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We analyzed parentage data collected over a ten-year period in a Zimbabwean DNA testing laboratory. Parentage case types, prevalence, exclusion data, mutations rates and observed genotyping irregularities were analyzed. We report analysis results from 1303 cases. DNA extraction and STR typing was conducted using standard commercial kits. Paternity was the most requested test (87.37%) followed by the indirect biological kinship tests (7.01%). Duo paternity (motherless) was the most common paternity test for both regular and court cases. We observed 367 paternity exclusions from 1135 cases, giving an overall paternity exclusion rate of 32.33%. Maternity had the lowest exclusion rate (8.33%), with criminal cases having the highest paternity (61.11%) and maternity (33.33%) exclusion rates. The number of mismatched STR loci ranged from 2–12 for duo cases and 4–18 for the trio cases. FGA, D2S1338, D18S51 and D2S441 were the most informative markers for exclusion. We detected 30 mutations out of 837 cases with an estimated paternal and maternal mutation rate of 0.0021 and 0.0011 respectively. Triallelic patterns were only observed at the TPOX locus with allele 10 and 11 being the extra alleles transmitted. Our report provides forensic parameters which can improve parentage and forensic analysis in Zimbabwe.

Pharmacogenomic testing may be used to improve treatment outcomes and reduce the frequency of adverse drug reactions (ADRs). Population specific, targeted pharmacogenetics (PGx) panel-based testing methods enable sensitive, accurate and economical implementation of precision medicine. We evaluated the analytical performance of the GenoPharm ® custom open array platform which evaluates 120 SNPs across 46 pharmacogenes. Using commercially available reference samples (Coriell Biorepository) and in-house extracted DNA, we assessed accuracy, precision, and linearity of GenoPharm ® . We then used GenoPharm ® on 218 samples from two Southern African black populations and determined allele and genotype frequencies for selected actionable variants. Across all assays, the GenoPharm ® panel demonstrated 99.5% concordance with the Coriell reference samples, with 98.9% reproducibility. We observed high frequencies of key genetic variants in people of African ancestry: CYP2B6*6 (0.35), CYP2C9*8, *11 (0.13, 0.03), CYP2D6*17 (0.21) and *29 (0.11). GenoPharm ® open array is therefore an accurate, reproducible and sensitive test that can be used for clinical pharmacogenetic testing and is inclusive of variants specific to the people of African ancestry.

Differences in the cervicovaginal microbiome may influence the persistence of HPV and therefore, the progression to cervical cancer. We aimed to analyze and compare the metatranscriptome of cervical cancers positive for HPV 16 and 18 with those positive for other HPV types to understand the microbiome’s influence on oncogenicity. RNA sequencing data from a total of 222 invasive cervical cancer cases (HPV16/18 positive (n=42) and HPV “Other types” (n=180)) were subjected to taxonomy classification (Kraken 2) including bacteria, virus and fungi to the level of species. With a median depth of 288,080.5 reads per sample, up to 107 species (38 bacterial, 16 viral and 53 fungal) were identified. Diversity analyses revealed no significant differences in viral or fungal species between HPV16/18 and other HPV types. Bacterial alpha diversity was significantly higher in the \"Other HPV types\" group for the Observed index (p=0.0074) (but not for Shannon). Cumulative species curves revealed greater species diversity in the “Other HPV types” group compared to “HPV16/18 but no significant differences in species abundance were found between HPV groups. The study did not detect strong significant microbiome differences between HPV 16/18 and other HPV types in cervical cancers. Further research is necessary to explore potential factors influencing the oncogenicity of different HPV types and their interaction with the cervical microbiome.

Background Tuberculosis (TB) is a global health challenge. Use of anti-TB drugs to treat TB is associated with high prevalence of side effects that include anti-TB drug induced liver injury (ATDILI). The aim of this study was to determine the incidence and associated clinical risk factors of ATDILI among South African patients on treatment for TB disease. Methods This was an ambispective case-control study of patients on treatment for TB disease receiving drug sensitive and drug resistant treatment regimens. The retrospective and prospective studies were done from January 2021 to June 2024, involving a total of 610 patients on treatment for TB disease from whom 13 had ATDILI. From the retrospective and prospective cohorts, we extracted 13 ATDILI cases and 276 controls. Additionally, 44 severe ATDILI cases were directly recruited from the hospital to enrich the number of cases in the study. Prospective patients were followed for up to 6 months, while retrospective participants had a single visit with follow-up durations determined by their parent studies. Logistic regression analysis was performed to identify clinical and demographic factors associated with the development of ATDILI). Results In the studied cohorts, the incidence of ATDILI was 2.1% (13/610). The ATDILI cases and controls consisted of 215 (64.6%) male patients; 57 patients were diagnosed with hepatotoxicity, 44 from the hospitalized cohort,12 from the retrospective cohort and 1 patient from the prospective cohort. The median time from the initiation of treatment to the onset of hepatotoxicity was approximately 30 days. Univariate logistic regression revealed significant differences ( p  < 0.05) in sex ( p  = 0.003), HIV status ( p  = 0.002), BMI ( p  = 0.038), hypertension ( p  = 0.047) smoking ( p  = 0.006), and alcohol consumption ( p  = 0.001) in relation to ATDILI. Multivariate analysis further revealed that female sex ( p  = 0.041), HIV status (0.022) and alcohol consumption (0.048) were independently associated with an increased risk of ATDILI. Conclusions The incidence of ATDILI in this study was 2.1%, lower than the previously reported range of 3–36% and highlights the need for standardized definitions of phenotypes across studies. In univariable analysis, female sex, HIV status, BMI, hypertension, smoking, and alcohol consumption were identified as potential risk factors for ATDILI. Among these, multivariable analysis suggested that female sex, HIV status and alcohol consumption were associated with an increased risk of developing ATDILI.

The contribution of high tuberculosis (TB) transmission pockets in propagating area-wide transmission has not been adequately described in Zimbabwe. This study aimed to describe the presence of hotspot transmission of TB cases in Harare city from 2011 to 2012 using geospatial techniques. Anonymised TB patient data stored in an electronic database at Harare City Health department was analysed using geospatial methods. Confirmed TB cases were mapped using geographic information system (GIS). Global Moran's I and Anselin Local Moran's I (LISA) were used to assess clustering and the local Getis-Ord Gi* was used to estimate hotspot phenomenon of TB cases in Harare City for the period between 2011 and 2012. A total of 12,702 TB cases were accessed and mapped on the Harare City map. In both 2011 and 2012, ninety (90%) of cases were new and had a high human immunodeficiency virus (HIV)/TB co-infection rate of 72% across all suburbs. Tuberculosis prevalence was highest in the Southern district in both 2011 and 2012. There were pockets of spatial distribution of TB prevalence across West South West, Southern, Western, South Western and Eastern health districts. TB hot spot occurrence was restricted to the West South West, parts of South Western, Western health districts. West South West district had an increased peri-urban population with inadequate social services including health facilities. These conditions were conducive for increased intensity of TB occurrence, a probable indication of high transmission especially in the presence of high HIV co-infection. Increased TB transmission was limited to a health district with high informal internal migrants with limited health services in Harare City. To minimise spread of TB into greater Harare, there is need to improve access to TB services in the peri-urban areas.

Africa bears the largest burden of morbidity and mortality from hypertension (HT) and related cardiovascular diseases. Thiazide diuretics, including hydrochlorothiazide (HCTZ), are the most prescribed hypertension medicines globally due to their cost effectiveness and minimal side effects. However, studies investigating the genetic variation in HCTZ‐related genes and their effect on drug response have been mainly conducted in European, American, and Asian populations. This study aimed to examine genetic variation in HCTZ response‐related genes among newly diagnosed hypertensives from Soweto, South Africa, irrespective of the treatment approach, and to assess its potential impact on medication response. Using targeted NGS on 364 newly diagnosed hypertensives with at least one follow‐up visit, we identified 1258 unique variants in 16 key HCTZ response genes. Among these, 89 were novel variants, of which 12 were protein‐altering, including 8 predicted to be deleterious. Association analyses with 882 independent variants revealed that carriers of the intronic variant rs1025450259 in GNB3 had significantly greater reduction in BP compared to other patients on heterogeneous treatment strategies, but no significant associations were detected in the subset of individuals treated with HCTZ monotherapy only (n = 103). For variants previously associated with HCTZ response, we did not replicate prior associations (e.g., rs2611316 in ALDH1A2) but highlight important allele frequency differences across global populations. Despite the limitations, the study outcomes support the need for larger, controlled trials to assess genetic influences on HT treatment outcomes, advancing personalized medicine for African populations. This research further underscores the importance of pharmacogenetic studies in continental African populations.

Pharmacogenomics studies how a person’s inherited genes influence response to therapeutic drugs. Many drugs do not work in all patients and pharmacogenomics can assist in the identification of patients who are better suited to particular drugs or patients who need adjusted drug doses to reach better treatment outcomes. This stratification of patients could be beneficial in Africa as it would allow drugs that would ordinarily be discontinued due to toxicity on a proportion of the populations to be used in a directed manner in people for whom it is not toxic. However, there has been limited use of pharmacogenomics. One of the key issues has been the need to demonstrate the economic benefits of adopting pharmacogenomics implementation and the impact on healthcare cost drivers. Integration of pharmacogenomics into clinical practice has huge potential in Africa due to the large genetic diversity in African populations. This Perspective article explores the current pharmacogenomics landscape, the health economics associated with its implementation, and future directions for pharmacogenomics research translation in Africa. Alimohamed et al. outline the current pharmacogenomics landscape in Africa. They explore the role of health economics in its clinical translation, and propose context-sensitive strategies for equitable implementation across the continent.

Capecitabine is an oral prodrug that is converted to 5-FU via three enzyme-catalysed steps: carboxylesterase (CES), cytidine deaminase (CDA), and thymidine phosphorylase (TYMS). Approximately 80-90% of 5-FU, whether from capecitabine or direct administration, is quickly inactivated by dihydropyrimidine dehydrogenase (DPD), encoded by DPYD. Preemptive testing for four pathogenic DPYD variants that reduce DPD activity is advised; however, currently, no evidence for CES, CDA, or TYMS has necessitated a similar recommendation despite polymorphisms in these genes potentially causing treatment toxicity. The current preemptive testing guidelines for 5-FU and capecitabine are similar. A 74-year-old black woman with a caecal adenocarcinoma diagnosis of pT G N M was prescribed adjuvant oxaliplatin and capecitabine post-hemicolectomy. On day 16 of the first cycle, she presented with severe gastrointestinal, myelosuppressive, hand and foot side effects and enterocolitis infection. She underwent a pharmacogenomic workup with whole-exome sequencing and was noted to be genetically DPD non-deficient (DPYD *1/*9A). She was found to express CDA rs3215400 (c.-33delC) and CDA rs1048977, both of which are associated with an increased risk of toxicity from capecitabine. CDA rs3215400 has been specifically described as an ultrametabolizer variant with an observation to increase enzyme activity by 3-7 fold and the occurrence of adverse drug events in capecitabine. After recovery and follow-up, she continued to receive 5-FU, leucovorin, and oxaliplatin therapy which she tolerated well and completed six months of therapy. This case shows that the severe adverse effects of capecitabine therapy in a patient with a CDA ultrametabolizer profile can be successfully switched to 5-FU-based therapy at a normal dose and tolerate this alternative fluoropyrimidine.

Children living with HIV who are not diagnosed in infancy often remain undiagnosed until they present with advanced disease. Provider-initiated testing and counselling (PITC) in health facilities is recommended for high-HIV-prevalence settings, but it is unclear whether this approach is sufficient to achieve universal coverage of HIV testing. We aimed to investigate the change in community burden of undiagnosed HIV infection among older children and adolescents following implementation of PITC in Harare, Zimbabwe. Over the course of 2 years (January 2013-January 2015), 7 primary health clinics (PHCs) in southwestern Harare implemented optimised, opt-out PITC for all attendees aged 6-15 years. In February 2015-December 2015, we conducted a representative cross-sectional survey of 8-17-year-olds living in the 7 communities served by the study PHCs, who would have had 2 years of exposure to PITC. Knowledge of HIV status was ascertained through a caregiver questionnaire, and anonymised HIV testing was carried out using oral mucosal transudate (OMT) tests. After 1 participant taking antiretroviral therapy was observed to have a false negative OMT result, from July 2015 urine samples were obtained from all participants providing OMTs and tested for antiretroviral drugs to confirm HIV status. Children who tested positive through PITC were identified from among survey participants using gender, birthdate, and location. Of 7,146 children in 4,251 eligible households, 5,486 (76.8%) children in 3,397 households agreed to participate in the survey, and 141 were HIV positive. HIV prevalence was 2.6% (95% CI 2.2%-3.1%), and over a third of participants with HIV were undiagnosed (37.7%; 95% CI 29.8%-46.2%). Similarly, among the subsample of 2,643 (48.2%) participants with a urine test result, 34.7% of those living with HIV were undiagnosed (95% CI 23.5%-47.9%). Based on extrapolation from the survey sample to the community, we estimated that PITC over 2 years identified between 18% and 42% of previously undiagnosed children in the community. The main limitation is that prevalence of undiagnosed HIV was defined using a combination of 3 measures (OMT, self-report, and urine test), none of which were perfect. Facility-based approaches are inadequate in achieving universal coverage of HIV testing among older children and adolescents. Alternative, community-based approaches are required to meet the Joint United Nations Programme on HIV/AIDS (UNAIDS) target of diagnosing 90% of those living with HIV by 2020 in this age group.

As we endeavour to examine rates of viral suppression in PLHIV, reliable data on ART adherence are needed to distinguish between the respective contributions of poor adherence and treatment failure on high viral load. Self-reported data are susceptible to response bias and although biomarker data on drug presence and concentration can provide a superior, alternative method of measurement, complications due to drug-drug interactions and genetic variations can cause some inaccuracies. We investigate the feasibility of combining both biomarker and self-report data to produce a potentially more accurate measure of ART adherence. Data were taken from a large general-population survey in the Manicaland province, Zimbabwe, conducted in 2009-2011. HIV-infected adults who had initiated ART (N = 560) provided self-report data on adherence and dried blood spot samples that were analysed for traces of ART medication. A new three-category measure of ART adherence was constructed, based on biomarker data but using self-report data to adjust for cases with abnormally low and high drug concentrations due to possible drug-drug interactions and genetic factors, and was assessed for plausibility using survey data on socio-demographic correlates. 94.3% (528/560) and 92.7% (519/560) of the sample reported faithful adherence to their medication and had traces of ART medication, respectively. The combined measure estimated good evidence of ART adherence at 69% and excellent evidence of adherence at 53%. The regression analysis results showed plausible patterns of ART adherence by socio-demographic status with men and younger participants being more likely to adhere poorly to medication, and higher socio-economic status individuals and those living in more urban locations being more likely to adhere well. Biomarker and self-reported measures of adherence can be combined in a meaningful way to produce a potentially more accurate measure of ART adherence. Results indicate that ART adherence in Manicaland is at best 69%, which not only allows for considerable room for improvement but also suggests that the area may be falling short of the UNAIDS' 90% target regarding viral suppression. Increased efforts are needed to improve ART adherence particularly amongst the young male population in rural areas of east Zimbabwe.