Plasmodium falciparum Infection Significantly Impairs Placental Cytokine Profile in HIV Infected Cameroonian Women

BACKGROUND:Placental cytokines play crucial roles in the establishment and maintenance of pregnancy as well as protecting the foetus from infections. Previous studies have suggested the implication of infections such as P. falciparum and HIV in the stimulation of placental cytokines. This study assessed the impact of P. falciparum on placental cytokine profiles between HIV-1 positive and negative women. MATERIALS AND METHODS:P. falciparum infection was checked in peripheral and placental blood of HIV-1 negative and positive women by the thick blood smear test. Cytokines proteins and messenger RNAs were quantified by ELISA and real time PCR, respectively. Non-parametric tests were used for statistical analyses. RESULTS:Placental and peripheral P. falciparum infections were not significantly associated with HIV-1 infection (OR: 1.4; 95% confidence interval (95%CI): 0.5-4.2; p = 0.50 and OR: 0.6; 95%CI: 0.3-1.4; p = 0.26, respectively). Conversely, placental P. falciparum parasitemia was significantly higher in the HIV-1 positive group (p = 0.04). We observed an increase of TNF-alpha mRNA median levels (p = 0.02) and a trend towards a decrease of IL-10 mRNA (p = 0.07) in placenta from HIV-1 positive women compared to the HIV negative ones leading to a median TNF-alpha/IL-10 mRNA ratio significantly higher among HIV-1 positive than among HIV-1 negative placenta (p = 0.004; 1.5 and 0.8, respectively). Significant decrease in median secreted cytokine levels were observed in placenta from HIV-1 positive women as compared to the HIV negative however these results are somewhat indicative since it appears that differences in cytokine levels (protein or mRNA) between HIV-1 positive and negative women depend greatly on P.falciparum infection. Within the HIV-1 positive group, TNF-alpha was the only cytokine significantly associated with clinical parameters linked with HIV-1 MTCT such as premature rupture of membranes, CD4 T-cell number, plasma viral load and delay of NVP intake before delivery. CONCLUSIONS:These results show that P. falciparum infection profoundly modifies the placenta cytokine environment and acts as a confounding factor, masking the impact of HIV-1 in co-infected women. This interplay between the two infections might have implications in the in utero MTCT of HIV-1 in areas where HIV-1 and P. falciparum co-circulate

Effectiveness of Multidrug Antiretroviral Regimens to Prevent Mother-to-Child Transmission of HIV-1 in Routine Public Health Services in Cameroon

International audienceBACKGROUND: Multidrug antiretroviral (ARV) regimens including HAART and short-course dual antiretroviral (sc-dARV) regimens were introduced in 2004 to improve Prevention of Mother-to-Child Transmission (PMTCT) in Cameroon. We assessed the effectiveness of these regimens from 6-10 weeks and 12 months of age, respectively. METHODOLOGY/FINDINGS: We conducted a retrospective cohort study covering the period from October 2004 to March 2008 in a reference hospital in Cameroon. HIV-positive pregnant women with CD4 or = 37 weeks, women received sd-NVP during labour [regimen 4]. Infants received sd-NVP plus ZDV and 3TC for 7 days or 30 days. Early diagnosis (6-10 weeks) was done, using b-DNA and subsequently RT-PCR. We determined early MTCT rate and associated risk factors using logistic regression. The 12-month HIV-free survival was assessed using Cox regression. Among 418 mothers, 335 (80%) received multidrug ARV regimens (1, 2, and 3) and MTCT rate with multidrug regimens was 6.6% [95%CI: 4.3-9.6] at 6 weeks, without any significant difference between regimens. Duration of mother's ARV regimen < 4 weeks [OR = 4.7, 95%CI: 1.3-17.6], mother's CD4 < 350 cells/mm(3) [OR = 6.4, 95%CI: 1.8-22.5] and low birth weight [OR = 4.0, 95%CI: 1.4-11.3] were associated with early MTCT. By 12 months, mixed feeding [HR = 8.7, 95%CI: 3.6-20.6], prematurity [HR = 2.3, 95%CI: 1.2-4.3] and low birth weight were associated with children's risk of progressing to infection or death. CONCLUSIONS: Multidrug ARV regimens for PMTCT are feasible and effective in routine reference hospital. Early initiation of ARV during pregnancy and proper obstetrical care are essential to improve PMTCT

A low proportion of HBeAg among HBsAg-positive pregnant women with known HIV status could suggest low perinatal transmission of HBV in Cameroon

<p>Abstract</p> <p>Background</p> <p>Transmission of hepatitis B virus (HBV) from HBV-positive mothers to their infants is common and usually occurs when the mother is hepatitis B e antigen (HBeAg) positive and/or has a high HBV DNA load. In this study, we determined the prevalence of hepatitis B surface antigen (HBsAg) and HBeAg among pregnant women with known HIV status.</p> <p>Findings</p> <p>A total of 650 pregnant women with a mean age of 26.2 years including 301 HIV-positives and 349 HIV-negatives were screened for HBsAg (Monolisa AgHBs Plus Biorad, France). Among the HBsAg-positives, HBeAg and anti-HBe were tested (Monolisa Ag HBe Plus Biorad, France). Overall, 51 (7.85%) were positive for HBsAg. The prevalence of HBsAg was not statistically different between HIV-positive and HIV-negative pregnant women [28/301 (9.3%) vs 23/349 (6.59%); p = 0.2]. None of the 45 HBsAg-positive samples was reactive for HBeAg.</p> <p>Conclusions</p> <p>Our study indicates a high prevalence of HBsAg with very low proportion of HBeAg in Cameroonian pregnant women. Since perinatal transmission of HBV is mostly effective when the mother is also HBeAg-positive, our data could suggest that perinatal transmissions play a minor role in HBV prevalence in Cameroon. In line with previous African studies, these findings further suggests that horizontal transmission could be the most common mechanism of HBV infections in Cameroon.</p

Higher placental anti-inflammatory IL-10 cytokine expression in HIV-1 infected women receiving longer zidovudine prophylaxis associated with nevirapine

Placental cytokine balance may be critical for the control of mother-to-child transmission (MTCT) of HIV. We assessed whether the type and duration of antiretrovirals used for prevention of HIV-1-MTCT modified the inflammatory cytokine profile. We investigated the levels of cytokine expression in the placentas of 61 HIV-1-infected women who received zidovudine (ZDV) plus single dose nevirapine (SD-NVP) or ZDV only for prevention of MTCT. Placentas of 38 HIV-1-uninfected women were included as controls. All placentas were obtained after vaginal delivery. Levels of mRNA and cytokine expression were quantified using real-time PCR and ELISA, respectively, in placental explants and 24-hour culture supernatants and analyzed in relation to the women's characteristics and the type and duration of antiretroviral prophylaxis. HIV-1-infected and uninfected women did not show any differences in the expression of placental cytokine secretion except for a trend toward lower TNF-10 mRNA levels in HIV-1-infected women. Within the HIV-1-infected group, women who were exposed to a long duration of ZDV (>72 days) or received SD-NVP less than 5h prior to delivery, more frequently expressed detectable levels of IL-10 in their placentas (32% versus 7% (p = 0.01) and 32% versus 5% (p = 0.02), respectively). No infant was found to be HIV-1-infected. Our results showed a normalization of the placental cytokine balance in HIV-1-infected women receiving antiretroviral prophylaxis. Furthermore, the type and duration of antiretroviral prophylaxis have an impact on the placental anti-inflammatory IL-10 expression level, which may contribute to controlling HIV replication at the placental level, thus reducing MTCT of HIV-1.Fil: Pornprasert, Sakorn. Chiang Mai University; TailandiaFil: Mary, Jean-Yves. Université Paris Diderot - Paris 7; FranciaFil: Faye, Albert. Institut National de la Santé et de la Recherche Médicale; FranciaFil: Leechanachai, Pannee. Chiang Mai University; TailandiaFil: Limtrakul, Aram. Health Promotion Center Region; TailandiaFil: Rugpao, Sungwal. Chiang Mai University; TailandiaFil: Sirivatanapa, Pannee. Chiang Mai University; TailandiaFil: Gomuthbutra, Vorapin. Nakornping Hospital; TailandiaFil: Matanasaravoot, Wanmanee. Lamphun Hospital; TailandiaFil: Le Coer, Sophie. Institut National d’Etudes Démographiques; FranciaFil: Lallemant, Marc. Centre National de la Recherche Scientifique. Institut de Recherche pour le Développement; FranciaFil: Barré-Sinoussi, Françoise. Instituto Pasteur; FranciaFil: Menu, Elisabeth. Instituto Pasteur; FranciaFil: Ngo Giang Huong, Nicole. Centre National de la Recherche Scientifique. Institut de Recherche pour le Développement; FranciaFil: Ayouba, Ahidjo. Instituto Pasteur; FranciaFil: Chailert, Sanupong. Chiang Mai University; Tailandia. Instituto Pasteur; FranciaFil: Chaouat, Gérard. Institut National de la Santé et de la Recherche Médicale; FranciaFil: Derrien, Muriel. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Dolcini, Guillermina Laura. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Sanidad Animal y Medicina Preventiva. Laboratorio de Virología; Argentina. Instituto Pasteur; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Eteki, Nicole. Hôpital Central de Yaoundé. Maternité Principale; CamerúnFil: Kfutwah, Anfumbom Jude. Instituto Pasteur; FranciaFil: Kouo, Odette. Instituto Pasteur; FranciaFil: Lemen, Brigitte. Instituto Pasteur; FranciaFil: Abal, Facundo Juan Pablo. Instituto Pasteur; FranciaFil: Nerrienet, Eric. Instituto Pasteur; FranciaFil: Njinku, Bernadette. Instituto Pasteur; FranciaFil: Scarlatti, Gabriella. Suan Dok Hospital; TailandiaFil: Tejiokem, Mathurin. Centre Pasteur du Cameroun; CamerúnFil: Téné, Gilbert. No especifíca

Feasibility of Early Infant Diagnosis of HIV in Resource-Limited Settings: The ANRS 12140-PEDIACAM Study in Cameroon

BACKGROUND: Early infant diagnosis (EID) of HIV is a key-point for the implementation of early HAART, associated with lower mortality in HIV-infected infants. We evaluated the EID process of HIV according to national recommendations, in urban areas of Cameroon. METHODS/FINDINGS: The ANRS12140-PEDIACAM study is a multisite cohort in which infants born to HIV-infected mothers were included before the 8(th) day of life and followed. Collection of samples for HIV DNA/RNA-PCR was planned at 6 weeks together with routine vaccination. The HIV test result was expected to be available at 10 weeks. A positive or indeterminate test result was confirmed by a second test on a different sample. Systematic HAART was offered to HIV-infected infants identified. The EID process was considered complete if infants were tested and HIV results provided to mothers/family before 7 months of age. During 2007-2009, 1587 mother-infant pairs were included in three referral hospitals; most infants (n = 1423, 89.7%) were tested for HIV, at a median age of 1.5 months (IQR, 1.4-1.6). Among them, 51 (3.6%) were HIV-infected. Overall, 1331 (83.9%) completed the process by returning for the result before 7 months (median age: 2.5 months (IQR, 2.4-3.0)). Incomplete process, that is test not performed, or result of test not provided or provided late to the family, was independently associated with late HIV diagnosis during pregnancy (adjusted odds ratio (aOR) = 1.8, 95%CI: 1.1 to 2.9, p = 0.01), absence of PMTCT prophylaxis (aOR = 2.4, 95%CI: 1.4 to 4.3, p = 0.002), and emergency caesarean section (aOR = 2.5, 95%CI: 1.5 to 4.3, p = 0.001). CONCLUSIONS: In urban areas of Cameroon, HIV-infected women diagnosed sufficiently early during pregnancy opt to benefit from EID whatever their socio-economic, marital or disclosure status. Reduction of non optimal diagnosis process should focus on women with late HIV diagnosis during pregnancy especially if they did not receive any PMTCT, or if complications occurred at delivery

In Vitro and In Vivo Human Herpesvirus 8 Infection of Placenta

Herpesvirus infection of placenta may be harmful in pregnancy leading to disorders in fetal growth, premature delivery, miscarriage, or major congenital abnormalities. Although a correlation between human herpesvirus 8 (HHV-8) infection and abortion or low birth weight in children has been suggested, and rare cases of in utero or perinatal HHV-8 transmission have been documented, no direct evidence of HHV-8 infection of placenta has yet been reported. The aim of this study was to evaluate the in vitro and in vivo susceptibility of placental cells to HHV-8 infection. Short-term infection assays were performed on placental chorionic villi isolated from term placentae. Qualitative and quantitative HHV-8 detection were performed by PCR and real-time PCR, and HHV-8 proteins were analyzed by immunohistochemistry. Term placenta samples from HHV-8-seropositive women were analyzed for the presence of HHV-8 DNA and antigens. In vitro infected histocultures showed increasing amounts of HHV-8 DNA in tissues and supernatants; cyto- and syncitiotrophoblasts, as well as endothelial cells, expressed latent and lytic viral antigens. Increased apoptotic phenomena were visualized by the terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end-labeling method in infected histocultures. Ex vivo, HHV-8 DNA and a latent viral antigen were detected in placenta samples from HHV-8-seropositive women. These findings demonstrate that HHV-8, like other human herpesviruses, may infect placental cells in vitro and in vivo, thus providing evidence that this phenomenon might influence vertical transmission and pregnancy outcome in HHV-8-infected women

Effet du VIH-1 et de la prophylaxie de la transmission mère-enfant (TME) associés ou non à une co-infection palustre sur la balance des cytokines/chimiokines au sein de l'environnement placentaire

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF