Continental-scale genomic analysis suggests shared post-admixture adaptation in the Americas

We thank the people working at the High Performance Computing Center of the University of Tartu for the help and support provided. We thank Marco Rosario Capodiferro for useful discussions. This work was supported by the European Union through the European Regional Development Fund (Project No. 20142020.4.01.16-0030 to LO, MMe, FM; Project No. 2014-2020.4.01.160271 to RF; Project No. 2014-2020.4.01.16-0125 to RF; Project No. 2014-2020.4.01.16-0024 to DM, LP). This work was supported by the Estonian Research Council grant PUT (PRG243) (to RF, MMe, LP). This work was supported by institutional research funding IUT (IUT24-1) of the EstonianMinistry of Education and Research (to TK). This research was supported by the European Union through Horizon 2020 grant no. 810645 (to MMe). This research was supported by the European Union through the Horizon 2020 research and innovation programme under grant no 810645 and through the European Regional Development Fund project no. MOBEC008 to MMo.American populations are one of the most interesting examples of recently admixed groups, where ancestral components from three major continental human groups (Africans, Eurasians and Native Americans) have admixed within the last 15 generations. Recently, several genetic surveys focusing on thousands of individuals shed light on the geography, chronology and relevance of these events. However, even though gene f low could drive adaptive evolution, it is unclear whether and how natural selection acted on the resulting genetic variation in the Americas. In this study, we analysed the patterns of local ancestry of genomic fragments in genome-wide data for ∼6000 admixed individuals from 10 American countries. In doing so, we identified regions characterized by a divergent ancestry profile (DAP), in which a significant over or under ancestral representation is evident. Our results highlighted a series of genomic regions with DAPs associated with immune system response and relevant medical traits, with the longest DAP region encompassing the human leukocyte antigen locus. Furthermore, we found that DAP regions are enriched in genes linked to cancer-related traits and autoimmune diseases. Then, analysing the biological impact of these regions, we showed that natural selection could have acted preferentially towards variants located in coding and non-coding transcripts and characterized by a high deleteriousness score. Taken together, our analyses suggest that shared patterns of post admixture adaptation occurred at a continental scale in the Americas, affecting more often functional and impactful genomic variants.European Commission 2014-2020.4.01.16-0030 2014-2020.4.01.16-0271 2014-2020.4.01.16-0125 2014-2020.4.01.16-0024 MOBEC008Estonian Research Council grant PUT PRG243institutional research funding IUT of the Estonian Ministry of Education and Research IUT24-1European Union through Horizon 2020 grant 81064

A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa.

The progression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Africa has so far been heterogeneous, and the full impact is not yet well understood. In this study, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations predominantly from Europe, which diminished after the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1, and C.1.1. Although distorted by low sampling numbers and blind spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a source for new variants

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Performance of point-of-care birth HIV testing in primary health care clinics: An observational cohort study.

BACKGROUND:Failure to timely diagnose HIV in infants is a major barrier for scaling-up paediatric antiretroviral treatment (ART). WHO recommends birth testing for earlier diagnosis and to improve test coverage, but current diagnosis takes 2-3 weeks to complete, thereby limiting the ability of care givers to provide follow-on care, especially in low-resource settings. We evaluated the benefit of implementing rapid diagnosis of HIV at birth in primary health care maternity wards in Mozambique. METHODS AND FINDINGS:Infants born to HIV-infected mothers delivering consecutively at eight primary health care clinics were tested within 24 hours of delivery using on-site POC (Alere q HIV1/2 Detect) and standard laboratory (Roche COBAS AmpliPrep/TaqMan HIV-1 qualitative assay v2.0) testing. Infants were also tested at 4-6 weeks of age with both assays. Of 2,350 HIV-exposed infants enrolled in this implementation research study, 33 tested HIV-positive at birth on both assays. Sensitivity and specificity of POC testing compared with laboratory testing at birth were 100% (95% CI 89·4-100·0) and 100% (95% CI 99·8-100·0), respectively. At 4-6 weeks of age, 61 infants were identified as HIV-positive; of these 29 (47·5%) had a positive test at birth. Testing at both birth and 4-6 weeks identified 71 HIV-positive infants compared with 61 infants by testing at 4-6 weeks alone, a 16% increase. Two infants tested positive at birth but tested HIV-negative during follow-up. CONCLUSIONS:Adding POC birth testing to the 4-6 week screen may increase access to HIV diagnosis and expedite ART initiation in primary health care settings within low resource settings. Guidance on appropriate confirmatory HIV testing algorithms for birth testing is needed

High rates of HIV seroconversion in pregnant women and low reported levels of HIV testing among male partners in southern Mozambique: Results from a mixed methods study

Introduction Prevention of acute HIV infections in pregnancy is required to achieve elimination of pediatric HIV. Identification and support for HIV negative pregnant women and their partners, particularly serodiscordant couples, are critical. A mixed method study done in Southern Mozambique estimated HIV incidence during pregnancy, associated risk factors and factors influencing partner\u27s HIV testing. Methods Between April 2008 and November 2011, a prospective cohort of 1230 HIV negative pregnant women was followed during pregnancy. A structured questionnaire, HIV testing, and collection of dried blood spots were done at 2–3 scheduled visits. HIV incidence rates were calculated by repeat HIV testing and risk factors assessed by Poisson regression. A qualitative study including 37 individual interviews with men, women, and nurses and 11 focus group discussions (n = 94) with men, women and grandmothers explored motivators and barriers to uptake of male HIV testing. Results HIV incidence rate was estimated at 4.28/100 women-years (95%CI: 2.33–7.16). Significant risk factors for HIV acquisition were early sexual debut (RR 3.79, 95%CI: 1.04–13.78, p = 0.04) and living in Maputo Province (RR 4.35, 95%CI: 0.97–19.45, p = 0.05). Nineteen percent of women reported that their partner had tested for HIV (93% knew the result with 8/213 indicating an HIV positive partner), 56% said their partner had not tested and 19% did not know their partner test status. Of the 14 seroconversions, only one reported being in a serodiscordant relationship. Fear of discrimination or stigma was reported as a key barrier to male HIV testing, while knowing the importance of getting tested and receiving care was the main motivator. Conclusions HIV incidence during pregnancy is high in Southern Mozambique, but knowledge of partners\u27 HIV status remains low. Knowledge of both partners\u27 HIV status is critical for maximal effectiveness of prevention and treatment services to reach elimination of pediatric HIV/AIDS

Evaluating the Impact of Sex-Biased Genetic Admixture in the Americas through the Analysis of Haplotype Data

This work was supported by the European Union through the European Regional Development Fund (Project No. 2014-2020.4.01.16-0030 to LO, LM, MM, FM; Project No. 2014-2020.4.01.16-0271 to RF; Project No. 2014-2020.4.01.16-0125 to RF; Project No. 2014-2020.4.01.16-0024 to LM, DM, LP; Project No. 2014-2020.4.01.15-0012 to MM; Project no. MOBEC008 to MM). This work was supported by the Estonian Research Council grant PUT (PRG243) to RF and MM and PUT (PRG1027) to KT. This research was supported by the European Union through Horizon 2020 research and innovation programme under grant no 810645 to MM and no 824110 to KT. AA and MRC received support from the Italian Ministry of Education, University and Research (MIUR) for Progetti PRIN2017 20174BTC4R and the Dipartimenti di Eccellenza Program (2018-2022).A general imbalance in the proportion of disembarked males and females in the Americas has been documented during the Trans-Atlantic Slave Trade and the Colonial Era and, although less prominent, more recently. This imbalance may have left a signature on the genomes of modern-day populations characterised by high levels of admixture. The analysis of the uniparental systems and the evaluation of continental proportion ratio of autosomal and X chromosomes revealed a general sex imbalance towards males for European and females for African and Indigenous American ancestries. However, the consistency and degree of this imbalance are variable, suggesting that other factors, such as cultural and social practices, may have played a role in shaping it. Moreover, very few investigations have evaluated the sex imbalance using haplotype data, containing more critical information than genotypes. Here, we analysed genome-wide data for more than 5000 admixed American individuals to assess the presence, direction and magnitude of sex-biased admixture in the Americas. For this purpose, we applied two haplotype-based approaches, ELAI and NNLS, and we compared them with a genotype-based method, ADMIXTURE. In doing so, besides a general agreement between methods, we unravelled that the post-colonial admixture dynamics show higher complexity than previously described.European Commission 2014-2020.4.01.16-0030 2014-2020.4.01.16-0271 2014-2020.4.01.16-0125 2014-2020.4.01.16-0024 2014-2020.4.01.15-0012MOBEC008Estonian Research Council grant PUT PRG243 PRG1027European Commission 810645 824110Ministry of Education, Universities and Research (MIUR) PRIN2017 20174BTC4

Performance of point-of-care birth HIV testing in primary health care clinics: An observational cohort study

<div><p>Background</p><p>Failure to timely diagnose HIV in infants is a major barrier for scaling-up paediatric antiretroviral treatment (ART). WHO recommends birth testing for earlier diagnosis and to improve test coverage, but current diagnosis takes 2–3 weeks to complete, thereby limiting the ability of care givers to provide follow-on care, especially in low-resource settings. We evaluated the benefit of implementing rapid diagnosis of HIV at birth in primary health care maternity wards in Mozambique.</p><p>Methods and findings</p><p>Infants born to HIV-infected mothers delivering consecutively at eight primary health care clinics were tested within 24 hours of delivery using on-site POC (Alere q HIV1/2 Detect) and standard laboratory (Roche COBAS AmpliPrep/TaqMan HIV-1 qualitative assay v2.0) testing. Infants were also tested at 4–6 weeks of age with both assays. Of 2,350 HIV-exposed infants enrolled in this implementation research study, 33 tested HIV-positive at birth on both assays. Sensitivity and specificity of POC testing compared with laboratory testing at birth were 100% (95% CI 89·4–100·0) and 100% (95% CI 99·8–100·0), respectively. At 4–6 weeks of age, 61 infants were identified as HIV-positive; of these 29 (47·5%) had a positive test at birth. Testing at both birth and 4–6 weeks identified 71 HIV-positive infants compared with 61 infants by testing at 4–6 weeks alone, a 16% increase. Two infants tested positive at birth but tested HIV-negative during follow-up.</p><p>Conclusions</p><p>Adding POC birth testing to the 4–6 week screen may increase access to HIV diagnosis and expedite ART initiation in primary health care settings within low resource settings. Guidance on appropriate confirmatory HIV testing algorithms for birth testing is needed.</p></div

Results of at birth point-of-care testing with the Alere q HIV-1/2 Detect system compared with reference birth laboratory testing using the Roche CAP/CTM Qualitative HIV-1 assay.

<p>Results of at birth point-of-care testing with the Alere q HIV-1/2 Detect system compared with reference birth laboratory testing using the Roche CAP/CTM Qualitative HIV-1 assay.</p

Patients with discordant test results between birth and after four weeks.

<p>Patients with discordant test results between birth and after four weeks.</p