SARS-CoV-2 seroprevalence among Beninese pregnant women in the third year of the pandemic.

BACKGROUND: Pregnant women are a vulnerable population to COVID-19 given an increased susceptibility to severe SARS-CoV-2 infection and pregnancy complications. However, few SARS-CoV-2 serological surveys have been performed among this population to assess the extent of the infection in sub-Saharan countries. The objectives of this study were to determine SARS-CoV-2 seroprevalence among Beninese pregnant women, to identify spatial seropositivity clusters and to analyse factors associated with the infection. METHODS: A cross-sectional study including women in their third trimester of pregnancy attending the antenatal care (ANC) clinics at Allada (south Benin) and Natitingou (north Benin) was conducted. Rapid diagnostic tests (RDT) for detection of IgG/IgM against the SARS-CoV-2 spike protein were performed using capillary blood. Seroprevalence of SARS-CoV-2 antibodies and associations between SARS-CoV-2 serostatus and maternal characteristics were analyzed by multivariate logistic regression. Spatial analyses were performed using the spatial scan statistics to identify spatial clusters of SARS-CoV-2 infection. RESULTS: A total of 861 pregnant women were enrolled between May 4 and June 29, 2022. 58/861 (6.7%) participants reported having received COVID-19 vaccine. None of the participants had been diagnosed with COVID-19 during their pregnancy. SARS-CoV-2 antibodies were detected in 607/802 (75.7%; 95% CI 72.56%-78.62%) of unvaccinated participants. Several urban and rural spatial clusters of SARS-CoV-2 cases were identified in Allada and one urban spatial cluster was identified in Natitingou. Unvaccinated participants from Allada with at least one previous morbidity were at a three-times higher risk of presenting SARS-CoV-2 antibodies (OR = 2.89; 95%CI 1.19%-7.00%). CONCLUSION: Three out of four pregnant women had SARS-CoV-2 antibodies, suggesting a high virus circulation among pregnant women in Benin, while COVID-19 vaccination coverage was low. Pregnant women with comorbidities may be at increased risk of SARS-CoV-2 infection. This population should be prioritized for COVID-19 diagnosis and vaccination in order to prevent its deleterious effects. TRIAL REGISTRATION: NCT06170320 (retrospectively registered on December 21, 2023).

Interest of seroprevalence surveys for the epidemiological surveillance of the SARS-CoV-2 pandemic in African populations: Insights from the ARIACOV project in Benin.

BACKGROUND: Many SARS-CoV-2 seroprevalence surveys since the end of 2020 have disqualified the first misconception that Africa had been spared by the pandemic. Through the analysis of three SARS-CoV-2 seroprevalence surveys carried out in Benin as part of the ARIACOV project, we argue that the integration of epidemiological serosurveillance of the SARS-CoV-2 infection in the national surveillance packages would be of great use to refine the understanding of the COVID-19 pandemic in Africa. METHODS: We carried out three repeated cross-sectional surveys in Benin: two in Cotonou, the economic capital in March and May 2021, and one in Natitingou, a semi-rural city in the north of the country in August 2021. Total and weighted-by-age-group seroprevalences were estimated and the risk factors for SARS-CoV-2 infection were assessed by multivariate logistic regression. RESULTS: In Cotonou, a slight increase in overall age-standardised SARS-CoV-2 seroprevalence from 29.77% (95% CI: 23.12%-37.41%) at the first survey to 34.86% (95% CI: 31.57%-38.30%) at the second survey was observed. In Natitingou, the globally adjusted seroprevalence was 33.34% (95% CI: 27.75%-39.44%). A trend of high risk for SARS-CoV 2 seropositivity was observed in adults over 40 versus the young (less than 18 years old) during the first survey in Cotonou but no longer in the second survey. CONCLUSIONS: Our results show that, however, rapid organisation of preventive measures aimed at breaking the chains of transmission, they were ultimately unable to prevent a wide spread of the virus in the population. Routine serological surveillance on strategic sentinel sites and/or populations could constitute a cost-effective compromise to better anticipate the onset of new waves and define public health strategies.

Measuring entomological parameters before implementing a study on asymptomatic carriers of Plasmodium falciparum in the Zè District in southern Benin.

BACKGROUND: The objective of this study was to estimate malaria transmission and insecticide resistance status in malaria vectors in Adjrako village from Zè District in Southern Benin. The present study was carried out prior to investigations on infectivity of blood from asymptomatic carriers of Plasmodium falciparum to malaria vector mosquitoes. METHODS: Human landing collections (HLCs) were performed in Adjrako village during the rainy season (September-November 2021). In this village, host-seeking mosquitoes were collected during three nights per survey from 22:00 to 06:00 in six randomly selected houses. Malaria vectors were dissected in orders to determinate their parity. Plasmodium falciparum infection in malaria vectors was determined by qPCR and the entomological inoculation rate (EIR) was calculated. The World Health Organization (WHO) insecticide susceptibility test-kits were used to evaluate the susceptibility of Anopheles gambiae sensu lato (s.l.) to deltamethrin at 0.05% and bendiocarb at 0.1%. RESULTS: A total of 3260 females of mosquitoes belonging to 4 genera (Anopheles, Culex, Aedes and Mansonia) were collected. Most of the mosquitoes collected were An. gambiae sensu lato (s.l.). The entomological inoculation rate (EIR) for the three collection months was 8.7 infective bites per person and the parity rate was 84%. Mortality rates of An. gambiae s.l. exposed to 0.05% deltamethrin and 0.1% bendiocarb were 18% and 96%, respectively, indicating that this vector population was resistant to deltamethrin and possibly resistant to bendiocarb in the study area. CONCLUSION: This study showed that malaria transmission is effective in the study area and that An. gambiae s.l. is the main malaria vector. The entomological parameters indicate this study area is potentially favourable for investigations on P. falciparum asymptomatic carriers.

Malaria in the First Trimester of Pregnancy and Fetal Growth: Results from a Beninese Preconceptional Cohort.

BACKGROUND: Malaria in early pregnancy occurs at a time when the placenta is developing, with possible consequences for placental function and fetal growth. We assessed the association between first trimester malaria and fetal growth documented through repeated ultrasound scans. METHODS: The RECIPAL preconceptional cohort included 411 Beninese pregnant women followed from 7 weeks' gestation (wg) until delivery. Among them, 218 had 4 scans for fetal monitoring at 16, 22, 28, and 34 wg. Multivariate seemingly unrelated regression models were used to assess association of microscopic malaria in the first trimester (<15 wg) with abdominal circumference, head circumference, biparietal diameter, and femur length throughout pregnancy. RESULTS: Of 39% (86/218) of women with at least 1 microscopic malarial infection during pregnancy, 52.3% (45/86) were infected in the first trimester. Most women (88.5%) were multiparous. There was no association between adjusted z-scores for fetal growth parameters and first trimester malaria. Parity, newborn sex, socioeconomic level, and maternal body mass index significantly influenced fetal growth. CONCLUSIONS: In a context where malaria infections in pregnancy are well detected and treated, their adverse effect on fetal growth may be limited. Our results argue in favor of preventing and treating infections as early as the first trimester.

The Role of Ultrasensitive Molecular Methods for Detecting Malaria-The Broader Perspective.

Ultrasensitive molecular diagnostics are lowering the limit of detection for malaria parasites in the blood and providing insights not captured by conventional tools such as microscopy and rapid antigen tests. Low-level malaria infections identified by molecular tools may influence clinical outcomes, transmission events, and elimination efforts. While many ultrasensitive molecular methods require well-equipped laboratories, technologies such as loop-mediated isothermal amplification and recombinase polymerase amplification provide more portable and analytically sensitive solutions. These tools may benefit asymptomatic patient screening, antenatal care, and elimination campaigns. We review the recent evidence, offer our perspective on the impact of these new tests, and identify future research priorities.

Suboptimal Intermittent Preventive Treatment in Pregnancy (IPTp) is Associated With an Increased Risk of Submicroscopic Plasmodium falciparum Infection in Pregnant Women: A Prospective Cohort Study in Benin.

BACKGROUND: Harmful maternal and neonatal health outcomes result from malaria in pregnancy, the prevention of which primarily relies on intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP). The World Health Organization recommends IPTp-SP in sub-Saharan Africa, but implementation is highly heterogeneous and often suboptimal in terms of the number of doses and their timing. In this study, we assessed the impact of this heterogeneity on malaria in pregnancy, mainly with respect to submicroscopic Plasmodium falciparum infections. METHODS: We used data from 273 Beninese women followed throughout pregnancy. Screening for P. falciparum infections, using both microscopy-based and polymerase chain reaction (PCR)-based methods, was performed monthly, and information on IPTp-SP doses was collected. Gestational age was estimated by repeated ultrasound scans. Using a negative binomial model, we investigated the effect of IPTp-SP doses and timing after 17 weeks of gestation on the number of P. falciparum infections, focusing on submicroscopic infections detectable only by PCR. RESULTS: At least 2 IPTp-SP doses were taken by 77.3% of the women. The median gestational age at the first IPTp-SP dose was 22 weeks. A late first IPTp-SP dose (>21.2 weeks) was marginally associated with an increased number of P. falciparum infections (adjusted incidence rate ratio [aIRR] = 1.3; P = .098). The number of IPTp-SP doses was not associated with the number of submicroscopic infections (aIRR = 1.2, P = .543). CONCLUSIONS: A late first IPTp-SP dose failed to provide optimal protection against P. falciparum, especially submicroscopic infections. This highlights the need for a new antimalarial drug for IPTp that could be taken early in pregnancy.

Dynamics of Submicroscopic Plasmodium falciparum Infections Throughout Pregnancy: A Preconception Cohort Study in Benin.

BACKGROUND: In the context of global malaria elimination efforts, special attention is being paid to submicroscopic Plasmodium falciparum infections. In pregnant, sub-Saharan African women, such infections are more prevalent than microscopic infections, and are thought to have adverse effects on both mothers' and newborns' health. However, no study has studied the dynamics and determinants of these infections throughout pregnancy. Retard de Croissance Intra-uterin et Paludisme (RECIPAL), a preconception cohort study carried out in Benin between 2014 and 2017, represented a unique opportunity to assess this issue. METHODS: We used data from 273 pregnant Beninese women who were followed-up from preconception to delivery. We studied the dynamics of and factors influencing submicroscopic (and microscopic) P. falciparum infections during the 3 trimesters of pregnancy, using an ordinal logistic mixed model. RESULTS: The incidence rate of submicroscopic P. falciparum infections during pregnancy was 12.7 per 100 person-months (95% confidence interval [CI] 10.8-14.9), compared to 6.7 per 100 person-months (95% CI 5.5-8.1) for microscopic infections. The prevalences were highest in the first trimester for both submicroscopic and microscopic infections. After adjustment for potential confounding factors, we found that those of young age and those with a submicroscopic P. falciparum infection prior to pregnancy were at significantly higher risks of submicroscopic and microscopic infections throughout pregnancy, with a more pronounced effect in the first trimester of pregnancy. CONCLUSIONS: The first trimester of pregnancy is a particularly high-risk period for P. falciparum infection during pregnancy, especially for the youngest women. Malaria prevention tools covering the preconception period and early pregnancy are urgently needed to better protect pregnant women and their newborns.

Correction to: Prevalence and clinical impact of malaria infections detected with a highly sensitive HRP2 rapid diagnostic test in Beninese pregnant women.

An amendment to this paper has been published and can be accessed via the original article.

Prevalence and clinical impact of malaria infections detected with a highly sensitive HRP2 rapid diagnostic test in Beninese pregnant women.

BACKGROUND: While sub-microscopic malarial infections are frequent and potentially deleterious during pregnancy, routine molecular detection is still not feasible. This study aimed to assess the performance of a Histidine Rich Protein 2 (HRP2)-based ultrasensitive rapid diagnostic test (uRDT, Alere Malaria Ag Pf) for the detection of infections of low parasite density in pregnant women. METHODS: This was a retrospective study based on samples collected in Benin from 2014 to 2017. A total of 942 whole blood samples collected in 327 women in the 1st and 3rd trimesters and at delivery were tested by uRDT, conventional RDT (cRDT, SD BIOLINE Malaria Ag Pf), microscopy, quantitative polymerase chain-reaction (qPCR) and Luminex-based suspension array technology targeting P. falciparum HRP2. The performance of each RDT was evaluated using qPCR as reference standard. The association between infections detected by uRDT, but not by cRDT, with poor maternal and birth outcomes was assessed using multivariate regression models. RESULTS: The overall positivity rate detected by cRDT, uRDT, and qPCR was 11.6% (109/942), 16.2% (153/942) and 18.3% (172/942), respectively. Out of 172 qPCR-positive samples, 68 were uRDT-negative. uRDT had a significantly better sensitivity (60.5% [52.7-67.8]) than cRDT (44.2% [36.6-51.9]) and a marginally decreased specificity (93.6% [91.7-95.3] versus 95.7% [94.0-97.0]). The gain in sensitivity was particularly high (33%) and statistically significant in the 1st trimester. Only 28 (41%) out of the 68 samples which were qPCR-positive, but uRDT-negative had detectable but very low levels of HRP2 (191 ng/mL). Infections that were detected by uRDT but not by cRDT were associated with a 3.4-times (95%CI 1.29-9.19) increased risk of anaemia during pregnancy. CONCLUSIONS: This study demonstrates the higher performance of uRDT, as compared to cRDTs, to detect low parasite density P. falciparum infections during pregnancy, particularly in the 1st trimester. uRDT allowed the detection of infections associated with maternal anaemia.

Increased Risk of Malaria During the First Year of Life in Small-for-Gestational-Age Infants: A Longitudinal Study in Benin.

BACKGROUND: According to the Developmental Origins of Health and Diseases paradigm, the fetal period is highly vulnerable and may have profound effects on later health. Few studies assessed the effect of small-for-gestational age (SGA), a proxy for fetal growth impairment, on risk of malaria during infancy in Africa. METHODS: We used data from a cohort of 398 mother-child pairs, followed from early pregnancy to age 1 year in Benin. Malaria was actively and passively screened using thick blood smear. We assessed the effect of SGA on risk of malaria infection and clinical malaria from birth to 12 months, after stratifying on the infant's age using a logistic mixed regression model. RESULTS: After adjustment for potential confounding factors and infant's exposure to mosquitoes, SGA was associated with a 2-times higher risk of malaria infection (adjusted odds ratio [aOR] = 2.16; 95% confidence interval [CI], 1.04-4.51; P = .039) and clinical malaria (aOR = 2.33; 95% CI, 1.09-4.98; P = .030) after age 6 months. CONCLUSION: Results suggest higher risk of malaria during the second semester of life in SGA infants, and argue for better follow-up of these infants after birth, as currently for preterm babies.

Contribution of Asymptomatic Plasmodium Infections to the Transmission of Malaria in Kayin State, Myanmar.

BACKGROUND: The objective of mass antimalarial drug administration (MDA) is to eliminate malaria rapidly by eliminating the asymptomatic malaria parasite reservoirs and interrupting transmission. In the Greater Mekong Subregion, where artemisinin-resistant Plasmodium falciparum is now widespread, MDA has been proposed as an elimination accelerator, but the contribution of asymptomatic infections to malaria transmission has been questioned. The impact of MDA on entomological indices has not been characterized previously. METHODS: MDA was conducted in 4 villages in Kayin State (Myanmar). Malaria mosquito vectors were captured 3 months before, during, and 3 months after MDA, and their Plasmodium infections were detected by polymerase chain reaction (PCR) analysis. The relationship between the entomological inoculation rate, the malaria prevalence in humans determined by ultrasensitive PCR, and MDA was characterized by generalized estimating equation regression. RESULTS: Asymptomatic P. falciparum and Plasmodium vivax infections were cleared by MDA. The P. vivax entomological inoculation rate was reduced by 12.5-fold (95% confidence interval [CI], 1.6-100-fold), but the reservoir of asymptomatic P. vivax infections was reconstituted within 3 months, presumably because of relapses. This was coincident with a 5.3-fold (95% CI, 4.8-6.0-fold) increase in the vector infection rate. CONCLUSION: Asymptomatic infections are a major source of malaria transmission in Southeast Asia.

Effects of Malaria in the First Trimester of Pregnancy on Poor Maternal and Birth Outcomes in Benin.

BACKGROUND: In sub-Saharan Africa, malaria in the first half of pregnancy is harmful for both the mother and her fetus. However, malaria in the first trimester of pregnancy, when women are usually not protected against malaria, has been little investigated. For the first time, we assessed the effects of malaria in the first trimester on maternal and birth outcomes using a preconceptional study design. METHODS: From June 2014 to March 2017, 1214 women of reproductive age were recruited and followed monthly until 411 became pregnant. The pregnant women were then followed from 5-6 weeks of gestation until delivery. Path analysis was used to assess the direct effect (ie, not mediated by malaria in the second or third trimester) of malaria in the first trimester on maternal anemia and poor birth outcomes. The cumulative effect of infections during pregnancy on the same outcomes was also evaluated. RESULTS: The prevalence of malaria infections in the first trimester was 21.8%. Malaria in the first trimester was significantly associated with maternal anemia in the third trimester (adjusted odds ratio 2.25, 95% confidence interval 1.11-4.55). While we did not find evidence of any direct effect of first trimester malaria infections on birth outcomes, their association with infections later in pregnancy tended to increase the risk of low birth weights. CONCLUSIONS: Malaria infections in the first trimester were highly prevalent and have deleterious effects on maternal anemia. They highlight the need for additional preventive measures, starting in early pregnancy or even before conception.

Plasmodium falciparum merozoite surface antigen-specific cytophilic IgG and control of malaria infection in a Beninese birth cohort.

BACKGROUND: Substantial evidence indicates that cytophilic IgG responses to Plasmodium falciparum merozoite antigens play a role in protection from malaria. The specific targets mediating immunity remain unclear. Evaluating antibody responses in infants naturally-exposed to malaria will allow to better understand the establishment of anti-malarial immunity and to contribute to a vaccine development by identifying the most appropriate merozoite candidate antigens. METHODS: The study was based on parasitological and clinical active follow-up of infants from birth to 18 months of age conducted in the Tori Bossito area of southern Benin. For 399 infants, plasma levels of cytophilic IgG antibodies with specificity for five asexual stage malaria vaccine candidate antigens were determined by ELISA in infants' peripheral blood at 6, 9, 12 and 15 months of age. Multivariate mixed logistic model was used to investigate the association between antibody levels and anti-malarial protection in the trimester following the IgG quantification. Moreover, the concentrations of merozoite antigen-specific IgG were compared between a group of infants apparently able to control asymptomatic malaria infection (CAIG) and a group of infants with no control of malaria infection (Control group (NCIG)). Protective effect of antibodies was also assessed after 15 months of malaria exposure with a Cox regression model adjusted on environmental risk. RESULTS: Cytophilic IgG responses to AMA1, MSP1, MSP2-3D7, MSP2-FC27, MSP3 and GLURP R2 were associated with increasing malarial infection risk in univariate analysis. The multivariate mixed model showed that IgG1 and IgG3 to AMA1 were associated with an increased risk of malarial infection. However infants from CAIG (n = 53) had significantly higher AMA1-, MSP2-FC27-, MSP3-specific IgG1 and AMA1-, MSP1-, MSP2-FC27-, MSP3 and GLURP-R2-specific IgG3 than those from NCIG (n = 183). The latter IgG responses were not associated with protection against clinical malaria in the whole cohort when protective effect is assessed after 15 months of malaria exposition. CONCLUSION: In this cohort, merozoite antigen-specific cytophilic IgG levels represent a marker of malaria exposure in infants from 6 to 18 months of age. However, infants with resolution of asymptomatic infection (CAIG) seem to have acquired naturally immunity against P. falciparum. This observation is encouraging in the context of the development of multitarget P. falciparum vaccines.

Prevalence and Associated Risk Factors of Malaria in the First Trimester of Pregnancy: A Preconceptional Cohort Study in Benin.

Background: There is a lack of data on the burden of malaria in the first trimester of pregnancy in Africa, mainly because pregnant women generally attend the maternity clinic late. Bed nets are rarely provided to women before the second trimester of pregnancy and intermittent preventive treatment with sulfadoxine-pyrimethamine is not recommended before the second trimester, leaving women insufficiently or not protected in early pregnancy. Methods: To assess the burden of first trimester malaria, 387 women were followed up monthly from preconception to delivery. They were screened for malaria monthly from early pregnancy until delivery. A logistic multilevel model was used to assess maternal factors associated with malaria during the first trimester. Results: The proportion of women with at least 1 microscopic malaria infection during the first trimester of pregnancy was 20.8%. Women infected with malaria preconception were more likely to be infected during the first trimester (adjusted odds ratio: 2.68; 95% confidence interval, 1.24-5.78). Early gestational age was also positively correlated with malaria infection. Conclusions: Using a preconceptional study design, we showed that malaria was highly prevalent in early pregnancy. This calls for the assessment of new strategies that could protect women as soon as the first trimester.

Is Placental Malaria a Long-term Risk Factor for Mild Malaria Attack in Infancy? Revisiting a Paradigm.

Background: Children born to mothers with placental malaria (PM) have been described as more susceptible to the occurrence of a first malaria infection. However, whether or not these children remain more at risk during infancy has never been explored. We aimed to determine if children born to mothers with PM are more susceptible to malaria and remain at higher risk between birth and 18 months. Methods: Five hundred fifty children were followed up weekly with control of temperature and, if >37.5°C, both a rapid diagnostic test for malaria and a thick blood smear were performed. Taking into account environmental risk of infection, the relationship between occurrences of malaria attacks from birth to 18 months was modeled using Cox models for recurrent events. Results: PM is not associated with an overall susceptibility to malaria but only with the delay of occurrence of the first malaria attack. Children born from mothers with PM tend to have an increased risk for the first malaria attack (hazard ratio [HR] = 1.33; P = .048) but not for subsequent ones (HR = 0.9; P = .46). Children who experienced 1 malaria attack were strongly at risk to develop subsequent infections independent of placental infection and environmental exposure. Conclusions: These results are consistent with the existence of an individual susceptibility to malaria unrelated to PM. From a public health point of view, protecting children born to infected placenta remains a priority, but seems insufficient to account for other frail children for whom a biomarker of frailty needs to be found.

Impact of the use and efficacy of long lasting insecticidal net on malaria infection during the first trimester of pregnancy - a pre-conceptional cohort study in southern Benin.

BACKGROUND: Malaria in pregnancy is prevalent in Sub-Saharan Africa. The first trimester of pregnancy is a critical period and the best preventive measure is Long Lasting Insecticidal Nets (LLIN). Unfortunately, few studies have been conducted which focuses on the usage and efficacy of LLIN on malaria prevention during the first trimester. METHODS: We assessed the use and effectiveness of LLIN in early pregnancy in Benin and its impact on malaria infection risk. We followed-up a cohort of 240 pregnant women from pre-conception to the end of the first trimester of pregnancy in Southern Benin. Parasitological, maternal and LLIN data were actively collected before, at the beginning and end of the first trimester of pregnancy. A Cox regression model was used to determine the relationship between the time to onset of the first malaria infection and the use, physical integrity, and bio-efficacy of the LLIN, adjusted for relevant covariables. RESULTS: The good use, good physical integrity and biological efficacy of LLIN were associated with a decreased risk of occurrence of the first malaria infection in early pregnancy (HRa = 0.38; (0.18-0.80); p < 0.001; HRa = 0.59; (0.29-1.19); p < 0.07; HRa = 0.97; (0.94-1.00); p < 0.04 respectively), after adjustment for other covariates. Primi/secundigravidity and malaria infection before pregnancy were associated with a risk of earlier onset of malaria infection. CONCLUSION: The classically used LLIN's indicators of possession and use may not be sufficient to characterize the true protection of pregnant women in the first trimester of pregnancy. Indicators of physical integrity and bio-efficacy should be integrated with those indicators in evaluation studies.

Use of an Anopheles Salivary Biomarker to Assess Malaria Transmission Risk Along the Thailand-Myanmar Border.

Background: The modalities of malaria transmission along the Thailand-Myanmar border are poorly understood. Here we address the relevance of using a specific Anopheles salivary biomarker to measure the risk among humans of exposure to Anopheles bites. Methods: Serologic surveys were conducted from May 2013 to December 2014 in 4 sentinel villages. More than 9400 blood specimens were collected in filter papers from all inhabitants at baseline and then every 3 months thereafter, for up to 18 months, for analysis by enzyme-linked immunosorbent assay. The relationship between the intensity of the human antibody response and entomological indicators of transmission (human biting rates and entomological inoculation rates [EIRs]) was studied using a multivariate 3-level mixed model analysis. Heat maps for human immunoglobulin G (IgG) responses for each village and survey time point were created using QGIS 2.4. Results: The levels of IgG response among participants varied significantly according to village, season, and age (P<.001) and were positively associated with the abundance of total Anopheles species and primary malaria vectors and the EIR (P<.001). Spatial clusters of high-IgG responders were identified across space and time within study villages. Conclusions: The gSG6-P1 biomarker has great potential to address the risk of transmission along the Thailand-Myanmar border and represents a promising tool to guide malaria interventions.

Evolution of the levels of human leukocyte antigen G (HLA-G) in Beninese infant during the first year of life in a malaria endemic area: using latent class analysis.

BACKGROUND: HLA-G, a non-classical HLA class I antigen, is of crucial interest during pregnancy by inhibiting maternal immune response. Its role during infections is discussed, and it has been described that high levels of soluble HLA-G during childhood increase the risk of malaria. To explore more precisely interactions between soluble HLA-G and malaria, latent class analysis was used to test whether distinct sub-populations of children, each with distinctive soluble HLA-G evolutions may suggest the existence of groups presenting variable malaria susceptibility. METHOD: A study was conducted in Benin from 2010 to 2013 and 165 children were followed from birth to 12 months. Evolution of soluble HLA-G was studied by the latent class method. RESULTS: Three groups of children were identified: one with consistently low levels of soluble HLA-G during follow-up, a second with very high levels and a last intermediate group. In all groups, low birth weight, high number of malaria infections and high exposure to malaria transmission were associated with high level of soluble HLA-G. Placental malaria was not. Presence of soluble HLA-G in cord blood increased the probability of belonging to the highest trajectory. CONCLUSION: These results, together with previous ones, confirm the important role of HLA-G in the individual susceptibility to malaria. Assaying soluble HLA-G at birth could be a good indicator of newborns more fragile and at risk of infections during childhood.

Infections with Plasmodium falciparum during pregnancy affect VAR2CSA DBL-5 domain-specific T cell cytokine responses.

BACKGROUND: Current knowledge of human immunological responses to pregnancy-associated malaria-specific Plasmodium falciparum protein VAR2CSA concerns almost exclusively B cell-driven antibody-mediated activity. Knowledge of VAR2CSA-specific T cell-mediated activity is minimal by comparison, with only a single published report of a study investigating VAR2CSA-derived peptide-specific T cell responses. The study described here represents an attempt to redress this balance. METHODS: Within the framework of a cohort study of 1037 pregnant Beninese, sub-groups were selected on the basis of the documented presence/absence of infection with P. falciparum and conducted detailed immunological assessments both at inclusion into the study and at delivery. Peripheral blood mononuclear cells were isolated, stimulated in vitro, and VAR2CSA DBL-5 domain-specific, IFN-γ-secreting T-cell frequencies and cytokine responses were quantified using flow cytometric techniques. Multivariate analyses were used to determine primarily whether the T cell-mediated DBL5-specific activity measured was associated with infection by P. falciparum adjusted for gravidity, anaemia and other cofactors. RESULTS: Infections with P. falciparum detected at inclusion were associated with enhanced non-specific TNF responses, whilst diminished non-specific and DBL-5-specific IL-10 responses were associated with infections detected at delivery. Infections during pregnancy led to enhanced non-specific and DBL-5-specific IFN-γ responses detectable at delivery but to concomitantly lower DBL-5-specific CD8+ IFN-γ responses. Prospective assessments indicated that non-specific pro-inflammatory responses detectable at inclusion in the study were associated with the occurrence of infections subsequently during pregnancy. CONCLUSIONS: The findings represent a first step in elucidating the quantity and quality of cellular immunological responses to VAR2CSA, which will help in the development of the primary vaccine candidate for prevention of pregnancy-associated malaria.