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1.
Vaccines (Basel) ; 9(10)2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34696290

RESUMO

Identification of a universal influenza vaccine candidate has remained a global challenge for both humans and animals. This study describes an approach that uses consensus sequence building to generate chimeric HAs (cHAs): two resultant H1 HA-based chimeras comprising of conserved sequences (within several areas spanning the head and stalk regions) of H1 and H5 or H9 HAs. These cHAs expressed in Drosophila cells (S2) were used to immunize mice. All immunized mice were protected from an infectious H1 virus challenge. Seroconverted mice sera to the H1 cHAs inhibited both the challenge virus and an H5 virus isolate by haemagglutination inhibition (HI) assay. These findings further emphasize that cHAs induce cross-reactive antibodies against conserved areas of both head and stalk regions of the seasonal influenza A (H1N1) pdm09 virus' HA and holds potential for further development of a universal influenza vaccine.

2.
Sci Rep ; 11(1): 13945, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230563

RESUMO

Acute gastroenteritis associated with diarrhea is considered a serious disease in Africa and South Asia. In this study, we examined the trends in the causative pathogens of diarrhea and the corresponding gut microbiota in Ghana using microbiome analysis performed on diarrheic stools via 16S rRNA sequencing. In total, 80 patients with diarrhea and 34 healthy adults as controls, from 2017 to 2018, were enrolled in the study. Among the patients with diarrhea, 39 were norovirus-positive and 18 were rotavirus-positive. The analysis of species richness (Chao1) was lower in patients with diarrhea than that in controls. Beta-diversity analysis revealed significant differences between the two groups. Several diarrhea-related pathogens (e.g., Escherichia-Shigella, Klebsiella and Campylobacter) were detected in patients with diarrhea. Furthermore, co-infection with these pathogens and enteroviruses (e.g., norovirus and rotavirus) was observed in several cases. Levels of both Erysipelotrichaceae and Staphylococcaceae family markedly differed between norovirus-positive and -negative diarrheic stools, and the 10 predicted metabolic pathways, including the carbohydrate metabolism pathway, showed significant differences between rotavirus-positive patients with diarrhea and controls. This comparative study of diarrheal pathogens in Ghana revealed specific trends in the gut microbiota signature associated with diarrhea and that pathogen-dependent dysbiosis occurred in viral gastroenteritis.


Assuntos
Disbiose/microbiologia , Disbiose/virologia , Gastroenterite/microbiologia , Gastroenterite/virologia , Microbioma Gastrointestinal , Adolescente , Adulto , Bactérias/classificação , Biodiversidade , Estudos de Casos e Controles , Criança , Pré-Escolar , Diarreia/microbiologia , Diarreia/virologia , Fezes/microbiologia , Feminino , Gana , Humanos , Masculino , Filogenia , Rotavirus/fisiologia
3.
Front Cell Infect Microbiol ; 11: 646467, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34084754

RESUMO

HIV-1 infected individuals under antiretroviral therapy can control viremia but often develop non-AIDS diseases such as cardiovascular and metabolic disorders. Gut microbiome dysbiosis has been indicated to be associated with progression of these diseases. Analyses of gut/fecal microbiome in individual regions are important for our understanding of pathogenesis in HIV-1 infections. However, data on gut/fecal microbiome has not yet been accumulated in West Africa. In the present study, we examined fecal microbiome compositions in HIV-1 infected adults in Ghana, where approximately two-thirds of infected adults are females. In a cross-sectional case-control study, age- and gender-matched HIV-1 infected adults (HIV+; n = 55) and seronegative controls (HIV-; n = 55) were enrolled. Alpha diversity of fecal microbiome in HIV+ was significantly reduced compared to HIV- and associated with CD4 counts. HIV+ showed reduction in varieties of bacteria including Faecalibacterium, the most abundant in seronegative controls, but enrichment of Proteobacteria. Ghanaian HIV+ exhibited enrichment of Dorea and Blautia; bacteria groups whose depletion has been reported in HIV-1 infected individuals in several other cohorts. Furthermore, HIV+ in our cohort exhibited a depletion of Prevotella, a genus whose enrichment has recently been shown in men having sex with men (MSM) regardless of HIV-1 status. The present study revealed the characteristics of dysbiotic fecal microbiome in HIV-1 infected adults in Ghana, a representative of West African populations.


Assuntos
Infecções por HIV , HIV-1 , Microbiota , Adulto , Estudos de Casos e Controles , Estudos Transversais , Disbiose , Feminino , Gana , Humanos , Masculino
4.
Jpn J Infect Dis ; 74(1): 42-47, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-32611986

RESUMO

Recent studies have indicated an association between gut microbiome composition and various disorders, including infectious diseases. The composition of the microbiome differs among ethnicities and countries, possibly resulting in diversified interactions between host immunity and the gut microbiome. Characterization of baseline microbiome composition in healthy people is an essential step for better understanding of the biological interactions associated with individual populations. However, data on the gut/fecal microbiome have not been accumulated for individuals in West Africa. In the present study, we examined the fecal microbiome composition in healthy adults in Ghana. Toward this, 16S rRNA gene libraries were prepared using bacterial fractions derived from 55 Ghanaian adults, which were then subjected to next-generation sequencing. The fecal microbiome of the Ghanaian adults was dominated by Firmicutes (Faecalibacterium, Subdoligranulum, and Ruminococcaceae UCG-014), Proteobacteria (Escherichia-Shigella and Klebsiella), and Bacteroidetes (Prevotella 9 and Bacteroides), consistent with previous observations in African cohorts. Further, our analysis revealed differences in microbiome composition and a lower diversity of the fecal microbiome in the Ghanaian cohort compared with those reported in non-African countries. This is the first study to describe substantial fecal microbiome data obtained using high-throughput metagenomic tools on samples derived from a cohort in Ghana. The data may provide a valuable basis for determining the association between the fecal microbiome and progression of various diseases in West African populations.


Assuntos
Fezes/microbiologia , Microbioma Gastrointestinal/genética , Adulto , Bacteroidetes/genética , Estudos Transversais , Feminino , Firmicutes/genética , Gana , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Metagenômica , Microbiota , Pessoa de Meia-Idade , Proteobactérias/genética , RNA Bacteriano/isolamento & purificação , RNA Ribossômico 16S/genética
5.
Jpn J Infect Dis ; 2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-34980705

RESUMO

Accurate monitoring of epidemics is a key strategy for the control of human immunodeficiency virus type-1 (HIV-1) infection. To delineate the characteristic of newly-diagnosed cases of HIV-1 infection, we assessed the proportion of recent HIV-1 infections using a recent infection testing algorithm (RITA). In 2015, 248 cases were newly diagnosed with HIV infection in Reginal Hospital Koforidua, Ghana. Of these, 234 cases (94.4%) were infected with HIV-1 only, four (1.6%) were infected with HIV-2 only, and 10 (4.0%) were co-infected with HIV-1 and HIV-2. All the HIV-1 single seropositive samples were applied to HIV-1 LAg avidity assay for RITA. Our analysis revealed that 18 cases (7.7%) were determined as recent infections, indicating that early diagnosis has not been achieved in Ghana. This is the first report assessing the proportion of recent infections in Ghana using a biomarker approach. Accumulation of these data would contribute to accurate estimation of HIV-1 incidence and prevalence in Ghana.

6.
BMC Infect Dis ; 19(1): 533, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208352

RESUMO

BACKGROUND: Distribution of Hepatitis C virus (HCV) genotypes varies significantly worldwide. Genomic diversity between genotypes has implications for treatment, vaccine development and optimal design of HCV diagnostic assays. Molecular characterization of HCV in different geographical areas is therefore very essential for management and public health control of HCV infection. This study investigated the molecular epidemiology and characteristics of HCV genotypes in healthy individuals in Accra, Ghana. METHODS: An experimental study was carried out on blood samples obtained from voluntary blood donors. Two hundred samples were initially screened for HCV antibodies and infection was confirmed by RNA detection through RT-PCR of the 5'-untranslated region (5'UTR). The core gene sequences were analysed for HCV genotype determination by genotype-specific PCR; and then by cloning and direct sequencing followed by phylogenetic analysis. The sequences were further analysed in detail by similarity plotting. RESULTS: Molecular diagnosis confirmed the presence of HCV RNA in 2 out of 200 (1%) blood donors. Initial genotyping by genotype-specific PCR identified all two infections as subtypes 2a and 2b of genotype 2. Extensive evolutionary and genetic analyses indicated two epidemiological profiles. First, phylogenetic tree topologies clearly showed that, collectively, the core sequences of the Ghanaian HCV isolates belong to a single, distinct genetic group within HCV genotype 2 cluster, with high genetic similarity and rapid sequence variation in a single individual. Second, the sequences are mosaics comprising 2e and other genotype 2 subtype fragments. The analyses underscore a unique and complex HCV genotype 2 core sequence profile of the Ghanaian isolates. CONCLUSIONS: Analysis of HCV core encoding sequences from Ghanaian blood donors in Accra confirmed predominance of genotype 2 HCV among healthy individuals. However, the isolates could not be classified into subtypes, possibly due to their complex sequence pattern that might suggest high mutability of the prevailing genotype. The core region of Ghanaian HCV therefore may not be suitable for distinguishing subtypes. These findings extend those from previous studies and thus underscore the need to search for subtype-informative region of Ghanaian HCV to elucidate the genetic diversity and factors determining outcome of HCV infections in Ghana.


Assuntos
Doadores de Sangue , Hepacivirus/genética , Hepatite C/virologia , Estudos Transversais , Genótipo , Gana/epidemiologia , Hepacivirus/isolamento & purificação , Hepatite C/epidemiologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Epidemiologia Molecular , Filogenia , Reação em Cadeia da Polimerase
7.
Int J Infect Dis ; 81: 231-234, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30776545

RESUMO

OBJECTIVE: To demonstrate the feasibility of applying next-generation sequencing (NGS) in medium-resource reference laboratories in Africa to enhance global disease surveillance. METHODS: A training program was developed to support implementation of NGS at Noguchi Memorial Institute for Medical Research (NMIMR), University of Ghana. The program was divided into two training stages, first at the Centers for Disease Control and Prevention (CDC) in Atlanta, GA, followed by on-site training at NMIMR for a larger cohort of scientists. RESULTS: Self-assessment scores for topics covered during the NGS training program were higher post-training relative to pre-training. During the NGS Training II session at NMIMR, six enterovirus isolates from acute flaccid paralysis cases in Ghana were successfully sequenced by trainees, including two echovirus 6, two echovirus 11 and one echovirus 13. Another genome was an uncommon type (EV-B84), which has not been reported in Africa since its initial discovery from a Côte d'Ivoire specimen in 2003. CONCLUSIONS: The success at NMIMR provides an example of how to approach transferring of NGS methods to international laboratories. There is great opportunity for collaboration between institutes that have genomics expertise to ensure effectiveness and long-term success of global NGS capacity building programs.


Assuntos
Infecções por Enterovirus/virologia , Enterovirus/isolamento & purificação , Laboratórios/organização & administração , Fortalecimento Institucional , Costa do Marfim , Enterovirus/classificação , Enterovirus/genética , Gana , Sequenciamento de Nucleotídeos em Larga Escala , Humanos
8.
Virol J ; 15(1): 143, 2018 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-30223845

RESUMO

BACKGROUND: Antiretrovirals have been available in Ghana since 2003 for HIV-1 positive pregnant women for prevention of mother-to-child transmission (PMTCT). Suboptimal responses to treatment observed post-PMTCT interventions necessitated the need to investigate the profile of viral mutations generated. This study investigated HIV-1 drug resistance profiles in mothers in selected centres in Ghana on treatment with a history of prophylaxis. METHODS: Genotypic Drug Resistance Testing for HIV-1 was carried out. Subtyping was done by phylogenetic analysis and Stanford HIV Database programme was used for drug resistance analysis and interpretation. To compare the significance between the different groups and the emergence of drug resistance mutations, p values were used. RESULTS: Participants who had prophylaxis before treatment, those who had treatment without prophylaxis and those yet to initiate PMTCT showed 32% (8), 5% (3) and 15% (4) HIV-1 drug resistance associated mutations respectively. The differences were significant with p value < 0.05. Resistance Associated Mutations (RAMs) were seen in 14 participants (35%) to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). The most common NRTI mutation found was M184 V; K103 N and A98G were the most common NNRTI mutations seen. Thymidine Analogue Mutations (TAMs) such as M41 L, K70R and T215Y were found in all the groups; the most common of the TAMs found were M41 L and T215Y. Majority of the subtypes were CRF02_AG (82%). CONCLUSION: In Ghana initiation of uninterrupted treatment upon diagnosis, coupled with drug resistance testing, would produce a better treatment outcome for HIV-1 positive pregnant women.


Assuntos
Fármacos Anti-HIV/farmacologia , Quimioprevenção/estatística & dados numéricos , Farmacorresistência Viral , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Mutação de Sentido Incorreto , Fármacos Anti-HIV/administração & dosagem , Feminino , Genótipo , Gana , Infecções por HIV/prevenção & controle , HIV-1/classificação , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Mães , Filogenia , Gravidez , Complicações Infecciosas na Gravidez/virologia , Análise de Sequência de DNA , Resultado do Tratamento
9.
PLoS Negl Trop Dis ; 12(3): e0006303, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29566044

RESUMO

INTRODUCTION: The WHO yaws eradication strategy consists of one round of total community treatment (TCT) of single-dose azithromycin with coverage of > 90%.The efficacy of the strategy to reduce the levels on infection has been demonstrated previously in isolated island communities in the Pacific region. We aimed to determine the efficacy of a single round of TCT with azithromycin to achieve a decrease in yaws prevalence in communities that are endemic for yaws and surrounded by other yaws-endemic areas. METHODS: Surveys for yaws seroprevalence and prevalence of skin lesions were conducted among schoolchildren aged 5-15 years before and one year after the TCT intervention in the Abamkrom sub-district of Ghana. We used a cluster design with the schools as the primary sampling unit. Among 20 eligible primary schools in the sub district, 10 were assigned to the baseline survey and 10 to the post-TCT survey. The field teams conducted a physical examination for skin lesions and a dual point-of-care immunoassay for non-treponemal and treponemal antibodies of all children present at the time of the visit. We also undertook surveys with non-probabilistic sampling to collect lesion swabs for etiology and macrolide resistance assessment. RESULTS: At baseline 14,548 (89%) of 16,287 population in the sub-district received treatment during TCT. Following one round of TCT, the prevalence of dual seropositivity among all children decreased from 10.9% (103/943) pre-TCT to 2.2% (27/1211) post-TCT (OR 0.19; 95%CI 0.09-0.37). The prevalence of serologically confirmed skin lesions consistent with active yaws was reduced from 5.7% (54/943) pre-TCT to 0.6% (7/1211) post-TCT (OR 0.10; 95% CI 0.25-0.35). No evidence of resistance to macrolides against Treponema pallidum subsp. pertenue was seen. DISCUSSION: A single round of high coverage TCT with azithromycin in a yaws affected sub-district adjoining other endemic areas is effective in reducing the prevalence of seropositive children and the prevalence of early skin lesions consistent with yaws one year following the intervention. These results suggest that national yaws eradication programmes may plan the gradual expansion of mass treatment interventions without high short-term risk of reintroduction of infection from contiguous untreated endemic areas.


Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Medicina Comunitária/estatística & dados numéricos , Erradicação de Doenças/métodos , Treponema pallidum/efeitos dos fármacos , Bouba/tratamento farmacológico , Bouba/prevenção & controle , Adolescente , Antibacterianos/administração & dosagem , Anticorpos Antibacterianos/sangue , Azitromicina/administração & dosagem , Criança , Pré-Escolar , Medicina Comunitária/métodos , Farmacorresistência Bacteriana , Feminino , Gana/epidemiologia , Humanos , Imunoensaio , Masculino , Projetos Piloto , Prevalência , Estudos Soroepidemiológicos , Pele/microbiologia , Pele/patologia , Treponema pallidum/imunologia , Treponema pallidum/isolamento & purificação , Organização Mundial da Saúde , Bouba/imunologia
10.
J Med Microbiol ; 66(11): 1663-1672, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29068286

RESUMO

PURPOSE: There have been hardly any reports on the human immunodeficiency virus type 1 (HIV-1) drug-resistance profile from northern Ghana since antiretroviral therapy (ART) was introduced over a decade ago. This study investigated prevailing HIV-1 subtypes and examined the occurrence of drug resistance in ART-experienced patients in Tamale, the capital of the Northern Region of Ghana. METHODOLOGY: A cross-sectional study was carried out on HIV-infected adult patients receiving first-line ART. HIV viral load (VL) and CD4+ T-cell counts were measured. The pol gene sequences were analysed for genotypic resistance by an in-house HIV-1 drug-resistance test; the prevailing HIV-1 subtypes were analysed in detail.Results/Key findings. A total of 33 subjects were studied. Participants comprised 11 males (33.3 %) and 22 (66.7 %) females, with a median age of 34.5 years [interquartile range (IQR) 30.0-40.3]. The median duration on ART was 12 months (IQR 8.0-24). Of the 24 subjects successfully genotyped, 10 (41.7 %) viruses possessed at least one mutation conferring resistance to nucleoside or non-nucleoside reverse-transcriptase inhibitors (NRTIs/NNRTIs). Two-class drug resistance to NRTI and NNRTI was mostly detected (25 %, 6/24). The most frequent mutations were lamivudine-resistance M184V and efavirenz/nevirapine-resistance K103N. HIV-1 subtype CRF02_AG was predominant (79.2 %). Other HIV-1 subtypes detected were G (8.3 %), A3 (4.2 %) and importantly two (8.3 %) unique HIV-1 recombinant forms with CRF02_AG/A3 mosaic. CONCLUSION: HIV-1 shows high genetic diversity and on-going viral genetic recombination in the study region. Nearly 42 % of the patients studied harboured a drug-resistant virus. The study underscores the need for continued surveillance of HIV-1 subtype diversity; and of drug-resistance patterns to guide selection of second-line regimens in northern Ghana.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral/genética , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/genética , Adulto , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Genótipo , Gana/epidemiologia , Humanos , Masculino , Mutação , Filogenia , Prevalência , RNA Viral , Carga Viral
12.
BMC Res Notes ; 8: 14, 2015 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-25612659

RESUMO

BACKGROUND: Military barracks in Ghana have backyard poultry populations but the methods used here involve low biosecurity measures and high risk zoonosis such as avian influenza A viruses or Newcastle disease. We assessed biosecurity measures intended to minimize the risk of influenza virus infection among troops and poultry keepers in military barracks. FINDINGS: We educated troops and used a questionnaire to collect information on animal populations and handling practices from 168 individuals within 203 households in military barracks. Cloacal and tracheal samples were taken from 892 healthy domestic and domesticated wild birds, 91 sick birds and 6 water samples for analysis using molecular techniques for the detection of influenza A virus. Of the 1090 participants educated and 168 that responded to a questionnaire, 818 (75%) and 129 (76.8%) respectively have heard of pandemic avian influenza and the risks associated with its infection. Even though no evidence of the presence of avian influenza infection was found in the 985 birds sampled, only 19.5% of responders indicated they disinfect their coops regularly and 28% wash their hands after handling their birds. Vaccination of birds and use of personal protective clothing while handling the birds were low putting the people at risk. CONCLUSION: Though some efforts have been made to improve biosecurity practices, interventions that help to protect the poultry flock from direct contact have to be practiced. Basic hygiene like washing of hands with soap and running water and regular cleaning of chicken coops are needed to prevent the spread of diseases among birds and between birds and humans.


Assuntos
Criação de Animais Domésticos/educação , Surtos de Doenças/prevenção & controle , Influenza Aviária/prevenção & controle , Militares/educação , Medidas de Segurança/organização & administração , Zoonoses/prevenção & controle , Adulto , Animais , Galinhas , Feminino , Gana , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Vírus da Influenza A/fisiologia , Influenza Aviária/transmissão , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Recursos Humanos
13.
Demogr Res ; 31: 861-888, 2014 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-25364298

RESUMO

BACKGROUND: HIV is spread through structured sexual networks, which are influenced by migration patterns, but network-oriented studies of mobility and HIV risk behavior have been limited. OBJECTIVE: We present a comprehensive description and initial results from our Migration & HIV in Ghana (MHG) study in Agbogbloshie, an urban slum area within Accra, Ghana. METHODS: The MHG study was a population-based cross-sectional study of adults aged 18-49 in Agbogbloshie in 2012. We used a one-year retrospective relationship history calendar to collect egocentric network data on sexual partners as well as migration and short-term mobility, and tested for prevalent HIV-1/2 infection. RESULTS: HIV prevalence was 5.5%, with prevalence among women (7.2%) over twice that of men (2.8%). Three-quarters of residents were born outside the Greater Accra region, but had lived in Agbogbloshie an average of 10.7 years. Only 7% had moved housing structures within the past year. However, short-term mobility was common. Residents had an average of 7.3 overnight trips in the last year, with women reporting more travel than men. Thirty-seven percent of men and 9% of women reported more than one sexual partner in the last year. CONCLUSIONS: Population-based surveys of migration and sexual risk behavior using relationship history calendars in low-resource settings can produce high quality data. Residents in Agbogbloshie are disproportionately affected by HIV, and have high levels of short-term mobility. HIV prevention interventions targeted to highly mobile populations in high prevalence settings may have far-reaching and long-term implications.

14.
J Infect Dis ; 206 Suppl 1: S14-21, 2012 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-23169960

RESUMO

BACKGROUND: In response to the potential threat of an influenza pandemic, several international institutions and governments, in partnership with African countries, invested in the development of epidemiologic and laboratory influenza surveillance capacity in Africa and the African Network of Influenza Surveillance and Epidemiology (ANISE) was formed. METHODS: We used a standardized form to collect information on influenza surveillance system characteristics, the number and percent of influenza-positive patients with influenza-like illness (ILI), or severe acute respiratory infection (SARI) and virologic data from countries participating in ANISE. RESULTS: Between 2006 and 2010, the number of ILI and SARI sites in 15 African countries increased from 21 to 127 and from 2 to 98, respectively. Children 0-4 years accounted for 48% of all ILI and SARI cases of which 22% and 10%, respectively, were positive for influenza. Influenza peaks were generally discernible in North and South Africa. Substantial cocirculation of influenza A and B occurred most years. CONCLUSIONS: Influenza is a major cause of respiratory illness in Africa, especially in children. Further strengthening influenza surveillance, along with conducting special studies on influenza burden, cost of illness, and role of other respiratory pathogens will help detect novel influenza viruses and inform and develop targeted influenza prevention policy decisions in the region.


Assuntos
Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Vigilância de Evento Sentinela , Adolescente , Adulto , África/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
15.
J Acquir Immune Defic Syndr ; 48(5): 599-606, 2008 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-18645511

RESUMO

BACKGROUND: In Ghana, programs to expand antiretroviral access are being implemented. In this context, the dynamic genetic evolution of HIV-1 requires continuous surveillance, particularly when diverse genetic forms co-circulate. METHODS: Phylogenetic and antiretroviral resistance analyses of HIV-1 partial pol sequences from plasma RNA samples from 207 Ghanaian individuals were performed. RESULTS: 66% of infections were CRF02_AG, whereas 25% were unique recombinant forms (URFs). All 52 URFs were characterized by bootscanning. CRF02_AG was parental strain in 87% of URFs, forming recombinants with genetic forms circulating in minor proportions: CRF06_cpx, sub-subtype A3, CRF09_cpx and subtypes G and D. Two triple recombinants (CRF02_AG/A3/CRF06_cpx and CRF02_AG/A3/CRF09_cpx) were identified. Antiretroviral resistance analyses revealed that six individuals, five of which were antiretroviral drug-experienced, harbored mutations conferring high level of resistance to reverse transcriptase inhibitors. No major resistance mutations were identified in the protease, although insertions of one and three amino acids were detected. CONCLUSIONS: The high frequency of URFs detected probably reflects a significant incidence of coinfections or superinfections with diverse viral strains, which increases the genetic complexity of the HIV-1 epidemic in West Africa. Monitoring of HIV-1 drug resistance might provide data on the implications of intersubtype recombination in response to antiretrovirals.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral/genética , Infecções por HIV/epidemiologia , HIV-1/genética , Mutação , Recombinação Genética , Genes pol , Gana/epidemiologia , Infecções por HIV/virologia , Inibidores da Protease de HIV/farmacologia , HIV-1/classificação , HIV-1/efeitos dos fármacos , HIV-1/isolamento & purificação , Humanos , Epidemiologia Molecular , Dados de Sequência Molecular , Filogenia , Polimorfismo Genético , Prevalência , Inibidores da Transcriptase Reversa/farmacologia
16.
PLoS One ; 2(12): e1312, 2007 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-18091987

RESUMO

OBJECTIVE: The objective of this trial was to determine the effectiveness of 1.0% C31G (SAVVY) in preventing male-to-female vaginal transmission of HIV infection among women at high risk. METHODOLOGY/PRINCIPAL FINDINGS: This was a Phase 3, double-blind, randomized, placebo-controlled trial. Participants made up to 12 monthly visits for HIV testing, adverse event reporting, and study product supply. The study was conducted between March 2004 and February 2006 in Accra and Kumasi, Ghana. We enrolled 2142 HIV-negative women at high risk of HIV infection, and randomized them to SAVVY or placebo gel. Main outcome measures were the incidence of HIV-1 and HIV-2 infection as determined by detection of HIV antibodies from oral mucosal transudate specimens and adverse events. We accrued 790 person-years of follow-up in the SAVVY group and 772 person-years in the placebo group. No clinically significant differences in the overall frequency of adverse events, abnormal pelvic examination findings, or abnormal laboratory results were seen between treatment groups. However, more participants in the SAVVY group reported reproductive tract adverse events than in the placebo group (13.0% versus 9.4%). Seventeen HIV seroconversions occurred; eight in participants randomized to SAVVY and nine in participants receiving placebo. The Kaplan-Meier estimates of the cumulative probability of HIV infection through 12 months were 0.010 in the SAVVY group and 0.011 in the placebo group (p = 0.731), with a hazard ratio (SAVVY versus placebo) of 0.88 (95% confidence interval 0.33, 2.27). Because of a lower-than-expected HIV incidence, we were unable to achieve the required number of HIV infections (66) to obtain the desired study power. CONCLUSIONS/SIGNIFICANCE: SAVVY was not associated with increased adverse events overall, but was associated with higher reporting of reproductive adverse events. Our data are insufficient to conclude whether SAVVY is effective at preventing HIV infection relative to placebo. TRIAL REGISTRATION: ClinicalTrials.gov NCT00129532.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/prevenção & controle , Administração Tópica , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Método Duplo-Cego , Feminino , Géis , Gana , Infecções por HIV/transmissão , Humanos , Masculino , Placebos
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