Extracellular vesicles (EV) secreted by pathogens function in a variety of biological processes. Here, we demonstrate that in the protozoan parasite Trypanosoma brucei, exosome secretion is induced by stress that affects trans-splicing. Following perturbations in biogenesis of spliced leader RNA, which donates its spliced leader (SL) exon to all mRNAs, or after heat-shock, the SL RNA is exported to the cytoplasm and forms distinct granules, which are then secreted by exosomes. The exosomes are formed in multivesicular bodies (MVB) utilizing the endosomal sorting complexes required for transport (ESCRT), through a mechanism similar to microRNA secretion in mammalian cells. Silencing of the ESCRT factor, Vps36, compromised exosome secretion but not the secretion of vesicles derived from nanotubes. The exosomes enter recipient trypanosome cells. Time-lapse microscopy demonstrated that cells secreting exosomes or purified intact exosomes affect social motility (SoMo). This study demonstrates that exosomes are delivered to trypanosome cells and can change their migration. Exosomes are used to transmit stress signals for communication between parasites. Trypanosomes are the causative agent of major parasitic diseases such as African sleeping sickness, leishmaniosis and Chagas' disease that affect millions of people. These parasites cycle between an insect and a mammalian host. Communication between the parasites and the host must be essential for executing a productive infection and for cycling of the parasite between its hosts. Exosomes are 40-100nm vesicles of endocytic origin, and were shown to affect a variety of biological processes and human diseases. Exosomes were also shown to help pathogens evade the immune system. In this study, we demonstrate that exosomes are secreted from Trypanosoma brucei parasites when trans-splicing is inhibited. These exosomes contain, among many other constituents, a type of RNA known as spliced leader RNA (SL RNA), which is essential in these parasites for formation of all mature mRNA. These exosomes are able to enter neighboring trypanosomes, and only intact exosomes affect the social motility of these parasites. We propose that exosomes can potentially control parasite migration in the insect host by acting as a repellent that drives the fit parasites away from either damaged cells or an unfavorable environment. This mechanism could secure a productive infection.

Melioidosis, caused by Burkholderia pseudomallei, is a potentially fatal infection, particularly affecting individuals with chronic conditions such as diabetes or kidney or liver diseases. This review examines melioidosis in India over the past two decades, focusing on its prevalence, risk factors and clinical manifestations. A PubMed search (2000–2024) identified a rise in melioidosis publications, with most from Southern India, followed by Eastern India, and an increase post-2019. Eight studies from 2010–2022 identified fever (86%), cough (26%) and joint pain (23%) as the most common symptoms, while diabetes (75%), alcohol abuse (19%) and cancer (6%) were primary predisposing factors. Severe clinical manifestations were also observed, including bacteremia (50%), pneumonia (37%) and splenic abscess (18%). Although environmental exposure risks were not significantly high, individuals with diabetes or chronic kidney disease, particularly those working in high-risk environments, were more likely to contract melioidosis. Cryptic environmental factors that might bridge known epidemiological risk factors are also addressed. The review emphasizes the increasing awareness and research in clinical epidemiology and also highlights a gap in studies on antimicrobial treatments, vaccines and environmental surveillance. Targeted interventions in diabetes and poverty hotspots could help control the disease more effectively.

Background: Viral hepatitis is of global importance and inflicts a huge healthcare cost in northeast India where its prevalence and the prevalence of drug-resistant variants are not well known. Hepatotropic viruses (hepatitis B virus, hepatitis A virus, hepatitis C virus and hepatitis E virus) are known to cause ‘viral hepatitis.’ This study documents the prevalence and genotype of Hepatitis C Virus (HCV) in northeast India.Aim: Identification of Hepatitis C Virus (HCV) genotypes with their resistance-associated variants (RAVs) could facilitate the development of selective antiviral drug regimens against HCV infection. The present study aims to identify the HCV genotype from six northeastern states of India.Methods: The study was carried out between 2018-2022 from hospitalised cases of viral hepatitis in six northeastern states of India namely Assam, Meghalaya, Mizoram, Nagaland, Tripura and Manipur. A total of 1300 subjects were enrolled, from whom 88 HCV-positive samples were processed for molecular characterisation.Results: Of the 88 samples evaluated for genotyping and sub-typing, 58 (66%) were HCV genotype 3b, 15 (17%) were 3a, 8 (9 %) were 6n, 2 (2%) were 6xa, 3 (3 %) were 1a, and 2 (2 %) were 1b respectively. Genotype 6n was common among injecting drug users (IDUs) (5/8; 62.5%). Resistance-associated variants (RAVs) 30K and 31M of HCV NS5A region were observed in 5/30 (16.6%) HCV genotype 3b. This could indicate likely resistance to directly acting antivirals (DAAs) targeting the NS5A of HCV. RAVs C316N mutation of NS5B region was also observed in 1/1 (100%) of HCV genotypes 1b.Conclusion: A higher prevalence of HCV genotype 3b was observed in the study population. Furthermore, overlapping of RAVs 30K and 31M of HCV NS5A region with HCV genotype 3b may pose treatment failure. Genotypes HCV 6n and HCV 6xa were also identified, which may be the first to be reported from northeastern parts of India.