Placental malaria

BACKGROUND: Stillbirth is a common adverse pregnancy outcome worldwide, with an estimated 2.6 million stillbirths yearly. In Cameroon, the reported rate in 2015 was 19.6 per 1000 live births. Several risk factors have been described, but region-specific risk factors are not known in the northwest region of Cameroon. This study aims to determine the stillbirth rate and associated factors at the Bamenda Regional hospital, North-West region of Cameroon. MATERIALS AND METHODS: A Hospital-based case‒control study conducted from December 2022 to June 2023 on medical files from 2018 to 2022 at the Bamenda Regional Hospital...

Placental accumulation of Plasmodium falciparum infected erythrocytes results in maternal anemia, low birth weight, and pregnancy loss. The parasite protein VAR2CSA facilitates the accumulation of infected erythrocytes in the placenta through interaction with the host receptor chondroitin sulfate A (CSA). Antibodies that prevent the VAR2CSA-CSA interaction correlate with protection from placental malaria, and VAR2CSA is a high-priority placental malaria vaccine antigen. Here, structure-guided design leveraging the full-length structures of VAR2CSA produced a stable immunogen that retains the critical conserved functional elements of VAR2CSA...

[This corrects the article DOI: 10.1371/journal.ppat.1011370.].

Severe malaria is a life-threatening condition that is associated with a high mortality. Severe Plasmodium falciparum infections are mediated primarily by high parasitemia and binding of infected red blood cells (iRBCs) to the blood vessel endothelial layer, a process known as sequestration. Here, we show that including the 5-amino-2-methoxybenzenesulfonate (AMBS) chemical modification in soluble biopolymers (polyglutamic acid and heparin) and poly(acrylic acid)-exposing nanoparticles serves as a universal tool to introduce a potent parasite invasion inhibitory function in these materials...

Blood group O is reported to confer some degree of protection from severe malaria in endemic setting. This protection is believed to be due to reduced and smaller rosette formation in people of blood group O which can easily be cleared by the host immune system. Also, sickle cell trait (HbAS) is reported to disrupt the adhesion of infected erythrocytes to microvascular endothelial walls, which could protect pregnant women from placental malaria. We determined the association between HbAS and ABO blood group, and placental malaria amongst pregnant women of all parities...

BACKGROUND: The efficacy of daily co-trimoxazole, an antifolate used for malaria chemoprevention in pregnant women living with HIV, is threatened by cross-resistance of Plasmodium falciparum to the antifolate sulfadoxine-pyrimethamine. We assessed whether addition of monthly dihydroartemisinin-piperaquine to daily co-trimoxazole is more effective at preventing malaria infection than monthly placebo plus daily co-trimoxazole in pregnant women living with HIV. METHODS: We did an individually randomised, two-arm, placebo-controlled trial in areas with high-grade sulfadoxine-pyrimethamine resistance in Kenya and Malawi...

BACKGROUND: Approximately 32 million pregnant women are at risk of malaria with up to 10,000 maternal deaths and 200,000 neonates at risk annually. Intermittent Preventive Treatment (IPT) with sulfadoxine-pyrimethamine (SP) is recommended by the World Health Organization (WHO) to reduce disease in pregnancy and adverse maternal and newborn outcomes. At least three doses of SP should be taken by pregnant women during antenatal consultation (ANC) beginning from the thirteenth week of pregnancy till parturition...

BACKGROUND: Based on understanding of placental pathological features and safe medication in pregnancy-associated malaria (PAM), establishment of a stable pregnant mouse infection model with Plasmodium was urgently needed. METHODS: ICR mice with vaginal plugs detected were randomly divided into post-pregnancy infection (Malaria+ ) and uninfected pregnancy (Malaria- ) cohorts. Age-matched mice that had not been mated were infected as pre-pregnancy infection group (Virgin control), which were subsequently mated with ICR males...

Plasmodium falciparum (Pf) is responsible for the most lethal form of malaria. VAR2CSA is an adhesin protein expressed by this parasite at the membrane of infected erythrocytes for attachment to the placenta, leading to pregnancy-associated malaria. VAR2CSA is a large 355 kDa multidomain protein composed of nine extracellular domains, a transmembrane helix, and an intracellular domain. VAR2CSA binds to Chondroitin Sulphate A (CSA) of the proteoglycan matrix of the placenta. Shear flow, as the one occurring in blood, has been shown to enhance the (VAR2CSA-mediated) adhesion of Pf-infected erythrocytes on the CSA-matrix...

BACKGROUND: Antibody-mediated complement fixation has previously been associated with protection against malaria in naturally acquired immunity. However, the process of early-life development of complement-fixing antibodies in infants, both in comparison to their respective mothers and to other immune parameters, remains less clear. RESULTS: We measured complement-fixing antibodies in newborns and their mothers in a malaria endemic area over 5 years follow-up and found that infants' complement-fixing antibody levels were highest at birth, decreased until six months, then increased progressively until they were similar to birth at five years...

BACKGROUND: Pregnant women have an increased risk of Plasmodium infections and disease. Malaria in pregnancy is a major public health problem in endemic areas. Assessment of the burden and risk factors of malaria in pregnancy across different malaria transmission settings is required to guide control strategies and for malaria elimination. Thus, the current study is generating such evidence from parturient women in northwest Ethiopia. METHODS: A cross-sectional study was conducted among 526 pregnant women admitted to the delivery rooms of selected health facilities in Jawi district, northwest Ethiopia, between November 2021 and July 2022...

BACKGROUND: Malaria and HIV are associated with preterm births possibly due to partial maternal vascular malperfusion resulting from altered placental angiogenesis. There is a paucity of data describing structural changes associated with malaria and HIV coinfection in the placentae of preterm births thus limiting the understanding of biological mechanisms by which preterm birth occurs. OBJECTIVES: This study aimed to determine the differences in clinical characteristics, placental parenchymal histological, and morphometric features of the terminal villous tree among women with malaria and HIV coinfection having preterm births...

Placental malaria vaccines (PMVs) are being developed to prevent severe sequelae of placental malaria (PM) in pregnant women and their offspring. The leading candidate vaccine antigen VAR2CSA mediates parasite binding to placental receptor chondroitin sulfate A (CSA). Despite promising results in small animal studies, recent human trials of the first two PMV candidates (PAMVAC and PRIMVAC) generated limited cross-reactivity and cross-inhibitory activity to heterologous parasites. Here we immunized Aotus nancymaae monkeys with three PMV candidates (PAMVAC, PRIMVAC and ID1-ID2a_M1010) adjuvanted with Alhydrogel, and exploited the model to investigate boosting of functional vaccine responses during PM episodes as well as with nanoparticle antigens...

INTRODUCTION: In 2021, India contributed for ~79% of malaria cases and ~ 83% of deaths in the South East Asia region. Here, we systematically and critically analyzed data published on malaria in pregnancy (MiP) in India. METHODS: Epidemiological, clinical, parasitological, preventive and therapeutic aspects of MiP and its consequences on both mother and child were reviewed and critically analyzed. Knowledge gaps and solution ways are also presented and discussed...

BACKGROUND: During pregnancy, pregnant women are susceptible to malaria, contributing significantly to maternal and infant mortality. OBJECTIVE: This research was conducted to study the effect of Plasmodium berghei infection in pregnant mice on fetal growth retardation through placental cell apoptosis and the change of local vascularization. METHODS: Eighteen pregnant Balb/c strain mice resulting from simultanously mating were divided into two groups those were nine pregnant mice used as non infected group and nine pregnant mice infected with Plasmodium berghei on day 9th post mating used as infected group respectively...

BACKGROUND: Malaria and preeclampsia are leading causes of maternal morbidity and mortality in sub-Saharan Africa. They contribute significantly to poor perinatal outcomes like low neonatal weight by causing considerable placental morphological changes that impair placental function. Previous studies have described the effects of either condition on the placental structure but the structure of the placenta in malaria-preeclampsia comorbidity is largely understudied despite its high burden...

PURPOSE: Intermittent preventive treatment with sulfadoxine-pyrimethamine is widely used for the prevention of malaria in pregnant women in Africa. Known resistance cases of sulfadoxine-pyrimethamine during pregnancy need to be follow up to support IPTp implementation in Burkina Faso. However, data on the development and spread of resistance to this molecule are lacking. This study aimed to investigating the genetic diversity of P. falciparum and the mutation prevalence in the dhfr and dhps genes infected from postpartum infected placentas...

BACKGROUND & OBJECTIVES: The utilization of Intermittent Preventive Treatment (sulphadoxine-pyrimethamine) in pregnancy (IPTp-SP) for combating malaria has indicated control over adverse birth outcomes and has been recommended for use by pregnant women. The aim of this study was to determine the effectiveness of IPTp-SP on maternal, neonatal and placental malaria in Port Harcourt, Nigeria. METHODS: 316 samples of maternal peripheral blood (MPB), placental blood (PLB), neonatal cord blood (NCB) and placental tissue (PT) were collected each from consenting mothers...

Placental malaria is caused by Plasmodium falciparum-infected erythrocytes (IEs) adhering to chondroitin sulfate proteoglycans in placenta via VAR2CSA-type PfEMP1. Human pentameric immunoglobulin M (IgM) binds to several types of PfEMP1, including VAR2CSA via its Fc domain. Here, a 3.6 Å cryo-electron microscopy map of the IgM-VAR2CSA complex reveals that two molecules of VAR2CSA bind to the Cµ4 of IgM through their DBL3X and DBL5ε domains. The clockwise and anti-clockwise rotation of the two VAR2CSA molecules on opposite faces of IgM juxtaposes C-termini of both VAR2CSA near the J chain, where IgM creates a wall between both VAR2CSA molecules and hinders its interaction with its receptor...

Intermittent preventive therapy during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended in areas of moderate to high malaria transmission intensity. As a result of the increasing prevalence of SP resistance markers, IPTp-SP was withdrawn from Rwanda in 2008. Nonetheless, more recent findings suggest that SP may improve birthweight even in the face of parasite resistance, through alternative mechanisms that are independent of antimalarial effects. The prevalence of single nucleotide polymorphisms in Plasmodium falciparum dihydropteroate synthase (pfdhps) and dihydrofolate reductase (pfdhfr) genes associated with SP resistance among 148 pregnant women from 2016 to 2018 within Rwanda's Southern Province (Huye and Kamonyi districts) was measured using a ligase detection reaction-fluorescent microsphere assay...