Efficacy and safety of ivermectin for the treatment of Plasmodium falciparum infections in asymptomatic male and female Gabonese adults - a pilot randomized, double-blind, placebo-controlled single-centre phase Ib/IIa clinical trial.

BACKGROUND: Ivermectin's mosquitocidal effect and in vitro activity against Plasmodium falciparum asexual stages are known. Its in vivo blood-schizonticidal efficacy is unknown. Ivermectin's tolerability and efficacy against P. falciparum infections in Gabonese adults were assessed. METHODS: The study consisted of a multiple dose stage and a randomized, double-blind, placebo-controlled stage. Adults with asymptomatic P. falciparum parasitaemia (200-5000 parasites/µl) were enrolled. First, three groups of five participants received 200 µg/kg ivermectin once daily for one, two, and three days, respectively, and then 34 participants were randomized to 300 µg/kg ivermectin or placebo once daily for 3 days. Primary efficacy outcome was time to 90% parasite reduction. Primary safety outcomes were drug-related serious and severe adverse events (Trial registration: PACTR201908520097051). FINDINGS: Between June 2019 and October 2020, 49 participants were enrolled. Out of the 34 randomized participants, 29 (85%) completed the trial as per protocol. No severe or serious adverse events were observed. The median time to 90% parasite reduction was 24.1 vs. 32.0 h in the ivermectin and placebo groups, respectively (HR 1.38 [95% CI 0.64 to 2.97]). INTERPRETATION: Ivermectin was well tolerated in doses up to 300 µg/kg once daily for three days and asymptomatic P. falciparum asexual parasitaemia was reduced similarly with this dose of ivermectin compared to placebo. Further studies are needed to evaluate plasmodicidal effect of ivermectin at higher doses and in larger samples. FUNDING: This study was funded by the Centre de Recherches Médicales de Lambaréné and the Centre for Tropical Medicine of the Bernhard Nocht Institute for Tropical Medicine.

Malaria Infections and Placental Blood Flow: A Doppler Ultrasound Study From a Preconception Cohort in Benin.

Background: Malaria in pregnancy (MiP) has been associated with fetal growth restriction, the underlying pathogenic mechanisms of which remain poorly understood. Malaria in pregnancy is suspected to induce abnormalities in placental vascularization, leading to impaired placental development. Our study evaluated MIP's effect on uterine artery (UtA) and umbilical artery (UA) blood flow. Methods: The analysis included 253 Beninese women followed throughout pregnancy and screened monthly for submicroscopic and microscopic malaria. Uterine artery Doppler measurement was performed once between 21 and 25 weeks' gestation (wg), and UA Doppler measurement was performed 1-3 times from 28 wg. Linear and logistic regression models were used to assess the effect of malaria infections on UtA Doppler indicators (pulsatility index and presence of a notch), whereas a logistic mixed model was used to assess the association between malaria infections and abnormal UA Doppler (defined as Z-score ≥2 standard deviation or absent/reversed UA end-diastolic flow). Results: Primigravidae represented 7.5% of the study population; 42.3% of women had at least 1 microscopic infection during pregnancy, and 29.6% had at least 1 submicroscopic infection (and no microscopic infection). Both microscopic and submicroscopic infections before Doppler measurement were associated with the presence of a notch (adjusted odds ratio [aOR] 4.5, 95% confidence interval [CI] = 1.2-16.3 and aOR 3.3, 95% CI = .9-11.9, respectively). No associations were found between malaria before the Doppler measurement and abnormal UA Doppler. Conclusions: Malaria infections in the first half of pregnancy impair placental blood flow. This highlights the need to prevent malaria from the very beginning of pregnancy.

A prospective, multi-site, cohort study to estimate incidence of infection and disease due to Lassa fever virus in West African countries (the Enable Lassa research programme)-Study protocol.

BACKGROUND: Lassa fever (LF), a haemorrhagic illness caused by the Lassa fever virus (LASV), is endemic in West Africa and causes 5000 fatalities every year. The true prevalence and incidence rates of LF are unknown as infections are often asymptomatic, clinical presentations are varied, and surveillance systems are not robust. The aim of the Enable Lassa research programme is to estimate the incidences of LASV infection and LF disease in five West African countries. The core protocol described here harmonises key study components, such as eligibility criteria, case definitions, outcome measures, and laboratory tests, which will maximise the comparability of data for between-country analyses. METHOD: We are conducting a prospective cohort study in Benin, Guinea, Liberia, Nigeria (three sites), and Sierra Leone from 2020 to 2023, with 24 months of follow-up. Each site will assess the incidence of LASV infection, LF disease, or both. When both incidences are assessed the LASV cohort (nmin = 1000 per site) will be drawn from the LF cohort (nmin = 5000 per site). During recruitment participants will complete questionnaires on household composition, socioeconomic status, demographic characteristics, and LF history, and blood samples will be collected to determine IgG LASV serostatus. LF disease cohort participants will be contacted biweekly to identify acute febrile cases, from whom blood samples will be drawn to test for active LASV infection using RT-PCR. Symptom and treatment data will be abstracted from medical records of LF cases. LF survivors will be followed up after four months to assess sequelae, specifically sensorineural hearing loss. LASV infection cohort participants will be asked for a blood sample every six months to assess LASV serostatus (IgG and IgM). DISCUSSION: Data on LASV infection and LF disease incidence in West Africa from this research programme will determine the feasibility of future Phase IIb or III clinical trials for LF vaccine candidates.

Performance of Field's Stain Compared with Conventional Giemsa Stain for the Rapid Detection of Blood Microfilariae in Gabon.

Filarial infections caused by Loa loa and Mansonella perstans are a considerable public health burden in rural regions of Central Africa. Rapid diagnostic tools for the detection of microfilariae in the blood are needed. Field's stain is a rapid staining technique for microscopic slides originally established for malaria diagnostics. It requires less than 1 minute of staining compared with conventional staining protocols requiring at least 15 to 20 minutes for staining and could thus significantly accelerate diagnostics for human filariasis. Here we evaluated Field's stain as a rapid staining technique in comparison to Giemsa stain for the detection of microfilariae in peripheral blood. Blood smears were collected from 175 participants residing in the region of Lambaréné and Fougamou, Gabon. Each participant's samples were stained in parallel with Field's stain and conventional Giemsa stain. Slides were then microscopically assessed and compared for qualitative and quantitative results by a blinded assessor for the two endemic filarial blood pathogens M. perstans and L. loa. Field's stain shows excellent diagnostic performance characteristics for L. loa microfilariae compared with Giemsa staining. Concordance was favorable for M. perstans although lower than for L. loa. Field's stain offers a rapid alternative to Giemsa stain for detection of L. loa microfilariae in thick blood smears. This could help accelerate diagnostics of blood filarial pathogens in mass screening programs or resource constrained health care institutions with high patient load.

Assessing fetal growth in Africa: Application of the international WHO and INTERGROWTH-21st standards in a Beninese pregnancy cohort.

BACKGROUND: Fetal growth restriction is a major complication of pregnancy and is associated with stillbirth, infant death and child morbidity. Ultrasound monitoring of pregnancy is becoming more common in Africa for fetal growth monitoring in clinical care and research, but many countries have no national growth charts. We evaluated the new international fetal growth standards from INTERGROWTH-21st and WHO in a cohort from southern Benin. METHODS: Repeated ultrasound and clinical data were collected in women from the preconceptional RECIPAL cohort (241 women with singleton pregnancies, 964 ultrasounds). We modelled fetal biometric parameters including abdominal circumference (AC) and estimated fetal weight (EFW) and compared centiles to INTERGROWTH-21st and WHO standards, using the Bland and Altman method to assess agreement. For EFW, we used INTERGROWTH-21st standards based on their EFW formula (IG21st) as well as a recent update using Hadlock's EFW formula (IG21hl). Proportions of fetuses with measurements under the 10th percentile were compared. RESULTS: Maternal malaria and anaemia prevalence was 43% and 69% respectively and 11% of women were primigravid. Overall, the centiles in the RECIPAL cohort were higher than that of INTERGROWTH-21st and closer to that of WHO. Consequently, the proportion of fetuses under 10th percentile thresholds was systematically lower when applying IG21st compared to WHO standards. At 27-31 weeks and 33-38 weeks, respectively, 7.4% and 5.6% of fetuses had EFW <10th percentile using IG21hl standards versus 10.7% and 11.6% using WHO standards. CONCLUSION: Despite high anemia and malaria prevalence in the cohort, IG21st and WHO standards did not identify higher than expected proportions of fetuses under the 10th percentiles of ultrasound parameters or EFW. The proportions of fetuses under the 10th percentile threshold for IG21st charts were particularly low, raising questions about its use to identify growth-restricted fetuses in Africa.

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.

Pre-conception serum ferritin concentrations are associated with metal concentrations in blood during pregnancy: A cohort study in Benin.

BACKGROUND: Iron deficiency is a common nutritional deficiency that impacts maternal health and fetal development and is also associated with increased uptake of toxic metals. Women in sub-Saharan Africa are highly exposed to both iron deficiency and metals in the environment. As research on the developmental origins of health and disease increasingly shows impacts of pre-conception maternal health on pregnancy and fetal health, these environmental exposures are of concern. OBJECTIVES: This study investigated the association between iron status pre-pregnancy and blood metal concentrations in the first trimester of pregnancy with potential implications for iron supplementation. METHODS: Pre-conception and first trimester blood samples taken from 262 Beninese women were tested for serum ferritin, inflammation markers, manganese (Mn), cadmium (Cd), lead (Pb), copper, zinc, selenium, mercury and arsenic. Associations between serum ferritin adjusted for inflammation and metal concentrations were analyzed using multivariate linear regression. RESULTS: Women with iron deficiency before conception (13%) were more likely to remain iron deficient in the first trimester (4%) (adjusted OR = 41.2, 95%CI 6.2; 275.0) even within the context of routine iron supplementation during pregnancy. Lower pre-pregnancy serum ferritin concentrations were significantly related to higher concentrations of Mn, Cd and Pb in the first trimester. Every 1% increase in serum ferritin concentration was associated with a 0.13% decrease in Mn (adjusted ß = -0.13, 95%CI -0.18; -0.07), a 0.22% decrease in Cd (adjusted ß = -0.22, 95%CI -0.28; -0.15) and a 0.06% decrease in Pb concentration (adjusted ß = -0.06, 95%CI -0.12; -0.006). DISCUSSION: These results suggest that increasing iron stores prior to pregnancy may prevent excessive uptake of toxic concentrations of the metals Mn, Cd and Pb and argue in favour of testing the effects of iron supplementation prior to pregnancy on metal concentrations.

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.

Poor maternal anthropometric status before conception is associated with a deleterious infant growth during the first year of life: a longitudinal preconceptional cohort.

BACKGROUND: According to the Developmental Origins of Health and Diseases concept, exposures in the preconception period may be critical. For the first time, we evaluated the effect of preconception poor anthropometric status on infant's growth in sub-Saharan Africa. METHODS: A mother-child cohort was followed prospectively from preconception to 1 year old in Benin. Maternal anthropometric status was assessed by prepregnancy body mass index (BMI), approximated by BMI at the first antenatal visit before 7 weeks' gestation, and gestational weight gain (GWG). BMI was categorized as underweight, normal, overweight, and obesity according to World Health Organization standards. GWG was categorized as low (<7 kg), mild (7-12 kg), and high (>12 kg). In infant, stunting and wasting were defined as length-for-age and weight-for-length z scores less than -2 SD, respectively. We evaluated the association between BMI/GWG and infant's weight and length at birth and during the first year of life, as well as with stunting and wasting at 12 months using mixed linear and logistic regression models. RESULTS: In multivariate, preconceptional underweight was associated with a lower infant's weight at birth and during the first year (-164 g; 95% CI, -307 to -22; and -342 g; 95% CI, -624 to -61, respectively) and with a higher risk of stunting at 12 months (adjusted odds ratio [aOR] = 3.98; 95% CI, 1.01-15.85). Furthermore, preconceptional obesity and a high GWG were associated with a higher weight and length at birth and during the first year. CONCLUSION: Underweight and obesity before conception as well as GWG were associated with infant's growth. These results argue for preventive interventions starting as early as the preconception period to support child long-term health.

Changes in women's dietary diversity before and during pregnancy in Southern Benin.

Dietary diversity before and during pregnancy is crucial to ensure optimal foetal health and development. We carried out a cohort study of women of reproductive age living in the Sô-Ava and Abomey-Calavi districts (Southern Benin) to investigate women's changes in dietary diversity and identify their determinants both before and during pregnancy. Nonpregnant women were enrolled (n = 1214) and followed up monthly until they became pregnant (n = 316), then every 3 months during pregnancy. One 24-hr dietary recall was administered before conception and during each trimester of pregnancy. Women's dietary diversity scores (WDDS) were computed, defined as the number of food groups out of a list of 10 consumed by the women during the past 24 hr. The analysis included 234 women who had complete data. Mixed-effects linear regression models were used to examine changes in the WDDS over the entire follow-up, while controlling for the season, subdistrict, socio-demographic, and economic factors. At preconception, the mean WDDS was low (4.3 ± 1.1 food groups), and the diet was mainly composed of cereals, oils, vegetables, and fish. The mean WDDS did not change during pregnancy and was equally low at all trimesters. Parity and household wealth index were positively associated with the WDDS before and during pregnancy in the multivariate analysis. Additional research is needed to better understand perceptions of food consumption among populations, and more importantly, efforts must be made to encourage women and communities in Benin to improve the diversity of their diets before and during pregnancy.

Maternal malaria but not schistosomiasis is associated with a higher risk of febrile infection in infant during the first 3 months of life: A mother-child cohort in Benin.

BACKGROUND: Malaria and schistosomiasis represent two of the most prevalent and disabling parasitic infections in developing countries. Few studies have evaluated the effect of maternal schistosomiasis and malaria in the peri-conceptional period on infant's risk of infection. METHODS: In Benin, women were followed from the preconception period until delivery. Subsequently, their children were followed from birth to 3 months of age. Pre-pregnancy malaria, malaria in pregnancy (MiP)-determined monthly using a thick blood smear-and urinary schistosomiasis-determined once before pregnancy and once at delivery using urine filtration-were the main maternal exposures. Infant's febrile infection (fever with respiratory, gastrointestinal and/or cutaneous clinical signs anytime during follow-up) was the main outcome. In a secondary analysis, we checked the relation of malaria and schistosomiasis with infant's hemoglobin (Hb) concentration. Both effects were separately assessed using logistic/mixed linear regression models. RESULTS: The prevalence of MiP was 35.7% with 10.8% occurring during the 1st trimester, and the prevalence of schistosomiasis was 21.8%. From birth to 3 months, 25.3% of infants had at least one episode of febrile infection. In multivariate analysis, MiP, particularly malaria in the 1st trimester, was significantly associated with a higher risk of infant's febrile infection (aOR = 4.99 [1.1; 22.6], p = 0.03). In secondary results, pre-pregnancy malaria and schistosomiasis were significantly associated with a lower infant's Hb concentration during the first 3 months. CONCLUSION: We evidenced the deleterious effect of maternal parasitic infections on infant's health. Our results argue in favor of the implementation of preventive strategies as early as in the peri-conception.

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.

Toxics (Pb, Cd) and trace elements (Zn, Cu, Mn) in women during pregnancy and at delivery, South Benin, 2014-2015.

During pregnancy, fetal development can be hindered by maternal exposure to toxic elements and abnormal concentrations of trace elements. Few data are available in African countries. Our goal was to assess the body burden of lead (Pb), cadmium (Cd), manganese (Mn), zinc (Zn) and copper (Cu) in pregnant women in Benin. The study was carried out in Sô-Ava district, from November 2015 to April 2016. Sixty women were recruited from the RECIPAL pre-conceptional cohort study. In all women, blood samples were collected during the first trimester of pregnancy. Thirty-two women had additional maternal and cord blood samples collected at delivery. Blood samples were analyzed by inductively coupled plasma mass spectrometry. At delivery, Cd median (IQR) concentration in maternal blood was 0.34 µg/L (0.24-0.46) in this non-smoking population. Pb median (IQR) concentration in maternal blood at delivery was 37.4 µg/L (30.5-52.0), with 31.3% of blood Pb levels above the 50 µg/L threshold. These pregnant women lived in semi-rural lakeside villages. Potential sources of Pb exposure identified during pregnancy were having water supply by drill pump and activities such as smoking fish by the woman and fishing by the household head. At delivery, Zn, Cu, and Mn median (IQR) concentrations in maternal blood were, respectively, 5415 µg/L (4894-5822), 1609 µg/L (1295-1771) and 16.0 µg/L (12.5-20.8). Pb, Cd, Mn and Cu blood concentrations were significantly higher at delivery than during the first trimester of pregnancy. Pb, Cd, Zn and Cu concentrations were significantly lower in cord blood than in maternal blood, contrary to Mn concentration, which was significantly higher in cord blood than in maternal blood at delivery. This exploratory study is the first one performed in Benin, and warns us about exposition of women from Sô-Ava district to Pb and Cd during pregnancy.

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.

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.

Cohort profile: effect of malaria in early pregnancy on fetal growth in Benin (RECIPAL preconceptional cohort).

PURPOSE: REtard de Croissance Intra-uterin et PALudisme (RECIPAL) is an original preconceptional cohort designed to assess the consequences of malaria during the first trimester of pregnancy, which is a poorly investigated period in Africa and during which malaria may be detrimental to the fetus. PARTICIPANTS: For this purpose, a total of 1214 women of reproductive age living in Sô-Ava and Akassato districts (south Benin) were followed up monthly from June 2014 to December 2016 until 411 of them became pregnant. A large range of health determinants was collected both before and during pregnancy from the first weeks of gestation to delivery. Five Doppler ultrasound scans were performed for early dating of the pregnancy and longitudinal fetal growth assessment. FINDINGS TO DATE: Pregnant women were identified at a mean of 6.9 weeks of gestation (wg). Preliminary results confirmed the high prevalence of malaria in the first trimester of pregnancy, with more than 25.4% of women presenting at least one microscopic malarial infection during this period. Most infections occurred before six wg. The prevalence of low birth weight, small birth weight for gestational age (according to INTERGROWTH-21st charts) and preterm birth was 9.3%, 18.3% and 12.6%, respectively. FUTURE PLANS: REtard de Croissance Intra-uterin et PALudisme (RECIPAL) represents at this time a unique resource that will provide information on multiple infectious (including malaria), biological, nutritional and environmental determinants in relation to health outcomes in women of reproductive age, pregnant women and their newborns. It will contribute to better define future recommendations for the prevention of malaria in early pregnancy and maternal malnutrition in Africa. It confirms that it is possible to constitute a preconceptional pregnancy cohort in Africa and provides valuable information for researchers starting cohorts in the future.