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BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) causes impairment of T and B cell responses, which begins during the acute phase of infection and is not completely restored by antiretroviral treatment. Regulatory T cell (Tregs) can improve overall disease outcome by controlling chronic inflammation but may also suppress beneficial HIV-1 specific immune responses. We aimed to analyze the profile of Tregs and their correlation with the status of T cells activation, the expression of IL-2 and IFNγ and the profile of HIV-1 specific antibodies response in Mozambican people living chronically with HIV-1 (PLWH-C). RESULTS: In PLWH-C, the proportion of total Tregs was positively correlated with the proportion of IL-2+CD4 T cells (r = 0.647; p = 0.032) and IL-2+IFNγ+CD8 T cells (r = 0.551; p = 0.014), while the proportions of Helios+Tregs correlated inversely with levels of IL-2+CD8 T cells (r = - 0.541; p = 0.017). Overall, PLWH-C, with (82%) or without virologic suppression (64%), were seronegative for at least HIV-1 p31, gp160 or p24, and the breadth of antibody responses was positively correlated with proportions of CD38+HLA-DR+CD8 T cells (r = 0.620; p = 0.012), viral load (r = 0.452; p = 0.040) and inversely with absolute CD4 T cells count (r = - 0.481; p = 0.027). Analysis of all individuals living HIV-1 showed that the breadth of HIV-1 antibody responses was inversely correlated with the proportion of Helios+Tregs (r = - 0.45; p = 0.02). CONCLUSION: Among Mozambican people living with HIV-1, seronegativity to some HIV-1 proteins is common, particularly in virologically suppressed individuals. Furthermore, lower diversity of HIV-specific antibodies is correlated to lower immune activation, lower viral replication and higher CD4 counts, in PLWH-C. Elevation in the proportion of Helios+Tregs is related to a reduction of CD8 T expressing intracellular IL-2, in PLWH-C, but may contribute to impairment of B cell function.
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Infecções por HIV , HIV-1 , Diversidade de Anticorpos , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Humanos , Interleucina-2/metabolismo , Ativação Linfocitária , Moçambique , Linfócitos T ReguladoresRESUMO
In sub-Saharan Africa, reported COVID-19 numbers have been lower than anticipated, even when considering populations' younger age. The extent to which risk factors, established in industrialised countries, impact the risk of infection and of disease in populations in sub-Saharan Africa, remains unclear. We estimated the incidence of mild and moderate COVID-19 in urban Mozambique and analysed factors associated with infection and disease in a population-based surveillance study. During December 2020-March 2022, 1,561 households (6,049 participants, median 21 years, 54.8% female, 7.3% disclosed HIV positive) of Polana Caniço, Maputo, Mozambique, were visited biweekly to report respiratory symptoms, anosmia, or ageusia, and self-administer a nasal swab for SARS-CoV-2 testing. Every three months, dried blood spots of a subset of participants (1,412) were collected for detection of antibodies against SARS-CoV-2 spike glycoprotein and nucleocapsid protein. Per 1000 person-years, 364.5 (95%CI 352.8-376.1) respiratory illness episodes were reported, of which 72.2 (95%CI 60.6-83.9) were COVID-19. SARS-CoV-2 seroprevalence rose from 4.8% (95%CI 1.1-8.6%) in December 2020 to 34.7% (95%CI 20.2-49.3%) in June 2021, when 3.0% were vaccinated. Increasing age, chronic lung disease, hypertension, and overweight increased risk of COVID-19. Older age increased the risk of SARS-CoV-2 seroconversion. We observed no association between socio-economic status, behaviour and COVID-19 or SARS-CoV-2 seroconversion. Active surveillance in an urban population confirmed frequent COVID-19 underreporting, yet indicated that the large majority of cases were mild and non-febrile. In contrast to reports from industrialised countries, social deprivation did not increase the risk of infection nor disease.
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INTRODUCTION: We previously assessed the effect of an onsite sanitation intervention in informal neighbourhoods of urban Maputo, Mozambique on enteric pathogen detection in children after 2 years of follow-up (Maputo Sanitation (MapSan) trial, ClinicalTrials.gov: NCT02362932). We found significant reductions in Shigella and Trichuris prevalence but only among children born after the intervention was delivered. In this study, we assess the health impacts of the sanitation intervention after 5 years among children born into study households postintervention. METHODS AND ANALYSIS: We are conducting a cross-sectional household study of enteric pathogen detection in child stool and the environment at compounds (household clusters sharing sanitation and outdoor living space) that received the pour-flush toilet and septic tank intervention at least 5 years prior or meet the original criteria for trial control sites. We are enrolling at least 400 children (ages 29 days to 60 months) in each treatment arm. Our primary outcome is the prevalence of 22 bacterial, protozoan, and soil transmitted helminth enteric pathogens in child stool using the pooled prevalence ratio across the outcome set to assess the overall intervention effect. Secondary outcomes include the individual pathogen detection prevalence and gene copy density of 27 enteric pathogens (including viruses); mean height-for-age, weight-for-age, and weight-for-height z-scores; prevalence of stunting, underweight, and wasting; and the 7-day period prevalence of caregiver-reported diarrhoea. All analyses are adjusted for prespecified covariates and examined for effect measure modification by age. Environmental samples from study households and the public domain are assessed for pathogens and faecal indicators to explore environmental exposures and monitor disease transmission. ETHICS AND DISSEMINATION: Study protocols have been reviewed and approved by human subjects review boards at the Ministry of Health, Republic of Mozambique and the University of North Carolina at Chapel Hill. Deidentified study data will be deposited at https://osf.io/e7pvk/. TRIAL REGISTRATION NUMBER: ISRCTN86084138.
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Diarreia , Saneamento , Humanos , Estudos Transversais , Diarreia/epidemiologia , Diarreia/prevenção & controle , Diarreia/microbiologia , Seguimentos , Moçambique/epidemiologia , Saneamento/métodos , Recém-Nascido , Lactente , Pré-EscolarRESUMO
The detection of vaccine-induced HIV antibody responses by rapid diagnostic tests (RDTs) may confound the interpretation of HIV testing results. We assessed the impact of vaccine-induced seroreactivity (VISR) on the diagnosis of HIV in sub-Saharan Africa. Samples collected from healthy participants of HIVIS and TaMoVac HIV vaccine trials after the final vaccination were analyzed for VISR using HIV testing algorithms used in Mozambique and Tanzania that employ two sequential RDTs. The samples were also tested for VISR using Enzygnost HIV Integral 4 ELISA and HIV western blot assays. Antibody titers to subtype C gp140 were determined using an in-house enzyme-linked immunosorbent assay (ELISA). The frequency of VISR was 93.4% (128/137) by Enzygnost HIV Integral 4 ELISA, and 66.4% (91/137) by western blot assay (WHO interpretation). The proportion of vaccine recipients that would have been misdiagnosed as HIV-positive in Mozambique was half of that in Tanzania: 26.3% (36/137) and 54.0% (74/137), respectively, p < 0.0001. In conclusion, the HIV RDTs and algorithms assessed here will potentially misclassify a large proportion of the HIV vaccine recipients if no other test is used. Increased efforts are needed to develop differential serological or molecular tools for use at the point of care.
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INTRODUCTION: In many African countries, laboratory reference values are not established for the local healthy adult population. In Mozambique, reference values are known for young adults (18-24yo) but not yet established for a wider age range. Our study aimed to establish hematological, biochemical and immunological reference values for vaccine trials in Mozambican healthy adults with high-risk for HIV acquisition. METHODS: A longitudinal cohort and site development study in Mozambique between November 2013 and 2014 enrolled 505 participants between 18 to 35 years old. Samples from these healthy participants, were analyzed to determine reference values. All volunteers included in the analysis were clinically healthy and human immunodeficiency virus (HIV), hepatitis B and C virus, and syphilis negative. Median and reference ranges were calculated for the hematological, biochemical and immunological parameters. Ranges were compared with other African countries, the USA and the US National Institute of Health (NIH) Division of AIDS (DAIDS) toxicity tables. RESULTS: A total of 505 participant samples were analyzed. Of these, 419 participants were HIV, hepatitis B and C virus and syphilis negative including 203 (48.5%) females and 216 (51.5%) males, with a mean age of 21 years. In the hematological parameters, we found significant differences between sex for erythrocytes, hemoglobin, hematocrit, MCV, MCH and MCHC as well as white blood cells, neutrophils and platelets: males had higher values than females. There were also significant differences in CD4+T cell values, 803 cells/µL in men versus 926 cells/µL in women. In biochemical parameters, men presented higher values than women for the metabolic, enzymatic and renal parameters: total and direct bilirubin, ALT and creatinine. CONCLUSION: This study has established reference values for healthy adults with high-risk for HIV acquisition in Mozambique. These data are helpful in the context of future clinical research and patient care and treatment for the general adult population in the Mozambique and underline the importance of region-specific clinical reference ranges.
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Células Sanguíneas/química , Infecções por HIV/prevenção & controle , Testes Hematológicos/normas , Adulto , Plaquetas/química , Estudos de Coortes , Feminino , Infecções por HIV/sangue , Hematócrito/normas , Hemoglobinas/análise , Humanos , Contagem de Leucócitos/normas , Leucócitos/química , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Moçambique/epidemiologia , Valores de Referência , Fatores de RiscoRESUMO
INTRODUCTION: CD4+ T-cell counting is usually performed on whole blood obtained from standard venipuncture. Venipuncture requires expertise, results in discomfort and generates biological waste. Capillary blood could be used to measure the levels of CD4+ T-cell in children, elderly and very ill patients. We studied the agreement between CD4+ T-cell counts and percent generated using venous blood with those obtained with capillary blood in HIV-infected adults and children in a resource-limited tropical setting. METHODS: This cross-sectional study consecutively enrolled a total of 152 adult and pediatric HIV-positive patients attending two outpatient clinics in Maputo City, Mozambique. We recruited individuals presenting for their routine clinical follow-up that included the determination of CD4+ T-cell counts in peripheral blood. For each subject, peripheral blood specimens were obtained by both venipuncture and finger prick. Specimens were tested using two flow cytometers, the FACSCount and the FACSCalibur. RESULTS: Absolute CD4+ T-cell counts obtained using capillary blood were in close agreement with those from venous blood both on the FACSCalibur (absolute bias=+12.3 cells/mm³, limits of agreement: -259.2 to +283.9, R²=0.96) and the FACSCount (absolute bias=+16.1 cells/mm³, limits of agreement: -209.2 to +241.5, R²=0.97). Percent CD4+ T-cell counts were measured only on the FACSCalibur also showed a good agreement with a bias of +0.6% and limits of agreement of -3.1 to +4.3. CONCLUSIONS: Absolute CD4+ T-cell counts and percent generated using capillary blood are in close agreement with those from venous blood. Point-Of-Care assays and standard flow cytometers can be deployed in a tiered laboratory network where both venous and capillary blood collection can be used for CD4+ T-cell enumeration.