Placental Malaria Infection Research Articles

Coverage and effectiveness of intermittent preventive treatment in pregnancy with sulfadoxine\u2013pyrimethamine (IPTp-SP) on adverse pregnancy outcomes in the Mount Cameroon area, South West Cameroon

BackgroundGrowing concerns about the waning efficacy of IPTp-SP warrants continuous monitoring and evaluation. This study determined coverage of IPTp-SP and compared the effectiveness of the 3-dose to 2-dose regimen on placental malaria (PM) infection and low birth weight (LBW) in the Mount Cameroon area.MethodsConsenting pregnant women were enrolled consecutively through a cross-sectional survey at delivery at four antenatal clinics, two each from semi-rural and semi-urban settings from November 2016 to December 2017. Reported IPTp-SP use, demographic and antenatal clinic (ANC) data of the mothers and neonate birth weights were documented. Maternal haemoglobin concentration was measured using a haemoglobinometer and PM infection diagnosed by placental blood microscopy. Logistic regression analysis was used to model study outcomes.ResultsAmong the 465 parturient women enrolled, 47.0% (203), 34.7% (150), 18.3% (79) and 7.1% (33) reported uptake of ≥ 3, 2.1 dose(s) and no SP, respectively. Uptake of ≥ 3 doses varied significantly (p < 0.001) according to type of medical facility, timing of ANC initiation and number of ANC visits. The prevalence of PM was 18.5% where uptake of ≥ 3 SP doses (AOR = 2.36: 95% CI 1.41–4.87), primiparity (AOR = 2.13: 95% CI 1.19–3.81), semi-rural setting (AOR = 1.85: 95% CI 1.12–3.04) increased odds of infection. Also, three or more dosing was associated (p < 0.001) with increased PM density notably among women from semi-urban areas. Compared with third trimester, ANC initiation in the second trimester (AOR: 0.39: 95% CI 0.20–0.74) lower odds of infection. The prevalence of LBW infants was 7.3% and were generally those of anaemic (AOR: 4.6: 95% CI 1.03–20.57) and semi-rural (AOR: 5.29: 95% CI 1.73–16.15) women. Although ≥ 3 (AOR: 0.31: 95% CI 0.11–0.87) and 2 (AOR: 0.32: 95% CI 0.11–0.93) doses of SP was associated with lower odds of LBW, ≥ 3 doses were not associated with additional increase in birth weight nor maternal haemoglobin levels when compared with 2 doses.ConclusionIn the Mount Cameroon area, reported uptake of IPTp with ≥ 3 SP doses did not provide observable prophylactic benefits. SP resistance efficacy studies are necessary.

Optimization of in vitro trophoblast assay for real-time impedimetric sensing of trophoblast-erythrocyte interactions in Plasmodium falciparum malaria.

Sequestration of Plasmodium falciparum-infected erythrocytes (IEs) is responsible for the pathophysiology of placental malaria, leading to serious complications such as intrauterine growth restriction and low birth weight. However, it is an experimental challenge to study the biology of human placenta. Conventional cell culture-based in vitro placental models rely on immunostaining techniques and high-magnification microscopy is limited in providing real-time quantitative analysis. Impedimetric sensing in combination with cell culture may offer a useful tool. In this paper, we report that real-time label-free measurement of cellular electrical impedance using xCELLigence technology can be used to quantify the proliferation, syncytial fusion, and long-term response of BeWo cells to IEs cytoadhesion. Specifically, we optimized key experimental parameters of cell seeding density and concentration of forskolin, a compound used to promote cell syncitiation, based on electrical signals and immunostaining results. Prolonged time of infection with IEs that led to cell-cell junction vanishment in BeWo cells and release of inflammatory cytokines were monitored in real time by continuous change in electrical impedance. The results suggest that the impedimetric technique is sensitive and can offer new opportunities for the study of cellular responses of trophoblast cells to IEs. The developed system can provide potentially a high-throughput screening tool of anti-adhesion or anti-inflammatory drugs for placental malaria infections.

Congenital Malaria in Newborns Delivered to Mothers with Malaria-Infected Placenta in Blue Nile State, Sudan.

Diagnosis of congenital malaria is complicated by the low density of the parasite circulating in the cord blood and/or the peripheral blood of the newborns. Molecular techniques are significantly more sensitive than blood smears in detecting low-level parasitemia. This study investigated the prevalence of congenital malaria by the use of the real-time polymerase chain reaction (real-time PCR) in 102 babies born to mothers with microscopically confirmed infected placenta from Blue Nile state, Sudan. At delivery time, placental, maternal peripheral and cord blood samples in addition to samples collected from the newborns' peripheral blood were examined for malaria infection using Giemsa-stained thick smear and parasite DNA detection by real-time PCR. The overall prevalence of congenital malaria includes the total babies with cord blood parasitaemia and peripheral blood parasitaemia was 18.6 and 56.8% using microscopy and real-time PCR, respectively. Even though all the neonates were aparasitaemic by microscopy, 19 (18.6%) of the babies had congenital malaria detected by real-time PCR, 15 (25.9%) of the babies with congenital malaria were born to mothers with both placental and peripheral blood malaria infections detected using the two techniques. Congenital malaria was significantly associated with cord blood malaria infections, maternal age and maternal haemoglobin level (p < 0.001). This first study investigating congenital malaria in Blue Nile state, Sudan shows that malaria-infected placenta resulted in infant and cord blood infections.

The immune response to malaria in utero.

Malaria causes tremendous early childhood morbidity and mortality, providing an urgent impetus for the development of a vaccine that is effective in neonates. However, the infant immune response to malaria may be influenced by events that occur well before birth. Placental malaria infection complicates one quarter of all pregnancies in Africa and frequently results in exposure of the fetus to malaria antigens in utero, while the immune system is still developing. Some data suggest that in utero exposure to malaria may induce immunologic tolerance that interferes with the development of protective immunity during childhood. More recently, however, a growing body of evidence suggests that fetal malaria exposure can prime highly functional malaria-specific T- and B-cells, which may contribute to postnatal protection from malaria. In utero exposure to malaria also impacts the activation and maturation of fetal antigen presenting cells and innate lymphocytes, which could have implications for global immunity in the infant. Here, we review recent advances in ourunderstanding of how various components of the fetal immune system are altered by in utero exposure to malaria, discuss factors that may tilt the critical balance between tolerance and adaptive immunity, and consider the implications of these findings for malaria prevention strategies.

Malaria in Pregnancy: What the Obstetric Provider in Nonendemic Areas Needs to Know.

Globally, more than 125 million women each year are at risk of malaria during pregnancy. Endemic regions carry the greatest burden; however, with globalization, providers in nonendemic regions are encountering increasing numbers of women exposed to or infected with malaria. The aim of this article is to provide obstetric providers in nonendemic areas with updated information on malaria infection in pregnancy focusing on pregnancy management and malaria prevention and treatment. This article is based on review of the most recent peer-reviewed articles and guidelines from the Centers for Disease Control and Prevention and the World Health Organization. Malaria infection in pregnancy causes maternal anemia, low birth weight, preterm birth, stillbirth, and miscarriages through placental malaria and severe infections. Pregnant women traveling to malaria-endemic areas should be advised against travel. If travel must occur, they should be provided with region-specific chemoprophylaxis and given methods for preventing infection. In the event that a pregnant patient has an acute malarial infection, prompt evaluation is needed to determine whether there are severe features. Medications for uncomplicated or severe malaria infection should be started as soon as the diagnosis is made. Malaria in pregnancy causes significant perinatal complications. Obstetric providers should be aware of the impact and how to prevent and treat malaria infection during pregnancy. Malaria infection should be suspected in women with concerning symptoms and recent travel to endemic areas. Providers should know the management of uncomplicated and severe malarial infection in pregnancy.

Hypergammaglobulinemia and Impaired Transplacental Transfer of Respiratory Syncytial Virus Antibody in Papua New Guinea.

Passively-acquired respiratory syncytial virus (RSV) neutralizing antibody (Ab) can protect against RSV-associated lower respiratory tract illness. Maternal RSV immunization is, therefore, an attractive strategy for protection of very young infants. Vaccines for this purpose are currently being evaluated in clinical trials, but conditions such as preterm birth, placental malaria, maternal hypergammaglobulinemia and HIV infection might threaten this strategy. Each has been shown to impair transplacental Ab transfer for a variety of pathogens, but RSV-specific data are limited. Work in The Gambia demonstrated that placental malaria impaired transplacental transfer of RSV Ab, but a subsequent study in malaria-endemic Papua New Guinea (PNG) indicated that such associations may have been confounded by hypergammaglobulinemia (IgG > 1700 mg/dL). Here we confirm and extend those findings by measuring RSV neutralizing Ab and maternal IgG in sera from a larger cohort of 325 mother/infant pairs in PNG, and demonstrate the applicability of a high-throughput assay for assessment of neutralizing Ab. One-third of mother-infant pairs demonstrated impaired RSV Ab transfer. Infants of hypergammaglobulinemic women were more likely to have both impaired transfer [cord-to-maternal titer ratio <1.0, adjusted odds ratio (OR): 3.36 (95% confidence interval: 1.81-6.30)] and the lowest RSV cord titers [adjusted OR: 5.09 (95% confidence interval: 1.95-13.32, P < 0.001)], but neither outcome was associated with placental malaria. Once maternal RSV vaccines become available, successful implementation will require clear understanding and mitigation of factors that can impair passive protection, necessitating epidemiologic studies of such relationships ahead of vaccine availability. This study underscores the need to focus on hypergammaglobulinemia as a condition of importance.

Placental Malaria and Pre-Eclampsia from the Lagos State University Teaching Hospital, Ikeja, Lagos Nigeria

Objective: To determine the relationship between placental malaria infection and pre-eclampsia in a holo-endemic zone. Design: Prospective case-control study. Materials and Methods: One hundred and twenty seven (127) pregnant women with a diagnosis of pre-eclampsia in labour or having caesarean section served as cases while controls were 127 normotensive parturient women. They were recruited from the maternity unit of Ifako Ijaiye and Isolo General Hospitals, Lagos that served as secondary care centers. At delivery, either spontaneous vaginal delivery or by caesarean section, a 2.0 cm × 2.0 cm placenta tissue was cut with scalpel and fixed in 10% formaldehyde in a specimen bottle and sent to the pathologist. Following this, 2.5 mls of Cord blood and 2.5 mls of the maternal venous blood were taken into separate EDTA bottles properly labeled at delivery, samples were sent to the haematology laboratory immediately for peripheral thick film smear for malaria parasite. Results were obtained from the laboratory and together with data from the case files, they were entered into SPSS version 16 for analysis. Independent Student t-test was used for significance for continuous variables while Chi-square was used for qualitative data. The significance was set at 0.05. Results: There were statistically significant differences between the cases and controls regarding the maternal age, number of pregnancies, p p > 0.05. There was statistically significant difference between the two groups regarding the diagnosis of placental malaria as well as past history of alcohol intake and occupation, p < 0.05. Binary logistic regression analysis showed that chronic placenta malaria infection was an independent risk factor for preeclampsia. Conclusion: Placental malaria infection was more common in patients with preeclampsia than their matched normotensive patients in our environment. At the same time, chronic malaria was found to be an independent risk factor for preeclampsia. More concerted efforts by all stake holders should be geared towards primary prevention together with early diagnosis and treatment of malaria especially in early pregnancy. This may reduce the incidence and complication of preeclampsia in our environment.

Accuracy of One Step malaria rapid diagnostic test (RDT) in detecting Plasmodium falciparum placental malaria infection in women living in Yaound\xe9, Cameroon

BackgroundPlasmodium falciparum infected erythrocytes sequestering in placental tissue release Plasmodium lactate dehydrogenase (pLDH) and histidine-rich protein-II (HRP-II). These proteins can be detected in peripheral blood using monoclonal antibody-based rapid diagnostic tests (RDTs). Nevertheless, studies to evaluate the reliability of RDTs in detecting placental malaria compared with microscopy of placental tissue impression smear (PTIS) as the gold standard are scarce.MethodsBetween August 2013 and January 2015, Giemsa-stained blood smears for peripheral blood smear (Pbs), placental intervillous space (IVS) blood smear and placental tissue impression smear (PTIS)] were prepared from HIV-negative women during delivery at the Marie Reine Medical Health Centre in Yaoundé, Cameroon. RDTs with monoclonal antibodies specific to HRP-II (P.f) or pLDH (Pan) antigens were used to screen maternal peripheral blood samples.ResultsThe prevalence of malaria was 16%, 7.5%, 11.5%, 8% and 13% for One Step malaria HRP-II and pLDH RDTs, peripheral blood smear, IVS blood and placental tissue impression smears, respectively. The proportion of women positive by One Step malaria pLDH RDT and Pbs increased with parasite density in PTIS, while One Step malaria HRP-II RDT detected high proportion of infected women even with low parasite density. Although the prevalence of malaria infection by both microscopy and RDTs decreased significantly with mother age (0.0008 ≤ p ≤ 0.025), parity seemed to have very little influence. The sensitivity of One Step malaria HRP-II and pLDH RDTs were 96.15% and 61.53%, respectively, compared to 80.76% for Pbs (p = 0.014 and 0.0029, respectively). The specificity of these RDTs was 96.49% and 100%, respectively, compared to 100% for Pbs (p ≥ 0.12). In addition, the positive predictive values were 80.64% and 100% for HRP-II and pLDH-based RDTs, respectively, compared to 100% for Pbs (p < 0.0001 and 1, respectively), while the negative predictive values were 99.40% and 94.48%, respectively, compared to 97.16% for Pbs (p ≥ 0.49). The combination of One Step malaria HRP-II RDT and Pbs showed the similar performance as that observed with One Step malaria HRP-II RDT only.ConclusionThese results depict One Step malaria HRP-II RDT to be better in detecting placental P. falciparum infection in pregnant women compared to Giemsa-stained peripheral thick blood smear. This is important for better case management since microscopic examination of PTIS cannot be employed during pregnancy.

Mefloquine for preventing malaria in pregnant women.

Mefloquine for preventing malaria in pregnant women.

Prenatal Plasmodium reactivity

Malaria Fetal immunity is generally thought to be skewed toward tolerance. Odorizzi et al. used samples from a study in Uganda to determine if placental malaria infection modulated fetal immune responses to malaria. They stimulated cord blood cells in vitro and found that the fetal cells from cases of placental malaria were more reactive to Plasmodium antigens. Moreover, clinical follow-up revealed that this increased T cell response correlated with protection from childhood malaria. Thus, protective immune responses in humans can develop even before birth. Sci. Transl. Med. 10 , eaat6176 (2018).

Chloroquine as weekly chemoprophylaxis or intermittent treatment to prevent malaria in pregnancy in Malawi: a randomised controlled trial

Sulfadoxine-pyrimethamine resistance threatens efficacy of intermittent preventive treatment of malaria during pregnancy, and alternative regimens need to be identified. With the return of chloroquine efficacy in southern Africa, we postulated that chloroquine either as an intermittent therapy or as weekly chemoprophylaxis would be more efficacious than intermittent sulfadoxine-pyrimethamine for prevention of malaria in pregnancy and associated maternal and newborn adverse outcomes. We did an open-label, single-centre, randomised controlled trial at Ndirande Health Centre, Blantyre, in southern Malawi. We enrolled pregnant women (first or second pregnancy) at 20-28 weeks' gestation who were HIV negative. Participants were randomly assigned in a 1:1:1 ratio using a computer-generated list to either intermittent sulfadoxine-pyrimethamine (two doses of 1500 mg sulfadoxine and 75 mg pyrimethamine, 4 weeks apart), intermittent chloroquine (two doses of 600 mg on day 1, 600 mg on day 2, and 300 mg on day 3), or chloroquine prophylaxis (600 mg on day 1 then 300 mg every week). The primary endpoint was placental malaria in the modified intent-to-treat population, which consisted of participants who contributed placental histopathology data at birth. Secondary outcomes included clinical malaria, maternal anaemia, low birthweight, and safety. This trial is registered with ClinicalTrials.gov, number NCT01443130. Between February, 2012, and May, 2014, we enrolled and randomly allocated 900 women, of whom 765 contributed histopathological data and were included in the primary analysis. 108 (14%) women had placental malaria, which was lower than the anticipated prevalence of placental malaria infection. Protection from placental malaria was not improved by chloroquine as either prophylaxis (30 [12%] of 259 had positive histopathology; relative risk [RR] 0·75, 95% CI 0·48-1·17) or intermittent therapy (39 [15%] of 253; RR 1·00, 0·67-1·50) compared with intermittent sulfadoxine-pyrimethamine (39 [15%] of 253). In protocol-specified analyses adjusted for maternal age, gestational age at enrolment, bednet use the night before enrolment, anaemia at enrolment, and malaria infection at enrolment, women taking chloroquine as prophylaxis had 34% lower placental infections than did those allocated intermittent sulfadoxine-pyrimethamine (RR 0·66, 95% CI 0·46-0·95). Clinical malaria was reported in nine women assigned intermittent sulfadoxine-pyrimethamine, four allocated intermittent chloroquine (p=0·26), and two allocated chloroquine prophylaxis (p=0·063). Maternal anaemia was noted in five women assigned intermittent sulfadoxine-pyrimethamine, 15 allocated intermittent chloroquine (p=0·038), and six assigned chloroquine prophylaxis (p>0·99). Low birthweight was recorded for 31 babies born to women allocated intermittent sulfadoxine-pyrimethamine, 29 assigned intermittent chloroquine (p=0·78), and 41 allocated chloroquine prophylaxis (p=0·28). Four women assigned intermittent sulfadoxine-pyrimethamine had adverse events possibly related to study product compared with 94 women allocated intermittent chloroquine (p<0·0001) and 26 allocated chloroquine prophylaxis (p<0·0001). Three women had severe or life-threatening adverse events related to study product, of whom all were assigned intermittent chloroquine (p=0·25). Chloroquine administered as intermittent therapy did not provide better protection from malaria and related adverse effects compared with intermittent sulfadoxine-pyrimethamine in a setting of high resistance to sulfadoxine-pyrimethamine. Chloroquine chemoprophylaxis might provide benefit in protecting against malaria during pregnancy, but studies with larger sample sizes are needed to confirm these results. US National Institutes of Health.

Mefloquine for preventing malaria in pregnant women.

Mefloquine for preventing malaria in pregnant women.

865: Malaria exposure in pregnancy: birth outcomes with placental and non-placental malaria infection

Malaria infection in pregnancy is a major source of adverse obstetric outcomes in malaria-endemic areas. Our aim was to determine if placental malaria (PM) infection results in worse obstetric outcomes than non-placental malaria infection in pregnancy and to identify risk factors for placental infection. Nested case-control study from a prospective, double-blind randomized control trial of intermittent preventive therapy (IPTp) during pregnancy in Uganda. Women were enrolled from June to October 2014 at 12 to 20 weeks gestational age (GA) and followed through delivery. Malaria exposure was defined as symptomatic infection with confirmatory blood smear or laboratory evidence of malaria infection by loop-mediated isothermal amplification (LAMP), which was performed monthly and at delivery. PM was defined as presence of parasites or pigment on histopathology, parasites on placental blood smear, or positive placental blood LAMP. Cases included malaria-exposed pregnancies with PM. Controls were defined as malaria exposure without PM. Wilcoxon Rank Sum and Fisher exact tests were used to compare continuous and categorical variables respectively. Logistic regression was used for multivariate analysis. Of the 241 patients with malaria exposure in pregnancy, 134 (55.6%) had no evidence of PM and 107 (44.4%) had PM. Median GA at delivery was earlier in the PM group (39.3 ± 2.3wk vs. 40.0 ± 2.0wk, p<0.01) and there was increased incidence of low birth weight <2500g (18.9% versus 7.2%, p=0.01). There was no significant difference in mode of delivery, type of IPTp received, hematologic abnormalities at delivery, pregnancy loss, small for GA infants, or 5 min APGAR score <7. In multivariate analysis, odds of PM were significantly increased in primigravidas (OR 4.3, 95% CI 2.0-9.1, p<0.001) and in women who initiated IPTp after 16 weeks GA (OR 2.4, 95% CI 1.23-4.76, p=0.01). For every year increase in maternal age, the odds of PM decreased by 10% (OR 0.9, 95% CI 0.8-0.98, p=0.02). PM was associated with a 4-fold increase in preterm delivery (OR 4.7, 95% CI 1.28-17.5, p=0.02). PM is most likely to occur in primigravidas and young women and is associated with significantly increased risk of preterm delivery as compared to malaria without placental infection. Early initiation of IPTp prior to 16 weeks GA reduces the risk of PM.

Risk factors and pregnancy outcomes associated with placental malaria in a prospective cohort of Papua New Guinean women

BackgroundPlasmodium falciparum in pregnancy results in substantial poor health outcomes for both mother and child, particularly in young, primigravid mothers who are at greatest risk of placental malaria (PM) infection. Complications of PM include maternal anaemia, low birth weight and preterm delivery, which contribute to maternal and infant morbidity and mortality in coastal Papua New Guinea (PNG).MethodsPlacental biopsies were examined from 1451 pregnant women who were enrolled in a malaria prevention study at 14–26 weeks gestation. Clinical and demographic information were collected at first antenatal clinic visits and women were followed until delivery. Placental biopsies were collected and examined for PM using histology. The presence of infected erythrocytes and/or the malaria pigment in monocytes or fibrin was used to determine the type of placental infection.ResultsOf 1451 placentas examined, PM infection was detected in 269 (18.5%), of which 54 (3.7%) were acute, 55 (3.8%) chronic, and 160 (11.0%) were past infections. Risk factors for PM included residing in rural areas (adjusted odds ratio (AOR) 3.65, 95% CI 1.76–7.51; p ≤ 0.001), being primigravid (AOR 2.45, 95% CI 1.26–4.77; p = 0.008) and having symptomatic malaria during pregnancy (AOR 2.05, 95% CI 1.16–3.62; p = 0.013). After adjustment for covariates, compared to uninfected women, acute infections (AOR 1.97, 95% CI 0.98–3.95; p = 0.056) were associated with low birth weight babies, whereas chronic infections were associated with preterm delivery (AOR 3.92, 95% CI 1.64–9.38; p = 0.002) and anaemia (AOR 2.22, 95% CI 1.02–4.84; p = 0.045).ConclusionsAmong pregnant PNG women receiving at least one dose of intermittent preventive treatment in pregnancy and using insecticide-treated bed nets, active PM infections were associated with adverse outcomes. Improved malaria prevention is required to optimize pregnancy outcomes.

Placental malaria and its effect on pregnancy outcomes in Sudanese women from Blue Nile State

BackgroundMalaria infection during pregnancy can result in placental malaria and is associated with adverse pregnancy outcomes particularly among primigravidae. The aim of this study was to assess the prevalence and risk factors for placental malaria and its effect on pregnancy outcomes in Blue Nile state, Sudan.MethodsA cross-sectional hospital-based study was conducted consecutively during January 2012–December 2015 in three main hospitals in Blue Nile State, Sudan. At delivery, peripheral and placental blood samples were collected from consenting women. Finger prick blood was used for preparation of peripheral smears and for haemoglobin measurement. Smears were stained with Giemsa and examined microscopically for malaria parasites. Pregnancy outcomes in association to placental malaria were investigated.ResultsA total of 1149 mothers and their newborns were recruited. The mean (SD) of the age was 23.3 (5.2) years. Detection of malaria parasites was confirmed in 37.8% of the peripheral blood films and 59.3% of the placental films with Plasmodium falciparum as the only species detected. In multivariate analysis, younger age ≤23.2 years old (AOR = 3.2, 95% CI 1.9–5.5; P < 0.001), primiparae (AOR = 3.9, CI 2.1–7.6; P < 0.001), secundiparae (AOR = 2.8, 95% CI 1.5–5.1; P < 0.001, no antenatal care (ANC) visits (AOR = 11.9, 95% CI 7.8–18.1; P < 0.001) and not using bed nets (AOR = 3.5, 95% CI 1.7–6.8; P < 0.001) were risk factors for placental malaria. Education and residence were not associated with placental malaria infection. Placental malaria was significantly associated with maternal anaemia (AOR = 41.6, 95% CI 23.3–74.4; P < 0.001) and low birth weight (LBW) (AOR = 25.2, 95% CI 15.1–41.3; P < 0.001).ConclusionDuring the study, there was a high prevalence of placental malaria in Blue Nile State-Sudan, as the enhanced control activities were not practiced, leading to adverse pregnancy outcomes, such as maternal anaemia and LBW.

Pregnant women carrying female fetuses are at higher risk of placental malaria infection.

BackgroundThe pathophysiology of the placental malaria is not fully understood. If there is a fetal sex–specific susceptibility to malaria infection, this might add to the previous knowledge on the immunology, endocrinology and pathophysiology of placental malaria infections.AimsThis study was conducted to assess whether the sex of the fetus was associated with placental malaria infections.Subjects and methodsA cross-sectional study was performed including a secondary analysis of a cohort of women who were investigated for prevalence and risk factors (including fetal sex) for placental malaria in eastern Sudan. Placental histology was used to diagnose placental malaria infections.ResultsAmong 339 women enrolled, the mean (SD) age was 25.8 (6.7) years and parity was 2.7 (2.2). Among the new born babies, 157 (46.3%) were male and 182 (53.7%) were female. Five (1.5%), 9 (2.7%) and 103 (30.4%) of the 339 placentas had active, active-chronic, past-chronic malaria infection on histopathology examination respectively, while 222 (65.5%) of them showed no malaria infection. Logistic regression analyses showed no associations between maternal age or parity and placental malaria infections. Women who have blood group O (OR = 1.95, 95% CI = 1.19–3.10; P = 0.007) and women who had female new born were at higher risk for placental malaria infections (OR = 2.55, 95% CI = 1.57–4.13; P< 0.001).ConclusionFetal gender may be a novel risk factor for placental malaria. In this work the female placentas were at higher risk for malaria infections than the male placentas.

Leptin, insulin like growth factor-I levels and histology-diagnosed placental malaria in an area characterized by unstable malaria transmission in central Sudan

Background: There are few published data on the association between leptin, insulin like growth factor-1 (IGF-1) and malaria during pregnancy. This study aimed to investigate maternal and umbilical cord leptin and IGF-1 levels and malaria during pregnancy, and their association - if any - with birth weight.Methods: A cross-sectional study was conducted at Medani, Sudan. Medical and obstetrics history was gathered from each parturient woman (n=175) and malaria was investigated by blood film and placental histology. Maternal and umbilical cord leptin and IGF-1 levels were measured using ELISA.Results: Upon histological examination, 48 women were infected with placental malaria, and 127 were found free from the disease. Out of the 48, 2 of the patients showed signs of active infection, 3 of chronic infection and 43 of previous infection. Placental malaria and preterm delivery were associated with low birth weight (&lt; 2500 g). Younger mothers and primigravidae had a higher risk for placental malaria infection. There was no significant difference in maternal and umbilical cord leptin and IGF-1 levels between women infected with placental malaria and those free from the disease.Conclusions: The current study showed that low birth weight was significantly associated with placental malaria. Young mothers and primigravidae had a higher risk to develop the infection. There was no significant difference in the levels of maternal and umbilical cord leptin and IGF-1 levels between women infected with placental malaria and those free from the disease. Both the levels of maternal and cord leptin and IGF-1were found not to be associated with birth weight.Abbreviations: IGF-1: Insulin like growth factor-1; LBW: Low birth weight; ELISA: Enzyme-linked immunosorbent assay; PM: Placental malaria.

IgG isotypic antibodies to crude Plasmodium falciparum blood-stage antigen associated with placental malaria infection in parturient Cameroonian women.

Few studies have reported an association between placental malaria (PM) infection and levels of isotypic antibodies against non-pregnancy associated antigens. To determine and evaluate IgG isotypic antibody levels to crude P. falciparum blood stage in women with and without PM infection. Levels of IgG (IgG1-IgG4) and IgM to crude P. falciparum blood stage antigen were measured by ELISA in 271 parturient women. Placental malaria infection was determined by placental blood microscopy and placental histology. Age, parity and intermittent preventive treatment during pregnancy with sulphadoxine-pyrimethamine (IPTp-SP) usage were considered during analysis. P. falciparum-specific IgG1 (96.5%) and IgG3 (96.7%) antibodies were predominant compared with IgG2 (64.6%) and IgG4 (49.1%). Active PM infection was associated with significant increased levels of IgG1, IgG4 and IgM while lower levels of these antibodies were associated with uptake of two or more IPTp-SP doses. PM infection was the only independent factor associated with IgG4 levels. Mean IgG1 + IgG3/IgG2 + IgG4 and IgG1 + IgG2 +IgG3/ IgG4 ratios were higher among the PM-uninfected group while IgG4/IgG2 ratio prevailed in the infected group. PM infection and IPTp-SP dosage influenced P. falciparum-specific isotypic antibody responses to blood stage antigens. An increase in IgG4 levels in response to PM infection is of particular interest.

Soluble human leukocyte antigen -G during pregnancy and infancy in Benin: Mother/child resemblance and association with the risk of malaria infection and low birth weight.

Human leukocyte antigen (HLA) G is a tolerogenic molecule involved in the maternal-fetal immune tolerance phenomenon. Its expression during some infectious diseases leading to immune evasion has been established. A first study conducted in Benin has shown that the production of soluble HLA-G (sHLA-G) during the first months of life is strongly correlated with the maternal level at delivery and associated with low birth weight and malaria. However sHLA-G measurements during pregnancy were not available for mothers and furthermore, to date the evolution of sHLA-G in pregnancy is not documented in African populations. To extend these previous findings, between January 2010 and June 2013, 400 pregnant women of a malaria preventive trial and their newborns were followed up in Benin until the age of 2 years. Soluble HLA-G was measured 3 times during pregnancy and repeatedly during the 2 years follow-up to explore how sHLA-G evolved and the factors associated. During pregnancy, plasma levels of sHLA-G remained stable and increased significantly at delivery (p<0.001). Multigravid women seemed to have the highest levels (p = 0.039). In infants, the level was highest in cord blood and decreased before stabilizing after 18 months (p<0.001). For children, a high level of sHLA-G was associated with malaria infection during the follow-up (p = 0.02) and low birth weight (p = 0.06). The mean level of sHLA-G during infancy was strongly correlated with the mother’s level during pregnancy (<0.001), and not only at delivery. Moreover, mothers with placental malaria infection had a higher probability of giving birth to a child with a high level of sHLA-g (p = 0.006). High sHLA-G levels during pregnancy might be associated with immune tolerance related to placental malaria. Further studies are needed but this study provides a first insight concerning the potential role of sHLA-G as a biomarker of weakness for newborns and infants.

Vitamin A and Zinc Supplementation Among Pregnant Women to Prevent Placental Malaria: A Randomized, Double-Blind, Placebo-Controlled Trial in Tanzania.

AbstractVitamin A and zinc are important for immune function and may improve host defense against malaria and reduce the risk of adverse pregnancy outcomes. Our objective was to determine whether daily oral supplementation with either or both nutrients starting in the first trimester reduces the risk of placental malaria and adverse pregnancy outcomes. We undertook a randomized, double-blind placebo-controlled trial with a factorial design among 2,500 human immunodeficiency virus-negative primigravid or secundigravid pregnant women in their first trimester of pregnancy in Dar es Salaam, Tanzania. We randomly allocated equal numbers of participants to 2,500 IU of vitamin A, 25 mg of zinc, both 2,500 IU of vitamin A and 25 mg of zinc, or a placebo until delivery. A total of 625 participants were allocated to each treatment group. Our primary outcome, placental malaria infection (past or current), was assessed in all randomized participants for whom placental samples were obtained at delivery (N = 1,404), which represents 56% of total participants and 62% of all pregnancies lasting 28 weeks or longer (N = 2,266). Birth outcomes were obtained for 2,434 of the 2,500 randomized participants. Secondary outcomes included small for gestational age (SGA) births and prematurity. All analyses were intent to treat. Those who received zinc had a lower risk of histopathology-positive placental malaria compared with those who did not receive zinc (risk ratio = 0.64, 95% confidence interval = 0.44, 0.91), but neither nutrient had an effect on polymerase chain reaction-positive malaria, SGA, or prematurity. No safety concerns were identified. We recommend additional studies in other geographic locations to confirm these findings.