• A case of AFE/ AES is defined as the acute onset of fever and a change in mental status (including symptoms such as confusion, disorientation, coma, or inability to talk) AND/OR new onset of seizures (excluding simple febrile seizures).
• The causes of AFE/AES are listed below
  - Acute bacterial meningitis
  - Acute viral encephalitis
  - Tubercular meningitis
  - Sepsis associated encephalopathy (due to systemic infections including UTI, pneumonia, enteric fever etc)
  - Cerebral malaria
  - Other pathogens: Mycoplasma, Rickettsia, Leptospira
• Non infectious causes: Reye’s syndrome, acute disseminated encephalomyelitis, metabolic/toxic encephalopathy, non convulsive status epilepticus (NCSE) and autoimmune encephalitis.
• Acute febrile encephalopathy is a medical emergency. The algorithm below details the approach towards diagnosis and management of a case of AFE/ AES in children but applies similarly to adults as well.
• Initial management includes resuscitation and stabilization based on the clinical condition followed by clinical evaluation, imaging and investigations to establish the diagnosis. Empiric therapy (may include ceftriaxone, acyclovir, doxycycline and artesunate) should be started immediately after drawing blood cultures pending results of tests. Supportive care should be continued and then therapy narrowed based on the results of investigations.

Causes of AFE with pointers to diagnosis and recommended tests

Cause	Pointers to diagnosis	Diagnostic test
Meningococcus	Petechial rash, adrenal hemorrhage	Blood and CSF cultures Latex/PCR in CSF for meningococcus
Herpes simplex virus 1 and 2	temporal lobe involvement, CSF rbc PLEDS on EEG, MRI showing temporal lobe involvement, CSF rbc	CSF HSV PCR for HSV-1 and II
HHV6, HHV 7	Rash	Specific PCR in CSF
EBV	Rash, generalized adenopathy, tonsillitis, organomegaly	EBV VCA IgM in blood EBV PCR in CSF
Varicella zoster	Antecedent rash	Varicella IgM in blood CSF varicella PCR
HIV	Fever, adenopathy, rash	HIV ELISA in blood HIV PCR in blood
Japanese encephalitis	Epidemiology, dystonic and extrapyramidal movements MRI shows changes in thalami, basal ganglia, substantia nigra	IgM antibody in serum and CSF
Measles	Antecedent or concurrent rash History of vaccination	Measles IgM in blood and CSF
Mumps	Antecedent/ concurrent parotitis, high amylase,low sugar in CSF	Mumps IgM in blood Mumps virus in CSF by PCR
Influenza	Respiratory prodrome, ongoing outbreak	Influenza PCR in throat swab
Dengue	Ongoing outbreak, rash, low WBC and platelets, biochemical hepatitis	Dengue specific PCR in CSF Dengue IgM, NS1 antigen in blood
Chikungunya	Ongoing outbreak, Rash, severe joint pains	Chinkungunya PCR in CSF Chinkungunya PCR in blood, IgM in blood
Enterovirus	Vesicular lesions in the mouth, GI symptoms, brain stem involvement	Specific PCR in CSF
Rabies	Epidemiology	Specific IgM antibody in CSF Nuchal skin biopsy/ conjunctival smears for direct fluorescent antibody Brain biopsy
Chandipura	Vesicular lesions in the mouth, GI symptoms, brain stem involvement	PCR in CSF, saliva/ IgM ELISA in CSF
Nipah	Epidemiology, contact with animals, fruit bats	PCR/ IgM ELISA in CSF
Mycoplasma	Respiratory illness, skin rash, haemolytic anemia	Mycoplasma IgM in blood Mycoplasma PCR in throat swab
Rickettsia	Epidemiology, rash, eschar, multisystem involvement	IgM & IgG antibodies in serum Scrub typhus DNA in whole blood, buffy coat, eschar/skin rash
Leptospirosis	Icterus, myalgia, renal failure	Leptospira PCR in blood Specific IgM in blood
Enteric fever	Protracted illness, hepatosplenomegaly	Blood cultures
Cerebral malaria	Pallor, splenomegaly	Smear or rapid antigen test for malaria
Sepsis associated encephalopath	Infection at extra CNS site	Blood, urine cultures, CXR, chest and abdominal CT

Empirical Treatment (must be started immediately after drawing blood cultures)

• Ceftriaxone
• Acyclovir (use in all suspected sporadic viral encephalitis)
• Artesunate (stop if peripheral smear and RDT are negative)
• Doxycyline

* If the diagnosis of HSV is made a treat for 14-21 days. Stop acyclovir if alternative diagnosis made/ if MRI imaging does not suggest HSV/if two PCR 48 hours apart are negative.
*Imaging should be done before a lumbar puncture in patients with those with focal deficit, papilloedema, immune compromised hosts and those with features of raised ICP. Other contraindications for a lumbar puncture include respiratory/ cardiovascular compromise, platelet counts of less than 30,000 or infection at the site of the lumbar puncture.