Human pegivirus 1 in Cabo Verde: prevalence and genotypic distribution among HIV-infected individuals.

Human pegivirus 1 (HPgV-1) belongs to the genus Pegivirus, family Flaviviridae, and until now has been considered a non-pathogenic agent, despite being considered a risk factor for non-Hodgkin lymphoma. However, a beneficial impact of HPgV-1 on HIV disease progression has been extensively reported. Given the high prevalence of HIV in sub-Saharan Africa and the scarcity of epidemiological data for many countries of West Africa, we conducted the first study of HPgV-1 in HIV-infected individuals from Cabo Verde. To obtain new data regarding prevalence and genetic diversity of HPgV-1 in Africa, serum samples from 102 HIV-infected Cabo Verdeans were tested for the presence of viral RNA, and the circulating genotypes were identified by sequencing of the 5' untranslated region. HPgV-1 RNA was detected in 19.6% (20/102) of the samples. In 72.2% (13/18) of the samples, the virus was identified as genotype 2 (11/13 subtype 2a and 2/13 subtype 2b), and in 27.8% (5/18), it was identified as genotype 1. The estimated substitution rate of HPgV-1 genotype 2 was 5.76 × 10-4, and Bayesian analysis indicated the existence of inner clusters within subtypes 2a and 2b. The prevalence of HPgV-1 viremia in Cabo Verde agrees with that reported previously in Africa. Genotypes 1 and 2 cocirculate, with genotype 2 being more common, and HIV/HPgV-1 coinfection was not associated with higher CD4 T cell counts in the studied population. This finding contributes for the expansion of the pegivirus research agenda in African countries.

Genetic architecture of skin and eye color in an African-European admixed population.

Variation in human skin and eye color is substantial and especially apparent in admixed populations, yet the underlying genetic architecture is poorly understood because most genome-wide studies are based on individuals of European ancestry. We study pigmentary variation in 699 individuals from Cape Verde, where extensive West African/European admixture has given rise to a broad range in trait values and genomic ancestry proportions. We develop and apply a new approach for measuring eye color, and identify two major loci (HERC2[OCA2] P = 2.3 × 10(-62), SLC24A5 P = 9.6 × 10(-9)) that account for both blue versus brown eye color and varying intensities of brown eye color. We identify four major loci (SLC24A5 P = 5.4 × 10(-27), TYR P = 1.1 × 10(-9), APBA2[OCA2] P = 1.5 × 10(-8), SLC45A2 P = 6 × 10(-9)) for skin color that together account for 35% of the total variance, but the genetic component with the largest effect (~44%) is average genomic ancestry. Our results suggest that adjacent cis-acting regulatory loci for OCA2 explain the relationship between skin and eye color, and point to an underlying genetic architecture in which several genes of moderate effect act together with many genes of small effect to explain ~70% of the estimated heritability.

Sex-biased admixture and assortative mating shape genetic variation and influence demographic inference in admixed Cabo Verdeans.

Genetic data can provide insights into population history, but first, we must understand the patterns that complex histories leave in genomes. Here, we consider the admixed human population of Cabo Verde to understand the patterns of genetic variation left by social and demographic processes. First settled in the late 1400s, Cabo Verdeans are admixed descendants of Portuguese colonizers and enslaved West African people. We consider Cabo Verde's well-studied historical record alongside genome-wide SNP data from 563 individuals from 4 regions within the archipelago. We use genetic ancestry to test for patterns of nonrandom mating and sex-specific gene flow, and we examine the consequences of these processes for common demographic inference methods and genetic patterns. Notably, multiple population genetic tools that assume random mating underestimate the timing of admixture, but incorporating nonrandom mating produces estimates more consistent with historical records. We consider how admixture interrupts common summaries of genomic variation such as runs of homozygosity. While summaries of runs of homozygosity may be difficult to interpret in admixed populations, differentiating runs of homozygosity by length class shows that runs of homozygosity reflect historical differences between the islands in their contributions from the source populations and postadmixture population dynamics. Finally, we find higher African ancestry on the X chromosome than on the autosomes, consistent with an excess of European males and African females contributing to the gene pool. Considering these genomic insights into population history in the context of Cabo Verde's historical record, we can identify how assumptions in genetic models impact inference of population history more broadly.

Genetic Characterization of a New HIV-1 Sub-Subtype A in Cabo Verde, Denominated A8.

Previous molecular characterization of Human immunodeficiency virus (HIV-1) samples from Cabo Verde pointed out a vast HIV-1 pol diversity, with several subtypes and recombinant forms, being 5.2% classified as AU-pol. Thus, the aim of the present study was to improve the characterization of these AU sequences. The genomic DNA of seven HIV-1 AU pol-infected individuals were submitted to four overlapping nested-PCR fragments aiming to compose the full-length HIV-1 genome. The final classification was based on phylogenetic trees that were generated using the maximum likelihood and bootscan analysis. The genetic distances were calculated using Mega 7.0 software. Complete genome amplification was possible for two samples, and partial genomes were obtained for the other five. These two samples grouped together with a high support value, in a separate branch from the other sub-subtypes A and CRF26_A5U. No recombination was verified at bootscan, leading to the classification of a new sub-subtype A. The intragroup genetic distance from the new sub-subtype A at a complete genome was 5.2%, and the intergroup genetic varied from 8.1% to 19.0% in the analyzed fragments. Our study describes a new HIV-1 sub-subtype A and highlights the importance of continued molecular surveillance studies, mainly in countries with high HIV molecular diversity.

Study of the Etiology of Acute Respiratory Infections in Children Under 5 Years at the Dr. Agostinho Neto Hospital, Praia, Santiago Island, Cabo Verde.

Background: Acute respiratory infections are one of the major causes of morbidity and mortality in children under 5 years in developing countries and are a challenge for the health system of these countries. In Cabo Verde, despite the lack of recent studies, data indicate that it affects thousands of children, being the fourth leading cause of infant mortality in 2013. The aim of this study was to identify and describe the etiological agents associated with acute respiratory tract infections in children under 5 years old, and their associated risk factors, such as clinical symptoms or socio-demographic characteristics. Methods: Naso-pharyngeal samples were collected from children under 5 years attending at Dr. Agostinho Neto Hospital (Praia, Santiago Island, Cabo Verde) with suspected ARI at different time-points during 2019. Samples were analyzed using FilmArray® Respiratory Panel v. 2.0 Plus to identify etiological agents of ARI. A questionnaire with socio-demographic information was also collected for each participant. Data analyses were carried out using the IBM SPSS version 25 (IBM Corporation, Armonk, NY) and R 3.5.1 statistical software. Results: A total of 129 naso-pharyngeal samples were included in the study. Seventeen different etiologic agents of respiratory infections were identified. HRV/EV was the most frequent agent detected, followed by FluA H3 and RSV. Coinfection with two or more pathogens was detected in up to 20% of positive samples. The results were analyzed in terms of age-group, sex, period of the year and other social and demographic factors. Conclusion: Viruses are the main causative agents of ARI in children <5 years attending at the pediatrics service at the Dr. Agostinho Neto Hospital in Praia city, Santiago Island, Cabo Verde. Some factors are described in this study as statistically associated with the presence of an infectious agent, such as having one or more children sharing the bedroom with an adult and the presence of some clinical symptoms. The data addresses the need for studies on respiratory tract infections in Cabo Verde.

A five-year retrospective study shows increasing rates of antimicrobial drug resistance in Cabo Verde for both Staphylococcus aureus and Escherichia coli.

OBJECTIVES: Data on baseline drug resistance important in informing future antimicrobial stewardship programs. So far, no data on the antimicrobial drug resistance of clinical isolates available for the African archipelago of Cabo Verde. METHODS: We performed a retrospective analysis over years (2013-17) of the drug susceptibility profiles of clinical isolates in the two main hospitals of Cabo Verde. For Escherichia coli and Staphylococcus aureus, representing 47% and 26% of all clinical isolates, the antimicrobial drug resistance profile was reported for six representative drugs. RESULTS: For E. coli we detected an increase in resistance to ampicillin, amoxicillin/clavulanic acid, ceftriaxone, ciprofloxacin and trimethoprim-and for S. aureus to methicillin, erythromycin and trimethoprim-sulfamethoxazole. This increase in both the most commonly isolated bacterial pathogens is alarm as it might compromise empirical treatment in a setting with limited access to laboratory testing. CONCLUSIONS: When compared to the published low resistance rates in carriage isolates, the more alarming situation in clinical isolates for S. aureus might encourage antimicrobial stewardship programs to reduce in hospital settings, possibly as part of the Cabo Verdean national plan against antimicrobial drug resistance.

Hepatitis B virus genotypes A1, A2 and E in Cape Verde: Unequal distribution through the islands and association with human flows.

Hepatitis B virus (HBV) diversity has not been previously studied in Cape Verde. The archipelago was discovered in 1460 by Portuguese explorers, who brought African slaves to colonise the islands. In this study, we investigated the HBV characteristics from 183 HBsAg-positive Cape Verdean individuals. Phylogenetic analysis of the pre-S/S region and the full-length genomes revealed 54 isolates with HBV/A1 (57%), 21 with HBV/A2 (22%), 19 with HBV/E (20%), and one with HBV/D (1%). HBV genotypes and subgenotypes were unequally distributed through the islands. In São Vicente, the main northern island, most isolates (84%) belonged to the African-originated HBV/A1, with the remaining isolates belonging to HBV/A2, which is prevalent in Europe. Interestingly, the HBV/A1 isolates from São Vicente were closely related to Brazilian sequences into the Asian-American clade, which suggests the dissemination of common African ancestors through slave trade. In contrast, in Santiago and nearby southern islands, where a recent influx from different populations circulates, a higher diversity of HBV was observed: HBV/A1 (40%); HBV/E (32%); HBV/A2 (28%); and HBV/D (1%). HBV/E is a recent genotype disseminated in Africa that was absent in the era of the slave trade. African and European human flows at different times of the history may explain the HBV diversity in Cape Verde. The possible origin and specifics of each HBV genotype circulating in Cape Verde are discussed.

Origin and Population Dynamics of a Novel HIV-1 Subtype G Clade Circulating in Cape Verde and Portugal.

The human immunodeficiency virus type 1 (HIV-1) subtype G is the most prevalent and second most prevalent HIV-1 clade in Cape Verde and Portugal, respectively; but there is no information about the origin and spatiotemporal dispersal pattern of this HIV-1 clade circulating in those countries. To this end, we used Maximum Likelihood and Bayesian coalescent-based methods to analyze a collection of 578 HIV-1 subtype G pol sequences sampled throughout Portugal, Cape Verde and 11 other countries from West and Central Africa over a period of 22 years (1992 to 2013). Our analyses indicate that most subtype G sequences from Cape Verde (80%) and Portugal (95%) branched together in a distinct monophyletic cluster (here called G(CV-PT)). The G(CV-PT) clade probably emerged after a single migration of the virus out of Central Africa into Cape Verde between the late 1970s and the middle 1980s, followed by a rapid dissemination to Portugal a couple of years later. Reconstruction of the demographic history of the G(CV-PT) clade circulating in Cape Verde and Portugal indicates that this viral clade displayed an initial phase of exponential growth during the 1980s and 1990s, followed by a decline in growth rate since the early 2000s. Our data also indicate that during the exponential growth phase the G(CV-PT) clade recombined with a preexisting subtype B viral strain circulating in Portugal, originating the CRF14_BG clade that was later disseminated to Spain and Cape Verde. Historical and recent human population movements between Angola, Cape Verde and Portugal probably played a key role in the origin and dispersal of the G(CV-PT )and CRF14_BG clades.

Profile of the HIV epidemic in Cape Verde: molecular epidemiology and drug resistance mutations among HIV-1 and HIV-2 infected patients from distinct islands of the archipelago.

HIV-1 and HIV-2 have been detected in Cape Verde since 1987, but little is known regarding the genetic diversity of these viruses in this archipelago, located near the West African coast. In this study, we characterized the molecular epidemiology of HIV-1 and HIV-2 and described the occurrence of drug resistance mutations (DRM) among antiretroviral therapy naïve (ARTn) patients and patients under treatment (ARTexp) from different Cape Verde islands. Blood samples, socio-demographic and clinical-laboratory data were obtained from 221 HIV-positive individuals during 2010-2011. Phylogenetic and bootscan analyses of the pol region (1300 bp) were performed for viral subtyping. HIV-1 and HIV-2 DRM were evaluated for ARTn and ARTexp patients using the Stanford HIV Database and HIV-GRADE e.V. Algorithm Homepage, respectively. Among the 221 patients (169 [76.5%] HIV-1, 43 [19.5%] HIV-2 and 9 [4.1%] HIV-1/HIV-2 co-infections), 67% were female. The median ages were 34 (IQR = 1-75) and 47 (IQR = 12-84) for HIV-1 and HIV-2, respectively. HIV-1 infections were due to subtypes G (36.6%), CRF02_AG (30.6%), F1 (9.7%), URFs (10.4%), B (5.2%), CRF05_DF (3.0%), C (2.2%), CRF06_cpx (0.7%), CRF25_cpx (0.7%) and CRF49_cpx (0.7%), whereas all HIV-2 infections belonged to group A. Transmitted DRM (TDRM) was observed in 3.4% (2/58) of ARTn HIV-1-infected patients (1.7% NRTI, 1.7% NNRTI), but not among those with HIV-2. Among ARTexp patients, DRM was observed in 47.8% (33/69) of HIV-1 (37.7% NRTI, 37.7% NNRTI, 7.4% PI, 33.3% for two classes) and 17.6% (3/17) of HIV-2-infections (17.6% NRTI, 11.8% PI, 11.8% both). This study indicates that Cape Verde has a complex and unique HIV-1 molecular epidemiological scenario dominated by HIV-1 subtypes G, CRF02_AG and F1 and HIV-2 subtype A. The occurrence of TDRM and the relatively high level of DRM among treated patients are of concern. Continuous monitoring of patients on ART, including genotyping, are public policies to be implemented.

The admixture structure and genetic variation of the archipelago of Cape Verde and its implications for admixture mapping studies.

Recently admixed populations offer unique opportunities for studying human history and for elucidating the genetic basis of complex traits that differ in prevalence between human populations. Historical records, classical protein markers, and preliminary genetic data indicate that the Cape Verde islands in West Africa are highly admixed and primarily descended from European males and African females. However, little is known about the variation in admixture levels, admixture dynamics and genetic diversity across the islands, or about the potential of Cape Verde for admixture mapping studies. We have performed a detailed analysis of phenotypic and genetic variation in Cape Verde based on objective skin color measurements, socio-economic status (SES) evaluations and data for 50 autosomal, 34 X-chromosome, and 21 non-recombinant Y-chromosome (NRY) markers in 845 individuals from six islands of the archipelago. We find extensive genetic admixture between European and African ancestral populations (mean West African ancestry = 0.57, sd = 0.08), with individual African ancestry proportions varying considerably among the islands. African ancestry proportions calculated with X and Y-chromosome markers confirm that the pattern of admixture has been sex-biased. The high-resolution NRY-STRs reveal additional patterns of variation among the islands that are most consistent with differentiation after admixture. The differences in the autosomal admixture proportions are clearly evident in the skin color distribution across the islands (Pearson r = 0.54, P-value<2e-16). Despite this strong correlation, there are significant interactions between SES and skin color that are independent of the relationship between skin color and genetic ancestry. The observed distributions of admixture, genetic variation and skin color and the relationship of skin color with SES relate to historical and social events taking place during the settlement history of Cape Verde, and have implications for the design of association studies using this population.

Epidemiologia molecular, evolução viral e perfil de resistência aos antirretrovirais em uma população de pacientes infectados por HIV-1 e/ou HIV-2 residentes em diferentes ilhas do arquipélago de Cabo Verde / Molecular epidemiology, viral evolution and profile of drug resistance mutations among HIV-1 and/or HIV-2 infected patients from distinct islands of the Cape Verde Archipelago

O diagnóstico sorológico da infecção pelo HIV-1 e HIV-2 teve início em Cabo Verde em 1987, mas pouco se sabe a respeito da diversidade genética desses vírus nessas ilhas, localizadas na costa Ocidental Africana. Neste estudo, caracterizamos a epidemiologia molecular do HIV-1 e HIV-2 em Cabo Verde, analisamos a origem dos principais clados de HIV introduzidos no país e descrevemos a ocorrência de mutações de resistência aos antirretrovirais (DRM) em indivíduos virgens de tratamento (ARTn) e pacientes em tratamento (ARTexp) oriundos das diferentes ilhas. Amostras de sangue, dados sociodemográfico e clínico-laboratoriais foram obtidos de 221 indivíduos HIV positivos entre 2010-2011. As amostras foram sequenciadas na região da polimerase (1300 pares de bases) e análises filogenéticas e de bootscan foram realizadas para a subtipagem viral. Os algoritmos disponibilizados nos sites Stanford HIV Database e HIV-GRADE e.V. Algorithm Homepage foram utilizados para avaliar a existência de DRM em pacientes positivos para HIV-1 e HIV-2, respectivamente. Os estudos evolutivos e filogeográficos foram realizados através do programa BEASTEntre os 221 pacientes analisados, sendo 169 (76,5 porcento) HIV-1, 43 (19,5 porcento) HIV-2 e 9 de (4,1 porcento) co-infectados pelo HIV-1 e pelo HIV-2, 67 porcento eram do sexo feminino. As medianas de idade foram de 34 (IQR = 1-75) e 47 (IQR = 12-84) para o HIV-1 e HIV-2, respectivamente. A infecção pelo HIV-1 é causada pelo subtipo G (36,6 porcento), CRF02_AG (30,6 porcento), subtipo F1, (9,7 porcento), URFs (10,4 porcento), subtipo B (5,2porcento), CRF05_DF (3,0 porcento), subtipo C (2,2 porcento), CRF06_cpx (0,7 porcento), CRF25_cpx (0,7 porcento) e CRF49_cpx (0,7 porcento), e todas as infecções por HIV-2 pertencem ao grupo A. De acordo com as análises filogeográficas e de origem do HIV, estimase que o HIV-2 foi o primeiro tipo viral introduzido em Cabo Verde e possui relações filogenéticas com sequências referências de Portugal...

HIV-1 and HIV-2 have been detected in Cape Verde since 1987, but little is known regarding the genetic diversity of these viruses in this archipelago, located near the West African coast. In this study, we characterized the molecular epidemiology of HIV-1 and HIV-2, analyzed the origin of the major clades of HIV introduced in CapeVerde and described the occurrence of drug resistance mutations (DRM) among antiretroviral therapy naïve (ARTn) patients and patients under treatment (ARTexp) from different Cape Verde islands. Blood samples, socio-demographic and clinicallaboratorydata were obtained from 221 HIV-positive individuals during 2010-2011.Genetic sequencing of the pol region (1300bp) was obtained and phylogenetic and bootscan analyses were performed for viral subtyping. The evolutionary and phylogeographic studies were performed using the program BEAST. HIV-1 and HIV-2 DRM were evaluated for ARTn and ARTexp patients using the Stanford HIVDatabase and HIV-GRADE e.V. Algorithm Homepage, respectively. Among the 221patients (169 [76.5 percent] HIV-1, 43 [19.5 percent] HIV-2 and 9 [4.1 percent] HIV-1/HIV-2 coinfections), 67 percent were female. The median ages were 34 (IQR=1-75) and 47(IQR=12-84) for HIV-1 and HIV-2, respectively. HIV-1 infections were due to subtypes G (36.6 percent), CRF02_AG (30.6 percent), F1 (9.7 percent), URFs (10.4 percent), B (5.2 percent), CRF05_DF (3.0 percent), C (2.2percent), CRF06_cpx (0.7 percent), CRF25_cpx (0.7 percent) and CRF49_cpx (0.7 percent), whereas all HIV-2 infections belonged to group A. According the HIV phylogeographic analyses, it is estimated that HIV-2 was the first viral type introduced in Cape Verde and has phylogenetic relationships with referral sequencesof Portugal...

Caracterização da epidemia HIV/Aids em Cabo Verde: uma abordagem soro-epidemiológica no período de 1987 a 2002 / Characterization of the epidemic HIV/AIDS in Cabo Verde: an seroepidemiologic approach in the period of 1987 to 2002

Cabo Verde é um arquipélago de 10 ilhas, situado a 445 Km da Costa Ocidental da África, politicamente estável e com uma população residente de 436.412 habitantes. A realização dos testes sorológicos para pesquisa de anticorpos anti-HIV-1 e 2 teve início em 1987, sendo diagnosticados no país os dois tipos virais circulantes (HIV-1 e HIV-2). Na expectativa de contribuir para o conhecimento da epidemia no país e na estruturação da rede de diagnóstico laboratorial do HIV, efetuamos um estudo descritivo, de natureza retrospectiva, com base nos dados disponíveis no laboratório de referência para diagnóstico de HIV em Cabo Verde. Foram preenchidas 1149 (Fichas de Investigação Individual Soro-Epidemiológica), sendo 993 pacientes com infecção pelo HIV e 156 pacientes com amostra indeterminada/inconclusiva. Observamos que, na população estudada, a epidemia vem crescendo em progressão linear, com padrão de transmissão predominantemente heterossexual, sendo as idades mais afetadas as que vão de 30 a 49 anos. Praia, o interior de Santiago e S. Vicente são as regiões em que se concentra o maior número de amostras positivas, sendo a maioria com Aids estabelecida. Entre 1987 a 1991, os pacientes eram em sua maioria devido ao HIV-2 e com uma maior participação proporcional do sexo masculino. De 1992 a 1998, observa-se uma nítida inversão do predomínio do tipo viral, com participação proporcional similar em ambos sexos. De 1999 a 2002, predominam os pacientes com infecção pelo HIV-1, com uma contribuição progressivamente maior de mulheres. Quanto às amostras indeterminadas/inconclusivas, a reanálise efetuada concluiu que a maioria deve ser considerada simplesmente (inconclusiva). O número expressivo de amostras inconclusivas para a infecção para o HIV-1 e/ou com positividade para apenas uma das glicoproteínas de membrana específica do HIV-1 exige estudos mais aprofundados, capazes de esclarecer o quanto às evidências laboratoriais disponíveis correspondem, de fato, à distribui...