Acute encephalopathy syndrome (AES) is characterized by sudden onset of seizures and altered sensorium of infectious or non-infectious origin. Seasonal outbreaks of fatal hypoglycaemic AES in children, associated with eating fruit from the Sapindaceae family (e.g., ackee, litchi), have been reported globally [1,2]. Since 1995, AES outbreaks have been reported during the litchi-harvesting season from May–July in Muzaffarpur, the largest commercial litchi-producing district of Bihar, India [3]. An AES outbreak investigation in Muzaffarpur in 2014 linked known toxins hypoglycin A and α-methylene cyclopropyl glycine (MCPG) in litchi fruit to hypoglycaemic AES in children [3]. Following the 2014 outbreak, the Government of Bihar implemented community-based interventions to prevent hypoglycemia in children. They also strengthened the clinical management of hypoglycaemic seizures in public health facilities [4]. The number of AES cases and deaths declined from 2015–18, suggesting that the interventions were effective. However, in May–June 2019, AES cases increased. We conducted a descriptive epidemiological analysis of the AES cases. | | Methods | | We identified AES cases from established hospital-based surveillance in the two tertiary referral hospitals in Muzaffarpur. We defined a suspected AES case as seizures or altered sensorium in a child aged ≤15 years admitted from 1 May to 2nd July 2019. We excluded patients aged six months to 6 years who were admitted for fever and a single generalized convulsion of <15 minutes in duration and recovered consciousness within 60 minutes of seizure. We conducted a review of medical records and abstracted data using a structured tool for socio-demographics, clinical history, duration of hospitalization, treatment, and laboratory profile. We also assembled a prospective cohort of probable cases admitted to the hospital during the investigation. We defined a probable AES case as new-onset seizures or altered sensorium of <7 days duration in a child aged ≤15 years admitted t from 1 May to 2 July 2019. For the cohort of probable cases, we interviewed the caregivers using a structured clinical-epidemiological questionnaire for socio-demographics, anthropometry, illness characteristics, treatment-seeking behavior, meal assessment, exposure to litchi fruit, and exposure to health messages. For anthropometry, we calculated Z-scores using the World Health Organization 2006 standardized growth tables [5]. | | Results | | Of the 655 suspected and probable AES cases identified, the case fatality rate (CFR) was 21% (139 deaths). The median age was four years (interquartile range: 3 months–14 years), and 58% (378) were females. The first case was reported on 5 May 2019, cases peaked on 15 June, and the last case on 2 July (Figure 1). Among cases with available data, 75% (389/518) had blood glucose levels of <70 mg/dL upon hospital admission, and 75% (476/638) were residents of Muzaffarpur district. We identified cases from 15 (94%) of 16 blocks in the Muzaffarpur district and calculated a district incidence of 22 per 100,000 children ≤15 years old. | | The prospective cohort comprised 94 probable AES cases; CFR was 26%. Among probable cases, 63% (49/78) of caregivers were wage workers, and 34% (31/91) were of low socioeconomic status. Symptoms were reported in the early morning (3 am to 8 am) for 67% (62/93) of cases, and 97% (90/93) presented with seizures. Among probable cases with anthropometry data, 62% (43/69) were underweight (i.e., weight-for-age Z score <-2), 44% (25/57) stunted (i.e., height-for-age Z score <-2), and 43% (10/23) wasted (i.e., weight-for-height Z score <-2). Primary health facilities referred 46% (43/93) of probable cases to the two tertiary hospitals for admission. Among cases referred, only 30% (13/43) received hypoglycemia and seizure management at the primary health facility. | | Eating litchis in the 24 hours and seven days before illness onset was reported by 57% (54/94) and 87% (59/68) of caregivers, respectively. Skipping any meal and skipping the evening meal in the 24 hours before illness onset was reported by 55% (48/88) and 44% (28/63) of caregivers, respectively. Among probable cases, 45% (27/60) of caregivers reported Government Supplementary Nutrition (GSN) programme enrollment. Sixty percent (50/83) of caregivers said a visit by health workers in the week before illness. Still, only 8% (7/83) reported receiving messages on AES prevention and early treatment by health workers in the past month. | | Conclusions | | The 2019 AES outbreak in Muzaffarpur district, Bihar, occurred among young children with hypoglycemia upon hospital admission and had high associated mortality. Although the Government of Bihar implemented community and clinical measures to prevent AES cases after the 2014 outbreak, a large proportion of the AES cases did not benefit from the prevention measures based on our investigation [4]. New state and district health leadership, turnover of community and facility-level healthcare workers, lack of ongoing training and focused community outreach, and competing health priorities might have been factors responsible for the resurgence. To prevent future AES cases, we recommended prompt emergency management of hypoglycemia and seizures at primary health facilities before referral. We recommend enrollment of all eligible children to GSN and enhanced community health communications to reinforce the importance of an evening meal for children and limiting the eating of litchi fruit during the harvesting season from May to July

BACKGROUND: Two suspected shellfish poisoning events were reported in Cuddalore District in Tamil Nadu, India, between January and April 2015. OBJECTIVES: The study was conducted to confirm the outbreaks and to identify the source and risk factors. METHODS: For both outbreaks, a case was defined as a person with nausea, vomiting, or dizziness. Sociodemographic details and symptoms were noted down. Data were also collected in a standard 3-day food frequency questionnaire, along with a collection of clam samples. A case-control study was initiated in the April outbreak. Stool samples were collected from cases, and clam vendors were interviewed. RESULTS: In an outbreak that happened in January, all the twenty people reported to be consumed clams were diagnosed as cases (100% attack rate, 100% exposure rate). In the April outbreak, we identified 199 cases (95% attack rate). In both outbreaks, the clams were identified as genus Meretrix meretrix. The most common reported symptoms were dizziness and vomiting. The clams heated and consumed within 30-60 min. No heavy metals or chemicals were detected in the clams, but assays for testing shellfish toxins were unavailable. All 64 selected cases reported clam consumption (100% exposure rate) as did 11 controls (17% exposure rate). Illness was associated with a history of eating of clams (odds ratio = 314, 95% confidence interval = 39-512). Of the six stool samples tested, all were culture negative for Salmonella, Shigella, and Vibrio cholerae. The water at both sites was contaminated with garbage and sewage. CONCLUSION: Coordinated and timely efforts by a multidisciplinary team of epidemiologists, marine biologists, and food safety officers led to the outbreaks' containment.

OBJECTIVE: Resistance to colistin, a last resort antibiotic, has emerged in India. We investigated colistin-resistant Klebsiella pneumoniae(ColR-KP) in a hospital in India to describe infections, characterize resistance of isolates, compare concordance of detection methods, and identify transmission events. DESIGN: Retrospective observational study. METHODS: Case-patients were defined as individuals from whom ColR-KP was isolated from a clinical specimen between January 2016 and October 2017. Isolates resistant to colistin by Vitek 2 were confirmed by broth microdilution (BMD). Isolates underwent colistin susceptibility testing by disk diffusion and whole-genome sequencing. Medical records were reviewed. RESULTS: Of 846 K. pneumoniae isolates, 34 (4%) were colistin resistant. In total, 22 case-patients were identified. Most (90%) were male; their median age was 33 years. Half were transferred from another hospital; 45% died. Case-patients were admitted for a median of 14 days before detection of ColR-KP. Also, 7 case-patients (32%) received colistin before detection of ColR-KP. All isolates were resistant to carbapenems and susceptible to tigecycline. Isolates resistant to colistin by Vitek 2 were also resistant by BMD; 2 ColR-KP isolates were resistant by disk diffusion. Moreover, 8 multilocus sequence types were identified. Isolates were negative for mobile colistin resistance (mcr) genes. Based on sequencing analysis, in-hospital transmission may have occurred with 8 case-patients (38%). CONCLUSIONS: Multiple infections caused by highly resistant, mcr-negative ColR-KP with substantial mortality were identified. Disk diffusion correlated poorly with Vitek 2 and BMD for detection of ColR-KP. Sequencing indicated multiple importation and in-hospital transmission events. Enhanced detection for ColR-KP may be warranted in India.