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BackgroundGlobally distributed with variable prevalence depending on geography, toxoplasmosis is a zoonosis caused by an obligate intracellular protozoan parasite, Toxoplasma gondii. This disease is usually benign but poses a risk for immunocompromised people and for newborns of mothers with a primary infection during pregnancy because of the risk of congenital toxoplasmosis (CT). CT can cause severe damage to fetuses-newborns. To our knowledge, no study has been conducted in sub-Saharan Africa on toxoplasmosis seroprevalence, seroconversion and CT in a large longitudinal cohort and furthermore, no observation has been made of potential relationships with malaria.MethodsWe performed a retrospective toxoplasmosis serological study using available samples from a large cohort of 1,037 pregnant women who were enrolled in a malaria follow-up during the 2008-2010 period in a rural area in Benin. We also used some existing data to investigate potential relationships between the maternal toxoplasmosis serological status and recorded malaria infections.ResultsToxoplasmosis seroprevalence, seroconversion and CT rates were 52.6%, 3.4% and 0.2%, respectively, reflecting the population situation of toxoplasmosis, without targeted medical intervention. The education level influences the toxoplasmosis serological status of women, with women with little or no formal education have greater immunity than others. Surprisingly, toxoplasmosis seropositive pregnant women tended to present lower malaria infection during pregnancy (number) or at delivery (presence) and to have lower IgG levels to Plasmodium falciparum Apical Membrane Antigen 1, compared to toxoplasmosis seronegative women.ConclusionsThe high toxoplasmosis seroprevalence indicates that prevention against this parasite remains important to deploy and must be accessible and understandable to and for all individuals (educated and non-educated). A potential protective role against malaria conferred by a preexisting toxoplasmosis infection needs to be explored more precisely to examine the environmental, parasitic and/or immune aspects.

BackgroundMalaria 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.MethodsIn 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.ResultsThe 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.ConclusionWe 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.

Table S1. Factors associated with delay in the first malaria infection during the first trimester of pregnancy, univariate Cox analysis (N = 240); Sô-ava and Akassato, Benin 2015–2016. (DOCX 23 kb)

Table S2. Factors associated with the number of malaria infections during the first trimester of pregnancy (multivariate Poisson regression model, N = 194 pregnant women); Sô-ava and Akassato, Benin 2015–2016. (DOCX 16 kb)

Clara Menéndez and colleagues conducted an open-label randomized controlled trial in HIV-negative pregnant women in Benin, Gabon, Mozambique, and Tanzania to evaluate the safety and efficacy of mefloquine compared to sulfadoxine-pyrimethamine for intermittent preventative therapy for malaria. Please see later in the article for the Editors' Summary, Background Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by WHO to prevent malaria in African pregnant women. The spread of SP parasite resistance has raised concerns regarding long-term use for IPT. Mefloquine (MQ) is the most promising of available alternatives to SP based on safety profile, long half-life, and high efficacy in Africa. We evaluated the safety and efficacy of MQ for IPTp compared to those of SP in HIV-negative women. Methods and Findings A total of 4,749 pregnant women were enrolled in an open-label randomized clinical trial conducted in Benin, Gabon, Mozambique, and Tanzania comparing two-dose MQ or SP for IPTp and MQ tolerability of two different regimens. The study arms were: (1) SP, (2) single dose MQ (15 mg/kg), and (3) split-dose MQ in the context of long lasting insecticide treated nets. There was no difference on low birth weight prevalence (primary study outcome) between groups (360/2,778 [13.0%]) for MQ group and 177/1,398 (12.7%) for SP group; risk ratio [RR], 1.02 (95% CI 0.86–1.22; p = 0.80 in the ITT analysis). Women receiving MQ had reduced risks of parasitemia (63/1,372 [4.6%] in the SP group and 88/2,737 [3.2%] in the MQ group; RR, 0.70 [95% CI 0.51–0.96]; p = 0.03) and anemia at delivery (609/1,380 [44.1%] in the SP group and 1,110/2743 [40.5%] in the MQ group; RR, 0.92 [95% CI 0.85–0.99]; p = 0.03), and reduced incidence of clinical malaria (96/551.8 malaria episodes person/year [PYAR] in the SP group and 130/1,103.2 episodes PYAR in the MQ group; RR, 0.67 [95% CI 0.52–0.88]; p = 0.004) and all-cause outpatient attendances during pregnancy (850/557.8 outpatients visits PYAR in the SP group and 1,480/1,110.1 visits PYAR in the MQ group; RR, 0.86 [0.78–0.95]; p = 0.003). There were no differences in the prevalence of placental infection and adverse pregnancy outcomes between groups. Tolerability was poorer in the two MQ groups compared to SP. The most frequently reported related adverse events were dizziness (ranging from 33.9% to 35.5% after dose 1; and 16.0% to 20.8% after dose 2) and vomiting (30.2% to 31.7%, after dose 1 and 15.3% to 17.4% after dose 2) with similar proportions in the full and split MQ arms. The open-label design is a limitation of the study that affects mainly the safety assessment. Conclusions Women taking MQ IPTp (15 mg/kg) in the context of long lasting insecticide treated nets had similar prevalence rates of low birth weight as those taking SP IPTp. MQ recipients had less clinical malaria than SP recipients, and the pregnancy outcomes and safety profile were similar. MQ had poorer tolerability even when splitting the dose over two days. These results do not support a change in the current IPTp policy. Trial registration ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001429343 Please see later in the article for the Editors' Summary, Editors' Summary Background Half the world's population is at risk of malaria, a mosquito-borne parasitic disease that kills about 600,000 people every year. Most of these deaths occur among young children in sub-Saharan Africa but pregnant women and their unborn children living in Africa are also very vulnerable to malaria. Infection with malaria during pregnancy can cause severe maternal anemia (reduced red blood cell numbers), stillbirths, and pre-term and low-birthweight babies, and is responsible for the deaths of many African babies and women. To prevent this loss of life, the World Health Organization (WHO) recommends a three-pronged approach—the delivery to pregnant women of the antimalarial drug sulfadoxine-pyrimethamine (SP) at each scheduled antenatal care visit given at least one month apart (intermittent preventive treatment in pregnancy; IPTp), the use of insecticide treated bed nets to protect pregnant women from the bites of infected mosquitoes, and effective case management of pregnant women with malarial illness. Why Was This Study Done? IPTp with SP reduces the delivery of low-birth-weight babies and neonatal deaths but malaria parasites are becoming resistant to SP. Thus, other antimalarial drugs need to be evaluated for use in IPTp. Suitable drugs need to remain in the body for a long time to maximize their prophylactic (preventative) effect, they need to be given as a single dose at antenatal clinic visits to ensure compliance, and they must not harm the unborn child. In this open-label, randomized controlled trial (RCT), the researchers compare the efficacy and safety of IPTp with SP and mefloquine (MQ, an antimalarial drug that matches these criteria) in HIV-negative women living in Africa. The study also compares the tolerability of two MQ regimens. RCTs compare outcomes in groups of people chosen to receive different interventions through the play of chance; in open-label RCTs, both the researchers and the study participants know which treatment is being administered. IPTp with SP is only recommended for HIV-negative women because SP interacts with cotrimoxazole, which is routinely given to HIV-positive individuals to prevent infections. What Did the Researchers Do and Find? The researchers assigned 4,749 pregnant women in Benin, Gabon, Mozambique, and Tanzania to one of three study groups. Participants in the SP and MQ groups received two doses of SP or MQ, respectively, administered at least one month apart. Participants in the split-dose MQ group received each MQ dose as half doses given on consecutive days. The prevalence of low-birth-weight deliveries (the study's primary outcome; the prevalence of a condition is the proportion of a population with that condition) was similar in the SP group and in the combined MQ groups. However, compared to women who received SP, women who received MQ had a lower risk of parasitemia (parasites in the blood), a lower risk of anemia at delivery, fewer episodes of clinical malaria, and fewer outpatient attendances. The prevalence of placental infection with malaria parasites and of adverse pregnancy outcomes such as stillbirth was similar in all the study groups. Finally, the tolerability of IPTp was poorer in the two MQ intervention groups than in the SP group, but similar proportions of adverse events (mainly dizziness and vomiting) were reported for the two MQ dosing regimens. What Do These Findings Mean? These findings indicate that HIV-negative African women taking MQ for IPTp had a similar risk of a low-birth-weight delivery (the study's primary outcome) and lower risk of malaria illness during pregnancy than women taking SP for IPTp. Because the study did not have a no-IPTp arm (for ethical reasons), these findings provide no information about the efficacy or safety or either MQ or SP per se; these findings only indicate that MQ is no more efficacious than SP in the prevention of low-birth-weight babies. Moreover, because the study was open-label, the accuracy of the findings related to the tolerability and safety of MQ compared to SP may be limited because of biases in the assessment of safety outcomes. Given that the MQ dose used here for IPTp was associated with poorer tolerability than that of SP, these findings do not support the use of MQ instead of SP for IPTp. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001733. A related PLOS Medicine Research Article by Raquel González and colleagues examines IPTp-MQ in HIV-infected women receiving cotrimoxazole prophylaxis This study is further discussed in a PLOS Medicine Perspective by Richard Steketee. Information is available from the World Health Organization on malaria (in several languages) and on malaria in pregnancy; information on IPTp and the updated WHO policy recommendation on IPTp with SP are available; the 2013 World Malaria Report provides details of the current global malaria situation The US Centers for Disease Control and Prevention also provides information on malaria; a personal story about malaria in pregnancy is available Information is available from the Roll Back Malaria Partnership on all aspects of global malaria control, including information on malaria in pregnancy The Malaria in Pregnancy Consortium is undertaking research into the prevention and treatment of malaria in pregnancy MedlinePlus provides links to additional information on malaria (in English and Spanish)

Pregnancy-associated malaria (PAM) can lead to severe complications for both mother and baby. Certain placental cytokine/chemokine profiles have been shown to reflect poor pregnancy outcomes, including maternal anemia and low birth weight. In intervillous plasma samples from 400 Beninese women living in an area where Plasmodium falciparum is endemic, we quantified 16 cytokines/chemokines. We assessed their profiles in groups with PAM, with maternal anemia, with preterm births, or with a low birth weight for gestational age. Repeated ultrasound measurements ensured that prematurity and low birth weight were highly accurate. Preliminary analyses revealed trends for lower cytokine/chemokine concentrations in placental plasma associated both with babies with low birth weight for gestational age and with P. falciparum infection during pregnancy, while, as a function of the latter, the concentration of gamma interferon (IFN-gamma)-inducible protein 10 (IP-10) was higher. Multivariate analyses showed that (i) higher placental plasma interleukin-10 (IL-10) levels were associated with P. falciparum infections and (ii) independently of P. falciparum infections, lower concentrations of both IFN-gamma and IL-5 were associated with low birth weight for gestational age. Our data further strengthen the idea that IL-10 and IP-10 could be useful diagnostic markers of P. falciparum infection during pregnancy. The concentrations of cytokines/chemokines in placental plasma may represent previously unrecognized markers of poor fetal growth.

The question of malaria in the postpartum period is controversial. Malaria was investigated during a randomized trial of intermittent preventive treatment in pregnancy in Benin. Women infected at delivery were tested for parasitemia in the early postpartum period; they had not received treatment unless they were symptomatic. Among the 35 of 1,346 infected women, parasitologic follow-up results could not be interpreted in 15 because they were treated for symptoms, 18 cleared parasitemia spontaneously within five days postpartum, and 2 had a strong decrease in parasitemia before being treated. Because the placenta is the privileged site for sequestration of parasites, it facilitates their persistence during pregnancy, and its elimination may rapidly induce their clearance.

International audience; 120 newly hatched snails of the species Cornu aspersum were reared on three diets of increasing energy value: 2200 kcal/kg = E- diet, 2300 kcal/kg = E diet, 2400 kcal/kg = E+ diet. When snails became adult, the BH subsample was allowed to mate and lay eggs once maturity was achieved...

Additional file 1. Type and volume of samples that were used for uRDT and cRDT testing, HRP2-assay and qPCR. RECIPAL, 2014–2017.

Additional file 2. Maternal and birth outcomes, according to type of concomitant malaria infection. RECIPAL, 2014–2017.

Additional file 3. Association between malaria and maternal and child outcomes (maternal Hb level during pregnancy and birthweight). RECIPAL, 2014–2017.

Additional file 3. Association between malaria and maternal and child outcomes (maternal Hb level during pregnancy and birthweight). RECIPAL, 2014–2017.

Additional file 2. Maternal and birth outcomes, according to type of concomitant malaria infection. RECIPAL, 2014–2017.

Additional file 1. Type and volume of samples that were used for uRDT and cRDT testing, HRP2-assay and qPCR. RECIPAL, 2014–2017.