HIV infection and placental malaria reduce maternal transfer of multiple antimalarial antibodies in Mozambican women / HIV infection and placental malaria reduce maternal transfer of multiple antimalarial antibodies in Mozambican women

Maternal Plasmodium falciparum-specific antibodies may contribute to protect infants against severe malaria. Our main objective was to evaluate the impact of maternal HIV infection and placental malaria on the cord blood levels and efficiency of placental transfer of IgG and IgG subclasses. Methods: In a cohort of 341 delivering HIV-negative and HIV-positive mothers from southern Mozambique, we measured total IgG and IgG subclasses in maternal and cord blood pairs by quantitative suspension array technology against eight P. falciparum antigens: Duffy-binding like domains 3-4 of VAR2CSA from the erythrocyte membrane protein 1, erythrocyte-binding antigen 140, exported protein 1 (EXP1), merozoite surface proteins 1, 2 and 5, and reticulocyte-binding-homologue-4.2 (Rh4.2). We performed univariable and multivariable regression models to assess the association of maternal HIV infection, placental malaria, maternal variables and pregnancy outcomes on cord antibody levels and antibody transplacental transfer. Results: Maternal antibody levels were the main determinants of cord antibody levels. HIV infection and placental malaria reduced the transfer and cord levels of IgG and IgG1, and this was antigen-dependent. Low birth weight was associated with an increase of IgG2 in cord against EXP1 and Rh4.2. Conclusions: We found lower maternally transferred antibodies in HIV-exposed infants and those born from mothers with placental malaria, which may underlie increased susceptibility to malaria in these children.

Reduced Placental Transfer of Antibodies Against a Wide Range of Microbial and Vaccine Antigens in HIV-Infected Women in Mozambique

Transplacental transfer of antibodies is essential for conferring protection in newborns against infectious diseases. We assessed the impact of different factors, including gestational age and maternal infections such as HIV and malaria, on the efficiency of cord blood levels and placental transfer of IgG subclasses. We measured total IgG and IgG subclasses by quantitative suspension array technology against 14 pathogens and vaccine antigens, including targets of maternal immunization, in 341 delivering HIV-uninfected and HIV-infected mother-infant pairs from southern Mozambique. We analyzed the association of maternal HIV infection, Plasmodium falciparum exposure, maternal variables and pregnancy outcomes on cord antibody levels and transplacental transfer. Our results show that maternal antibody levels were the main determinant of cord antibody levels. Univariable and multivariable analysis showed that HIV reduced the placental transfer and cord levels of IgG and IgG1 principally, but also IgG2 to half of the antigens tested. P. falciparum exposure and prematurity were negatively associated with cord antibody levels and placental transfer, but this was antigen-subclass dependent. Our findings suggest that lower maternally transferred antibodies may underlie increased susceptibility to infections of HIV-exposed infants. This could affect efficacy of maternal vaccination, especially in sub-Saharan Africa, where there is a high prevalence of HIV, malaria and unfavorable environmental factors

Reduced Placental Transfer of Antibodies Against a Wide Range of Microbial and Vaccine Antigens in HIV-Infected Women in Mozambique

Transplacental transfer of antibodies is essential for conferring protection in newborns against infectious diseases. We assessed the impact of different factors, including gestational age and maternal infections such as HIV and malaria, on the efficiency of cord blood levels and placental transfer of IgG subclasses. We measured total IgG and IgG subclasses by quantitative suspension array technology against 14 pathogens and vaccine antigens, including targets of maternal immunization, in 341 delivering HIV-uninfected and HIV-infected mother-infant pairs from southern Mozambique. We analyzed the association of maternal HIV infection, Plasmodium falciparum exposure, maternal variables and pregnancy outcomes on cord antibody levels and transplacental transfer. Our results show that maternal antibody levels were the main determinant of cord antibody levels. Univariable and multivariable analysis showed that HIV reduced the placental transfer and cord levels of IgG and IgG1 principally, but also IgG2 to half of the antigens tested. P. falciparum exposure and prematurity were negatively associated with cord antibody levels and placental transfer, but this was antigen-subclass dependent. Our findings suggest that lower maternally transferred antibodies may underlie increased susceptibility to infections of HIV-exposed infants. This could affect efficacy of maternal vaccination, especially in sub-Saharan Africa, where there is a high prevalence of HIV, malaria and unfavorable environmental factors.

Community-based progress indicators for prevention of mother-to-child transmission and mortality rates in HIV-exposed children in rural Mozambique

Background: Eliminating mother-to-child HIV-transmission (EMTCT) implies a case rate target of new pediatric HIV-infections< 50/100,000 live-births and a transmission rate < 5%. We assessed these indicators at community-level in Mozambique, where MTCT is the second highest globally.. Methods: A cross-sectional household survey was conducted within the Manhiça Health Demographic Surveillance System in Mozambique (October 2017-April 2018). Live births in the previous 4 years were randomly selected, and mother/child HIV-status was ascertained through documentation or age-appropriate testing. Estimates on prevalence and transmission were adjusted by multiple imputation chained equation (MICE) for participants with missing HIV-status. Retrospective cumulative mortality rate and risk factors were estimate by Fine-Gray model. Results: Among 5000 selected mother-child pairs, 3486 consented participate. Community HIV-prevalence estimate in mothers after MICE adjustment was 37.6% (95%CI:35.8-39.4%). Estimates doubled in adolescents aged < 19 years (from 8.0 to 19.1%) and increased 1.5-times in mothers aged < 25 years. Overall adjusted vertical HIV-transmission at the time of the study were 4.4% (95% CI:3.1-5.7%) in HIV-exposed children (HEC). Pediatric case rate-infection was estimated at 1654/100,000 live-births. Testing coverage in HEC was close to 96.0%; however, only 69.1% of them were tested early(< 2 months of age). Cumulative child mortality rate was 41.6/1000 live-births. HIV-positive status and later birth order were significantly associated with death. Neonatal complications, HIV and pneumonia...

Loss to follow-up and opportunities for reengagement in HIV care in rural Mozambique. A prospective cohort study

Patients lost to follow-up (LTFU) over the human immunodeficiency virus (HIV) cascade have poor clinical outcomes and contribute to onward HIV transmission. We assessed true care outcomes and factors associated with successful reengagement in patients LTFU in southern Mozambique. Newly diagnosed HIV-positive adults were consecutively recruited in the Manhiça District. Patients LTFU within 12 months after HIV diagnosis were visited at home from June 2015 to July 2016 and interviewed for ascertainment of outcomes and reasons for LTFU. Factors associated with reengagement in care within 90 days after the home visit were analyzed by Cox proportional hazards model. Among 1122 newly HIV-diagnosed adults, 691 (61.6%) were identified as LTFU. Of those, 557 (80.6%) were approached at their homes and 321 (57.6%) found at home. Over 50% had died or migrated, 10% had been misclassified as LTFU, and 252 (78.5%) were interviewed. Following the visit, 79 (31.3%) reengaged in care. Having registered in care and a shorter time between LTFU and visit were associated with reengagement in multivariate analyses: adjusted hazards ratio of 3.54 [95% confidence interval (CI): 1.81­ 6.92; P<.001] and 0.93 (95% CI: 0.87­1.00; P=.045), respectively. The most frequently reported barriers were the lack of trust in the HIV-diagnosis, the perception of being in good health, and fear of being badly treated by health personnel and differed by type of LTFU. Estimates of LTFU in rural areas of sub-Saharan Africa are likely to be overestimated in the absence of active tracing strategies. Home visits are resource-intensive but useful strategies for reengagement for at least one-third of LTFU patients when applied in the context of differentiated care for those LTFU individuals who had already enrolled in HIV care at some point.