Aakash Shrivastava

Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study.

BACKGROUND Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute neurological illness with high mortality among children occur annually in Muzaffarpur, the countrys largest litchi cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness. METHODS In this hospital-based surveillance and nested age-matched case-control study, we did laboratory investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood, cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness were expressed as matched odds ratios and odds ratios (unmatched analyses). FINDINGS Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched odds ratio [mOR] 9·6 [95% CI 3·6 - 24]) and absence of an evening meal (2·2 [1·2-4·3]) in the 24 h preceding illness onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis on illness (odds ratio [OR] 7·8 [95% CI 3·3-18·8], without evening meal; OR 3·6 [1·1-11·1] with an evening meal). Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in 48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12·4 μg/g to 152·0 μg/g and MCPG ranged from 44·9 μg/g to 220·0 μg/g. INTERPRETATION Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations, underscoring the importance of using systematic methods in other unexplained illness outbreaks. FUNDING US Centers for Disease Control and Prevention.

Kyasanur Forest Disease Outbreak and Vaccination Strategy, Shimoga District, India, 2013–2014

We investigated a Kyasanur Forest disease outbreak in Karnataka, India during December 2013–April 2014. Surveillance and retrospective study indicated low vaccine coverage, low vaccine effectiveness, and spread of disease to areas beyond those selected for vaccination and to age groups not targeted for vaccination. To control disease, vaccination strategies need to be reviewed.

Lychee-associated acute hypoglycaemic encephalopathy outbreaks in Muzaffarpur, India – Author's reply

www.thelancet.com/lancetgh Vol 5 September 2017 e861 to hypoglycin A and MCPG toxicity in cases but not controls, provided the conclusive data to confirm the lychee– hypoglycin A–MCPG hypothesis. During prospective surveillance, we used a highly sensitive case definition to ensure that all potential cases were captured. This is not unusual in investigations of unexplained, severe illnesses, and also helped to ensure patients received appropriate and prompt clinical management. If there had been misclassification between cases and controls, as Das and John suggest, the significant associations identified between lychee consumption, absence of evening meal, and illness would have, at worst, been biased toward the null. Both case-patients and controls were residents of villages in the Muzaffarpur district—ie, the same community. Controls were identified among children who were admitted to the same hospitals where case-patients were admitted. The presence of lychee orchards and agricultural fields, and the availability of lychees were ubiquitous in the Muzaffarpur villages where both case-patients and controls lived. It was with these data, and after a multisectoral meeting of stakeholders from district-level, state-level, and national-level agencies in February, 2015, that the Director General of Health Services, Government of India, issued official recommendations to the Government of Bihar to encourage parents and carers in the affected Muzaffarpur area to minimise children’s lychee consumption and ensure they eat an evening meal, and to re-emphasise the need for clinicians to rapidly test for, and correct, hypoglycaemia among children with suspected illness. After this, the NCDC and, more broadly, the Ministry of Health and Family Welfare, and the Ministry of Women and Child Development have continued to support the Government of Bihar’s response to the Muzaffarpur outbreaks in 2015 and 2016, and Lychee-associated acute hypoglycaemic encephalopathy outbreaks in Muzaffarpur, India