OVERVIEW: What every practitioner needs to know
Are you sure your patient has encephalitis? What are the typical findings for the disease?
Any inflammation of the brain constitutes encephalitis, whether caused by direct invasion of the brain by an infectious agent (primary encephalitis), by immune response to an infectious process (parainfectious or post-infectious encephalitis), or by a process with no known connection to an infectious etiology (e.g., auto-immune encephalitis or paraneoplastic encephalitis).
Encephalitis may occur in isolation or may be accompanied by inflammation of the meninges (meningoencephalitis) or spinal cord (encephalomyelitis). This chapter will focus primarily on acute infectious encephalitis, whose clinical features are as numerous and as diverse as the organisms with which they are associated.
Determination of encephalitis etiology is often difficult and requires astute skills in epidemiologic investigation. Definitive management of encephalitis can be highly organism specific, yet for many of the infectious etiologies the lack of effective antimicrobial therapy necessitates a general approach and patience in the face of an uncertain prognosis.
Clinical manifestations of acute infectious encephalitis
Clinical manifestations of acute infectious encephalitis can be highly variable, even among patients afflicted by the same organism, and depend on the severity of infection, anatomic sites involved, and host factors such as immune response.
Neurologic symptoms and findings are universal, but they can be varied. Patients with diffuse disease may experience alterations in mental status such as decreased consciousness, behavioral or personality changes, or generalized seizures. When encephalitis is more localized, neurologic manifestations may include focal seizures, hemiparesis, aphasias, hallucinations, memory lapses, cranial nerve dysfunction, movement disorders, incontinence, or ataxia. In either situation, progression to obtundation, coma and death is possible (and in some cases inevitable) depending on the organism and availability of specific therapy.
The clinical progression of acute infectious encephalitis typically occurs over days to weeks. In certain cases, patients may present with neurologic complaints as the initial manifestation (e.g., with neurocysticercosis). More commonly, neurologic manifestations follow an initial presentation consistent with a nonspecific systemic illness, which may include fever, headache, nausea and vomiting, malaise, and irritability (or screaming spells in infants and young children). Fever in particular is an extremely common (though not universal) component of acute infectious encephalitis.
Neurologic and systemic symptoms may also be accompanied by localized manifestations associated with the specific agent involved, e.g., respiratory, gastrointestinal, exanthems and enanthams. In cases of post-infectious encephalitis, an infectious (usually viral) illness or vaccination is followed days to weeks later by onset of neurologic symptoms, which may develop abruptly (as with acute cerebellar ataxia and brainstem encephalitis) or subacutely (as with acute demyelinating encephalomyelitis).
Certain infectious agents cause encephalitis associated with characteristic features, summarized in Table I.
|Limbic encephalitis (anterograde amnesia)||Human herpesvirus type 6 (in hematopoietic cell transplant patients)|
|Cerebellar ataxia||Varicella zoster, Epstein-Barr, mumps, St. Louis encephalitis, Trypanosoma brucei gambiense|
|Cranial nerve palsies||Herpes simplex, Epstein-Barr, Listeria monocytogenes, Mycobacterium tuberculosis, Treponema pallidum, Borrelia burgdorferi, Cryyptococcus neoformans, Coccioides imitis, Histoplasma capsulatum|
|Dementia||HIV, measles, Treponema pallidum|
|Parkinsonism||Japanese encephalitis, West Nile, St. Louis encephalitis, Nipah, Toxoplasma gondii, Trypanosoma brucei gambiense|
|Flaccid paralysis||Japanese encephalitis, West Nile, tickborne encephalitis, enteroviruses|
|Rhombencephalitis (brainstem encephalitis and cerebritis)||Herpes simplex, West Nile, enterovirus 71, Listeria monocytogenes|
Clinical manifestations – chronic infectious encephalitis
Certain infectious agents are associated with encephalitic processes that are characterized by slow progressive neurologic deterioration occurring over months to years. Examples include measles virus (subacute sclerosing panencephalitis) and Trypanosoma brucei gambiense (West African sleeping sickness). These processes should be distinguished from chronic infectious encephalopathies, which are characterized by slow progressive neurologic deterioration without evidence of inflammation.
Organisms causing chronic infectious encephalopathies include JC, SV40, and BK viruses (progressive multifocal leukoencephalopathy), HIV and HIV (AIDS encephalopathy), and prions (Kuru, Creutzfeldt-Jacob disease, and other spongiform encephalopathies).
What other disease/condition shares some of these symptoms?
Any encephalopathic condition can mimic the symptoms of encephalitis, including fever when inflammation is present outside the central nervous system. Causes of encephalopathy include:
- Systemic infectious diseases (viral, bacterial, fungal, parasitic)
- Post-infectious processes (Guillain-Barre syndrome, nonencephalitic acute cerebellar ataxia)
- Demyelinating disorders (multiple sclerosis, infectious and noninfectious leukoencephalopathies)
- Alcohol and recreational drug intoxications, and neurologic toxicities associated with prescription or over-the-counter medication
- Reye syndrome
- Embolic lesions resulting from endocarditis or intravascular thrombosis
- Metabolic disorders (hypoglycemia, diabetic ketoacidosis, uremic encephalopathy, hepatic encephalopathy, inborn errors of glucose or ammonia metabolism
- Primary seizure disorders (especially non-convulsive status epilepticus)
- Intracranial mass lesions (tumor, abscess)
- Subarachnoid hemorrhage and other cerebrovascular disorders
- Acute confusional migraines
What caused this disease to develop at this time?
Acute infectious encephalitis usually develops in the context of a systemic infection where there is direct invasion of the organism into the central nervous system. Since the first step in this process is acquisition of the causative agent, there should be an appropriate predisposing environmental exposure. However, eliciting a history of such an exposure can prove difficult. Medical history for a patient with encephalitis should include a meticulous account of activities within the 2-3 weeks prior to the onset symptoms, including detailed travel history, exposures to animals and insects, recreational activities (e.g., swimming, boating, camping, spelunking), and sick contacts.
Epidemiologic associations are outlined in the epidemiology section below for each of organisms linked to infectious encephalitis.
In some cases (most notably with parasitic causes of encephalitis), involvement of the central nervous system is typical in the natural history of infection and represents the only clinically relevant manifestation. More commonly, however, it is unclear why certain individuals develop encephalitis as a result of infection with a particular organism whereas other individuals do not.
Immunodeficiencies in general can predispose individuals toward both infection with particular organisms and encephalitis as a particular manifestation of infection. Defects in cellular immunity (such as in the setting of HIV infection or bone marrow transplant) are associated with an increased risk of encephalitis due to opportunistic organisms (Toxoplasma gondii and Cryptococcus neoformans) as well as certain viruses (herpes simplex viruses types 1 and 2, varicella zoster virus, Epstein Barr virus, cytomegalovirus, human herpesvirus type 6, JC virus, and BK virus).
Enterovirus encephalitis is more common among individuals with defects in humoral immunity (agammaglobulinemia) compared to healthy individuals.
Defects in effectors of the innate immune system may also be associated with an increased risk of encephalitis due to certain pathogens. For example, defects in the function of toll-like receptor 3 (TLR-3) appear to predispose children to encephalitis caused by herpes simplex virus type 1.
Little is also known about the factors that predispose certain individuals to develop post-infectious encephalitis. Cases have been attributed to a myriad of different organisms, though often the preceding infection is nonspecific (usually upper respiratory), and no specific agent is identified. In up to one quarter of cases, there is no recollection of any recent infectious illness. Post-immunization encephalitis has been described in association with vaccines for smallpox, rabies, typhoid-paratyphoid, influenza, Japanese B encephalitis virus, measles, mumps, vaccinia, and yellow fever virus.
What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
Definitive diagnosis of encephalitis requires microscopic examination of brain tissue to demonstrate inflammation, and definitive diagnosis of the etiology requires direct detection or recovery of the causative organism from brain tissue. Since these methods are infrequently available in clinical practice, a presumptive diagnosis is often based on the combination of consistent neurologic symptoms and signs, cerebrospinal fluid (CSF) analysis and imaging to demonstrate central nervous system inflammation, and ancillary laboratory and epidemiologic findings to suggest the etiology.
The routine evaluation of suspected encephalitis should also include peripheral blood evaluation for complete blood count (which may provide clues to suggest certain infectious and non-infectious processes) and chemistries (in particular sodium, glucose, and ammonia) for which severe abnormalities may suggest a non-infectious etiology to explain the clinical presentation.
Lumbar puncture for CSF analysis should be performed, if safe and practical, on any patient suspected of having encephalitis. Care should be taken to identify patients at risk for herniation due to increased intracranial pressure, such as those with posterior fossa tumors, and lumbar puncture should be avoided in such patients.
Papilledema on fundoscopic examination is an indicator of increased intracranial pressure and should prompt neuroimaging to identify mass lesions. Many practitioners would advocate for routine neuroimaging (in particular computed tomography scan if readily available) prior to lumbar puncture.
CSF analysis should include at minimum white blood cell (WBC) count and differential, red blood cell (RBC) count, protein and glucose concentrations, Gram stain and bacterial culture, and PCR for enteroviruses (especially during the enterovirus season from late spring to early fall),and herpes simplex viruses 1 and 2.
- WBC count can range from zero to several thousand depending on the etiology, and there is no reliable way to distinguish the type of infectious agent based on CSF WBC count.
- Polymorphonuclear cell predominance is typical early in the course of viral encephalitis; CSF eosinophilia should raise concern for a parasitic process.
- Elevated RBC count may be due to traumatic lumbar puncture but can also suggest HSV as the etiology. Other causes of elevated RBC count in the CSF include subarachnoid hemorrhage and acute hemorrhagic leukoencephalitis, a rare, often fatal, form of acute disseminated encephalomyelitis.
- Protein concentration is typically normal to minimally elevated with viral encephalitis but may be significantly elevated with other organisms, in particular with bacterial or tuberculous meningoencephalitis.
- Glucose concentration is also typically initially normal (compared to systemic glucose concentration) with viral encephalitis but may be significantly decreased with bacterial or tuberculous meningoencephalitis.
Additional microscopic, culture, PCR or serologic analysis of CSF may be helpful if history and physical exam findings raise suspicion for specific organisms, and PCR or serologic studies of peripheral blood should be considered similarly (see Table II). In general, a 4-fold rise in specific IgG titer between acute and convalescent serum samples is considered supportive of infection with a particular agent.
Viral cultures should be performed on blood, stool, and throat swab from any patient with suspected viral encephalitis of undetermined etiology. PCR or antigen detection assays of upper respiratory specimens can also provide supportive evidence of active or recent infection with respiratory viruses (e.g., influenza, parainfluenza, adenovirus, respiratory syncitial virus, human metapneumovirus, enterovirus) as well as Mycoplasma pneumoniae (see Table II).
An electroencephalogram (EEG) should be obtained for most patients with suspected encephalitis, both to evaluate for subclinical seizure activity and to potentially elicit findings suggestive of a specific etiology. EEG findings in most patients with encephalitis are normal or show diffuse slowing, which is nonspecific.
The presence of periodic lateralized epileptiform discharges (PLEDs) is associated with HSV encephalitis but may also be consistent with seizure activity, EBV encephalitis, subacute sclerosing panencephalitis due to measles virus, or prion disease. Patients with HSV encephalitis may also have generalized slowing early, followed by focal slowing over the affected temporal lobe(s) and then progression to PLEDs.
With subacute sclerosing panencephalitis due to measles, EEG typically shows well-defined periodic complexes in synchrony with myoclonic jerks.
Would imaging studies be helpful? If so, which ones?
While computed tomography (CT) scan of the head is accomplished rapidly and is useful for ruling out mass lesions (tumor, abscess) prior to lumbar puncture, it is relatively insensitive for detection of subtle inflammatory changes most commonly associated with encephalitis. Normal findings or nonspecific areas of increased radiodensity are the most frequent results of CT scan.
Magnetic resonance imaging (MRI) of the brain is more time consuming than CT scan and often requires sedation in children; however, MRI is more sensitive than CT scan and should be included in the evaluation of suspected encephalitis whenever available and practical.
The likelihood of findings increases with use of T2-weighted imaging, fluid attenuated inversion recovery (FLAIR), and diffusion-weighted imaging. In many cases, MRI demonstrates normal results or diffuse, subtle inflammatory changes that support the diagnosis of encephalitis but do not suggest a specific etiology. Several distinct patterns of brain inflammation have been described in association with particular organisms, but these are not necessarily universal or pathognomonic:
- With herpes simplex virus encephalitis (HSV), MRI characteristically shows involvement of the medial temporal lobes, inferior frontal cortex, and insula. The association of temporal lobe abnormalities with HSV is the strongest among all described MRI findings and is often used to establish a presumptive diagnosis, even in the setting of negative PCR results from CSF. In neonates, however, it is more common to see widespread involvement of the periventricular white matter with sparing of the temporal lobes and frontal cortex. In older infants with HSV encephalitis, MRI may demonstrate yet another pattern involving the cortex and adjacent white matter of the cerebral hemispheres.
- Involvement of the basal ganglia, brain stem, and thalami has been associated with encephalitis due to West Nile virus, Eastern equine encephalitis virus, Japanese encephalitis virus, and enterovirus 71.
- Varicella zoster encephalitis may be associated with cerebral large vessel arteritis, ischemic or hemorrhagic infarctions, and periventricular enhancement.
- The characteristic cysts of neurocysticercosis can be identified by either CT scan or MRI, but only MRI will demonstrate the pericystic inflammatory changes that coincide with clinical symptoms.
- CNS toxoplasmosis in patients with AIDS is associated with multiple ring enhancing lesions on MRI.
- Post-infectious encephalitis is most often associated with increased T2 signal in white matter, consistent with oligodendrocyte involvement.
- With acute disseminated encephalomyelitis (ADEM), MRI typically reveals multifocal white matter lesions in the brain and spinal cord. In contrast to ADEM, MRI findings with multiple sclerosis (which can present in a similar fashion) are more likely to be smaller (< 4cm), have sharply demarcated borders, and involve the corpus collosum. In children with suspected HSV encephalitis, CT findings of temporal lobe lesions within the first 1-2 days of symptoms should also raise concern for acute hemorrhagic leukoencephalitis, a rare, often fatal, form of ADEM.
Head ultrasonography in neonates and infants can be useful to detect intracranial calcifications that may occur with central nervous system involvement of congenitally acquired cytomegalovirus (periventricular distribution), HSV (diffuse distribution), or toxoplasmosis (diffuse distribution with or without hydrocephalus).
Single photon emission computed tomography (SPECT) may be useful for detecting abnormalities in situations where HSV encephalitis is strongly suspected but MRI is normal and electroencephalography is nondiagnostic. SPECT imaging requires intravenous infusion of a radionuclide (Tc 99m hexamethylpropyleneamine oxime seems to be most sensitive) and is generally less accessible compared to other imaging modalities.
If you are able to confirm that the patient has encephalitis, what treatment should be initiated?
Children with encephalitis often require complex, high-level care, and admission to an intensive care unit is usually appropriate.
The primary concern for any child with altered mental status is airway protection. Patients who are unable to maintain a patent airway or who are in imminent danger of losing airway protective capacity (in general Glasgow Coma Score < 8) should have an artificial airway placed following rapid sequence induction (RSI) and will typically require mechanical ventilation. The choice of RSI agents and artificial airway (usually intubation with an oral endotracheal tube) will depend on the specific circumstances of the clinical presentation, differential diagnosis, and experience and comfort level of the practitioner.
Patients who present with or develop seizure activity should be treated aggressively with standardized anti-epileptic therapy, usually lorazepam 0.1-0.2 mg/kg (maximum 4 mg) or with fosphenytoin 18-20 mg/kg (maximum 1000 mg) if seizures are not controlled with two rounds of lorazepam. Alternatives to fosphenytoin include phenytoin 18-20 mg/kg (maximum 1000 mg) over 20 minutes (may cause sclerosis of the veins or cardiac arrhythmias), midazolam 0.1-0.2 mg/kg load over 5 minutes followed by maintenance infusion at 0.05-0.4 mg/kg/hr), or propofol (generally requires administration by an anesthesiologist).
Close monitoring of fluid and electrolyte status is required due to the close association of encephalitis with syndrome of inappropriate anti-diuretic hormone (SIADH), as well as the frequent need for parenteral hydration and nutrition and likelihood of iatrogenically induced fluid and electrolyte perturbations.
In cases where increased intracranial pressure (ICP) is a concern, invasive ICP monitoring may be necessary. Control of increased ICP may be attempted through hyperventilation, osmotic diuretics, CSF removal, or if necessary barbiturate coma. Inflammatory cerebral edema may result in both ICP elevation and cerebral anoxia. Measures to decrease cerebral edema include hypertonic saline (2-3%), intravenous mannitol (0.25-1 g/kg of a 20% solution over 30-60 minutes, every 8-12 hours), enteral glycerol (0.5-1 mL/kg by nasogastric tube, diluted 1:3 in orange juice, every 6 hours), and intravenous dexamethasone (0.1-0.2 mg/kg initially followed by 0.05-0.1 mg/kg every 6 hours).
Dexamethasone 1 mg/kg/day (or methylprednisolone 10-30 mg/kg/day) for 3-5 days is likely to be beneficial in the treatment of post-infectious encephalitis, in particular ADEM, based on the results of observational studies. Treatment should be followed by an oral glucocorticoid taper. Dexamethasone is also beneficial for treatment of tuberculous meningoencephalitis and for controlling inflammation and encephalopathy during initial treatment of parasitic infections with CNS involvement (neurocysticercosis, African trypanosomiasis, baylisascariasis).
Conversely, dexamethasone should probably not be used when active viral infection is suspected because its anti-inflammatory activity may worsen the infection.
Other non-specific adjunctive therapies have been used for treatment of acute viral encephalidites to varying degrees of success. These include intravenous immune globulin (IVIG), interferon alpha, and plasmapheresis. Since none of these adjunctive therapies has been investigated in controlled trials, evidence to support their use routinely is lacking.
Plasmapheresis or IVIG (1-2 g/kg as a single dose or divided over 3-5 days) may be beneficial in cases of ADEM where there is no response to therapy with glucocorticoids. No studies have compared these therapies directly to glucocorticoids or to each other.
Empiric intravenous antibiotic therapy should be directed toward the most common treatable infectious etiologies and should be initiated as soon as possible, preferably following collection of CSF and other appropriate specimens for microbiologic studies. Empiric therapy should not be delayed for patients who are too clinically unstable to undergo lumbar puncture initially. Antibiotic doses will depend on the patient’s age.
Empiric antibacterial regimens for suspected bacterial meningoencephalitis are generally the same as for meningitis (see Table III). Empiric therapy should be continued until microbiologic studies provide reassuring evidence against bacterial meningoencephalitis (typically 48 hours of no bacterial growth for CSF collected prior to initiation of antibiotics).
Empiric antiviral therapy (acyclovir) should cover herpes simplex viruses. Acyclovir may be discontinued once HSV PCR of the CSF has been documented, assuming there are no other findings particularly concerning for HSV infection. If HSV PCR is positive or if HSV is still suspected despite negative PCR, duration of acycolvir therapy should be at least 21 days (longer if HSV PCR of the CSF is persistently positive).
Empiric oseltamivir therapy should be considered for all patients with recent exposure to an area where influenza virus has been active. The usual treatment duration is 5 days, but longer courses (up to 10 days) may be considered for immunocompromised patients. Regional oseltamivir resistance rates should also be considered, with alternatives being peramivir (intravenous, not FDA-approved for use in children) and zanamivir (inhaled, FDA-approved for treatment of children 7 years of age and older).
Empiric doxycycline should be strongly considered for any patient with exposure history, physical exam findings, or laboratory findings suggestive of infection with Rickettsia spp., Ehrlichia spp., or Coxiella burnetii.
Specific antimicrobial therapies exist for many of the infectious causes of encephalitis and are summarized in Table III. In general, these therapies should be initiated only when the relevant organism has been implicated as the confirmed or probable causative agent.
What are the adverse effects associated with each treatment option?
Each of the general and pathogen-specific therapies for encephalitis is associated with one or more potential toxicities. The overall list of adverse effects is too long to be discussed here in detail. Risk-benefit analyses regarding any therapy being considered for treatment of encephalitis should take into account not only the probability and potential severity of each treatment-related toxicity but also the severity of the illness, expected prognosis without treatment, and the likelihood that the therapy being considered will address the true etiology of the disease.
What are the possible outcomes of encephalitis?
The prognosis of any particular case of encephalitis is uncertain, with a few exceptions where a fatal outcome is the rule (e.g., rabies virus). For most other etiologies, potential outcomes can range from complete recovery to near-complete recovery with mild disability to partial recovery with severe disability to death. Even among similar organisms (such as arboviruses), the mortality rates and proportions of survivors with severe neurologic sequalae are quite variable and depend upon the particular virus, the age of the patient, and the acute phase clinical presentation (such as the presence of seizures).
In one retrospective study of 462 children diagnosed with encephalitis over 20 years, infants younger than 1 year were 5-fold more likely to die or have severe neurologic damage than are older children. Children who were unconscious prior to admission were 25-fold more likely to die or have severe neurologic damage compared to children who had a normal level of consciousness. Particular organisms were associated with higher likelihood of death or severe neurologic damage compared to all other identified organisms, including HSV (nearly 12-fold higher) and Mycoplasma pneumoniae (7-fold higher).
What causes this disease and how frequent is it?
Among pediatric encephalitides, viruses have historically accounted for the greatest percentage of identified pathogens, and enteroviruses represent the most commonly detected viral agents. In a 10-year survey of hospital discharge diagnoses among patients of all ages in the United States, viral encephalitis accounted for approximately 19,000 admissions and 1400 deaths.
The true epidemiology of encephalitis has only recently begun to emerge. A 7-year study of encephalitis in over 1500 patients of all ages (the California Encephalitis Project) revealed that a confirmed or probable causative infectious agent was identified in only 16% of cases. Among these cases, 69% were viral, 20% bacterial, 7% prion-related, 3% parasitic, and 1% fungal. Possible infectious etiologies were identified for another 13% of cases (6% Mycoplasma pneumoniae, 1.5% influenza, 1% adenovirus, 0.6% Chlamydia spp.), non-infectious etiologies accounted for 8% of all cases, and no etiology was identified for 63% of cases.
More recently, the Centers for Disease Control and Prevention Emerging Infections Program reported a combined analysis of data from surveillance conducted between 1997 and 2010 as part of the California Encephalitis Project and two other sites in New York and Tennessee. In this analysis of >5,000 patients of all ages, a confirmed or probable etiology was identified in only one third of cases. Perhaps the most significant finding was that among patients <30 years of age, anti-NMDA receptor auto-immune encephalitis accounted for more cases than the most commonly identified infectious agents (HSV, West Nile virus, and varicella zoster virus) combined.
In considering potential etiologies for a patient with suspected infectious or post-infectious encephalitis, important clues often arise from a careful epidemiologic history, including recent travels, activities, animal or insect exposures, sick contacts, and vaccinations. Table IV lists epidemiologic features of infectious agents associated with encephalitis.
How do these pathogens/genes/exposures cause the disease?
For acute infectious encephalitis, the unifying mechanism of pathogenesis is invasion of the causative agent into the central nervous system. For most described etiologies, the proven or presumed route of invasion is through the blood brain barrier following hematogenous dissemination from a remote site of inoculation or latency. Several pathogens are known to enter the central nervous system via retrograde transport along or within nerves. These pathogens include neurotropic viruses (herpes simplex viruses, varicella zoster virus, and rabies virus) as well as the protozoal parasite Nagleria fowleri.
Encephalitic symptoms may be caused either by direct infection of brain cells by the pathogen (as with herpes simplex, enteroviruses, arboviruses, and rabies virus) or by indirect inflammatory effects on brain cells by toxins, vascular disorders, and other processes (as with bacterial meningoencephalidities, rickettsial infections, and possibly cerebral malaria).
For post-infectious (or post-immunization) encephalitides, autoimmune demyelinating processes are thought to represent the predominant mechanism of pathogenesis. The details of these processes are not well understood, though as an example anti-GQ1b antibodies have been found in the serum of some patients diagnosed with brain stem encephalitis.
In the cases of several described etiologies (such as measles virus, Mycoplasma pneumoniae, and others), there is considerable debate about whether the pathogenesis arises from CNS invasion, post-infectious or para-infectious immunologic mechanisms, or a combination of all of these processes.
What complications might you expect from the disease or treatment of the disease?
Potential neurologic sequelae (for those who survive) include temporary or permanent impairment of intellectual, sensorimotor, psychiatric, visual, or auditory function, as well as the possibility of persistent seizure disorder.
End-organ damage as a result of the primary process or as a complication of treatment can affect any system, potentially permanently.
How can encephalitis be prevented?
Pediatric vaccines are licensed in the United States for the prevention of varicella zoster, influenza, measles, mumps, rubella, hepatitis A, hepatitis B, rotavirus, polio, rabies, Japanese encephalitis, yellow fever, Haemophilus influenzae type b, Streptococcus pneumoniae (13 serotypes), and Neisseria meningitidis (4 serogroups A, B, C, Y, and W-135).
Pre-exposure antimicrobial prophylaxis is recommended for travel to malaria-endemic areas.
Post-exposure prophylaxis (vaccine and/or organism-specific hyperimmune globulin) is recommended for susceptible individuals who have been exposed to rabies and should be considered for susceptible individuals who have been exposed to varicella zoster, hepatitis B, and cytomegalovirus.
Any animal bite wound should be aggressively decontaminated with soap and water. Antimicrobial prophylaxis with 14 days of oral valacyclovir or acyclovir should be considered for prevention of Simian herpesvirus (Herpesvirus B) following a macaque bite.
Behavioral strategies to prevent disease transmission include bednets, protective clothing, and insect repellent for arthropod-transmitted infections and consistent practice of good hand hygiene for human-transmitted infections.
Risk of peripartum HSV vertical transmission is reduced by suppressive therapy with valacyclovir or by Cesarean section delivery for women with active genital lesions. Risk of HIV vertical transmission is reduced by good virologic control in pregnant women with HAART, intrapartum AZT, and in high-risk situations antiretroviral therapy for exposed infants.
What is the evidence?
Most of the recommendations for diagnosis and generalized management of encephalitis are based on opinions of respected authorities, clinical experience, descriptive studies, or reports of expert committees. Several of the specific antimicrobial treatment recommendations, plus the recommendation for MRI imaging, are based on the results of one or more clinical trials.
For full details of the evidence underlying encephalitis management recommendations, please refer to the Infectious Diseases Society of America’s clinical practice guidelines:
Tunkel, AR, Glaser, CA, Bloch, KC. “The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America”. Clin infect Dis. vol. 47. 2008. pp. 303-27.
Cherry, J.D., Shields, W.D., Bronstein, D.E., Feigin. “Cherry’s textbook of Pediatric Infectious Diseases, 6th Edition”. 2009. (An excellent comprehensive review of the epidemiology, pathogenesis, diagnosis, and management of pediatric encephalitis.)
For recent data on the epidemiology of pediatric encephalitis in the United States, please refer to the 3 articles below:
Bloch, KC, Glaser, CA. “Encephalitis Surveillance through the Emerging Infections Program, 1997-2010”. Emerg Infect Dis. vol. 21. 2015. pp. 1562-7. (Emerging Infections Program prospective study.)
Glaser, CA, Honarmand, S, Anderson, LJ. “Beyond viruses: clinical profiles and etiologies associated with encephalitis”. Clin Infect Dis. vol. 43. 2006. pp. 1565-77. (California Encephalitis Project prospective study.)
Khetsuriani, N, Holman, RC, Anderson, LJ. “Burden of encephalitis-associated hospitalizations in the United States, 1988-1997”. Clin Infect Dis. vol. 35. 2002. pp. 175-82. (Retrospective review of National Hospital Discharge data from 1988-1997.)
Specific recommendations for prevention and treatment of individual pathogens associated with encephalitis, including pre-exposure and post-exposure immunoprophylaxis and chemoprophylaxis, are available in the current edition of the AAP Red Book.
Dean, NP, Carpenter, JL, Campos, JM, DeBiasi, RL. “A Systematic Approach to the Differential Diagnosis of Encephalitis in Children”. J Ped Infect Dis. vol. 3. 2014. pp. 175-179. (This journal article outlines the common and uncommon infectious and non-infectious etiologies of encephalitis in children and presents a diagnostic algorithm for use in clinical practice.)
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- OVERVIEW: What every practitioner needs to know
- Are you sure your patient has encephalitis? What are the typical findings for the disease?
- What other disease/condition shares some of these symptoms?
- What caused this disease to develop at this time?
- What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
- Would imaging studies be helpful? If so, which ones?
- If you are able to confirm that the patient has encephalitis, what treatment should be initiated?
- What are the adverse effects associated with each treatment option?
- What are the possible outcomes of encephalitis?
- What causes this disease and how frequent is it?
- How do these pathogens/genes/exposures cause the disease?
- What complications might you expect from the disease or treatment of the disease?
- How can encephalitis be prevented?