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1.
Artigo em Inglês | MEDLINE | ID: mdl-33594740

RESUMO

As breastfeeding is of utmost importance for child development and survival, identifying whether breast milk is a route of transmission for human viruses is critical. Based on the principle of Koch's postulate, we propose an analytical framework to determine the plausibility of viral transmission by breast milk. This framework is based on five criteria: viral infection in children receiving breastmilk from infected mothers; the presence of virus, viral antigen or viral genome in the breast milk of infected mothers; the evidence for the virus in breast milk being infectious; the attempts to rule out other transmission modalities; and the reproduction of viral transmission by oral inoculation in an animal model. We searched for evidence in published reports to determine whether the 5 criteria are fulfilled for 16 human viruses that are suspected to be transmissible by breast milk. We considered breast milk transmission is proven if all 5 criteria are fulfilled, as probable if 4 of the 5 criteria are met, as possible if 3 of the 5 criteria are fulfilled and as unlikely if less than 3 criteria are met. Only five viruses have proven transmission through breast milk: human T-cell lymphotropic virus 1, human immunodeficiency virus, human cytomegalovirus, dengue virus and Zika virus. The other 11 viruses fulfilled some but not all criteria and were categorized accordingly. Our framework analysis is useful for guiding public health recommendations and for identifying knowledge gaps amenable to original experiments.

2.
Sci Rep ; 11(1): 3173, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542437

RESUMO

In the ANRS 12174 trial, HIV-exposed uninfected African neonates who received lopinavir-ritonavir (LPV/r) prophylaxis for 1 year exhibited slower growth from birth to week 50 compared with those receiving lamivudine (3TC). We assessed whether this difference in growth persisted over time, and was accompanied by differences in neuropsychological and clinical outcomes. Between February 2017 and February 2018, we conducted a cross-sectional clinical evaluation among former trial participants who completed the 50-week follow-up and who were not HIV-infected. In addition to clinical examination, neuropsychological outcomes were assessed using the tests Kaufman-ABCII, Test of Variables of Attention, Movement Assessment Battery for Children and the Strengths and Difficulties questionnaire, parent version. Of 1101 eligible children, aged 5-7 years, 553 could be traced and analysed (274 in the LPV/r and 279 in the 3TC groups). Growth, clinical and neuropsychological outcomes did not differ between treatment groups. At school age, children exposed to LPV/r and 3TC at birth for 1 year had comparable growth and neuropsychological outcomes without evidence of long-term side-effects of LPV/r. It provides reassuring data on clinical outcomes for all HIV-infected children treated with this antiretroviral drug in early life.

3.
J Clin Med ; 9(11)2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33207772

RESUMO

Infant antiretroviral (ARV) prophylaxis given to children who are human immunodeficiency virus (HIV)-exposed but uninfected (CHEU) to prevent HIV transmission through breastfeeding previously proved its efficacy in the fight against the pediatric epidemic. However, few studies have investigated the short- and long-term safety of prophylactic regimens. We previously reported a decrease of mitochondrial DNA (mtDNA) content among CHEU who received one year of lamivudine (3TC) or lopinavir-boosted ritonavir (LPV/r) as infant prophylaxis. We aimed to describe mtDNA content at six years of age among these CHEU, including those for whom we identified mtDNA depletion at week 50 (decrease superior or equal to 50% from baseline), and to compare the two prophylactic drugs. We also addressed the association between mtDNA depletion at week 50 with growth, clinical, and neuropsychological outcomes at year 6. Quantitative PCR was used to measure mtDNA content in whole blood of CHEU seven days after birth, at week 50, and at year 6. Among CHEU with identified mtDNA depletion at week 50 (n = 17), only one had a persistent mtDNA content decrease at year 6. No difference between prophylactic drugs was observed. mtDNA depletion was not associated with growth, clinical, or neuropsychological outcomes at year 6. This study brought reassuring data concerning the safety of infant 3TC or LPV/r prophylaxis.

4.
BMJ Open ; 10(11): e039234, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208326

RESUMO

INTRODUCTION: In Vietnam, people who inject drugs (PWID), who are the major population infected by hepatitis C virus (HCV), remain largely undiagnosed and unlinked to HCV prevention and care despite recommended universal hepatitis C treatment. The data on the outcomes of HCV treatment among PWID also remain limited in resource-limited settings. The DRug use & Infections in ViEtnam-hepatitis C (DRIVE-C) study examines the effectiveness of a model of hepatitis C screening and integrated care targeting PWID that largely uses community-based organisations (CBO) in Hai Phong, Vietnam. In a wider perspective, this model may have the potential to eliminate HCV among PWID in this city. METHODS AND ANALYSIS: The model of care comprises large community-based mass screening, simplified treatment with direct-acting antivirals (DAAs) and major involvement of CBO for PWID reaching out, linkage to care, treatment adherence and prevention of reinfection. The effectiveness of DAA care strategy among PWID, the potential obstacles to widespread implementation and its impact at population level will be assessed. A cost-effectiveness analysis is planned to further inform policy-makers. The enrolment target is 1050 PWID, recruited from the DRIVE study in Hai Phong. After initiation of pan-genotypic treatment consisting of sofosbuvir and daclatasvir administrated for 12 weeks, with ribavirin added in cases of cirrhosis, participants are followed-up for 48 weeks. The primary outcome is the proportion of patients with sustained virological response at week 48, that will be compared with a theoretical expected rate of 70%. ETHICS AND DISSEMINATION: The study was approved by Haiphong University of Medicine and Pharmacy's Ethics Review Board and the Vietnamese Ministry of Health. The sponsor and the investigators are committed to conducting this study in accordance with ethics principles contained in the World Medical Association's Declaration of Helsinki (Ethical Principles for Medical Research Involving Human Subjects). Informed consent is obtained before study enrolment. The data are anonymised and stored in a secure database. The study is ongoing. Results will be presented at international conferences and submitted to international peer-review journals. TRIAL REGISTRATION NUMBER: NCT03537196.

5.
Drug Alcohol Depend ; 216: 108334, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33038638

RESUMO

BACKGROUND: Psychiatric comorbidities are frequent among people who inject drugs, they are associated with a poorer prognosis and need to be addressed. Their interaction with daily heroin injection requires clarification. METHODS: A cross-sectional survey was conducted among PWID recruited in the city of Haiphong, Vietnam, by respondent-driven sampling. The inclusion criteria were age 18 or older and current injection drug use, verified by skin marks and positive urine tests for heroin or methamphetamine. Data on socio-demographic characteristics, drug use, sexual behaviour and access to treatment were collected using face-to-face questionnaires by trained interviewers. PWID were screened by trained psychiatrists for depression, psychotic disorder and suicidality, using the MINI questionnaire. RESULTS: 418 participants were included in the analyses. All were injected heroin users, 21 % were diagnosed with a current major depressive disorder, 15 % with a current psychotic disorder and 12 % presented a suicide risk. In the bivariate analyses, regular meth use, cannabis use and ketamine use were positively associated with presenting at least one psychiatric condition while daily heroin injection and being currently treated with methadone were negatively associated. In the multivariate model, poly-substance use was positively associated with depression (methamphetamine and drinking in addition to heroin) and psychotic disorder (methamphetamine and/or hazardous drinking in addition to heroin) while daily heroin injection and current methadone treatment were negatively and independently associated with depression and psychotic syndrome. CONCLUSIONS: Our survey confirms the burden of methamphetamine use and the protective effect of methadone but also a possible protective effect of daily heroin injection.

6.
AIDS ; 34(15): 2305-2311, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33048884

RESUMO

OBJECTIVE: To determine whether it is possible to 'end an HIV epidemic' among persons who inject drugs (PWID) in a low/middle income country. DESIGN: Serial cross-sectional surveys with a cohort of HIV seronegative participants with 6-month follow-up visits recruited from surveys. METHODS: Surveys of PWID using respondent driven and snowball sampling were conducted in 2016, 2017, 2018, and 2019 (N = 1383, 1451, 1444, and 1268). HIV recency testing was used to identify possible seroconversions in the window period prior to study entry. Structured interviews covering drug use histories, current drug use, and use of HIV-related services were administered by trained interviewers. Urinalysis was used to confirm current drug use. HIV and hepatitis C virus testing were conducted. Electronic fingerprint readers were used to avoid multiple participation in each survey and to link participants across surveys. A cohort of HIV seronegative participants with 6-month follow-up visits was recruited from the surveys, 480 from 2016, 233 from 2017, and 213 from 2018. RESULTS: Participants were predominantly male (95%), mean age approximately 40, all reported injecting heroin, HIV prevalence ranged between 26 and 30%. We had three seroconversions in 1483 person-years at risk (PYAR) in the cohort study, and 0 in 696 PYAR among repeat survey participants, and 0 seroconversions in 1344 PYAR in recency testing. Overall HIV incidence was 0.085/100 PYAR, 95% confidence interval 0.02-0.25/100 PYAR. CONCLUSION: The data from Hai Phong clearly demonstrate that it is possible to achieve very low HIV incidence - 'end an HIV epidemic' - among PWID in a middle-income country.

7.
Front Cell Infect Microbiol ; 10: 546189, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33102251

RESUMO

Human milk is a significant source of different CD133+ and/or CD34+ stem/progenitor-like cell subsets in healthy women but their cell distribution and percentages in this compartment of HIV-positive women have not been explored. To date, a decrease of CD34+ hematopoietic stem and progenitor cell frequencies in peripheral blood and bone marrow of HIV-positive patients has been reported. Herein, human milk and peripheral blood samples were collected between day 2-15 post-partum from HIV-positive and HIV-negative women, and cells were stained with stem cell markers and analyzed by flow cytometry. We report that the median percentage of CD45+/highCD34-CD133+ cell subset from milk and blood was significantly higher in HIV-positive than in HIV-negative women. The percentage of CD45dimCD34-CD133+ cell subset from blood was significantly higher in HIV-positive than HIV-negative women. Moreover, percentages of CD45dimCD34+, CD45dimCD34+CD133-, and CD45+highCD34+CD133- cell subsets from blood were significantly lower in HIV-positive than HIV-negative women. The CD133+ stem/progenitor-like cell subsets are increased in early human milk and blood of HIV-positive women and are differentially distributed to CD34+ cell subset frequencies which are decreased in blood.

8.
Talanta ; 219: 121344, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32887073

RESUMO

The detection of DNA molecules by agglutination assays has suffered from a lack of specificity. The specificity can be improved by introducing a hybridization step with a specific probe. We developed a setting that captured biotinylated DNA targets between magnetic nanoparticles (MNPs) grafted with tetrathiolated probes and anti-biotin antibodies. The agglutination assay was enhanced using a series of magnetization cycles. This setting allowed to successfully detect a synthetic single stranded DNA with a sensitivity as low as 9 pM. We next adapted this setting to the detection of PCR products. We first developed an asymmetric pan-flavivirus amplification. Then, we demonstrated its ability to detect dengue virus with a limit of detection of 100 TCID50/mL. This magnetic field-enhanced agglutination assay is an endpoint readout, which benefits from the advantages of using nanoparticles that result in particular from a very reduced duration of the test; in our case it lasts less than 5 min. This approach provides a solution to develop new generation platforms for molecular diagnostics.

9.
Biomed Res Int ; 2020: 8037193, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32964044

RESUMO

People who inject drugs (PWID) are a dominant risk group afflicted by blood-borne viruses, mental health disorders, and social precariousness. Risk reduction interventions are administered to PWID regardless of their characteristics or specific risks. The objective of this cross-sectional analysis was to empirically identify profiles of PWID regarding their drug use, risk behaviors, and mental health in order to tailor adapted interventions taking into account limited access to comprehensive care in middle-income countries. PWID were recruited using respondent-driven sampling. PWID with urine testing positive for heroin or methamphetamine and manifesting recent skin injection marks were enrolled. Classification of participants was based on drug use, injection, risky sexual behavior, and mental health data. This was subjected to multiple correspondence analysis followed by hierarchical cluster analysis combined with K-means methodology. From October 2016 to January 2017, 1490 participants were recruited of which 1383 were eligible and enrolled. HCV prevalence was 70.5% and HIV prevalence 29.4%. The cluster analysis identified five distinct profiles: profile 1: recent injection practices and high alcohol consumption, profile 2: at-risk injection and sexual behaviors with precarious situations, profile 3: no sexual activity and older age, profile 4: frequent injections with high methamphetamine use, and profile 5: stable partnerships and less frequent injections. Our study has identified profiles of PWID at particularly high risks, and they should thus be targeted for interventions tailored to their specific risks.

10.
J Clin Med ; 9(9)2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32937988

RESUMO

Children who are human immunodeficiency virus (HIV)-exposed but uninfected (CHEU) accumulate maternal HIV and antiretroviral exposures through pregnancy, postnatal prophylaxis, and breastfeeding. Here, we compared the dynamics of mitochondrial DNA (mtDNA) parameters in African breastfed CHEU receiving lopinavir/ritonavir (LPV/r) or lamivudine (3TC) pre-exposure prophylaxis during the first year of life. The number of mtDNA copies per cell (MCN) and the proportion of deleted mtDNA (MDD) were assessed at day 7 and at week 50 post-delivery (PrEP group). mtDNA depletion was defined as a 50% or more decrease from the initial value, and mtDNA deletions was the detection of mtDNA molecules with large DNA fragment loss. We also performed a sub-analysis with CHEU who did not receive a prophylactic treatment in South Africa (control group). From day seven to week 50, MCN decreased with a median of 41.7% (interquartile range, IQR: 12.1; 64.4) in the PrEP group. The proportion of children with mtDNA depletion was not significantly different between the two prophylactic regimens. Poisson regressions showed that LPV/r and 3TC were associated with mtDNA depletion (reference: control group; LPV/r: PR = 1.75 (CI95%: 1.15-2.68), p < 0.01; 3TC: PR = 1.54 (CI95%: 1.00-2.37), p = 0.05). Moreover, the proportion of children with MDD was unexpectedly high before randomisation in both groups. Long-term health impacts of these mitochondrial DNA parameters should be investigated further for both CHEU and HIV-infected children receiving LPV/r- or 3TC- based regimens.

11.
AIDS ; 34(13): 1875-1882, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32910061

RESUMO

OBJECTIVE: We assessed the association between methamphetamine use and lack of viral suppression among a cohort of HIV-seropositive persons who inject drugs (PWID) in Hai Phong, Vietnam. DESIGN: Cohort study with random effects logit modeling and mediation analysis for antiretroviral therapy (ART) adherence. METHODS: PWID were recruited from October 2016 to October 2017; HIV-seropositive PWID were enrolled in a cohort to assess HIV viral loads, changes in drug use, risk behaviors, and ART adherence during 24-month follow-up. Methamphetamine use in last 30 days was divided into three categories: 0 days (no use), 1-19 days (intermediate), and 20 or more days (heavy). Bivariate and a multivariable random effects logit models were used to assess the relationship between methamphetamine use and not being virally suppressed. We also assessed self-reported ART adherence as a mediating factor. RESULTS: A total of 645 HIV-seropositive PWID were included at baseline; 95% male, average age 40 (SD = 6.4). At baseline, methamphetamine use in last 30 days was 64% no use, 32% intermediate use, 4% heavy use. Approximately 74% of PWID reported high/complete adherence; 76% were at viral suppression. In random effects analysis, recent methamphetamine use was associated with not being virally suppressed during follow-up (adjusted odds ratio: 1.84, 95% confidence interval: 1.06, 3.17); the effect was not explained by a mediating effect of self-reported adherence to ART. CONCLUSION: Recent methamphetamine use is associated with not being virally suppressed among PWID. The results of this study indicate the need for targeted interventions for methamphetamine use with special focus on those with HIV infection.

12.
Sci Rep ; 10(1): 6999, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32332986

RESUMO

In Vietnam, harm reduction programs to control HIV among people who inject drugs (PWID) were implemented approximately 10 years ago. Since then, the HIV prevalence has declined in this population, however, the impact of these programs on the rate of new HIV and Hepatitis C (HCV) infections remains unknown as high mortality can exceed the rate of new infections. We evaluated HIV and HCV incidences in a cohort of active PWID in HaiPhong in 2014, who were recruited from a community-based respondent driven sampling (RDS) survey and followed for 1 year. Only HIV-negative or HCV-negative participants not on medication assisted treatment (MAT) were eligible. HIV/HCV serology was tested at enrollment and at 32- and 64-week follow-up visits. Among 603 RDS participants, 250 were enrolled in the cohort, including 199 HIV seronegative and 99 HCV seronegative PWID. No HIV seroconversion was reported during the 206 person-years (PY) of follow-up (HIV incidence of 0/100PY, one-sided 97.5%CI:0-1.8/100 PY). Eighteen HCV seroconversions were reported for an incidence of 19.4/100 PY (95%CI;11.5-30.7). In multivariate analysis, "Injecting more than twice daily" was associated with HCV seroconversion with an adjusted odds ratio of 5.8 (95%CI;1.8-18.1). In Hai Phong, in a context that demonstrates the effectiveness of HIV control programs, the HCV incidence remains high. New strategies such as mass access to HCV treatment should be evaluated in order to tackle HCV transmission among PWID.

13.
Front Microbiol ; 11: 20, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32117090

RESUMO

The existence of an antisense Open Reading Frame (ORF) that encodes a putative AntiSense Protein (ASP) on the proviral genome of Human Immunodeficiency Virus type 1 (HIV-1) was a source of debate for 30 years. During the last years, some progresses have been made to characterize the cellular immune response against ASP in HIV-1 seropositive patients. However, no tools were available for the detection of antibodies to ASP in the plasma of HIV-1-infected patients during the natural course of the infection. The aim of our study was to develop a Luciferase Immuno-Precipitation System (LIPS) to monitor the quantitative detection of ASP-specific antibodies in the plasma of HIV-1-infected patients [antiretroviral therapy (ART) naive-patients, patients under ART and HIV-1 controllers], patients who discontinued antiretroviral drugs (ARV). We further used this approach to delineate the epitopes of ASP targeted by antibodies. Antibodies directed against ASP were detected in 3 out of 19 patients who discontinued ARV (15%) and in 1 out of 10 ART-naive patients (10%), but were neither detected in HIV-1 infected patients under ART nor in HIV-1 controllers. Individual variations in levels of ASP-specific antibodies were detected overtime. Both the conserved prolin-rich motif and the core 60-189 region of ASP were found to be essential for antibody recognition in the four patients tested positive for anti-ASP antibodies, who were all untreated at the time of sampling. Moreover, for two of these patients, increased levels of ASP-specific antibodies were observed concomitantly to viremia declines. Overall, our method may represent a useful tool to detect a humoral response to ASP in HIV-1-infected patients, which allowed us to confirm the expression of ASP during the course of HIV-1 infection. Further studies will be needed to fully characterize the humoral response to ASP in HIV-1-infected patients.

14.
Clin Infect Dis ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32067040

RESUMO

BACKGROUND: Immune control of Epstein-Barr virus (EBV) infection is impaired in HIV-infected individuals. We explored maternal factors associated with EBV acquisition in HIV-exposed uninfected (HEU) infants and the relationship between EBV infection and serious adverse events (SAE) during the first year of life. METHODS: Two hundred and one HEU infants from Uganda enrolled in the ANRS12174 trial were tested for anti-viral capsid antigen (VCA) antibodies at week 50 of life. The date of infection was estimated by testing of EBV DNA at weeks 1, 6, 14, 26, 38 and 50 postpartum on dried blood spot (DBS). RESULTS: Eighty-seven (43%) infants were tested positive for anti-VCA IgG at week 50. Among the 59 infants positive for EBV DNA, 25% were infected within the first 26 weeks. Almost half of them (12%) were infected before week 14. Shedding of EBV in breast milk was associated with EBV DNA in maternal plasma (P=.009), HIV RNA detection (P=.039), lower CD4 count (P=.001) and was correlated with plasma EBV DNA levels (P=.002). EBV infant infection at week 50 was associated with shedding of EBV in breast milk (P=.009) and young maternal age (P=.029). Occurrence of a clinical SAE, including malaria and pneumonia, was associated with higher levels of EBV DNA in infants (P=.010). CONCLUSIONS: By assessing EBV infection in HEU infants we observed that infection during the first year of life is determined by HIV and EBV maternal factors and that EBV DNA levels was higher among infants with clinical SAE.

15.
Clin Infect Dis ; 71(4): 1030-1039, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31633158

RESUMO

BACKGROUND: Perinatal treatment with lopinavir boosted by ritonavir (LPV/r) is associated with steroidogenic abnormalities. Long-term effects in infants have not been studied. METHODS: Adrenal-hormone profiles were compared at weeks 6 and 26 between human immunodeficiency virus (HIV)-1-exposed but uninfected infants randomly assigned at 7 days of life to prophylaxis with LPV/r or lamivudine (3TC) to prevent transmission during breastfeeding. LPV/r in vitro effect on steroidogenesis was assessed in H295R cells. RESULTS: At week 6, 159 frozen plasma samples from Burkina Faso and South Africa were assessed (LPV/r group: n = 92; 3TC group: n = 67) and at week 26, 95 samples from Burkina Faso (LPV/r group: n = 47; 3TC group: n = 48). At week 6, LPV/r-treated infants had a higher median dehydroepiandrosterone (DHEA) level than infants from the 3TC arm: 3.91 versus 1.48 ng/mL (P < .001). Higher DHEA levels (>5 ng/mL) at week 6 were associated with higher 17-OH-pregnenolone (7.78 vs 3.71 ng/mL, P = .0004) and lower testosterone (0.05 vs 1.34 ng/mL, P = .009) levels in LPV/r-exposed children. There was a significant correlation between the DHEA and LPV/r AUC levels (ρ = 0.40, P = .019) and Ctrough (ρ = 0.40, P = .017). At week 26, DHEA levels remained higher in the LPV/r arm: 0.45 versus 0.13 ng/mL (P = .002). Lopinavir, but not ritonavir, inhibited CYP17A1 and CYP21A2 activity in H295R cells. CONCLUSIONS: Lopinavir was associated with dose-dependent adrenal dysfunction in infants. The impact of long-term exposure and potential clinical consequences require evaluation. CLINICAL TRIALS REGISTRATION: NCT00640263.

16.
J Hum Lact ; 36(2): 303-309, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31815589

RESUMO

BACKGROUND: Stem/progenitor cells have been identified in human milk. However, characterization and percentages of cell subsets in human milk using hematopoietic stem and progenitor cell markers according to the differential expression of CD45, i.e., as CD45dim/+ (mainly hematopoietic stem/progenitor cells) and CD45- (mainly non-hematopoietic stem/progenitor cells), have not been assessed to date. RESEARCH AIM: To characterize stem/progenitor-like cell phenotypes in human milk and to report the percentages of these cells at two different lactation stages compared to peripheral blood. METHODS: Human milk samples paired with peripheral blood samples (N = 10) were analyzed by flow cytometry using CD45, CD34, CD133, CD38, and lineage-negative markers. The percentage of cell subsets was analyzed in colostrum (Day 3 postpartum) and transitional milk (Day 5/6 postpartum) and compared with the peripheral blood counterpart. RESULTS: The percentage of CD45-CD34+ cells was predominant in both colostrum and transitional milk. The percentage of CD45+/highCD133+ cells was high in colostrum while the percentage of CD45-CD133+ cells was high in transitional milk. Furthermore, the median percentages of the CD45-CD34+, CD45-CD133+, and CD45dimCD133+ cell subsets were higher in colostrum than its peripheral blood counterpart (0.11% vs. 0.002%; 0.17% vs. 0.0005%; 0.09% vs. 0.05%, p = .04, respectively); also CD45-CD34-CD133+ and CD45dimCD34-CD133+ cell subsets were higher in colostrum than peripheral blood (1.32% vs. 0.0% and 2.4% vs. 0.06%, p = .04), respectively). CONCLUSION: Early human milk is an abundant reservoir of hematopoietic stem/progenitor-like cells in the CD45+/high population and non-hematopoietic stem/progenitor-like cells in the CD45- population.

18.
Medicine (Baltimore) ; 98(44): e17383, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689745

RESUMO

The risk of postnatal HIV transmission exists throughout the breastfeeding period. HIV shedding in breast milk beyond six months has not been studied extensively. The aim of this study was to determine prevalence and determinants of HIV shedding in breast milk during continued breastfeedingA cross-sectional study was nested in the PROMISE-PEP trial in Lusaka, Zambia to analyze breast milk samples collected from both breasts at week 38 post-partum (mid-way during continued breastfeeding). We measured concurrent HIV deoxyribonucleic acid (DNA) and HIV ribonucleic acid (RNA) as proxies for cell-associated HIV (CAV) and cell-free HIV (CFV) shedding in breast milk respectively. Participants' socio-demographic date, concurrent blood test results, sub clinical mastitis test results and contraceptive use data were available. Logistic regression models were used to identify determinants of HIV shedding in breast milk (detecting either CAV or CFV).The prevalence of HIV shedding in breast milk at 9 months post-partum was 79.4% (95%CI: 74.0 - 84.0). CAV only, CFV only and both CAV and CFV were detectable in 13.7%, 17.3% and 48.4% mothers, respectively. The odds of shedding HIV in breast milk decreased significantly with current use of combined oral contraceptives (AOR: 0.37; 95%CI: 0.17 - 0.83) and increased significantly with low CD4 count (AOR: 3.47; 95%CI: 1.23 - 9.80), unsuppressed plasma viral load (AOR: 6.27; 95%CI: 2.47 - 15.96) and severe sub-clinical mastitis (AOR: 12.56; 95%CI: 2.48 - 63.58).This study estimated that about 80% of HIV infected mothers not on ART shed HIV in breast milk during continued breastfeeding. Major factors driving this shedding were low CD4 count, unsuppressed plasma viral load and severe sub-clinical mastitis. The inverse relationship between breast milk HIV and use of combined oral contraceptives needs further clarification. Continued shedding of CAV may contribute to residual postnatal transmission of HIV in mothers on successful ART.


Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Leite Humano/virologia , Adulto , Antirretrovirais , Aleitamento Materno , Contagem de Linfócito CD4 , Ácidos Nucleicos Livres , Anticoncepcionais Orais Combinados/administração & dosagem , Estudos Transversais , DNA Viral , Feminino , Humanos , Transmissão Vertical de Doença Infecciosa , Modelos Logísticos , Mastite/epidemiologia , Mães , Prevalência , RNA Viral , Fatores Socioeconômicos , Carga Viral , Eliminação de Partículas Virais/fisiologia , Adulto Jovem , Zâmbia
19.
Pediatr Allergy Immunol ; 30(4): 479-487, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30758074

RESUMO

BACKGROUND: Human breast milk cells remain poorly characterized for the presence of unconventional T lymphocytes and innate lymphoid cells (ILCs). METHODS: Early breast milk was collected from eight HIV-uninfected and 11 HIV-infected women 3-12 days after delivery. Mucosal-associated invariant T cells (MAIT cells), TCR γδ cells, and innate lymphoid cells (ILCs) were analyzed in breast milk and paired blood samples. RESULTS: CD161+/TRAV1-2 + MAIT cells were detected in breast milk, accounting for a median (IQR) of 0.08% (0.06-0.16) and 0.17% (0.16-0.31) of CD45+ breast milk cells in HIV-uninfected and HIV-infected women, respectively. A selective compartmentalization of γδ T lymphocytes was observed in breast milk. Median (IQR) frequency of γδ T lymphocytes was 8.95% (8.64-12.14) among breast milk lymphocyte cells compared to 2.54% (1.81-4.10) in blood (P = 0.03) in HIV-uninfected women, and 7.26% (4.22-10.54) in breast milk versus 3.31% (2.54-3.80) in blood (P = 0.004) from HIV-infected women. The proportion of group 1 ILC (ILC1) among total ILCs was higher in breast milk compared to blood in HIV-uninfected women (P = 0.03) and HIV-infected women (P = 0.001). The frequency of ILC2 among total ILCs tends to be lower in breast milk compared to blood in HIV-uninfected women (P = 0.06) and HIV-infected women (P = 0.03). CONCLUSION: Unconventional T cells and ILCs that may be involved in both the protection against infection of the lactating mammary gland and maturation of infant's gut and microbiomes account for a detectable fraction of breast milk cells.


Assuntos
Células Sanguíneas/imunologia , Infecções por HIV/imunologia , HIV-1/fisiologia , Linfócitos/imunologia , Leite Humano/imunologia , Células T Invariáveis Associadas à Mucosa/imunologia , Separação Celular , Feminino , Citometria de Fluxo , Humanos , Imunidade Inata , Imunofenotipagem , Lactação , Contagem de Linfócitos , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo
20.
Bull World Health Organ ; 96(11): 750-759, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30455530

RESUMO

Objective: To estimate population-wide hepatitis B and C seroprevalence using dried blood spot samples acquired for human immunodeficiency virus (HIV) surveillance as part of the 2010-2011 Demographic and Health Survey in Burkina Faso. Methods: We used the database acquired during the multistage, clustered, population-based survey, in which 15 377 participants completed questionnaires and provided dried blood spot samples for HIV testing. We extracted sociodemographic and geographic data including age, sex, ethnicity, education, wealth, marital status and region for each participant. We performed hepatitis B and C assays on 14 886 HIV-negative samples between March to October 2015, and calculated weighted percentages of hepatitis seroprevalence for each variable. Findings: We estimated seroprevalence as 9.1% (95% confidence interval, CI: 8.5-9.7) for the hepatitis B surface antigen and 3.6% (95% CI: 3.3-3.8) for hepatitis C virus antibodies, classifying Burkina Faso as highly endemic for hepatitis B and low-intermediate for hepatitis C. The seroprevalence of hepatitis was higher in men than in women, and varied significantly for both with age, education, ethnicity and region. Extremely high HCV-Ab seroprevalence (13.2%; 95% CI: 10.6-15.7) was identified in the Sud-Ouest region, in particular within the youngest age group (15-20 years), indicating an ongoing epidemic. Conclusion: Our population-representative hepatitis seroprevalence estimates in Burkina Faso advocate for the inclusion of hepatitis serological tests and risk factor questionnaire items in future surveys, the results of which are crucial for the development of appropriate health policies and infection control programmes.


Assuntos
Hepatite B/epidemiologia , Hepatite C/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Burkina Faso/epidemiologia , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Características de Residência , Fatores de Risco , Estudos Soroepidemiológicos , Distribuição por Sexo , Fatores Socioeconômicos , Adulto Jovem
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