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Background Substance misuse is a global public health problem. In addition to social and economic concerns, consumption of tobacco and alcohol is associated with susceptibility to cardiovascular, respiratory, and infectious diseases, cancers, and risk of transition to substance use disorders. African data suggest regional differences in the prevalence and patterns of substance use, but a number of key questions remain. This cross-sectional population-based study of middle-aged adults aims to examine prevalence and socio-demographic correlates of substance use in four sub-Saharan African countries, in rural and urban settings. Methods Participants aged between 40 and 60 years were recruited from six research centres as part of the Africa Wits-INDEPTH partnership for Genomic Research study. Data on patterns of tobacco and alcohol consumption was captured, and the latter further assessed using the CAGE (cut-annoyed-guilty-eye) questionnaire. Results Data from 10,703 participants suggested that more men (68.4%) than women (33.3%) were current substance users. The prevalence of current smoking was significantly higher in men than in women (34.5% vs 2.1%, p Conclusions Regional variation in the patterns and prevalence of substance use was observed across study sites, and in rural and urban settings. The high levels of substance use recorded in this study are of concern due to the increased risk of associated morbidities. Further longitudinal data will be valuable in determining trends in substance misuse in Africa.

First reported case of Takenouchi–Kosaki syndrome in an African patient with a de novo likely pathogenic missense variant identified in the CDC42 gene., First reported case of Takenouchi–Kosaki syndrome in an African patient with a de novo, likely pathogenic missense variant identified in the CDC42 gene.

Background: Approximately 25% of the risk of Schistosoma mansoni is associated with host genetic variation. We will test 24 candidate genes, mainly in the T h2 and T h17 pathways, for association with S. mansoni infection intensity in four African countries, using family based and case-control approaches. Methods: Children aged 5-15 years will be recruited in S. mansoni endemic areas of Ivory Coast, Cameroon, Uganda and the Democratic Republic of Congo (DRC). We will use family based (study 1) and case-control (study 2) designs. Study 1 will take place in Ivory Coast, Cameroon, Uganda and the DRC. We aim to recruit 100 high worm burden families from each country except Uganda, where a previous study recruited at least 40 families. For phenotyping, cases will be defined as the 20% of children in each community with heaviest worm burdens as measured by the circulating cathodic antigen (CCA) assay. Study 2 will take place in Uganda. We will recruit 500 children in a highly endemic community. For phenotyping, cases will be defined as the 20% of children with heaviest worm burdens as measured by the CAA assay, while controls will be the 20% of infected children with the lightest worm burdens. Deoxyribonucleic acid (DNA) will be genotyped on the Illumina H3Africa SNP (single nucleotide polymorphisms) chip and genotypes will be converted to sets of haplotypes that span the gene region for analysis. We have selected 24 genes for genotyping that are mainly in the Th2 and Th17 pathways and that have variants that have been demonstrated to be or could be associated with Schistosoma infection intensity. Analysis: In the family-based design, we will identify SNP haplotypes disproportionately transmitted to children with high worm burden. Case-control analysis will detect overrepresentation of haplotypes in extreme phenotypes with correction for relatedness by using whole genome principal components.

Friedreich ataxia is the most common inherited ataxia in the world, but yet to be reported in black African. We report the first genetically confirmed case in a West African family. Studying genetic diseases in populations with diverse backgrounds may give new insights into their pathophysiology for future therapeutic targets.

Background With growth of genomics research in Africa, concern has arisen about comprehension and adequacy of informed consent given the highly technical terms used in this field. We therefore decided to study whether there are linguistic and cultural concepts used to communicate heritability of characters, traits and diseases in an indigenous African population. Methods We conducted Focus Group Discussions among 115 participants stratified by sex, age and socio-economic status and Key Informant Interviews among 25 stakeholders and Key Opinion Leaders among Yoruba living in Ibadan, Nigeria. We used Atlas-ti v.8.3.17 software to analyze the data, using thematic approach. Results The study participants identified several linguistic and cultural concepts including words, proverbs, and aphorisms that are used to describe heritable characters, traits and diseases in their local dialect. These included words that can be appropriated to describe dominant and recessive traits, variations in penetrance and dilution of strength of heritable characteristics by time and inter-marriage. They also suggested that these traits are transmitted by “blood”, and specific partner’s blood may be stronger than the other regardless of sex. Conclusions Indigenous Yoruba populations have words and linguistic concepts that describe the heritability of characters, traits and diseases which can be appropriated to improve comprehension and adequacy of informed consent in genomics research. Our methods are openly available and can be used by genomic researchers in other African communities.

Background: Human African trypanosomiasis (HAT) is a protozoal disease transmitted by tsetse flies. Infection with trypanosomes can lead directly to active HAT or latent infection with no detectable parasites, which may progress to active HAT or to spontaneous self-cure. Genetic variation could explain these differences in the outcome of infection. To test this hypothesis, polymorphisms in 17 candidate genes were tested (APOL1 [G1 and G2], CFH, HLA-A, HPR, HP, IL1B, IL12B, IL12RB1, IL10, IL4R, MIF, TNFA, IL6, IL4, IL8, IFNG, and HLA-G). Methods: Samples were collected in Democratic Republic of the Congo. 233 samples were genotyped: 100 active HAT cases, 33 from subjects with latent infections and 100 negative controls. Commercial service providers genotyped polymorphisms at 96 single nucleotide polymorphisms (SNPs) on 17 genes. Data were analyzed using Plink V1.9 software and R. Loci, with suggestive associations (uncorrected p < 0.05) validated using an additional 594 individuals, including 164 cases and 430 controls. Results: After quality control, 87 SNPs remained in the analysis. Two SNPs in IL4 and two in IFNG were suggestively associated (uncorrected p

The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed(1). Here we performed whole-genome sequencing analyses of 426 individualscomprising 50 ethnolinguistic groups, including previously unsampled populations-to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon-but in other genes, variants denoted as `likely pathogenic' in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health.

Africa contains more human genetic variation than any other continent, but the majority of the population-scale analyses of the African peoples have focused on just two of the four major linguistic groups, the Niger-Congo and Afro-Asiatic, leaving the Nilo-Saharan and Khoisan populations under-represented. In order to assess genetic variation and signatures of selection within a Nilo-Saharan population and between the Nilo-Saharan and Niger-Congo and Afro-Asiatic, we sequenced 50 genomes from the Nilo-Saharan Lugbara population of North-West Uganda and 250 genomes from 6 previously unsequenced Niger-Congo populations. We compared these data to data from a further 16 Eurasian and African populations including the Gumuz, another putative Nilo-Saharan population from Ethiopia. Of the 21 million variants identified in the Nilo-Saharan population, 3.57 million (17%) were not represented in dbSNP and included predicted non-synonymous mutations with possible phenotypic effects. We found greater genetic differentiation between the Nilo-Saharan Lugbara and Gumuz populations than between any two Afro-Asiatic or Niger-Congo populations. F3 tests showed that Gumuz contributed a genetic component to most Niger-Congo B populations whereas Lugabara did not. We scanned the genomes of the Lugbara for evidence of selective sweeps. We found selective sweeps at four loci (SLC24A5, SNX13, TYRP1, and UVRAG) associated with skin pigmentation, three of which already have been reported to be under selection. These selective sweeps point toward adaptations to the intense UV radiation of the Sahel.

TrypanoGEN Research Group., H3Africa Consortium., The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed1. Here we performed whole-genome sequencing analyses of 426 individuals—comprising 50 ethnolinguistic groups, including previously unsampled populations—to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon—but in other genes, variants denoted as ‘likely pathogenic’ in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health., We thank the members of the wider H3Africa Consortium (www.h3africa.org). WGS in H3Africa cohorts was supported by a grant from the National Human Genome Research Institute, National Institutes of Health (NIH/NHGRI) U54HG003273. The African Collaborative Center for Microbiome and Genomics Research (ACCME) is funded by NIH/NHGRI grant U54HG006947. The AWI-Gen Collaborative Centre is funded by NIH grant U54HG006938. The Exploring Perspectives on Genomics and Sickle Cell Public Health Interventions was funded by NHGRI/NIH grant U01HG007459. The Clinical and Genetic Studies of Hereditary Neurological Disorders in Mali study was funded by the NHGRI/NIH grant U01HG007044. The Collaborative African Genomics Network (CAfGEN) is funded by the National Institute of Allergy and Infectious Diseases (NIAID) of NIH and the NHGRI of the NIH (U54AI110398). ‘TrypanoGEN: an integrated approach to the identification of genetic determinants of susceptibility to trypanosomiasis’, was funded by the Wellcome Trust (099310/Z/12/Z). L.R.B. was supported by the CERCA Programme/Generalitat de Catalunya and by the Spanish Ministry of Economy and Competitiveness, through the ‘Severo Ochoa Programme for Centres of Excellence in R&D’ 2016–2019 (SEV-2015-0533). N.M. (principal investigator), S.A., G.B., G.W., J.K., Y.J.F., T.O., O.F., E.A., S.H., G. Mazandu, M. Mbiyvanga, A.B., S.K.K., E.R.C. and A. Moussa are funded by the NIH H3ABioNet grant under award number U24HG006941.

In the past decade, there has been an increase in genomic research and biobanking activities in Africa. Research initiatives such as the Human Heredity and Health in Africa (H3Africa) Consortium are contributing to the development of scientific capacity and infrastructure to support these studies on the continent. Despite this growth, genomic research and biobanking have raised important ethical challenges for key research stakeholders, including members of research ethics committees. One of these is the limited ethical and regulatory frameworks to guide the review and conduct of genomic studies, particularly in Africa. This paper is a reflection on a series of consultative activities with research ethics committees in Africa which informed the development of an ethics and governance framework for best practices in genomic research and biobanking in Africa. The paper highlights the engagement process and the lessoned learned.

Trypanosoma brucei (T.b.) rhodesiense is the cause of the acute form of human African trypanosomiasis (HAT) in eastern and southern African countries. There is some evidence that there is diversity in the disease progression of T.b. rhodesiense in different countries. HAT in Malawi is associated with a chronic haemo-lymphatic stage infection compared to other countries, such as Uganda, where the disease is acute with more marked neurological impairment. This has raised the question of the role of host genetic factors in infection outcomes. A candidate gene association study was conducted in the northern region of Malawi. This was a case-control study involving 202 subjects, 70 cases and 132 controls. All individuals were from one area; born in the area and had been exposed to the risk of infection since birth. Ninety-six markers were genotyped from 17 genes: IL10, IL8, IL4, HLA-G, TNFA, IL6, IFNG, MIF, APOL, HLA-A, IL1B, IL4R, IL12B, IL12R, HP, HPR, and CFH. There was a strong significant association with APOL1 G2 allele (p = 0.0000105, OR = 0.14, CI95 = [0.05–0.41], BONF = 0.00068) indicating that carriers of the G2 allele were protected against T.b. rhodesiense HAT. SNP rs2069845 in IL6 had raw p < 0.05, but did not remain significant after Bonferroni correction. There were no associations found with the other 15 candidate genes. Our finding confirms results from other studies that the G2 variant of APOL1 is associated with protection against T.b. rhodesiense HAT., Author summary Though some work has been done on the genetics of trypanosome infections in animals, relatively little is known about the genetics of human African trypanosomiasis (HAT) infections. To test whether any variants are associated with reduced or increased risk of trypanosomiasis, 96 variants in 17 genes were genotyped in patients diagnosed with T. b. rhodesiense HAT and individuals without the disease in this study. From the 96 variants, only one variant G2 in the APOL1 gene was found to be strongly associated with protection from trypanosomiasis. The results reported here will contribute to the knowledge of the role of human genetics in disease progression, which could offer opportunities for development of much needed new diagnostics and intervention strategies.

Background Studies on the determinants of carotid intima-media thickness ( CIMT ), a marker of sub-clinical atherosclerosis, mostly come from white, Asian, and diasporan black populations. We present CIMT data from sub-Saharan Africa, which is experiencing a rising burden of cardiovascular diseases and infectious diseases. Methods and Results The H3 (Human Hereditary and Health) in Africa's AWI-Gen (African-Wits-INDEPTH partnership for Genomic) study is a cross-sectional study conducted in adults aged 40 to 60 years from Burkina Faso, Kenya, Ghana, and South Africa. Cardiovascular disease risk and ultrasonography of the CIMT of right and left common carotids were measured. Multivariable linear and mixed-effect multilevel regression modeling was applied to determine factors related to CIMT. Data included 8872 adults (50.8% men), mean age of 50±6 years with age- and sex-adjusted mean (±SE) CIMT of 640±123μm. Participants from Ghana and Burkina Faso had higher CIMT compared with other sites. Age (β = 6.77, 95%CI [6.34-7.19]), body mass index (17.6[12.5-22.8]), systolic blood pressure (7.52[6.21-8.83]), low-density lipoprotein cholesterol (5.08[2.10-8.06]) and men (10.3[4.75- 15.9]) were associated with higher CIMT. Smoking was associated with higher CIMT in men. High-density lipoprotein cholesterol (-12.2 [-17.9- -6.41]), alcohol consumption (-13.5 [-19.1--7.91]) and HIV (-8.86 [-15.7--2.03]) were inversely associated with CIMT. Conclusions Given the rising prevalence of cardiovascular diseases risk factors in sub-Saharan Africa, atherosclerotic diseases may become a major pan-African epidemic unless preventive measures are taken particularly for prevention of hypertension, obesity, and smoking. HIV -specific studies are needed to fully understand the association between HIV and CIMT in sub-Saharan Africa.

Background Charcot‐Marie‐Tooth (CMT) disease is a very heterogeneous neurological condition with more than 90 reported genetic entities. It is the most common inherited peripheral neuropathy; however, cases are rarely reported in sub‐Saharan Africa. In addition, only few families, mostly of Caucasian ancestry, have been reported to have Charcot‐Marie‐Tooth disease type 2D (CMT2D) mutations. To date no case of CMT2D was reported in Africa. We present here a consanguineous family with CMT phenotype in which a novel mutation in the GARS (glycyl‐tRNA synthetase) gene was identified. Methods Patients were examined thoroughly and nerve conduction studies (NCS) were performed. DNA from the proband was used for CMT gene panel testing (including 50 genes, PMP22 duplication and mtDNA). Putative mutations were verified in all available family members to check for segregation. Results Two individuals, a male and a female, were found to be affected. Symptoms started in their teenage years with muscle weakness and atrophy in hands. Later, distal involvement of the lower limbs was noticed. Patients complained of minor sensory impairment. NCS showed no response in the upper as well as the lower limbs. Genetic testing surprisingly identified a novel heterozygous missense mutation c.794C>A (p.Ser265Tyr) in the GARS gene associated with CMT2D. This variant segregated with the disease in the family and was also seen in the mother who presented no symptoms. Conclusion This is the first report of a genetically confirmed CMT2D case in Africa, expanding its genetic epidemiology. Increasing access to genetic testing may reveal more novel CMT variants or genes in the African population that could be relevant to other populations and further our understanding of their mechanism.

Background Human African Trypanosomiasis (HAT) is a neglected tropical disease caused by infections due to Trypanosoma brucei subspecies. In addition to the well-established environmental and behavioural risks of becoming infected, there is evidence for a genetic component to the response to trypanosome infection. We undertook a candidate gene case-control study to investigate genetic associations further. Methodology We genotyped one polymorphism in each of seven genes (IL1A, IL1RN, IL4RN, IL6, HP, HPR, and HLA-G) in 73 cases and 250 controls collected from 19 ethno-linguistic subgroups stratified into three major ethno-linguistic groups, 2 pooled ethno-linguistic groups and 11 ethno-linguistic subgroups from three Cameroonian HAT foci. The seven polymorphic loci tested consisted of three SNPs, three variable numbers of tandem repeat (VNTR) and one INDEL. Results We found that the genotype (TT) and minor allele (T) of IL1A gene as well as the genotype 1A3A of IL1RN were associated with an increased risk of getting Trypanosoma brucei gambiense and develop HAT when all data were analysed together and also when stratified by the three major ethno-linguistic groups, 2 pooled ethno-linguistic subgroups and 11 ethno-linguistic subgroups. Conclusion This study revealed that one SNP rs1800794 of IL1A and one VNTR rs2234663 of IL1RN were associated with the increased risk to be infected by Trypanosoma brucei gambiense and develop sleeping sickness in southern Cameroon. The minor allele T and the genotype TT of SNP rs1800794 in IL1A as well as the genotype 1A3A of IL1RN rs2234663 VNTR seem to increase the risk of getting Trypanosoma brucei gambiense infections and develop sleeping sickness in southern Cameroon., Author summary Human African Trypanosomiasis (HAT), or sleeping sickness, is a parasitic disease caused by flagellated parasites of the genus Trypanosoma. This disease has been included into the WHO roadmap for neglected tropical diseases with elimination as a public health problem targeted for 2020 and the interruption of transmission to humans for 2030. To achieve these elimination and interruption goals, it is important to identify and understand the factors that may hamper these goals. Understanding the contribution of human genetics to the response of trypanosome infections is important for the development of new control strategies. In this study, polymorphism in seven genes was investigated between controls and sleeping sickness patients of three sleeping sickness foci of Southern Cameroon in order to see if there is any association with the development of disease. Results of this study have shown that the genotype (TT) and minor allele (T) of IL1A gene and the genotype 1A3A VNTR of IL1RN are associated with an increased risk of getting T. b. gambiense infections and develop sleeping sickness in major ethno-linguistic groups of the Cameroonian population. They suggest that the association between host genetic determinants and the susceptibility to T. b. gambiense infections could vary according to the population studied. These results will improve our knowledge on the role of human genetics determinants and the risk to be infected by T. b. gambiense and develop sleeping sickness. They could thus lead to the identification of novel biomarkers which could open a frame work for the development of new diagnostics, treatments and intervention strategies.

Trypanosoma brucei (T.b.) rhodesiense is the cause of the acute form of human African trypanosomiasis (HAT) in eastern and southern African countries. There is some evidence that there is diversity in the disease progression of T.b. rhodesiense in different countries. HAT in Malawi is associated with a chronic haemo-lymphatic stage infection compared to other countries, such as Uganda, where the disease is acute with more marked neurological impairment. This has raised the question of the role of host genetic factors in infection outcomes. A candidate gene association study was conducted in the northern region of Malawi. This was a case-control study involving 202 subjects, 70 cases and 132 controls. All individuals were from one area; born in the area and had been exposed to the risk of infection since birth. Ninety-six markers were genotyped from 17 genes: IL10, IL8, IL4, HLA-G, TNFA, IL6, IFNG, MIF, APOL, HLA-A, IL1B, IL4R, IL12B, IL12R, HP, HPR, and CFH. There was a strong significant association with APOL1 G2 allele (p = 0.0000105, OR = 0.14, CI95 = [0.05-0.41], BONF = 0.00068) indicating that carriers of the G2 allele were protected against T.b. rhodesiense HAT. SNP rs2069845 in IL6 had raw p < 0.05, but did not remain significant after Bonferroni correction. There were no associations found with the other 15 candidate genes. Our finding confirms results from other studies that the G2 variant of APOL1 is associated with protection against T.b. rhodesiense HAT.

[This corrects the article DOI: 10.1371/journal.pone.0206326.].

Purpose There is a dearth of data on clearance of cervical human papillomavirus (HPV) infection among women in West Africa. We examined the clearance of low-risk (lr) and high-risk (hr) cervical HPV infections, and the factors associated with these measures in HIV-negative and HIV-positive women. Methods We studied 630 Nigerian women involved in a study of HPV infection using short polymerase chain reaction fragment-10 assay and line probe assay-25. Research nurses used a cervical brush to collect samples of exfoliated cervical cells from all the study participants. Cox proportional hazards models were used to estimate associations between HIV and HPV infections. Results The mean age of the study participants was 38 (standard deviation, ± 8) years; 51% were HIV positive. The rate of clearing any HPV infection was 2.0% per month among all women in the study population, 2.5% per month among HIV-negative women, and 1.6% per month, among HIV-positive women. The clearance rate per 1,000 person-months of observation for any lrHPV infection and any hrHPV infection were 9.21 and 8.83, respectively, for HIV-negative women, and 9.38 and 9.37, respectively, for HIV-positive women. In multivariate models, the hazard ratios for HIV-positive compared with HIV-negative women were 0.85 (95% CI, 0.51 to 1.43; P = .55) and 0.95 (95% CI, 0.54 to 1.65; P = .85) for cleared infections with any lrHPV and any hrHPV, respectively. The hazard ratio for HIV-positive compared with HIV-negative women was 0.39 (95% CI, 0.17 to 0.88; P = .02) for cleared infections with any multiple HPV and 0.13 (95% CI, 0.03 to 0.58; P = .007) for cleared infections with multiple hrHPV. Conclusion In this study population, we observed that HIV-positive women were less likely to clear infections with multiple hrHPV types.

Background: Obesity and associated cardiometabolic diseases are increasing in urban sub-Saharan Africa due to a complex epidemiological and nutritional transition. Related data on rural communities is scarce. Objectives: The study characterized the socio-demographic and behavioural factors influencing body mass index (BMI) among adults in rural Northern Ghana Methods: A population-based cross-sectional study involving adults aged 40–60 years residing in the Kassena-Nankana districts was undertaken. Demographic, socio-economic and behavioural data were collected along with measures of anthropometry. We determined factors associated with BMI among women and men. Results: A total of 2014 adults were studied. The median age was 51 (IQR 45–57) years and 54% were women. The prevalence of overweight/obesity was higher among women than men (18.4% vs. 7.2%; p

Background: African populations are characterised by diversity at many levels including: demographic history, genetic ancestry, language, wealth, socio-political landscape, culture and behaviour. Several of these have a profound impact on body fat mass. Obesity, a key risk factor for cardiovascular and metabolic diseases, in the wake of the epidemiological and health transitions across the continent, requires detailed analysis together with other major risk factors. Objective: To compare regional and sex-specific body mass index (BMI) distributions, using a cross-sectional study design, in adults aged 40–60 years across six study sites in four sub-Saharan African (SSA) countries and to compare the determinants of BMI at each. Methods: Anthropometric measurements were standardised across sites and BMI calculated. Median BMI and prevalence of underweight, lean, overweight and obesity were compared between the sexes and across sites. Data from multivariable linear regression models for the principal determinants of BMI were summarised from the site-specific studies. Results: BMI was calculated in 10,702 participants (55% female) and was significantly higher in women than men at nearly all sites. The highest prevalence of obesity was observed at the three South African sites (42.3–66.6% in women and 2.81–17.5% in men) and the lowest in West Africa (1.25–4.22% in women and 1.19–2.20% in men). Across sites, higher socio-economic status and educational level were associated with higher BMI. Being married and increased dietary intake were associated with higher BMI in some communities, whilst smoking and alcohol intake were associated with lower BMI, as was HIV infection in the regions where it was prevalent. Conclusion: In SSA there is a marked variation in the prevalence of obesity both regionally and between men and women. Our data suggest that the drive for social upliftment within Africa will be associated with rising levels of obesity, which will require the initiation of targeted sex-specific intervention programmes across specific African communities.

Human African Trypanosomiasis (HAT) or sleeping sickness is a Neglected Tropical Disease. Long regarded as an invariably fatal disease, there is increasing evidence that infection by T. b. gambiense can result in a wide range of clinical outcomes, including latent infections, which are long lasting infections with no parasites detectable by microscopy. The determinants of this clinical diversity are not well understood but could be due in part to parasite or host genetic diversity in multiple genes, or their interactions. A candidate gene association study was conducted in Côte d’Ivoire using a case-control design which included a total of 233 subjects (100 active HAT cases, 100 controls and 33 latent infections). All three possible pairwise comparisons between the three phenotypes were tested using 96 SNPs in16 candidate genes (IL1, IL4, IL4R, IL6, IL8, IL10, IL12, IL12R, TNFA, INFG, MIF, APOL1, HPR, CFH, HLA-A and HLA-G). Data from 77 SNPs passed quality control. There were suggestive associations at three loci in IL6 and TNFA in the comparison between active cases and controls, one SNP in each of APOL1, MIF and IL6 in the comparison between latent infections and active cases and seven SNP in IL4, HLA-G and TNFA between latent infections and controls. No associations remained significant after Bonferroni correction, but the Benjamini Hochberg false discovery rate test indicated that there were strong probabilities that at least some of the associations were genuine. The excess of associations with latent infections despite the small number of samples available suggests that these subjects form a distinct genetic cluster different from active HAT cases and controls, although no clustering by phenotype was observed by principle component analysis. This underlines the complexity of the interactions existing between host genetic polymorphisms and parasite diversity., Author summary Since it was first identified, human African trypanosomiasis (HAT) or sleeping sickness has been described as invariably fatal. Recent data however suggest that infection by T. b. gambiense can result in a wide range of clinical outcomes in its human host including long lasting infections, that can be detected by the presence of antibodies, but in which parasites cannot be seen by microscopy; these cases are known as latent infections. While the factors determining, this varied response have not been clearly characterized, the effectors of the immune responses have been partially implicated as key players. We collected samples from people with active HAT, latent infections and controls in endemic foci in the Côte d’Ivoire. We tested the role of single nucleotide polymorphisms (SNPs) in 16 genes on susceptibility/resistance to HAT by means of a candidate gene association study. There was some evidence that variants of the genes for IL4, IL6, APOL1, HLAG, MIF and TNFA modified the risk of developing HAT. These proteins regulate the inflammatory response to many infections or are directly involved in killing the parasites. In this study, the results were statistically weak and would be inconclusive on their own, however other studies have also found associations in these genes, increasing the chance that the variants that we have identified play a genuine role in the response to trypanosome infection in Côte D’Ivoire.

Background: The introduction of genomics and biobanking methodologies to the African research context has also introduced novel ways of doing science, based on values of sharing and reuse of data and samples. This shift raises ethical challenges that need to be considered when research is reviewed by ethics committees, relating for instance to broad consent, the feedback of individual genetic findings, and regulation of secondary sample access and use. Yet existing ethics guidelines and regulations in Africa do not successfully regulate research based on sharing, causing confusion about what is allowed, where and when. \ud \ud Methods: In order to understand better the ethics regulatory landscape around genomic research and biobanking, we conducted a comprehensive analysis of existing ethics guidelines, policies and other similar sources. We sourced 30 ethics regulatory documents from 22 African countries. We used software that assists with qualitative data analysis to conduct a thematic analysis of these documents.\ud \ud Results: Surprisingly considering how contentious broad consent is in Africa, we found that most countries allow the use of this consent model, with its use banned in only three of the countries we investigated. In a likely\ud response to fears about exploitation, the export of samples outside of the continent is strictly regulated, sometimes in conjunction with regulations around international collaboration. We also found that whilst an essential and critical component of ensuring ethical best practice in genomics research relates to the governance framework that accompanies sample and data sharing, this was most sparingly covered in the guidelines.\ud \ud Conclusions: There is a need for ethics guidelines in African countries to be adapted to the changing science policy landscape, which increasingly supports principles of openness, storage, sharing and secondary use. Current guidelines are not pertinent to the ethical challenges that such a new orientation raises, and therefore fail to provide accurate guidance to ethics committees and researchers.

BackgroundSickle cell disease (SCD) has a high prevalence in sub-Saharan Africa. There are several cardiovascular phenotypes in SCD that contribute to its morbidity and mortality.DiscussionSCD is characterised by marked clinical variability, with genetic factors playing key modulating roles. Studies in Tanzania and Cameroon have reported that singlenucleotide polymorphisms in BCL11A and HBS1L-MYB loci and co-inheritance of alpha-thalassaemia impact on foetal haemoglobin levels and clinical severity. The prevalence of overt stroke among SCD patients in Cameroon (6.7%) and Nigeria (8.7%) suggests a higher burden than in high-income countries. There is also some evidence of high burden of kidney disease and pulmonary hypertension in SCD; however, the burden and genetics of these cardiovascular conditions have seldom been investigated in Africa.ConclusionsSeveral H3Africa projects are focused on cardiovascular diseases and present major opportunities to build genome-based research on existing SCD platforms in Africa to transform the health outcomes of patients.