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.

Our study addresses the sepsis research gap in lower middle-income countries, notably India. Here, we investigate community-acquired sepsis comprehensively and explore the impact of tropical microbiology on aetiology and outcomes. MARS-India was a prospective observational study from Dec-2018 to Sep-2022 in a tertiary-care hospital in South India. Adult patients within 24hrs of ICU admission meeting the Sepsis 3.0 definition were enrolled, with 6-months follow-up (http://clinicaltrials.gov number NCT03727243). Over 4000 patients were screened on ICU admission, with 1000 unique patients meeting the inclusion criteria. Median age was 55 years (IQR: 44-65) with a male preponderance (66%). Almost half the cohort resided in villages (46.5%) and 74.6% worked in the primary sector. Mortality in-hospital was 24.1%. Overall, ∼54% had confirmed microbiological diagnosis. Over 18% had a viral cause of sepsis. Surprisingly, we identified leptospirosis (10.6%), scrub typhus (4.1%), dengue (3.7%) and Kyasanur forest disease (1.6%) as notables causes of sepsis. All these infections showed seasonal variation around the monsoon. In community-acquired infections we observed substantial resistance to 3^rd generation cephalosporins and carbapenems. In India, sepsis disproportionally affects a younger and lower socio-economic demographic, yielding high mortality. Tropical and viral sepsis carry a significant burden. Analyzing local data, we pinpoint priorities for public health and resources, offering valuable insights for global sepsis research.

Melioidosis, attributable to the soil-dwelling bacterium Burkholderia pseudomallei, stands as a paramount global health challenge, necessitating extended courses of antibiotics. While murine studies identified gut microbiota as modulator of bacterial dissemination during melioidosis, human intestinal microbiota during melioidosis remain uncharacterized. Here, we characterized gut microbiota composition and antimicrobial resistance (AMR)-genes at diagnosis, during treatment, and post-discharge for melioidosis. We hypothesized that the gut microbiota of melioidosis patients would be extensively distorted. In this prospective observational cohort, stool samples of patients with culture-confirmed melioidosis admitted to a tertiary care hospital in India were collected at diagnosis, two weeks after that or at discharge (whichever occurred first), and six months post-infection. Family members or neighbours served as community controls. Gut microbiota and resistome were profiled by shotgun metagenomic sequencing. We longitudinally analysed the gut microbiota of 70 faecal samples from 28 patients and 16 community controls. At diagnosis, gut microbiota of patients differed from controls, characterized by high abundances of potentially pathogenic bacteria, a loss of butyrate-producing bacteria, and higher levels of AMR genes. Microbiota composition and resistome remained different from community controls at six months, driven by total antibiotic exposure. During hospitalization, gut microbiota profiles were associated with secondary Klebsiella pneumoniae infections. This first study on gut microbiota composition and resistome in human melioidosis showed extensive disruptions during hospitalization, with limited signs of restoration six months post-infection. Given the adverse outcomes linked with microbiome perturbations, limiting microbiota disruptions or microbiota-restorative therapies (e.g. butyrate-producing probiotics) may be beneficial. This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/microbial-resilience-in-human-melioidosis-understanding-gut-microbiome-and-resistome-dynamics-in-diagnosis-to-recovery-ffba86d1-98ab-4a6c-8340-37ca243314da

Characterising the host response in sepsis is essential to understand its biological heterogeneity and to inform more precise diagnostic and therapeutic strategies. Existing evidence on sepsis comes predominantly from studies conducted in high-income countries (HICs), despite the highest burden in low- and middle-income countries (LMICs). We aimed to address this gap by identifying shared and pathogen-specific host response patterns among different infectious causes of sepsis in a tertiary care centre in India. Patients fulfilling sepsis-3 criteria were enrolled within 24 h of intensive care unit admission in a tertiary care centre in Manipal, Karnataka, India. We measured 27 plasma biomarkers reflecting key pathophysiological domains (endothelial activation and coagulation, organ damage and inflammation, cytokine response, and chemokine release) to delineate host response profiles across sepsis aetiologies. We included 956 sepsis patients, and a causative pathogen was identified in 54·1% (338 bacterial, 146 viral, 33 polymicrobial). The causative pathogen explained a significant proportion of biomarker variation (34·5% of explained variance; 9·4% of all variances). While bacterial sepsis was associated with stronger host response changes across all domains when compared to viral sepsis, notable variation was found within these microbial categories. Orientia tsutsugamushi (causing scrub typhus) triggered the most profound host response alterations among bacterial causes, whereas viral haemorrhagic fever (dengue, Kyasanur forest disease) causing pathogens induced higher biomarker levels across all pathophysiological domains compared to SARS-CoV-2 or influenza within viral sepsis. These findings highlight the biological heterogeneity of sepsis and the complexity of host–pathogen interactions in a setting with a diverse range of causative organisms. 10.13039/501100000780 European Union , 10.13039/100019573 Amsterdam UMC , and 10.13039/100019305 Manipal Academy of Higher Education .