An Update on JE Vaccine Development and Use

Japanese encephalitis (JE) is an emerging and re- emerging arboviral infection of global significance. Its causative agent Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis in Asia, Southeast Asia and Pacific. Nearly 3 billion people living in JE endemic areas account for 10000- 15000 deaths annually. The disease has high fatality rate (~30%) and nearly 50% survivors develop permanent neuropsychiatric sequelae. There is no specific treatment for JE. Vaccination is the only effective strategy available for prevention and control of JE. The wider availability and inclusion of JE vaccination in the national immunization programme in many of the affected countries have resulted in better prospects for control of JE. This review is an update on vaccines currently available, their development, recommended immunization schedule for them as well as the upcoming challenges related with cross- protectivity against hetrologous genotypes

Molecular Epidemiology and Sequence Analysis of Rabies Virus Isolates from North and North East India

In the present study phylogenetic analysis of 30 rabies virus (RV) isolates collected from North and North East India between 2013 and 2016 was carried out. Analysis of two sets of sequence of non-coding G-L intergenic region, based upon a 132-nucleotide region of the cytoplasmic domain (CD) of the G gene (G-CD) and a 549-nucleotide (Psi-L) was done. The phylogenetic tree constructed using 549 nucleotide sequence of hyper variable region (Psi-L) showed the same topology as that obtained on the basis of 132 nucleotide sequence of G-CD region. Four different genetic clusters (GCs) distributed among three geographical regions were identified. Comparison of deduced amino acid (aa) sequences showed four amino acid changes - aa462G, aa465H/R and aa468K in G-CD region. The change observed at position aa465R indicated the spillover of Indian wild strain (mongoose) to domestic animals in Delhi region. The homology among the Indian RV isolates shared >97% nucleotide similarity irrespective of their geographical regions and hosts. The study revealed that the RV isolates are region specific, not host specific and all belonged to genotype 1

Phylogenetic studies reveal existence of multiple lineages of a single genotype of DENV-1 (genotype III) in India during 1956–2007

<p>Abstract</p> <p>Background</p> <p>Dengue virus type 1 (DENV-1) have been mostly circulating silently with dominant serotypes DENV-2 and DENV-3 in India. However recent times have marked an increase in DENV-1 circulation in yearly outbreaks. Many studies have not been carried out on this virus type, leaving a lacunae pertaining to the circulating genotypes, since its earliest report in India. In the present study, we sequenced CprM gene junction of 13 DENV-1 isolated from Delhi and Gwalior (North India) between 2001–2007 and one 1956 Vellore isolate as reference. For comparison, we retrieved 11 other Indian and 70 global reference sequences from NCBI database, making sure that Indian and global isolates from all decades are available for comparative analysis.</p> <p>Results</p> <p>The region was found to be AT rich with no insertion or deletion. Majority of the nucleotide substitutions were silent, except 3 non-conservative amino acid changes (I → T, A → T and L → S at amino acid positions 59,114 and 155 respectively) in the Indian DENV-1 sequences, sequenced in this study. Except two 1997–98 Delhi isolates, which group in genotype I; all other Indian isolates group in genotype III. All Indian genotype III DENV-1 exhibited diversity among them, giving rise to at least 4 distinct lineages (India 1–4) showing proximity to isolates from diverse geographic locations.</p> <p>Conclusion</p> <p>The extensive phylogenetic analysis revealed consistent existence of multiple lineages of DENV-1 genotype III during the last 5 decades in India.</p

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

Scrub typhus meningitis from Urban Delhi – An atypical presentation

Scrub typhus, a mite-transmitted zoonosis is caused byOrientiatsutsugamushi. It is transmitted by the larval mites (chiggers) of theLeptotrombidiumdeliensegroup.Clinical manifestations vary from acute febrile illness to multiple organ dysfunction syndrome. Neurological involvement is also seen.3,4 We report a case of scrub typhus from North Delhi which presented as acute febrile illness with meningitis, without eschar