Genetic structure of Anopheles gambiae populations on islands in northwestern Lake Victoria, Uganda

BACKGROUND: Alternative means of malaria control are urgently needed. Evaluating the effectiveness of measures that involve genetic manipulation of vector populations will be facilitated by identifying small, genetically isolated vector populations. The study was designed to use variation in microsatellite markers to look at genetic structure across four Lake Victoria islands and two surrounding mainland populations and for evidence of any restriction to free gene flow. METHODS: Four Islands (from 20–50 km apart) and two surrounding mainland populations (96 km apart) were studied. Samples of indoor resting adult mosquitoes, collected over two consecutive years, were genotyped at microsatellite loci distributed broadly throughout the genome and analysed for genetic structure, effective migration (Nem) and effective population size (Ne). RESULTS: Ne estimates showed island populations to consist of smaller demes compared to the mainland ones. Most populations were significantly differentiated geographically, and from one year to the other. Average geographic pair-wise FST ranged from 0.014–0.105 and several pairs of populations had Ne m < 3. The loci showed broad heterogeneity at capturing or estimating population differences. CONCLUSION: These island populations are significantly genetically differentiated. Differences reoccurred over the study period, between the two mainland populations and between each other. This appears to be the product of their separation by water, dynamics of small populations and local adaptation. With further characterisation these islands could become possible sites for applying measures evaluating effectiveness of control by genetic manipulation

Intrapatient Evolutionary Dynamics of Human Immunodeficiency Virus Type 1 in Individuals Undergoing Alternative Treatment Strategies with Reverse Transcriptase Inhibitors.

Structured treatment interruption (STI) has been trialed as an alternative to lifelong antiretroviral therapy (ART). We retrospectively performed single genome sequencing of the HIV-1 pol region from three patients representing different scenarios. They were either failing on continuous therapy (CT-F), failing STI (STI-F), or suppressing on STI (STI-S). Over 460 genomes were generated from three to five different time points over a 2-year period. We found multiple-linked-resistant mutations in both treatment failures. However, the CT-F patient showed a stepwise accumulation of diverse, linked mutations whereas the STI-F patient had lineage turnover between treatment periods with recirculation of wild-type and resistant variants from reservoirs. The STI-F patient showed a 7-fold increase in the third codon position substitution rate relative to the first and second positions compared to a 2-fold increase for CT-F and increased purifying selection in the pol gene (62 vs. 22 sites, respectively). An understanding of intrapatient viral dynamics could guide the future direction of treatment interruption strategies

The H3ABioNet helpdesk: an online bioinformatics resource, enhancing Africa’s capacity for genomics research

Abstract Background Currently, formal mechanisms for bioinformatics support are limited. The H3Africa Bioinformatics Network has implemented a public and freely available Helpdesk (HD), which provides generic bioinformatics support to researchers through an online ticketing platform. The following article reports on the H3ABioNet HD (H3A-HD)‘s development, outlining its design, management, usage and evaluation framework, as well as the lessons learned through implementation. Results The H3A-HD evaluated using automatically generated usage logs, user feedback and qualitative ticket evaluation. Evaluation revealed that communication methods, ticketing strategies and the technical platforms used are some of the primary factors which may influence the effectivity of HD. Conclusion To continuously improve the H3A-HD services, the resource should be regularly monitored and evaluated. The H3A-HD design, implementation and evaluation framework could be easily adapted for use by interested stakeholders within the Bioinformatics community and beyond

The effect of HIV on morbidity and mortality in children with severe malarial anaemia

<p>Abstract</p> <p>Background</p> <p>Malaria and HIV are common causes of mortality in sub-Saharan Africa. The effect of HIV infection on morbidity and mortality in children with severe malarial anaemia was assessed.</p> <p>Methods</p> <p>Children <5 years old were followed as part of a prospective cohort study to assess the transfusion-associated transmission of blood-borne pathogens at Mulago Hospital, Kampala, Uganda. All children were hospitalized with a diagnosis of severe malarial anaemia requiring blood transfusion. Survival to different time points post-transfusion was compared between HIV-infected and uninfected children. Generalized estimating equations were used to analyse repeated measurement outcomes of morbidity, adjusting for confounders.</p> <p>Findings</p> <p>Of 847 children, 78 (9.2%) were HIV-infected. Median follow-up time was 162 days (inter-quartile range: 111, 169). HIV-infected children were more likely to die within 7 days (Hazard ratio [HR] = 2.86, 95% Confidence interval [CI] 1.30–6.29, P = 0.009) and within 28 days (HR = 3.70, 95% CI 1.91–7.17, P < 0.001) of an episode of severe malarial anaemia, and were more likely to die in the 6 months post-transfusion (HR = 5.70, 95% CI 3.54–9.16, P < 0.001) compared to HIV-uninfected children. HIV-infected children had more frequent re-admissions due to malaria within 28 days (Incidence rate ratio (IRR) = 3.74, 95% CI 1.41–9.90, P = 0.008) and within 6 months (IRR = 2.66, 95% CI 1.17 – 6.07, P = 0.02) post-transfusion than HIV-uninfected children.</p> <p>Conclusion</p> <p>HIV-infected children with severe malarial anaemia suffered higher all-cause mortality and malaria-related mortality than HIV-uninfected children. Children with HIV and malaria should receive aggressive treatment and further evaluation of their HIV disease, particularly with regard to cotrimoxazole prophylaxis and antiretroviral therapy.</p

Development of Bioinformatics Infrastructure for Genomics Research:

Although pockets of bioinformatics excellence have developed in Africa, generally, large-scale genomic data analysis has been limited by the availability of expertise and infrastructure. H3ABioNet, a pan-African bioinformatics network, was established to build capacity specifically to enable H3Africa (Human Heredity and Health in Africa) researchers to analyze their data in Africa. Since the inception of the H3Africa initiative, H3ABioNet's role has evolved in response to changing needs from the consortium and the African bioinformatics community

Spatio-temporal genetic structure of Anopheles gambiae in the Northwestern Lake Victoria Basin, Uganda: implications for genetic control trials in malaria endemic regions

Abstract Background Understanding population genetic structure in the malaria vector Anopheles gambiae (s.s.) is crucial to inform genetic control and manage insecticide resistance. Unfortunately, species characteristics such as high nucleotide diversity, large effective population size, recent range expansion, and high dispersal ability complicate the inference of genetic structure across its range in sub-Saharan Africa. The ocean, along with the Great Rift Valley, is one of the few recognized barriers to gene flow in this species, but the effect of inland lakes, which could be useful sites for initial testing of genetic control strategies, is relatively understudied. Here we examine Lake Victoria as a barrier between the Ugandan mainland and the Ssese Islands, which lie up to 60 km offshore. We use mitochondrial DNA (mtDNA) from populations sampled in 2002, 2012 and 2015, and perform Bayesian cluster analysis on mtDNA combined with microsatellite data previously generated from the same 2002 mosquito DNA samples. Results Hierarchical analysis of molecular variance and Bayesian clustering support significant differentiation between the mainland and lacustrine islands. In an mtDNA haplotype network constructed from this and previous data, haplotypes are shared even between localities separated by the Rift Valley, a result that more likely reflects retention of shared ancestral polymorphism than contemporary gene flow. Conclusions The relative genetic isolation of An. gambiae on the Ssese Islands, their small size, level terrain and ease of access from the mainland, the relative simplicity of the vectorial system, and the prevalence of malaria, are all attributes that recommend these islands as possible sites for the testing of genetic control strategies

Data from: Spatio-temporal genetic structure of Anopheles gambiae in the Northwestern Lake Victoria Basin, Uganda: implications for genetic control trials in malaria endemic regions

Background: Understanding population genetic structure in the malaria vector Anopheles gambiae (s.s.) is crucial to inform genetic control and manage insecticide resistance. Unfortunately, species characteristics such as high nucleotide diversity, large effective population size, recent range expansion, and high dispersal ability complicate the inference of genetic structure across its range in sub-Saharan Africa. The ocean, along with the Great Rift Valley, is one of the few recognized barriers to gene flow in this species, but the effect of inland lakes, which could be useful sites for initial testing of genetic control strategies, is relatively understudied. Here we examine Lake Victoria as a barrier between the Ugandan mainland and the Ssese Islands, which lie up to 60 km offshore. We use mitochondrial DNA (mtDNA) from populations sampled in 2002, 2012 and 2015, and perform Bayesian cluster analysis on mtDNA combined with microsatellite data previously generated from the same 2002 mosquito DNA samples. Results: Hierarchical analysis of molecular variance and Bayesian clustering support significant differentiation between the mainland and lacustrine islands. In an mtDNA haplotype network constructed from this and previous data, haplotypes are shared even between localities separated by the Rift Valley, a result that more likely reflects retention of shared ancestral polymorphism than contemporary gene flow. Conclusions: The relative genetic isolation of An. gambiae on the Ssese Islands, their small size, level terrain and ease of access from the mainland, the relative simplicity of the vectorial system, and the prevalence of malaria, are all attributes that recommend these islands as possible sites for the testing of genetic control strategies

Reduced-representation sequencing identifies small effective population sizes of Anopheles gambiae in the north-western Lake Victoria basin, Uganda

Abstract Background Malaria is the leading cause of global paediatric mortality in children below 5 years of age. The number of fatalities has reduced significantly due to an expansion of control interventions but the development of new technologies remains necessary in order to achieve elimination. Recent attention has been focused on the release of genetically modified (GM) mosquitoes into natural vector populations as a mechanism of interrupting parasite transmission but despite successful in vivo laboratory studies, a detailed population genetic assessment, which must first precede any proposed field trial, has yet to be undertaken systematically. Here, the genetic structure of Anopheles gambiae populations in north-western Lake Victoria is explored to assess their suitability as candidates for a pilot field study release of GM mosquitoes. Methods 478 Anopheles gambiae mosquitoes were collected from six locations and a subset (N = 96) was selected for restriction site-associated DNA sequencing (RADseq). The resulting single nucleotide polymorphism (SNP) marker set was analysed for effective size (Ne), connectivity and population structure (PCA, FST). Results 5175 high-quality genome-wide SNPs were identified. A principal components analysis (PCA) of the collinear genomic regions illustrated that individuals clustered in concordance with geographic origin with some overlap between sites. Genetic differentiation between populations was varied with inter-island comparisons having the highest values (median FST 0.0480–0.0846). Ne estimates were generally small (124.2–1920.3). Conclusions A reduced-representation SNP marker set for genome-wide An. gambiae genetic analysis in the north-western Lake Victoria basin is reported. Island populations demonstrated low to moderate genetic differentiation and greater structure suggesting some limitation to migration. Smaller estimates of Ne indicate that an introduced effector transgene will be more susceptible to genetic drift but to ensure that it is driven to fixation a robust gene drive mechanism will likely be needed. These findings, together with their favourable location and suitability for frequent monitoring, indicate that the Ssese Islands contain several candidate field locations, which merit further evaluation as potential GM mosquito pilot release sites