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Biology subjects

Sethi, A. K.

Publications and source records attributed to Sethi, A. K..

3 recordsLinked to original sources

Antimicrobial use contributes to resistance gene enrichment across cattle groups on commercial dairy farms

Antimicrobial use (AMU) in agricultural systems is frequently linked to antimicrobial resistance (AMR). Yet, the scale at which AMU reshapes host-associated resistomes remains unclear. This gap arises, in part, from the scarcity of farm-level AMU data from commercial production systems. Here, we combine detailed AMU records from commercial dairy farms with metagenomic analyses of bovine fecal resistomes from calves, lactating cows, sick cows, and cull cows. At a broad level, resistome profiles were similar regardless of farm AMU. Resistance associated with historically common antibiotics, such as tetracyclines, was frequent on low- and high-AMU farms, indicating that some resistance classes are ubiquitous in dairy systems regardless of current AMU. In contrast, resistance to other drug classes varied systematically with AMU. Higher AMU was associated with increased resistance to aminoglycosides, {beta}-lactams, and macrolides, drug classes that are critical for treating mastitis and bovine respiratory disease. Resistance gene richness and diversity were highest in calves, underscoring the importance of accounting for host traits alongside AMU when evaluating resistance patterns. Together, these findings underscore the need for detailed, farm-level AMU data to understand how management practices shape AMR and to inform strategies for sustaining the effectiveness of existing antimicrobials in agricultural and public-health contexts.

genomics↗

The landscape of antibody binding to SARS-CoV-2

The search for potential antibody-based diagnostics, vaccines, and therapeutics for pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused almost exclusively on the spike (S) and nucleocapsid (N) proteins. Coronavirus membrane (M), ORF3a, and ORF8 proteins are humoral immunogens in other coronaviruses (CoVs) but remain largely uninvestigated for SARS-CoV-2. Here we use ultradense peptide microarray mapping to show that SARS-CoV-2 infection induces robust antibody responses to epitopes throughout the SARS-CoV-2 proteome, particularly in M, in which one epitope achieved excellent diagnostic accuracy. We map 79 B cell epitopes throughout the SARS-CoV-2 proteome and demonstrate that antibodies that develop in response to SARS-CoV-2 infection bind homologous peptide sequences in the six other known human CoVs. We also confirm reactivity against four of our top-ranking epitopes by enzyme-linked immunosorbent assay (ELISA). Illness severity correlated with increased reactivity to nine SARS-CoV-2 epitopes in S, M, N, and ORF3a in our population. Our results demonstrate previously unknown, highly reactive B cell epitopes throughout the full proteome of SARS-CoV-2 and other CoV proteins.

immunology↗

Effectiveness of a mobile antiretroviral pharmacy and HIV care intervention on the continuum of HIV care in rural Uganda

IntroductionAdherence to antiretroviral therapy (ART) is critical in order to achieve viral suppression, one of three UNAIDS targets set for achievement before 2020. One of the main barriers to adherence is the long distance between patient residences and healthcare facilities. We designed an intervention, Mobile Antiretroviral Therapy and HIV care (MAP-HC) in rural southwestern Uganda aimed to reduce travel distance and hypothesized that MAP-HC would improve ART adherence and rates of viral load suppression. MethodsThe study was conducted at two sites, Kitagata and Itojo Hospitals, and these are public health facilities located in rural southwestern Uganda. Patients who lived >5km from the hospital were provided the option to participate. For each hospital, we identified 4 health centres in the catchment area to serve as site for the mobile pharmacy. Each site was visited once a month to provide ART refills, adherence counseling and treatment of other illnesses. We measured patient waiting time, adherence and viral load suppression before and after the intervention. ResultsWe conducted baseline assessment among 292 patients at the two hospitals. The mean waiting time at Kitagata Hospital changed from 4.48 hours before the intervention but increased to 4.76 hours after the intervention (p=0.13). The proportion of patients who missed an ART dose in the last 30 days dropped from 20% at baseline to 8.5% at 12 months after the intervention (p=0.009). The proportion of patients with detectable viral load from 19.9% to 7.4% after the intervention (p=0.001). ConclusionsOur study has showed that a mobile pharmacy intervention in rural Uganda is feasible and resulted in improvement in adherence and viral load suppression. Although it did not reduce patient waiting time at the clinic, we recommend a scale-up of this intervention in rural areas where patients face challenges of transportation to the clinic.

epidemiology↗