Genome-wide association study of nevirapine hypersensitivity in a sub-Saharan African HIV-infected population

The initial GWAS was funded by the International Serious Adverse Events Consortium (iSAEC). The iSAEC is a non-profit organization dedicated to identifying and validating DNA variants useful in predicting the risk of drug-related serious adverse events. The Consortium brings together the pharmaceutical industry, regulatory authorities and academic centres to address clinical and scientific issues associated with the genetics of drug-related serious adverse events. The iSAEC’s current funding members include: Abbott, Amgen, AstraZeneca, Daiichi Sankyo, GlaxoSmithKline, Merck, Novartis, Pfizer, Takeda and the Wellcome Trust. Mas Chaponda was funded by a 3 year Wellcome Trust training fellowship WT078857MA administered through the University of Liverpool. Malawi-Liverpool-Wellcome Trust Clinical Research Programme is funded through a Core Programme Grant award from the Wellcome Trust. Munir Pirmohamed is a National Institute for Health Research Senior Investigator, and also wishes to thank the MRC Centre for Drug Safety Science for support. The DART study was supported by the UK Medical Research Council (grant number G0600344), the UK Department for International Development and the Rockefeller Foundation. Andrew P. Morris is a Wellcome Trust Senior Research Fellow in Basic Biomedical Science (grant number WT098017). Louise Y. Takeshita is funded by a PhD fellowship from CNPq (National Council for Scientific and Technological Development, Brazil). Panos Deloukas’ work forms part of the research themes contributing to the translational research portfolio of Barts Cardiovascular Biomedical Research Unit which is supported and funded by the National Institute for Health Research

The impact of changing the diagnostic algorithm for TB in Manicaland, Zimbabwe.

SETTING: Governmental health facilities performing TB diagnostics in Manicaland, Zimbabwe. OBJECTIVE: To investigate the effect of making Xpert® MTB/RIF the primary TB diagnostic for all patients presenting with presumptive TB on 1) the number of samples investigated for TB, 2) the proportion testing TB-positive, and 3) the proportion of unsuccessful results over time. DESIGN: This retrospective study used data from GeneX-pert downloads, laboratory registers and quality assurance reports between 1 January 2017 and 31 December 2018. RESULTS: The total number of Xpert tests performed in Manicaland increased from 3,967 in the first quarter of 2017 to 7,011 in the last quarter of 2018. Mycobacterium tuberculosis DNA was detected in 4.9-8.6% of the samples investigated using Xpert, with a higher yield in 2017 than in 2018. The overall proportion of unsuccessful Xpert assays due to "no results", errors and invalid results was 6.3%, and highly variable across sites. CONCLUSION: Roll out of more sensitive TB diagnostics does not necessarily result in an increase of microbiologically confirmed TB diagnosis. While the number of samples tested using Xpert increased, the proportion of TB-positive tests decreased. GeneXpert soft- and hardware infrastructure needs to be strengthened to reduce the rate of unsuccessful assays and therefore, costs and staff time

Geo-Spatial Distribution of Frequencies of MTB/RIF Detected Specimens based on Requesting Health Facilities in Manicaland Zimbabwe for 2017 and 2018

Objectives: The aim of this study was to produce Geo Spatial Distribution of Frequencies of MTB/RIF Detected Specimens based on  Requesting Health Facilities in Manicaland Zimbabwe for 2017 and 2018, so as to give insight to TB program managers. Focusing  elimination interventions on hot pockets of Tuberculosis (TB) strengthens rationale use of resources in resource limited countries like Zimbabwe. Early detection and early treatment is backbone of breaking TB transmission. Drug resistant tuberculosis (DRTB) control interventions like Programmatic Management of Drug Resistant TB or mentoring on Short, all Oral Regimen for Rifampicin resistant Tuberculosis (ShORRT) will be driven by science.Materials and Methods: The retrospective study was carried out in Manicaland, Zimbabwe. Manicaland one of the 10 provinces in  Zimbabwe, has 7 districts with 308 health facilities. During this retrospective cross sectional study 2221 MTB detected results of 2017 and 2018, downloaded from 14 of the 15 Genexpert sites in Manicaland were employed to generate hotspot maps. Fifteenth Genexpert site lost its electronic records when Genexpert CPU crushed. Geographical Positioning System (GPS) of the health facilities were recorded. The  study used MTB detected frequencies at a facility in relation to surrounding facilities in Manicaland, then ran optimised hotspot analysis function in Arc Map 10.5 to implement the Gi*statistic.Results: Overall provincial MTB detected positivity was 2221/36055 (6.2%).Overall provincial Rifampicin Resistant (RR) positivity was .111.2221(5.0%).Geo-spatial map of Manicaland showed 10 facilities that are RR hotspots with 7/10 (70%) of the facilities in Buhera district. Chipinge district had facilities that were MTB detected high hotspots.For the whole of Manicaland, Buhera district had100% MTB detected low hotspots facilities. Ninety percent hotspots were clustered around 2 of the 15 Genexpert Sites in Manicaland, namely Murambinda Mission Hospital and Chipinge District Hospital.Conclusion: Study identified health facilities with high frequencies of RR areas. For the identified health facilities with high frequencies of RR specimens, NTP may focus DRTB control interventions like PMDT, or mentoring on ShORRT. For the health facilities with high frequencies of MTB detected NTP can focus trainings in TB Case Management. Instead of uniformly spreading the limited resources to all 325 facilities, efforts streamlined to manageable number of 20 facilities in commensurate with identified gap( e.g. objective selection of cadres for training, data driven supportive supervision & targeted awareness campaigns)