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Abstract 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. Based on a preconceptional cohort in Benin, we evidenced that malaria infection in the first trimester of pregnancy was highly prevalent, particularly in the first weeks of pregnancy, and was significantly predicted by malaria infection before conception.

According to the current World Health Organization guidelines, the drug prevention of malaria during pregnancy does not adequately cover the first trimester of gestation in high-transmission areas. Although the pathophysiological mechanisms of early infections are not completely understood yet, a review of the most recent studies on the topic suggests that their consequences are serious in terms of maternal anemia and low birth weight. Consequently, there is a need to focus on the awareness of women in a period hard to access, to develop safe drugs to be used in the first trimester, and to consider preconceptional interventions in teenage girls, such as a new malaria vaccine to be used in pregnancy.

Background Plasmodium vivax malaria elimination can only be achieved by the deployment of 8-aminoquinolines (primaquine and tafenoquine) in combination with ACT to kill both blood and liver-stage parasites. However, primaquine and the other 8-aminoquinolines cause dose-dependent haemolysis in subjects with G6PD deficiency, an X-linked disorder of red blood cells that is very common in populations living in tropical and subtropical areas. In order to inform safer use of 8-aminoquinolines in the Greater Mekong Subregion, a multi-centre study was carried out to assess the prevalence of G6PD deficiency and to identify the main G6PD variants in samples collected in Cambodia, Lao PDR, Myanmar, Thailand and Vietnam. Methods Blood samples were collected in the five countries during National Malaria Surveys or during Population Surveys. During Population Surveys samples were characterized for G6PD phenotype using the Fluorescent Spot Test. Samples were then genotyped for a panel of G6PD mutations. Results G6PD deficiency was found to be common in the region with an overall mean prevalence of deficient or mutated hemizygous males of 14.0%, ranging from a mean 7.3% in Thailand, 8.1% in Lao PDR, 8.9% in Vietnam, 15.8% in Myanmar and 18.8% in Cambodia. Mahidol and Viangchan mutations were the most common and widespread variants found among the nine investigated. Conclusions Owing to the high prevalence of G6PD deficiency in the Greater Mekong Subregion, strategies for vivax malaria elimination should include point-of-care G6PD testing (both qualitative and quantitative) to allow safe and wide treatment with 8-aminoquinolines.

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. 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. 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. 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.

Background. Few studies have evaluated the effect of malaria on intrauterine growth restriction on the basis of the fetal growth rate, rather than just the small-for-gestational age z score. Here, we assessed the impact of malaria on IUGR, using data from a longitudinal, ultrasonography-based follow-up study of Beninese women. Methods. A total of 1016 women were followed up from gestational week 17 to delivery. Malaria was detected every month. Women underwent ultrasonography 4 times for gestational age determination and fetal biometry. We assessed the effect of malaria on birth weight-for-gestational age z score (n = 735 women) and fetal growth velocity (n = 664), defined as a change in fetal weight z score over time. Results. Malaria was detected in 43% of women. Fetal growth velocity was negative overall, decreasing further at the end of the third trimester. Women with ≥2 malarial parasite infections tended to have lower z scores than uninfected women. Malaria both in early and late pregnancy was associated with a reduction in fetal growth velocity, which occurred either immediately or with a delay after infection. Discussions. We confirmed the deleterious effect of malaria during both early and late pregnancy on fetal growth. This stresses the importance of starting preventive measures against malaria as early as possible during pregnancy.

A Stakeholder engagement meeting on the implementation of post-discharge malaria chemoprevention (PDMC) in Benin, Kenya, Malawi, and Uganda was held in Nairobi, Kenya, on 27 September 2023. Representatives from the respective National Malaria Control Programmes, the World Health Organization (WHO) Geneva, Africa Regional and Kenya offices, research partners, non-governmental organizations, and the Medicines for Malaria Venture participated. PDMC was recommended by the WHO in June 2022 and involves provision of a full anti-malarial treatment course at regular intervals during the post-discharge period in children hospitalized with severe anaemia in areas of moderate-to-high malaria transmission. The WHO recommendation followed evidence from a meta-analysis of three clinical trials and from acceptability, delivery, cost-effectiveness, and modelling studies. The trials were conducted in The Gambia using monthly sulfadoxine-pyrimethamine during the transmission season, in Malawi using monthly artemether-lumefantrine, and in Kenya and Uganda using monthly dihydroartemisinin-piperaquine, showing a significant reduction in all-cause mortality by 77% (95% CI 30–98) and a 55% (95% CI 44–64) reduction in all-cause hospital readmissions 6 months post-discharge. The recommendation has not yet been implemented in sub-Saharan Africa. There is no established platform for PDMC delivery. The objectives of the meeting were for the participating countries to share country contexts, plans and experiences regarding the adoption and implementation of PDMC and to explore potential delivery platforms in each setting. The meeting served as the beginning of stakeholder engagement within the PDMC Saves Lives project and will be followed by formative and implementation research to evaluate alternative delivery strategies in selected countries. Meeting highlights included country consensus on use of dihydroartemisinin-piperaquine for PDMC and expansion of the target group to \"severe anaemia or severe malaria \", in addition to identifying country-specific options for PDMC delivery for evaluation in implementation research. Further exploration is needed on whether the age group should be extended to school-age children.

Four studies previously indicated that the effect of malaria infection during pregnancy on the risk of low birthweight (LBW; <2,500 g) may depend upon maternal nutritional status. We investigated this dependence further using a large, diverse study population. We evaluated the interaction between maternal malaria infection and maternal anthropometric status on the risk of LBW using pooled data from 14,633 pregnancies from 13 studies (6 cohort studies and 7 randomized controlled trials) conducted in Africa and the Western Pacific from 1996-2015. Studies were identified by the Maternal Malaria and Malnutrition (M3) initiative using a convenience sampling approach and were eligible for pooling given adequate ethical approval and availability of essential variables. Study-specific adjusted effect estimates were calculated using inverse probability of treatment-weighted linear and log-binomial regression models and pooled using a random-effects model. The adjusted risk of delivering a baby with LBW was 8.8% among women with malaria infection at antenatal enrollment compared to 7.7% among uninfected women (adjusted risk ratio [aRR] 1.14 [95% confidence interval (CI): 0.91, 1.42]; N = 13,613), 10.5% among women with malaria infection at delivery compared to 7.9% among uninfected women (aRR 1.32 [95% CI: 1.08, 1.62]; N = 11,826), and 15.3% among women with low mid-upper arm circumference (MUAC <23 cm) at enrollment compared to 9.5% among women with MUAC ≥ 23 cm (aRR 1.60 [95% CI: 1.36, 1.87]; N = 9,008). The risk of delivering a baby with LBW was 17.8% among women with both malaria infection and low MUAC at enrollment compared to 8.4% among uninfected women with MUAC ≥ 23 cm (joint aRR 2.13 [95% CI: 1.21, 3.73]; N = 8,152). There was no evidence of synergism (i.e., excess risk due to interaction) between malaria infection and MUAC on the multiplicative (p = 0.5) or additive scale (p = 0.9). Results were similar using body mass index (BMI) as an anthropometric indicator of nutritional status. Meta-regression results indicated that there may be multiplicative interaction between malaria infection at enrollment and low MUAC within studies conducted in Africa; however, this finding was not consistent on the additive scale, when accounting for multiple comparisons, or when using other definitions of malaria and malnutrition. The major limitations of the study included availability of only 2 cross-sectional measurements of malaria and the limited availability of ultrasound-based pregnancy dating to assess impacts on preterm birth and fetal growth in all studies. Pregnant women with malnutrition and malaria infection are at increased risk of LBW compared to women with only 1 risk factor or none, but malaria and malnutrition do not act synergistically.

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. 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. 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. 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.

In areas of moderate to intense Plasmodium falciparum transmission, malaria in pregnancy remains a significant cause of low birth weight, stillbirth, and severe anaemia. Previously, fetal sex has been identified to modify the risks of maternal asthma, pre-eclampsia, and gestational diabetes. One study demonstrated increased risk of placental malaria in women carrying a female fetus. We investigated the association between fetal sex and malaria in pregnancy in 11 pregnancy studies conducted in sub-Saharan African countries and Papua New Guinea through meta-analysis using log binomial regression fitted to a random-effects model. Malaria infection during pregnancy and delivery was assessed using light microscopy, polymerase chain reaction, and histology. Five studies were observational studies and six were randomised controlled trials. Studies varied in terms of gravidity, gestational age at antenatal enrolment and bed net use. Presence of a female fetus was associated with malaria infection at enrolment by light microscopy (risk ratio 1.14 [95% confidence interval 1.04, 1.24]; P = 0.003; n = 11,729). Fetal sex did not associate with malaria infection when other time points or diagnostic methods were used. There is limited evidence that fetal sex influences the risk of malaria infection in pregnancy.

Background There are no data on the burden of malaria in pregnancy (MiP) in Laos, where malaria still remains prevalent in the south. Methods Two cross-sectional surveys were conducted in 2014 to assess the prevalence of MiP in Vapi District, Salavan Province, southern Laos: the first consisted of screening 204 pregnant women during pregnancies [mean (95 % CI) gestational age: 23 (22–25) weeks] living in 30 randomly selected villages in Vapi District; the second was conducted among 331 pregnant women, who delivered during the study period in Vapi and Toumlane District Hospitals and in Salavan Provincial Hospital. Peripheral and placental malaria was detected using rapid diagnostic tests (RDT), thick blood smears (TBS) and real-time quantitative polymerase chain reactions (RT-qPCR). Factors associated with low birth weight (LBW) and maternal anaemia were assessed. Results In the villages, 12/204 women (5.9 %; 95 % CI 3.1–10.0) were infected with malaria as determined by RT-qPCR: 11 were Plasmodium vivax infections and 1 was mixed Plasmodium vivax / Plasmodium falciparum infection, among which 9 were sub-microscopic (as not detected by TBS). History of malaria during current pregnancy tended to be associated with a higher risk of MiP (aIRR 3.05; 95 % CI 0.94–9.88). At delivery, two Plasmodium falciparum sub-microscopic infections (one peripheral and one placental) were detected (4.5 %; 0.6–15.5) in Vapi District. In both surveys, all infected women stated they had slept under a bed net the night before the survey, and 86 % went to the forest for food-finding 1 week before the survey in median. The majority of infections (94 %) were asymptomatic and half of them were associated with anaemia. Overall, 24 % of women had LBW newborns. Factors associated with a higher risk of LBW were tobacco use (aIRR 2.43; 95 % CI 1.64–3.60) and pre-term delivery (aIRR 3.17; 95 % CI 2.19–4.57). Factors associated with a higher risk of maternal anaemia were no iron supplementation during pregnancy, Lao Theung ethnicity and place of living. Conclusions The prevalence of MiP in this population was noticeable. Most infections were asymptomatic and sub-microscopic vivax malaria, which raises the question of reliability of recommended national strategies for the screening and prevention of MiP in Laos.