Causal effects on low Apgar at 5-min and stillbirth in a malaria maternal–fetal health outcome investigation: a large perinatal surveillance study in the Brazilian Amazon

Background Malaria elimination in Brazil poses several challenges, including the control of Plasmodium falciparum foci and the hidden burden of Plasmodium vivax in pregnancy. Maternal malaria and fetal health outcomes were investigated with a perinatal surveillance study in the municipality of Cruzeiro do Sul, Acre state, Brazilian Amazon. The research questions are: what are the causal effects of low birth weight on low Apgar at 5-min and of perinatal anaemia on stillbirth? Methods From November 2018 to October 2019, pregnant women of ≥ 22 weeks or puerperal mothers, who delivered at the referral maternity hospital (Juruá Women and Children’s Hospital), were recruited to participate in a malaria surveillance study. Clinical information was obtained from a questionnaire and abstracted from medical reports. Haemoglobin level and presence of malarial parasites were tested by haematology counter and light microscopy, respectively. Low Apgar at 5-min and stillbirth were the outcomes analysed in function of clinical data and epidemiologic risk factors for maternal malaria infection using both a model of additive and independent effects and a causal model with control of confounders and use of mediation. Results In total, 202 (7.2%; N = 2807) women had malaria during pregnancy. Nearly half of malaria infections during pregnancy (n = 94) were P. falciparum. A total of 27 women (1.03%; N = 2632) had perinatal malaria (19 P. vivax and 8 P. falciparum). Perinatal anaemia was demonstrated in 1144 women (41.2%; N = 2779) and low birth weight occurred in 212 newborns (3.1%; N = 2807). A total of 75 newborns (2.7%; N = 2807) had low (< 7) Apgar scores at 5-min., and stillbirth occurred in 23 instances (30.7%; n = 75). Low birth weight resulted in 7.1 higher odds of low Apgar at 5-min (OR = 7.05, 95% CI 3.86–12.88, p < 0.001) modulated by living in rural conditions, malaria during pregnancy, perinatal malaria, and perinatal anaemia. Stillbirth was associated with perinatal anaemia (OR = 2.56, 95% CI 1.02–6.42, p = 0.0444) modulated by living in rural conditions, falciparum malaria during pregnancy, perinatal malaria, and perinatal fever. Conclusions While Brazil continues its path towards malaria elimination, the population still faces major structural problems, including substandard living conditions. Here malaria infections on pregnant women were observed having indirect effects on fetal outcomes, contributing to low Apgar at 5-min and stillbirth. Finally, the utility of employing multiple statistical analysis methods to validate consistent trends is vital to ensure optimal public health intervention designs.

Neurocognitive outcomes in Malawian children exposed to malaria during pregnancy: An observational birth cohort study

Background Annually 125 million pregnancies are at risk of malaria infection. However, the impact of exposure to malaria in pregnancy on neurodevelopment in children is not well understood. We hypothesized that malaria in pregnancy and associated maternal immune activation result in neurodevelopmental delay in exposed offspring. Methods and findings Between April 2014 and April 2015, we followed 421 Malawian mother–baby dyads (median [IQR] maternal age: 21 [19, 28] years) who were previously enrolled (median [IQR] gestational age at enrollment: 19.7 [17.9, 22.1] weeks) in a randomized controlled malaria prevention trial with 5 or 6 scheduled assessments of antenatal malaria infection by PCR. Children were evaluated at 12, 18, and/or 24 months of age with cognitive tests previously validated in Malawi: the Malawi Developmental Assessment Tool (MDAT) and the MacArthur–Bates Communicative Development Inventories (MCAB-CDI). We assessed the impact of antenatal malaria (n [%] positive: 240 [57.3]), placental malaria (n [%] positive: 112 [29.6]), and maternal immune activation on neurocognitive development in children. Linear mixed-effects analysis showed that children exposed to antenatal malaria between 33 and 37 weeks gestation had delayed language development across the 2-year follow-up, as measured by MCAB-CDI (adjusted beta estimate [95% CI], −7.53 [−13.04, −2.02], p = 0.008). Maternal immune activation, characterized by increased maternal sTNFRII concentration, between 33 and 37 weeks was associated with lower MCAB-CDI language score (adjusted beta estimate [95% CI], −8.57 [−13.09, −4.06], p < 0.001). Main limitations of this study include a relatively short length of follow-up and a potential for residual confounding that is characteristic of observational studies. Conclusions This mother–baby cohort presents evidence of a relationship between malaria in pregnancy and neurodevelopmental delay in offspring. Malaria in pregnancy may be a modifiable risk factor for neurodevelopmental injury independent of birth weight or prematurity. Successful interventions to prevent malaria during pregnancy may reduce the risk of neurocognitive delay in children.

1345Uptake of Intermittent Preventive Treatment for malaria during pregnancy with Sulphadoxine-Pyrimethamine in Malawi

Background This study aimed to estimate the proportion of and identify factors associated with uptake of ≥ 3 doses of Intermittent preventive treatment of malaria during pregnancy with sulphadoxine-pyrimethamine (IPTp-SP) among pregnant women in Malawi after adoption of the 2012 updated WHO IPTp-SP policy. Methods The 2015–16 Malawi Demographic and Health Survey dataset was re-analysed. Only 1069 women were included in the analysis from 1219 women who had live births, born after July 2015. Logistic regression was used in data analysis considering complex survey sample design. Results Of the 1069 women, 447 (42%) received ≥3 doses (optimal) of IPTp-SP, while 47% managed to attend ≥4 antenatal care (ANC) clinics. Only 52% received optimal SP doses among those who made ≥4 ANC visits. The number of ANC visits was associated with the optimal uptake of SP. Women who attended ANC three times only and those who visited ANC at most twice were less likely to receive optimal doses than those who managed to attend ANC ≥4 times during pregnancy (AOR = 0.71, 95% CI 0.49–1.02) and (AOR = 0.12, 95% CI 0.06–0.21) respectively. Conclusions There is low uptake of optimal SP doses in Malawi. This seems to be associated with the number of ANC visits. However, there is limited effectiveness of increased number of ANC visits on the uptake of optimal SP doses. Key messages Increased number of ANC visits is not enough to increase uptake of optimal doses of IPTp-SP. There is need for continued and varied efforts.

Falciparum but not vivax malaria increases the risk of hypertensive disorders of pregnancy in women followed prospectively from the first trimester

Background Malaria and hypertensive disorders of pregnancy (HDoP) affect millions of pregnancies worldwide, particularly those of young, first-time mothers. Small case-control studies suggest a positive association between falciparum malaria and risk of pre-eclampsia but large prospective analyses are lacking. Methods We characterized the relationship between malaria in pregnancy and the development of HDoP in a large, prospectively followed cohort. Pregnant women living along the Thailand-Myanmar border, an area of low seasonal malaria transmission, were followed at antenatal clinics between 1986 and 2016. The relationships between falciparum and vivax malaria during pregnancy and the odds of gestational hypertension, pre-eclampsia, or eclampsia were examined using logistic regression amongst all women and then stratified by gravidity. Results There were 23,262 singleton pregnancies in women who presented during the first trimester and were followed fortnightly. Falciparum malaria was associated with gestational hypertension amongst multigravidae (adjusted odds ratio (AOR) 2.59, 95%CI 1.59–4.23), whereas amongst primigravidae, it was associated with the combined outcome of pre-eclampsia/eclampsia (AOR 2.61, 95%CI 1.01–6.79). In contrast, there was no association between vivax malaria and HDoP. Conclusions Falciparum but not vivax malaria during pregnancy is associated with hypertensive disorders of pregnancy.

Assessment of the Nutritional Status and Risk Factors of Malaria among Pregnant Mothers in Owerri Rural Communities, Southeastern Nigeria

Malaria during pregnancy remains a serious public health problem, with substantial risk for the mother, her fetus and the new born. A crosssectional study was conducted in Owerri rural hospitals among 150 pregnant mothers in Emekuku and Uratta rural communities in Owerri, Imo State using questionnaire. Ninety (90) pregnant women from Holy Rosary Hospital Emekuku and 60 pregnant women from Redeemed Jesus People hospital and maternity, Uratta, Owerri within the age range of 20-50 years were involved in this study. Anthropometric data, age, weight and height were collected using standard scale and the meter rule. Cluster analysis was applied for the identification of the groups with similar nutritional habits and anthropometric parameters. At the end of the data collection and analysis, it was obtained that 40.7% of the women lived in a moderately bushy environment, 13.3% in a very bushy environment, 6.6% lived in a bushy environment while 39.4% however lived in a very clean environment. In assessing the nutritional status the result indicates that 45.3% skipped meals while 54.7% do not. 82.7% of the women had a history of malaria while 17.3% had none. 22% of the pregnant women were malaria positive while 78% were negative. 56.7% of the women had mosquito net while 43.3% did not. 53.3% of the women disliked some food, 82% took supplement, and 36.7% took multivitamins. About 50 % of the pregnant women were overweight. The anthropometric characteristics of respondents showed that women from 40-50 years had high mean in their respective variables and no significant difference (p>0.05) in their ranges. The use of Insecticide-Treated Mosquito nets (ITNs) was found to be associated with malaria infection; pregnant women who did not use ITNs frequently were more affected by malaria as compared to those who did.

Severe malaria during pregnancy at the maternity ward of the municipal medical center of Ratoma, Guinea-Conakry

Background: Gestational malaria remains a major public health problem in malarious areas. The objectives of this work were to describe the socio-demographic, clinical, paraclinical, therapeutic and prognostic characteristics of patients who developed severe malaria during pregnancy.Methods: It was a descriptive prospective study carried out in the maternity ward of Ratoma municipal medical center, which was carried out over a period of 6 months from 01 October 2018 to 31 March 2019. This study involved all pregnant women who had presented severe malaria according to WHO criteria.Results: The incidence of severe malaria during pregnancy was 7%. The average age of our patients was 22.4 years with extremes of 15 and 47 years. The symptomatology that motivated the consultation was variable, the most frequent signs were: hyperthermia (100%), headache (79%), vomiting (99%). The general examination at admission objectified a fever with an average temperature of 39°C with extremes of 38-40.4°C. All patients had a positive rapid diagnostic test (RDT) as well as their thicker drop. The hemogram revealed the existence of a more or less severe anemia in 89.9% of cases. All patients were treated with parenteral quinine (100%). Maternal lethality was 1.8%. After severe malaria, 70 patients (62.5%) carried their pregnancy to term and 40 delivered an eutrophic child (35.71%), 30 (26.78%) delivered a hypotrophic child, 20 (17.85%) had a spontaneous abortion, premature delivery was observed in 10 patients (8.9%), and fetal death in utero was observed in 12 patients (10.71%).Conclusions: All patients had received parenteral quinine curative therapy. Maternal and perinatal complications were common. To improve this prognosis, intermittent preventive treatment and the use of insecticide-treated nets, which are the most effective prevention method at this time, must be further promoted in anticipation of the much hoped-for vaccine.

A tablet derived from Andrographis paniculata complements dihydroartemisinin-piperaquine treatment of malaria in pregnant mice

Objectives The use of standard antimalarial drugs, such as dihydroartemisinin-piperaquine (DHP) for the treatment of malaria during pregnancy is limited due to the risk of teratogenicity. The alternative is therefore required although few exist. Here we show a phytopharmaceutical drug derived from Andrographis paniculata (AS201-01), which is effective as herbal antimalarial both in vitro and in vivo and may be a suitable alternative when used in complementary treatment with DHP. Methods Plasmodium berghei infected pregnant BALB/c mice were divided into four groups: G1 (negative control), G2 (AS201-01), G3 (DHP), and G4 (combination of DHP and AS201-01). Pheripheral blood was collected during therapy for counting parasitemia. Placental samples were analyzed for the expression of IFN-γ, TNF- α, IL-10, placental parasite counts and foetal morphology. Results Groups G4 and G3 both showed a 100% inhibition of peripheral parasitemia. However, the treatment in G4 was found to be less effective than that in G2 and G3 in preventing placental parasitemia. The G4 treatment was able to reduce the expression of IFN-γ and IL-10, whereas TNF-α was not significantly different from the control group. Foetal morphologic abnormalities were observed in all groups except G2; G4 showed lower percentage of abnormalities compared to G3 and G1. Conclusions A combination of A. paniculata tablet (AS201-01) with DHP has the potential to reduce the toxicity of DHP in malaria treatment.

VAR2CSA-Mediated Host Defense Evasion of Plasmodium falciparum Infected Erythrocytes in Placental Malaria

Over 30 million women living in P. falciparum endemic areas are at risk of developing malaria during pregnancy every year. Placental malaria is characterized by massive accumulation of infected erythrocytes in the intervillous space of the placenta, accompanied by infiltration of immune cells, particularly monocytes. The consequent local inflammation and the obstruction of the maternofetal exchanges can lead to severe clinical outcomes for both mother and child. Even if protection against the disease can gradually be acquired following successive pregnancies, the malaria parasite has developed a large panel of evasion mechanisms to escape from host defense mechanisms and manipulate the immune system to its advantage. Infected erythrocytes isolated from placentas of women suffering from placental malaria present a unique phenotype and express the pregnancy-specific variant VAR2CSA of the Plasmodium falciparum Erythrocyte Membrane Protein (PfEMP1) family at their surface. The polymorphic VAR2CSA protein is able to mediate the interaction of infected erythrocytes with a variety of host cells including placental syncytiotrophoblasts and leukocytes but also with components of the immune system such as non-specific IgM. This review summarizes the described VAR2CSA-mediated host defense evasion mechanisms employed by the parasite during placental malaria to ensure its survival and persistence.