The epidemiological and neurological risk factors of Japanese encephalitis virus in the population of Assam, Northeast India

Japanese encephalitis is one of the world's most common public health issues, particularly it is prevalent in the north-eastern Indian states of Assam. This study aimed to find out the risk factors linked to clinical and epidemiological characteristics. A total of 245 cases were found as PCR-positive in Assam. The most common clinical symptoms were fever (87%), seizure (65%), altered sensorium (60%), cold with shivering (74%), vomiting (68%), throat irritation (31%), cough (67%), chest pain (10%), joint pain (18%), mouth ulcer (18%), diarrhea (29%), pain in the abdomen (42.9%), runny nose (64%), redness in eyes (78%), jaundice (25%), and blood in the sputum (25%).   Further, the neurological symptoms included vision problems (66.5%), hearing difficulties (55 %), neck stiffness (62%), limb numbness (65%), dizziness (77%), headaches (75.5%), speaking difficulties (63%), hydrophobia (47%), and abnormal behavior (66%). The epidemiological risk factors included contact with pigs (57%), bats (21%), cattle (32%), and rates (66%). In addition, 24.5% of patients observed the death of animals/birds. The protection measure included window screening, sleeping under a mosquito net, and use of insect repellent while sleeping in open compounds (29%) and floods (63%) are considered important risk factors. JE-positive cases include daily habits like working in agriculture fields (28%), in standing water (16%), swimming in nearby lakes (24%), traveling outside their village (40%), and wearing shirts while working in the field (20%), storing water in open containers in or outside the house (62%). These were the epidemiological factors that affected the abundance of the potential mosquito vectors of the JE infection

Detection of Nucleoside/Nucleotide Drug Resistant Mutants in Liver Cancer Cases: An Experience from India

Abstract Use of nucleoside and nucleotide analogues to treat patients infected with hepatitis B virus (HBV) has been found to be associated with mutations in the polymerase gene of the virus. The current study was carried out in HBV-related hepatocellular carcinoma (HCC) cases to trace the presence of drug-related mutants. A total of 75 HBV-related HCC cases were included for the study as per Bruix et al., 2001 EASL guidelines. HBV viral DNA was isolated by the previously standardized manual phenol-chloroform methods. The 3.2 kb genome of HBV was amplified by six sets of overlapping primers. The amplicons were sequenced commercially [Macrogen, South Korea (ABI PRISM)]. Sequences for the polymerase gene were analyzed using commercial bioinformatics software (http://www.hepseq.org/Public/Tool/annotator_tool.php). The different drug-resistant mutations detected were confirmed twice, ahead of reporting. Four drug-resistant mutations were detected in total: L80I (lamivudine), N236T (adefovir), I169T (entecavir) and A181V (lamivudine/adefovir). Interestingly, all four of the drug-resistant mutants were found in genotype D of HBV. The low number (only four) of drug-resistant mutations detected in this study population can be attributed to the fact that most of the cases were not treated and presented late. This study's findings confirm the presence of previously reported drug-resistant mutations in the HBV genome infecting Indian patients; however, its associations with late stage disease and with the virus genotype D, in particular, need to be further studied in a larger population

Does classical immunity acquired by the subcontinent population become advantageous to manage COVID-19 due to the low rate of mortality?

The global pandemic due to the COVID-19 has severely affected the entire world risking human life and economy. Every possible attempt becomes inadequate in controlling the disease as the number rising each passing day. Indeed, a highly populated country like India has so far successful in mitigating the outbreak within the country. Meanwhile, the strategy based on a preliminary model of assumption with massive awareness program on social (physical) distancing, compulsory wearing of a mask and nationwide lockdown might have contributed immensely to controlling such an emergency. However, the influence of the immune-competent genetic architecture of the Indian racing population and comparatively a dominant young age group population cannot be ruled out completely. Moreover, a suitable environment for viral propagation and characteristics of viral strain are other such factors that simultaneously could add a real scientific justification. However, the current global scenario indicating the countries with higher median age are severely affected compared to the Indian and African subcontinent thereby survived an outbreak with a low mortality rate. At the same time, we never claimed for complete immunity for the COVID-19 depending on age or immunity. The increased incidence of positive cases might slowly also increase the death rate within India, but so far recorded low compared to other parts of the globe.&nbsp;</p

Toll-like receptor 2-mediated downstream cytokine levels as determinant of malaria pathogenesis

Background & objectives: Toll-like receptors (TLRs) are transmembrane proteins that recognize specific molecular patterns and activate downstream cytokine production usually for the eradication of invading pathogens. The objective of this study was to evaluate the genetic polymorphism of TLR2 Arg753Gln (rs 5743708) and soluble cytokines and TLR2 expression levels in malaria disease cases. Methods: The study included prospectively collected 2 ml blood samples from 153 individuals clinically suspected for malaria and confirmed by microscopy and RDT from Assam. Stratification of the study groups was done as healthy control (HC, n=150), uncomplicated malaria (UC-M, n=128) and severe malaria (SM, n=25). The PCR-restriction fragment length polymorphism (RFLP) method was applied for the analysis of TLR2 Arg753Gln polymorphism and following the ELISA for soluble serum TLR2 (sTLR2) and its associated downstream cytokines, viz. tumour necrosis factor (TNF)-α and interferon (IFN)-γ levels. Results: Variation in TLR2 Arg753Gln gene showed no association with the susceptibility and the severity of malarial infection. Soluble TLR2 expression was significantly higher in uncomplicated malaria (UC-M) cases compared to healthy controls (P=0.045) and in terms of SM cases, the expression was also found to be higher in UC-M cases (P=0.078). The TNF-α expression was significantly higher in SM cases compared to both UC-M and control (P=0.003 and P=0.004). Similarly, significantly elevated expression of IFN-γ was noted in SM cases compared to both UC-M (P=0.001) and healthy controls (P<0.001). Interpretation & conclusions: The present study suggests the association of deregulated TLR2 pathway that leads to the deleterious downstream immune response in the development of malarial pathogenicity

Evaluation of adefovir & lamivudine in chronic hepatitis B: Correlation with HBV viral kinetic, hepatic-necro inflammation & fibrosis

Background &amp; objectives : Chronic hepatitis B is an important cause of morbidity and mortality. We conducted a study comparing the efficacy of adefovir and lamivudine with respect to their impact on serum and hepatic viral DNA clearance, and improvement in hepatic necro-inflammatory score, in naive patients of chronic hepatitis B. Methods: This prospective randomized pilot study was conducted in Lok Nayak Hospital, New Delhi, involving 30 patients of chronic hepatitis B (both e antigen positive and negative); 15 were randomly selected to receive either adefovir or lamivudine for a period of 6 months. Quantification of serum and hepatic HBV DNA levels was done by real time PCR and liver biopsy was done at the beginning and end of 6 months. Results: Serum ALT was elevated to 2 or more times normalized in both the groups. In the adefovir group, two patients became HBeAg negative. In the lamivudine group, one patient became HBeAg negative. After therapy HBV DNA was negative in 26.7 per cent patients from adefovir group and 13.3 per cent patients from lamivudine group. Serum HBV DNA levels were correlated with the hepatic levels before therapy (r=0.843; P&#60;0.001) and after therapy (r=0.713, P&#60;0.001) showing strong correlation. There was a median reduction of 1.92 and 2.06 log copies per ml in serum HBV DNA load after adefovir and lamivudine therapy, respectively. The mean reduction in the histotogy activity index (HAI) score was 2 and 1.53, fibrosis score was 2.33 and 3.06 after adefovir and lamivudine therapy respectively. Interpretation &amp; conclusions : Adefovir and lamivudine treatment caused biochemical and serological improvement when administered for about 6 months with significant reduction in HBV DNA, serum and hepatic viral load without completely clearing the virus from either serum or liver. It also helped in reduction of the necro-inflammatory and fibrosis score of patients with chronic hepatitis B. Our study also showed significant correlation between serum and hepatic HBV DNA levels both before and after therapy. There was not enough evidence to show therapeutic advantage of one drug over the other in any of the parameters measured

Association of Toll-like Receptor 9 (TLR9) Alterations in Malaria Susceptibility and Severity: ATribal Population Based Study in the Malaria Endemic State of Assam, India

Background: Toll-like receptors (TLRs) are group of trans-membrane proteins that recognizes specific molecular pattern and activates the downstream cytokines for the efficient clearance of pathogens. Objectives: To evaluate the role of TLR9 1486T/C polymorphism and its association with the malarial pathogenicity and severity. Material and Methods: Present study was a cohort based study and a total number of 150 samples were drawn from three major tribal population group's viz., Karbi, Dimasa and Boro- Kachari. TLR9 (1486T/C) gene polymorphism was assessed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Differential TLR9 m-RNA expression was assessed using Real time PCR (RT-PCR). Results: TLR9 1486T/C genotype variant showed increased risk for the susceptibility of malarial infection (p=0.141) compared to controls. The variant genotype showed significant increased risk with susceptibility to severe malaria infection (p=0.047) compared to uncomplicated malaria (UC-M). TLR9 mRNA level expression showed up-regulation in UC-M compared to controls. Decreased TLR9 expression was found in SM cases compared to UC-M (p=0.312). Significant down-regulation of TLR9 gene was found in UC-M with variant C genotype cases compared to wild types (p= 0.039). Conclusion: Our finding indicates the association of the TLR9 gene polymorphism and linked differential expression modulation in the development of malarial pathogenicity