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Swaminathan, M.

Publications and source records attributed to Swaminathan, M..

2 recordsLinked to original sources
bioRxiv2024

Identification of genetic variation in genes linked to buparvaquone resistance in Theileria sp infecting dairy cattle in India.

Buparvaquone (BQO) is used for treatment of bovine theileriosis, a tickborne disease caused by parasites of the Theileria genus. Studies on T. annulata have linked the mechanism of BQO resistance predominantly to genetic variations in the parasite cytochrome b (cytb) gene. In addition, cryptic mechanisms of resistance involving the parasite peptidyl-prolyl isomerase (pin1) and dihydroorotate dehydrogenase (dhodh) genes require assessment. In India, where bovine theileriosis is endemic, and BQO is widely used for treatment, monitoring and establishing the link between genetic variations in cytb, dhodh and pin1 genes and BQO resistance is essential. In this study, multiplexed PCR amplification and nanopore sequencing approaches were used for genotyping the complete gene loci of the target genes. Analysis of 420 T. annulata field samples collected from seven different states of India revealed the presence of previously reported variations S129G, A146T and P253S in cytb and A53P in pin1, which are linked to BQO resistance. The role of A146T, a highly prevalent variation which mostly co-occurred with I203V, in BQO resistance needs to be evaluated. From 60 samples having T. orientalis infection, the genetic variations identified from the three genes were found to be mostly natural variations based on the reference genotypes and were distinct from T. annulata variations. This study has revealed the presence of BQO resistance-linked cytb gene mutations in T. annulata infecting dairy cattle in India and establishes a nanopore sequencing method for molecular surveillance of genetic variation in field samples. Author SummaryBuparvaquone (BQO) is the most effective drug that is available for the treatment of cattle theileriosis caused by parasites of the Theileria genus. However, treatment failure due to drug resistance is reported, and gene mutations linked to BQO resistance have been reported in African and Middle Eastern countries. These mutations occur in the cytochrome b (cytb) and peptidyl-prolyl isomerase (pin1) genes in the parasite. In this study, genetic variations occurring in these two genes and the parasite dihydroorotate dehydrogenase (dhodh) gene have been mapped using PCR amplification and Nanopore sequencing from field samples collected from seven different states of India. At least three previously reported mutations linked to BQO resistance were found in the T. annulata cytb gene sequence obtained from field samples. While one of these mutations (A146T) was highly prevalent, the other two were found to occur in only a few samples. Similarly, the BQO resistance linked to A53P mutation in the T. annulata pin1 gene was present in only a few samples. Despite their low frequency, the presence of these mutations reveals the existence of BQO resistance due to genetic variations in the parasite population present in India. This is the first comprehensive report of BQO resistance-conferring mutations occurring in Theileria parasites affecting dairy cattle in India and establishes a scalable method for large-scale molecular surveillance studies.

genomics↗
bioRxiv2019

Health workers’ perspectives on the outcomes, enablers, and barriers to the implementation of HIV “Treat All” guidelines in Abuja Nigeria

IntroductionTo improve access to lifesaving treatment for all people living with HIV (PLHIV), Nigeria implemented the Treat All guidelines in 2016. However, health workers perspectives on the implementation of the guidelines have not been evaluated.\n\nMethodsWe conducted in-depth interviews to explore health workers perspectives on the Treat All guidelines. Using purposive sampling, 20 health workers providing HIV patient care were recruited from six primary health care hospitals in Abuja to participate in semi-structured interviews. Data exploration was conducted using thematic content analysis.\n\nResultsThe five main themes that emerged were (1) the perceived benefits of guidelines use, (2) the perceived disadvantages of using the guidelines, (3) reported patients response to guideline change, (4) perceived barriers/enablers to guideline use and (5) health workers recommendations for improvement. Health workers perceived that the implementation of the Treat All guidelines has considerably improved patient care, particularly in increasing access to skilled health care, reducing stress on patients, and increasing hope for a better health outcome among patients. Other perceived benefits were reduced mortality, reduced pre-treatment attrition, reduction in delays between case detection and initiation on treatment. Perceived major disadvantages were increased workload and overcrowded clinics. Health workers reported that most patients were willing to start treatment early. Perceived key factors enabling guidelines use were health workers interest, patient benefits, training and availability of tools for implementation of guidelines, government supervisory visits and hospital management support. Perceived key barriers were poverty, inadequate human resources, lack of familiarity with guidelines, and lack of consistent supply of HIV test kits at some sites.\n\nConclusionsImplementation of the Treat All guidelines led to perceived improvement in patient care. Further improvements could be achieved by implementing an efficient supply chain system for HIV rapid test kits, and through guidelines distribution and training. Additionally, implementing differentiated approaches that decongest clinics, and programs that economically empower patients could improve access to treatment.

epidemiology↗