Immunoinhibitory effects of anti-tuberculosis therapy induce the host vulnerability to tuberculosis recurrence.

The host immune responses play a pivotal role in the establishment of long-term memory responses, which effectively aids in infection clearance. However, the prevailing anti-tuberculosis therapy, while aiming to combat tuberculosis (TB), also debilitates innate and adaptive immune components of the host. In this study, we explored how the front-line anti-TB drugs impact the host immune cells by modulating multiple signaling pathways and subsequently leading to disease relapse. Administration of these drugs led to a reduction in innate immune activation and also the cytokines required to trigger protective T cell responses. Moreover, these drugs led to activation-induced cell death in the mycobacterial-specific T cell leading to a reduced killing capacity. Furthermore, these drugs stalled the T cell differentiation into memory subsets by modulating the activation of STAT3, STAT4, FOXO1, and NFκB transcription factors and hampering the Th1 and Th17-mediated long-term host protective memory responses. These findings suggest the urgent need to augment directly observed treatment, short-course (DOTS) therapy with immunomodulatory agents to mitigate the adverse effects linked to the treatment.IMPORTANCEAs a central component of TB eradication initiatives, directly observed treatment, short-course (DOTS) therapy imparts immune-dampening effects during the course of treatment. This approach undermines the host immune system by delaying the activation process and lowering the immune response. In our investigation, we have unveiled the impact of DOTS on specific immune cell populations. Notably, the signaling pathways involving STAT3 and STAT4 critical for memory responses and NFκß associated with pro-inflammation were substantially declined due to the therapy. Consequently, these drugs exhibit limited effectiveness in preventing recurrence of the disease. These observations highlight the imperative integration of immunomodulators to manage TB infection.

Phylogenetic analysis of hepatitis e virus in northwest India.

Genotyping and subtyping are important to understand epidemiology of the hepatitis E virus so as to improve control measures to prevent transmission of virus in the community. Hence, the aim of the current study was to identify the prevalent HEV genotypes in Rajasthan in acute sporadic hepatitis E cases with varying degree of liver failure. We studied hepatitis E virus (HEV) isolates from hospitalized patients in Rajasthan, western India. In a total of seventeen HEV sequences, six acute viral hepatitis, seven acute liver failure, and 4 acute- on-chronic cases were analyzed. Subtypes 1a and 1c of HEV are prevalent in Northwest India.

Contribution of hepatitis E virus in acute sporadic hepatitis in north western India.

BACKGROUND & OBJECTIVES: Hepatitis E virus (HEV) causes acute viral hepatitis. Majority of the documented studies on hepatitis E have been focused on the incidence of this disease in northern and south central India. Limited data are available on HEV infection among acute sporadic hepatitis cases in north western India. The present study was undertaken to investigate the contribution of hepatitis E virus infection in sporadic hepatitis cases in Rajasthan and neighbouring States. METHODS: Seven hundred and thirty six patients suspected to have viral hepatitis were screened for the hepatotropic viral markers, hepatitis A, B, C and E by using commercial enzyme immunoassay kits with a high sensitivity and specificity. The acute nature of HEV infection was also confirmed by the detection of HEV RNA by nested RT-PCR. RESULTS: Hepatitis E was found to be the major cause of acute sporadic viral hepatitis (49.7%) in this region of India. Mixed infections of HEV-HAV (1.2%), HEV-HBV (6.1%), and HEV-HCV (1.7%) were also detected. No viral marker was detected in 32 per cent cases. INTERPRETATION & CONCLUSION: HEV was found as the major aetiological agent of acute sporadic viral hepatitis in Rajasthan (north western India). It is important to screen primarily for all the common enterically and parenterally transmitted hepatotropic viral markers in acute sporadic viral hepatitis. There is a need to do additional serological and molecular tests to identify the aetiological agent in the cases of acute hepatitis.