Muzaffarpur district, suffers repeated epidemics of acute encephalopathy
in children for the past 16-17 years. An outbreak of this mystery
disease, with high case fatality (63.3%) was reported in children from
Muzaffarpur district, Bihar, in June 2011. We report here our findings
of the investigations carried out to confirm the etiology and to
describe the clinico-epidemiological features.
Clinically, the presentation indicated Acute
encephalitis syndrome (AES). We studied 80 children from age group of
2-10 (median, 3.5) years belonging to low socioeconomic background.
Almost all cases were from rural area. Following clinical criteria were
used to select a case of AES: Rapid onset of unconsciousness in a
previously healthy child after attack of convulsion, and presence of
fever >40°C.
The main presenting features were fever and
convulsions (100%), unconsciousness (100%), decerebrate rigidity (50%),
tachycardia (80%), tachypnea (80%), and absent splenomegaly. The CSF was
normal but under raised pressure (100%). Hematological investigations
revealed leucocytosis with neutrophil predominance (80%). Biochemical
investigation revealed hyponatremia (90%), hypokalemia (5%), mild raised
SGPT (50-100IU/L) (30%), mild raised blood urea (40-50mg/dL) (40%), and
normal creatinine. Smears for malarial parasites were negative. CT scan
was done in 8 cases; two showed feature of cerebral edema, rest was
normal. ECG showed non-specific ST changes and tachyarrhythmia
The requisite clinical samples were collected from 55
patients and sent to National Institute of Virology, Pune and National
Communicable Disease Center, New Delhi for virological testing. These
included 31 CSF samples, 59 serum samples, 19 nasal swabs, 48 throat
swabs, 44 rectal swabs, 2 urine samples, 2 postmortem brain needle
biopsy material by nasal route, and 1 postmortem liver biopsy specimen.
All clinical samples were negative for known virus causing acute
encephalitis like JE, Nipah, West Nile and chandipura virus. Some
specimens were processed for the discovery of novel agents. However, no
agent has been found which can be attributed to the cause of the mystery
disease in Muzaffarpur [1].
The presentation, seasonal distribution, climatic
condition and investigations of the cases did suggest a diagnosis of
encephalopathy of heat stroke (HS), as similar picture has been
described in few other studies also [2,3]. Between April and June, the
climate of Muzaffarpur is extremely hot and humid (28/40°C, 90%
humidity) and most epidemics occurred at the height of temperature
(38-40°C) and humidity (70%-80%) suggesting the possibility of HS. The
number of cases suddenly decreases with the onset of rain and resultant
sudden drop in temperature.
Heat stroke is a life threatening medical emergency –
defined clinically as core temperature >40.6°C accompanied by central
nervous system dysfunction. It is a diagnosis of exclusion. After other
similar entities such as drug withdrawal syndrome, neuroleptic malignant
syndrome, septicemia, cerebral malaria, CNS infection, thyroid storm,
drug toxicity (anticholinergic) have been excluded [2]. Despite the
advances in last 50 years, mortality due to heat stroke continues to be
as high as 10-50% [3]. Since Japanese encephalitis (JE) occurs in many
parts of India, especially in outbreaks, physician and investigators
have a focus on JE virus. This has not been wasteful but distracts
investigators from other possible explanations and etiologies. Thus, the
mystery of undiagnosed outbreaks persists [4,5]. Neuro-pathological
study of 15 cases of autopsy of brain, conducted by ICMR during 1967 and
1968, failed to provide any stigmata of encephalitis, but confirms the
presence of "encephalopathy", caused by high environmental temperature
per se or secondarily in association with other endogenous cause
[6].
The disease entity has been occurring in months of
May-June every year in this district of since 1995. The causative
factors and mechanism, which is triggering the disease every year in
this region, needs a systemic epidemiological study. For the interim,
awareness on prevention of heat stroke may possibly contribute to a
reduction in the number of affected children.
References
1. National Institute of Virology. Report on
investigation of an outbreak of acute encephalitis syndrome (AES) in
Muzaffarpur, Bihar. Director, National Institute of Virology, Pune.
NIV/MCC/EPD/755, November 23, 2011.
2. Srimachari S. Heat hyperpyrexia: time to act.
Indian Med Res. 2004;119:VII-X.
3. Kuan-Che Lu, Tzong-Luen Wang. Heat stroke. Ann
Disaster Med. 2004;2:97-109.
4. George K. Investigating outbreaks of uncertain
etiologies. Indian J Med Res. 2007;125:505-7.
5. Kumar S. Inadequate research facilities fail to
tackle mystery disease. BMJ. 2003;326:12.
6. Sriramachari S, Patoria NK. Pathology of acute
encephalopathy syndrome in children in summer. Indian J Med Res.
1976;64:296-313.