meningitis (ie, BMS = 0 and without any of the exclusions listed above), supportive care alone is reasonable provided that (algorithm 1):

●The physical examination is reassuring (including stable vital signs), and

●Symptoms have improved following LP or with antipyretic/analgesic therapy and hydration, and

●Tick-borne illnesses, including Lyme meningitis, are not a consideration (see "Lyme disease: Clinical manifestations in children", section on 'Meningitis'), and

●Adequate follow-up can be assured (within 24 hours in most cases)

If any of these conditions are not met, the decision to treat with empiric antibiotics is individualized based upon the age and clinical status of the child, season, exposure history, findings of the initial evaluation, and adequacy of follow-up care. In view of the serious consequences of delayed treatment for bacterial meningitis, the threshold to initiate empiric antibiotic therapy should be relatively low.

It is important to recognize that while the BMS and MSE can help identify patients at very low risk of bacterial meningitis, they do not discriminate between viral meningitis and other types of aseptic meningitis that may require antimicrobial therapy, such as Lyme meningitis. In Lyme-endemic areas during the summer and fall, it can be difficult to distinguish Lyme meningitis from EV meningitis unless the patient had a preceding tick bite and/or erythema migrans. Facial nerve palsy is also strongly suggestive of Lyme disease. (See "Lyme disease: Clinical manifestations in children", section on 'Meningitis'.)

Risk is NOT low — Children in whom the risk of bacterial meningitis is not low (ie, BMS ≥1 or with any of the exclusions listed above) should be hospitalized and treated with empiric antibiotics (algorithm 1). (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Empiric therapy'.)

In select circumstances (eg, an older child or adolescent with normal neurologic examination who received antibiotic therapy prior to the LP and in whom the only feature suggestive of bacterial meningitis is a neutrophil-predominant CSF pleocytosis), it may be reasonable to observe the patient with or without administration of antimicrobials and repeat the LP 24 hours after the initial procedure [2,7-10]. Repeating the LP may help clarify the likely etiology; a shift to mononuclear predominance supports a viral process, while persistent neutrophil predominance supports a bacterial process. However, persistence of neutrophils can also occur with viral meningitis and this should not be used as the only criterion to distinguish between bacterial and viral disease [11].

Empiric regimen — The empiric antibiotic regimen should cover the most likely bacterial pathogens in the individual host. For pediatric patients beyond the neonatal period, an appropriate empiric regimen includes vancomycin and high doses of a third-generation cephalosporin (eg, ceftriaxone, cefotaxime [if available]). In severely ill or immunocompromised patients, empiric therapy for unusual bacterial pathogens also may be warranted. Additional details are provided separately. (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Empiric therapy'.)

The addition of doxycycline may be appropriate in endemic areas for tick-borne infections. (See "Treatment of Rocky Mountain spotted fever" and "Human ehrlichiosis and anaplasmosis", section on 'Treatment'.)

Empiric therapy for neonates with suspected bacterial meningitis is discussed separately. (See "Bacterial meningitis in the neonate: Treatment and outcome", section on 'Empiric therapy'.)

Duration of antibiotic therapy — In patients who improve symptomatically, empiric antibiotic therapy is usually discontinued when bacterial cultures are negative after 24 to 48 hours and/or an alternative diagnosis is made (eg, by viral PCR) [1]. In patients with persistent symptoms, additional evaluation may be necessary. (See 'Persistent symptoms' below.)

Empiric acyclovir — Most children with uncomplicated viral meningitis do not require empiric antiviral therapy pending results of bacterial cultures and PCR studies. However, empiric treatment with acyclovir is appropriate in the following circumstances:

●Acute encephalitis – Empiric acyclovir therapy is warranted for infants and children presenting with clinical signs of acute encephalitis (eg, CSF pleocytosis accompanied by focal findings on neurologic examination, depressed or altered mental status, seizures, abnormal neuroimaging findings, or abnormal electroencephalography) [1]. Treatment of acute encephalitis is discussed separately. (See "Acute viral encephalitis in children: Treatment and prevention", section on 'Empiric acyclovir'.)

●Concern for neonatal HSV infection – Acyclovir therapy is indicated in neonates with suspected HSV infection. Clinical features suggestive of HSV infection in neonates include mucocutaneous vesicles (picture 1A-C), seizures, lethargy, respiratory distress, thrombocytopenia, coagulopathy, hypothermia, sepsis-like illness, hepatomegaly, ascites, or elevated transaminases (figure 1). The role of acyclovir therapy in neonates with CSF pleocytosis who are otherwise well-appearing is less clear. This issue is discussed separately. (See "Neonatal herpes simplex virus infection: Management and prevention", section on 'Initial antiviral therapy' and "The febrile infant (29 to 90 days of age): Management", section on 'Herpes simplex virus' and "The febrile neonate (28 days of age or younger): Outpatient evaluation and initial management", section on 'Herpes simplex virus infection'.)

●Immunocompromised patients – Acyclovir may be warranted when HSV or varicella-zoster virus are possible etiologies in an immunocompromised patient. (See 'Treatment of specific viral causes' below.)

Alternatives to acyclovir that can be used in the event of an acyclovir shortage are discussed separately. (See "Acyclovir: An overview", section on 'If there is an acyclovir shortage'.)

In patients who are clinically improved, empiric acyclovir may be discontinued when CSF HSV PCR is negative (in neonates, HSV surface cultures and whole-blood or plasma HSV PCR [if obtained] should also be negative) or an alternative diagnosis is made (eg, by EV or multiplex PCR).

In patients with persistent symptoms, continuation of empiric acyclovir and/or additional evaluation may be necessary. (See 'Persistent symptoms' below.)

Treatment of specific viral causes — With the exception of HSV, most cases of confirmed viral meningitis are treated symptomatically and the role of specific antiviral therapy is limited. (See 'Supportive care' above.)

●EV and HPeV – Therapeutic options for serious EV and HPeV infection are limited. This is discussed in greater detail separately. (See "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Treatment'.)

●HSV – HSV meningitis is treated with acyclovir [1,12]. Dosing is as follows [13,14]:

•For neonatal HSV, 60 mg/kg per day intravenously, divided every eight hours, for a minimum of 21 days (see "Neonatal herpes simplex virus infection: Management and prevention", section on 'Initial antiviral therapy')

•For central nervous system infections in children aged 3 months to 11 years, 30 to 45 mg/kg per day intravenously, divided every eight hours, for a minimum of 14 to 21 days

•For central nervous system infections in children ≥12 years old, 30 mg/kg per day intravenously, divided every eight hours, for a minimum of 14 to 21 days

Alternatives to acyclovir that can be used in the event of an acyclovir shortage are discussed separately. (See "Acyclovir: An overview", section on 'If there is an acyclovir shortage'.)

●Arboviruses and lymphocytic choriomeningitis virus – Most arboviral and lymphocytic choriomeningitis virus infections of the central nervous system are treated symptomatically. Investigative therapies for West Nile virus are discussed separately. (See "Arthropod-borne encephalitides" and "Treatment and prevention of West Nile virus infection".)

●Cytomegalovirus (CMV) – CMV infection in immunocompromised children is treated with ganciclovir. Treatment may also be warranted in immunocompetent children with serious symptomatic CMV infection; however, data are limited. Treatment of CMV in children is discussed in detail separately. (See "Overview of cytomegalovirus infections in children", section on 'Treatment'.)

●Epstein-Barr virus – Epstein-Barr virus infection rarely requires more than supportive therapy. Even in clinical situations where an antiviral treatment would be desirable, it is not clear that the virus responds. This is discussed in greater detail separately. (See "Clinical manifestations and treatment of Epstein-Barr virus infection", section on 'Treatment'.)

●Influenza – For patients with confirmed or suspected influenza who are hospitalized or who have severe, complicated, or progressive illness, antiviral treatment should be started as soon as possible after symptom onset. Dosing recommendations for the available agents are summarized in the table (table 3). Treatment of influenza infection in children is discussed in greater detail separately. (See "Seasonal influenza in children: Management", section on 'Antiviral therapy'.)

●Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – Treatment of children with acute SARS-CoV-2 infection is discussed separately. (See "COVID-19: Management in children".)

●Varicella-zoster virus – Treatment with acyclovir may improve outcomes, although data are limited in pediatric patients [15]. Treatment of varicella-zoster virus is discussed in greater detail separately. (See "Treatment of herpes zoster", section on 'Neurologic complications'.)

Persistent symptoms — When symptoms persist or worsen in patients with aseptic meningitis, nonviral causes must be considered (table 4). Additional evaluation may include [7,16]:

●Repeat LP with removal of 3 to 5 mL of CSF, if possible, for additional PCR testing and fungal and mycobacterial cultures.

●Imaging of the central nervous system and sinuses with magnetic resonance imaging or computed tomography to look for parameningeal infection and acute disseminated encephalomyelitis. (See "Acute disseminated encephalomyelitis (ADEM) in children: Pathogenesis, clinical features, and diagnosis".)

●Evaluation for Lyme disease, ehrlichiosis, and rickettsial infection. (See "Diagnosis of Lyme disease" and "Human ehrlichiosis and anaplasmosis" and "Clinical manifestations and diagnosis of Rocky Mountain spotted fever".)

●Evaluation for parasitic infection. (See "Cysticercosis: Clinical manifestations and diagnosis" and "Trichinellosis" and "Toxoplasmosis: Acute systemic disease" and "Eosinophilic meningitis", section on 'Parasitic etiologies'.)

●If infectious etiologies have been excluded, noninfectious causes of aseptic meningitis should be considered, including autoimmune encephalitis, neoplasms, and drug-induced meningitis. (See "Autoimmune (including paraneoplastic) encephalitis: Clinical features and diagnosis" and "Aseptic meningitis in adults", section on 'Neoplasms of the leptomeninges' and "Aseptic meningitis in adults", section on 'Drug-induced meningitis'.)

PROGNOSIS — Most children with viral meningitis recover completely [17-19]. Some may complain of several weeks of fatigue, irritability, decreased concentration, muscle weakness and spasm, and incoordination after the acute illness [19].

Prognosis depends upon the age of the child and the etiologic agent. Enteroviral meningitis typically has a benign clinical course, which by definition lacks the neurologic abnormalities that characterize encephalitis or myelitis [20]. The morbidity and mortality are not precisely known, since widespread disease occurs each year and enterovirus (EV) meningitis is not a reportable condition. For particularly susceptible neonatal or immune-compromised hosts, the rates of sequelae and mortality may be as high as 74 and 10 percent, respectively. When death occurs, it is usually due to hepatic failure (with echoviruses) or myocarditis (coxsackieviruses) [21,22].

The duration of symptoms in children is usually less than one week; many report clinical improvement after lumbar puncture (LP) [20,23]. Adolescents and young adults may have a prolonged convalescent stage, with symptoms persisting for several weeks [24].

Children with EV meningitis generally recover without neurologic sequelae. Several studies have suggested possible long-term neurologic, cognitive, developmental, and language abnormalities in young children following EV meningitis; however, these observations have been inconsistent [18,25-27]. EV71 central nervous system infection with cardiopulmonary involvement has been associated with neurologic sequelae, including delayed development and reduced cognitive function [28].

Long-term neurologic sequelae have also been reported following human parechovirus (HPeV) meningitis, particularly when infection occurs in early infancy [29,30]. In long-term follow-up studies, developmental delays and other neurologic disabilities have been identified in approximately one-quarter of young infants with HPeV meningitis [29].

The immune clearance of EV and HPeV is dependent upon an appropriate antibody-mediated response. Individuals with hereditary or acquired defects in B lymphocyte function (eg, agammaglobulinemia, hypogammaglobulinemia, common variable immunodeficiency) may develop persistent, sometimes fatal, chronic meningitis or meningoencephalitis [31]. (See "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Immunocompromised patients'.)

PREVENTION

●Hygiene – Simple hygienic measures, such as hand washing, particularly after diaper changing, are important to prevent the spread of enteroviruses (EVs). (See "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Prevention'.)

●Vaccines – Vaccines are available to prevent poliovirus, influenza, rabies, and some arboviruses (eg, Japanese encephalitis virus, tick-borne encephalitis). An inactivated enterovirus A71 vaccine is licensed in China. Target groups for these vaccines are discussed separately. (See "Poliovirus vaccination" and "Rabies immune globulin and vaccine" and "Immunizations for travel" and "Seasonal influenza in children: Prevention with vaccines", section on 'Target groups' and "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Vaccines'.)

●Personal protection – Personal protection measures to avoid mosquito and tick exposure are a mainstay of prevention. A variety of insect repellants are available. (See "Prevention of arthropod and insect bites: Repellents and other measures".)

●Infection control – When children are hospitalized with aseptic meningitis, contact precautions are indicated for the duration of illness [32]. (See "Infection prevention: Precautions for preventing transmission of infection", section on 'Contact precautions'.)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, 'The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Meningitis in children (The Basics)" and "Patient education: Viral meningitis (The Basics)")

●Beyond the Basics topic (see "Patient education: Meningitis in children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Indications for hospitalization – Indications for hospitalization may include (see 'Indications for hospitalization' above):

•Ill appearance or signs of encephalitis (eg, altered or depressed mental status, focal neurologic abnormalities, seizures)

•Need for empiric antimicrobial therapy

•Need for intravenous hydration or aggressive pain control

•Immunocompromised host

•Age <1 year

●Supportive care – Supportive care for children with viral meningitis may include (see 'Supportive care' above):

•Rest in a quiet, dimly lit room

•Acetaminophen and/or ibuprofen for headache, pain, and fever

•Intravenous fluid therapy if poor oral intake and/or prolonged emesis have resulted in hypovolemia

●Empiric antibiotic therapy – Viral meningitis may be suspected on the basis of epidemiologic data, clinical features, and initial cerebrospinal fluid (CSF) studies (table 1). The results of the initial evaluation can be used to determine the likelihood of bacterial meningitis, which informs the decision to treat with empiric antibiotics pending results of bacterial cultures and polymerase chain reaction (PCR) studies (algorithm 1) (see 'Assessing risk of bacterial meningitis' above):

•Risk of bacterial meningitis is very low – For most children with suspected viral meningitis who are assessed as having very low risk of bacterial meningitis (algorithm 1), we suggest supportive care alone rather than empiric antibiotic therapy (Grade 2C), provided that:

-The physical examination is reassuring (including stable vital signs), and

-Symptoms have improved following lumbar puncture (LP) or with antipyretic/analgesic therapy and hydration, and

-Tick-borne and Lyme meningitis are not considerations, and

-Adequate follow-up can be assured (within 24 hours in most cases)

If any of these conditions are not met, the decision to treat with empiric antibiotics is individualized based upon the age and clinical status of the child, season, exposure history, findings of the initial evaluation, and adequacy of follow-up care. In view of the serious consequences of delayed treatment for bacterial meningitis, the threshold to initiate empiric antibiotic therapy should be relatively low. (See 'Risk is very low' above.)

•Risk of bacterial meningitis is NOT low – Children in whom the risk of bacterial meningitis is not low should be hospitalized and treated with empiric antibiotics, as summarized in the table (table 5) and discussed separately. (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Empiric therapy'.)

•Duration of empiric antibiotic therapy – For children who improve symptomatically, empiric antibiotic therapy is usually discontinued when bacterial cultures are negative after 24 to 48 hours and/or an alternative diagnosis is made. (See 'Duration of antibiotic therapy' above.)

●Empiric acyclovir – Most children with viral meningitis do not require empiric antiviral therapy pending results of PCR testing. However, empiric treatment with acyclovir is appropriate in the following circumstances (see 'Empiric acyclovir' above):

•Children presenting with clinical signs of encephalitis (eg, focal neurologic findings, depressed or altered mental status, seizures, abnormal neuroimaging findings, or abnormal electroencephalography) (see "Acute viral encephalitis in children: Treatment and prevention", section on 'Empiric acyclovir')

•Neonates with concern for herpes simplex virus (HSV) infection (see "Neonatal herpes simplex virus infection: Management and prevention", section on 'Initial antiviral therapy')

•Immunocompromised patients in whom HSV or varicella-zoster virus are possible etiologies

●Specific antiviral therapy – With the exception of HSV, most cases of confirmed viral meningitis are treated symptomatically and the role of specific antiviral therapy is limited. Considerations for specific viral etiologies are discussed above. (See 'Treatment of specific viral causes' above.)

●Persistent symptoms – When symptoms persist or worsen, nonviral causes of aseptic meningitis must be considered (table 4). Additional evaluation may be necessary. (See 'Persistent symptoms' above.)