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Genetic variation in CYP2B6 and CYP2A6 is known to impact interindividual response to antiretrovirals, nicotine, and bupropion, among other drugs. However, the full catalogue of clinically relevant pharmacogenetic variants in these genes is yet to be established, especially across African populations. This study therefore aimed to characterize the star allele (haplotype) distribution in CYP2B6 and CYP2A6 across diverse and understudied sub‐Saharan African (SSA) populations. We called star alleles from 961 high‐depth full genomes using StellarPGx, Aldy, and PyPGx. In addition, we performed CYP2B6 and CYP2A6 star allele frequency comparisons between SSA and other global biogeographical groups represented in the new 1000 Genomes Project high‐coverage dataset (n = 2,000). This study presents frequency information for star alleles in CYP2B6 (e.g., *6 and *18; frequency of 21–47% and 2–19%, respectively) and CYP2A6 (e.g., *4, *9, and *17; frequency of 0–6%, 3–10%, and 6–20%, respectively), and predicted phenotypes (for CYP2B6), across various African populations. In addition, 50 potentially novel African‐ancestry star alleles were computationally predicted by StellarPGx in CYP2B6 and CYP2A6 combined. For each of these genes, over 4% of the study participants had predicted novel star alleles. Three novel star alleles in CYP2A6 (*54, *55, and *56) and CYP2B6 apiece, and several suballeles were further validated via targeted Single‐Molecule Real‐Time resequencing. Our findings are important for informing the design of comprehensive pharmacogenetic testing platforms, and are highly relevant for personalized medicine strategies, especially relating to antiretroviral medication and smoking cessation treatment in Africa and the African diaspora. More broadly, this study highlights the importance of sampling diverse African ethnolinguistic groups for accurate characterization of the pharmacogene variation landscape across the continent. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The introduction of highly active antiretroviral therapy (HAART) in the treatment of HIV infection has provided different good results: like long-term viral suppression, the decrease of opportunistic infections, and repair of the immune system. METHODS: we carried out a hospital-based cross-sectional analytic study involving 315 participants 228 were on HAART (group 1) and 87 were HAART-naive (group 2) at the HIV treatment centre of the Bamenda regional hospital with our study population being all people living with HIV (PLWHIV) in the North West region of Cameroon. The sampling was performed from the 15th of March to the 30th of June 2017. The questionnaire was administered face to face with participants and their vital signs taken. Blood pressure was measured using an automated electronic blood pressure monitor and hypertension (HTN) was considered as systolic blood pressure (BP) e" 140 mmHg and/or diastolic BP e" 90mmHg. RESULTS: the prevalence of hypertension in the HAART group was 36.44% (n=82, CI: 30.15%-43.10%) compared to that of the HAART-naive group which was 13.33% (n=12, CI: 7.08%-22.13%, P=0.01). HAART was associated with HTN after controlling for gender, family history of hypertension, body mass index (BMI), smoking and alcohol consumption. The odds ratio of the HAART-treated versus the HAART-naive was 3.86 (95% CI: 1.98-7.50). we also found an association between TDF/3TC/EFV (OR=2.83), AZT/3TC/NVP (OR=2.82), AZT/3TC+EFV (OR=3.48) and TDF/3TC+NVP (OR=2.36) and HTN whereas those on AZT+3TC+ATV/r (OR=0.84) and TDF+3TC+ATV/r (OR=0.45) were not associated to hypertension. CONCLUSION: our result suggests that blood pressure should be periodically measured and treated when necessary in PLWHIV on HAART.

Human African trypanosomiasis (HAT) has been targeted for zero transmission to humans by 2030. Animal reservoirs of gambiense-HAT could jeopardize these elimination goals. This study was undertaken to identify potential host reservoirs for Trypanosoma brucei gambiense by detecting its natural infections in domestic animals of Chadian HAT foci. Blood samples were collected from 267 goats, 181 sheep, 154 dogs, and 67 pigs. Rapid diagnostic test (RDT) and capillary tube centrifugation (CTC) were performed to search for trypanosomes. DNA was extracted from the buffy coat, and trypanosomes of the subgenus Trypanozoon as well as T. b. gambiense were identified by PCR. Of 669 blood samples, 19.4% were positive by RDT and 9.0% by CTC. PCR revealed 150 animals (22.4%) with trypanosomes belonging to Trypanozoon, including 18 (12%) T. b. gambiense. This trypanosome was found in all investigated animal species and all HAT foci. Between animal species or villages, no significant differences were observed in the number of animals harboring T. b. gambiense DNA. Pigs, dogs, sheep and goats appeared to be potential reservoir hosts for T. b. gambiense in Chad. The identification of T. b. gambiense in all animal species of all HAT foci suggests that these animals should be considered when designing new control strategies for sustainable elimination of HAT. Investigations aiming to decrypt their specific role in each epidemiological setting are important to achieve zero transmission of HAT.

During the last 30 years, investigations on the microbiome of different tsetse species have generated substantial data on the bacterial flora of these cyclical vectors of African trypanosomes, with the overarching goal of improving the control of trypanosomiases. It is in this context that the presence of Wolbachia and Sodalis glossinidius was studied in wild populations of Glossina fuscipes quanzensis from the Democratic Republic of Congo. Tsetse flies were captured with pyramidal traps. Of the 700 Glossina f. quanzensis captured, 360 were dissected and their midguts collected and analyzed. Sodalis glossinidius and Wolbachia were identified by PCR. The Wolbachia-positive samples were genetically characterized with five molecular markers. PCR revealed 84.78% and 15.55% midguts infected by Wolbachia and S. glossinidius, respectively. The infection rates varied according to capture sites. Of the five molecular markers used to characterize Wolbachia, only the fructose bis-phosphate aldolase gene was amplified for about 60% of midguts previously found with Wolbachia infections. The sequencing results confirmed the presence of Wolbachia and revealed the presence of S. glossinidius in the midgut of Glossina f. quanzensis. A low level of midguts were naturally co-infected by both bacteria. The data generated in this study open a framework for investigations aimed at understanding the contribution of these symbiotic microorganisms to the vectorial competence of Glossina fuscipes quanzensis.

Cytochrome P450 2D6 (CYP2D6) is a key enzyme in drug response owing to its involvement in the metabolism of ~ 25% of clinically prescribed medications. The encoding CYP2D6 gene is highly polymorphic, and many pharmacogenetics studies have been performed worldwide to investigate the distribution of CYP2D6 star alleles (haplotypes); however, African populations have been relatively understudied to date. In this study, the distributions of CYP2D6 star alleles and predicted drug metabolizer phenotypes—derived from activity scores—were examined across multiple sub‐Saharan African populations based on bioinformatics analysis of 961 high‐depth whole genome sequences. This was followed by characterization of novel star alleles and suballeles in a subset of the participants via targeted high‐fidelity Single‐Molecule Real‐Time resequencing (Pacific Biosciences). This study revealed varying frequencies of known CYP2D6 alleles and predicted phenotypes across different African ethnolinguistic groups. Twenty‐seven novel CYP2D6 star alleles were predicted computationally and two of them were further validated. This study highlights the importance of studying variation in key pharmacogenes such as CYP2D6 in the African context to better understand population‐specific allele frequencies. This will aid in the development of better genotyping panels and star allele detection approaches with a view toward supporting effective implementation of precision medicine strategies in Africa and across the African diaspora. [ABSTRACT FROM AUTHOR]

Tsetse flies are the cyclical vector of human and animal African trypanosomiasis. To improve vector control in order to achieve the elimination of human African trypanosomiasis (HAT) and boost the control of animal diseases, investigations have been undertaken on the tripartite association between tsetse, trypanosome, and symbionts. It is in this light that Sodalis glossinidius and different trypanosomes were identified in Glossina palpalis palpalis caught in Fontem in southern Cameroon. For this study, DNA was extracted from whole flies, and S. glossinidius and different trypanosome species were identified by polymerase chain reaction (PCR). Statistical analyses were performed to compare the trypanosome and S. glossinidius infection rates and to look for an association between these microorganisms. Of the 274 G. p. palpalis caught, 3.3% (9/274) were teneral. About 35% (96/274) of these flies harbored S. glossinidius. Of the 265 non-teneral flies, 37.7% were infected by trypanosomes. The infection rates of Trypanosoma congolense “forest type” and Trypanosoma vivax were 26.04% and 18.11%, respectively. About 6.41% of tsetse harbored mixed infections of T. congolense and T. vivax. Of the 69 tsetse with T. congolense infections, 33.33% (23/69) harbored S. glossinidius while 71.86% (69/96) of flies harboring S. glossinidius were not infected by trypanosomes. No association was observed between S. glossinidius and trypanosome infections. Some wild tsetse harbor S. glossinidius and trypanosomes, while others have no infection or are infected by only one of these microorganisms. We conclude that the presence of S. glossinidius does not favor trypanosome infections in G. p. palpalis of the Fontem focus.

Despite the economic impact of trypanosome infections, few investigations have been undertaken on the population genetics and transmission dynamics of animal trypanosomes. In this study, microsatellite markers were used to investigate the population genetics of Trypanosoma congolense “forest type”, with the ultimate goal of understanding its transmission dynamics between tsetse flies and domestic animals. Blood samples were collected from pigs, sheep, goats and dogs in five villages in Fontem, South-West region of Cameroon. In these villages, tsetse were captured, dissected and their mid-guts collected. DNA was extracted from blood and tsetse mid-guts and specific primers were used to identify T. congolense “forest type”. All positive samples were genetically characterized with seven microsatellite markers. Genetic analyses were performed on samples showing single infections of T. congolense “forest type”. Of the 299 blood samples, 137 (46%) were infected by T. congolense “forest type”. About 3% (54/1596) of tsetse fly mid-guts were infected by T. congolense “forest type”. Of 182 samples with T. congolense “forest type”, 52 were excluded from the genetic analysis. The genetic analysis on the 130 remaining samples revealed polymorphism within and between subpopulations of the target trypanosome. The dendrogram of genetic similarities was subdivided into two clusters and three sub-clusters, indicating one major and several minor genotypes of T. congolense “forest type” in tsetse and domestic animals. The low FSTvalues suggest low genetic differentiation and no sub-structuration within subpopulations. The same T. congolense genotypes appear to circulate in tsetse and domestic animals.

Background: Schistosomiasis control relies mainly on mass drug administration of Praziquantel (PZQ) to school aged children (SAC). Although precision mapping has recently guided decision making, the sub-districts and the epidemiological differences existing between bio-ecological settings in which infected children come from were not taken into consideration. This study was designed to fill this gap by using POC-CCA and KK to comparatively determine the prevalence and infection intensities of Schistosoma mansoni (S. mansoni) and to perform fine-scale mapping of S. mansoni infections and its infection intensities with the overarching goal of identifying sub-districts presenting high transmission risk where control operations must be boosted to achieve schistosomiasis elimination. Methodology: During a cross- sectional study conducted in Makenene, 1773 stool and 2253 urine samples were collected from SAC of ten primary schools. S. mansoni infections were identified using the point of care circulating cathodic antigen (POC-CCA) and Kato-Katz (KK) test respectively on urine and stool samples. Geographical coordinates of houses of infected SAC were recorded using a global position system device. Schistosome infections and infection intensities were map using QGIS software. Results: The prevalence of S. mansoni inferred from POC-CCA and KK were 51.3% and 7.3% respectively. Most infected SAC and those bearing heavy infections intensities were clustered in sub-districts of Baloua, Mock-sud and Carrière. Houses with heavily-infected SAC were close to risky biotopes. Conclusion: This study confirms the low sensitivity of KK test compared to POC-CCA to accurately identify children with schistosome infection and bearing different schistosome burden. Fine-scale mapping of schistosome infections and infection intensities enabled to identify high transmission sub-districts where control measures must be boosted to reach schistosomiasis elimination. Author summary: Although some disparities in terms of prevalence and infection intensities have been acknowledged within and between schistosomiasis endemic areas, the current control measures did not take into consideration the disparities within endemic areas. To improve the control of schistosomiasis, a fine-scale mapping of schistosome infections and their intensities were undertaken using KK in comparison to POC-CCA to identify sub-districts with potential high transmission risk and where control operations must be boosted to achieve elimination. After the identification of schistosome infections by the point of care circulating cathodic antigen (POC-CCA) and Kato-Katz (KK) test, the geographical coordinates of each infected child's house were recorded using a global position system device (GPS). QGIS software was used to create a map showing schistosome infections and their infection intensities. Our results showed that the majority of infected children and those bearing heavy infection intensities were clustering mostly in Baloua, Carrière and Mock-Sud sub-districts of Makenene while children with light and moderate infection intensity were widely distributed and far away from risky biotopes. The fine-scale mapping of schistosome infections and their infection intensities enable to identify hotspot transmission sites where control strategy must be boosted to achieve the elimination of intestinal schistosomiasis in Makenene. [ABSTRACT FROM AUTHOR]