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 country's 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.

Outbreaks of unexplained neurologic illness - Muzaffarpur, India, 2013-2014.

Outbreaks of an unexplained acute neurologic illness affecting young children and associated with high case-fatality rates have been reported in the Muzaffarpur district of Bihar state in India since 1995. The outbreaks generally peak in June and decline weeks later with the onset of monsoon rains. There have been multiple epidemiologic and laboratory investigations of this syndrome, leading to a wide spectrum of proposed causes for the illness, including infectious encephalitis and exposure to pesticides. An association between illness and litchi fruit has been postulated because Muzaffarpur is a litchi fruit-producing region. To better characterize clinical and epidemiologic features of the illness that might suggest its cause and how it can be prevented, the Indian National Centre for Disease Control (NCDC) and CDC investigated outbreaks in 2013 and 2014. Clinical and laboratory findings in 2013 suggested a noninflammatory encephalopathy, possibly caused by a toxin. A common laboratory finding was low blood glucose (<70 mg/dL) on admission, a finding associated with a poorer outcome; 44% of all cases were fatal. An ongoing 2014 investigation has found no evidence of any infectious etiology and supports the possibility that exposure to a toxin might be the cause. The outbreak period coincides with the month-long litchi harvesting season in Muzaffarpur. Although a specific etiology has not yet been determined, the 2014 investigation has identified the illness as a hypoglycemic encephalopathy and confirmed the importance of ongoing laboratory evaluation of environmental toxins to identify a potential causative agent, including markers for methylenecyclopropylglycine (MCPG), a compound found in litchi seeds known to cause hypoglycemia in animal studies. Current public health recommendations are focused on reducing mortality by urging affected families to seek prompt medical care, and ensuring rapid assessment and correction of hypoglycemia in ill children.

Bio-detoxification of phorbol esters and other anti-nutrients of Jatropha curcas seed cake by fungal cultures using solid-state fermentation.

Jatropha seed cake, a byproduct after biodiesel extraction, has several anti-nutrients and toxins. Solid-state fermentation was carried out for the detoxification of the Jatropha seed cake (JSC) using different fungal cultures. The reduction in the anti-nutritional components such as tannins, phytates, saponins, lectin and protease inhibitor, and phorbol esters on 6th, 9th, and 12th day of fermentation was analyzed. The phorbol ester content in the unfermented JSC was 0.83 mg/g, and the maximum degradation of phorbol esters to the extent of 75% was observed in the case of JSC fermented with Cunninghamella echinulata CJS-90. The phytate degradation in the fermented JSC was in the range of 65-96%. There was a gradual reduction of saponin content in the JSC from 6th to 12th day, and the reduction of saponin was in the range of 55-99% after solid-state fermentation. The trypsin inhibitor activity and lectin were 1,680 trypsin inhibitor units (TIU) per gram and 0.32 hemagglutinating unit in the unfermented JSC, respectively. Trypsin inhibitor activity and lectin could not be detected in JSC after 12th day of solid-state fermentation. Tannins accounted for 0.53% in unfermented JSC, and there was a marginal increase of tannins after solid-state fermentation. The results indicate that biological detoxification could be a promising method to reduce anti-nutritional compounds and toxins in the JSC.

High-resolution MRI evaluation of neonatal brachial plexus palsy: A promising alternative to traditional CT myelography.

BACKGROUND AND PURPOSE: Despite recent improvements in perinatal care, the incidence of neonatal brachial plexus palsy remains relatively common. CT myelography is currently considered to be the optimal imaging technique for evaluating nerve root integrity. Recent improvements in MR imaging techniques have made it an attractive alternative to evaluate nerve root avulsions (preganglionic injuries). We aim to demonstrate utility of MR imaging in the evaluation of normal and avulsed spinal nerve roots. MATERIALS AND METHODS: All study patients with clinically diagnosed neonatal brachial plexus palsy underwent MR imaging by use of a high-resolution, heavily T2-weighted (driven equilibrium) sequence. MR imaging findings were reviewed for presence of nerve root avulsion from C5-T1 and for presence of pseudomeningocele. The intraoperative findings were reviewed and compared with the preoperative MR imaging findings. RESULTS: Thirteen patients (9 male, 4 female) underwent MR imaging; 6 patients underwent nerve reconstruction surgery, during which a total of 19 nerve roots were evaluated. Eight avulsions were noted at surgery and in the remainder, the nerve injury was more distal (rupture/postganglionic injury). Six of the 8 nerve root avulsions identified at surgery were at C5-6 level, whereas 1 nerve root avulsion was identified at C7 and C8 levels, respectively. The overall sensitivity and specificity of MR imaging for nerve root avulsions was 75% and 82%, respectively. CONCLUSIONS: Our preliminary results demonstrate that high-resolution MR imaging offers an excellent alternative to CT myelography for the evaluation of neonatal brachial plexus palsy with similar sensitivity compared with CT myelography.

Fish diversity with relation to water quality of Bhadra River of Western Ghats (INDIA).

Water quality assessment and freshwater fish diversity of Bhadra river, Western Ghats, Karnataka was examined. River water was clear except at one station (BV Site) with rocky and sandy substrate. The mean water quality of study sites were as following, pH 6.98, air temperature 22.66 degrees C, water temperature 20.16 degrees C, dissolved oxygen 8.74 mg/l, total hardness 27 mg/l, alkalinity 48 mg/l (as CaCO(3)), conductivity 135.5 mhos/cm, COD (15.16 mg/l), and BOD (3.78 mg/l), respectively. Altogether, 56 species of fish representing 31 genera and 15 families were recorded. The Cyprinid family was dominant in the present study. Various diversity index packages have been used to assess the fish diversity. Fish diversity is also correlated with physicochemical variables.

PCR-restriction fragment length analysis of aflR gene for differentiation and detection of Aspergillus flavus and Aspergillus parasiticus in maize.

Contamination of food and feedstuffs by Aspergillus species and their toxic metabolites is a serious problem as they have adverse effects on human and animal health. Hence, food contamination monitoring is an important activity, which gives information on the level and type of contamination. A PCR-based method of detection of Aspergillus species was developed in spiked samples of sterile maize flour. Gene-specific primers were designed to target aflR gene, and restriction fragment length polymorphism (RFLP) of the PCR product was done to differentiate Aspergillus flavus and Aspergillus parasiticus. Sterile maize flour was inoculated separately with A. flavus and A. parasiticus, each at several spore concentrations. Positive results were obtained only after 12-h incubation in enriched media, with extracts of maize inoculated with A. flavus (101 spores/g) and A. parasiticus (104 spores/g). PCR products were subjected to restriction endonuclease (HincII and PvuII) analysis to look for RFLPs. PCR-RFLP patterns obtained with these two enzymes showed enough differences to distinguish A. flavus and A. parasiticus. This approach of differentiating these two species would be simpler, less costly and quicker than conventional sequencing of PCR products.

Induction of colony morphology variation in Rhodotorula gracilis by UV irradiation.

Nonlethal UV irradiation induced an unusually high frequency of colony morphology variation in Rhodotorula gracilis. The variation was not fixed but indicated further variability in subsequent platings. Microscopic examination of the cultures indicated that UV-irradiated variants had grossly varying types of shapes and arrangements of cells in contrast to the uniformly shaped and budding cells of the nonirradiated culture. Flow-cytometric analysis of a colony variant suggested a slightly higher proportion of cells with variable DNA content than the nonirradiated culture. Extensive biochemical characterization revealed only one difference in that the nonirradiated culture had a partial requirement for pantothenate while the colony variant was completely independent of this requirement. We speculate that UV triggers a yet unstudied means of variability in R. gracilis with possible accompanying recombinational events.