Placental Parasites Research Articles

Parasitic Effects on the Congenital Transmission of Trypanosoma cruzi in Mother-Newborn Pairs.

Maternal parasitemia and placental parasite load were examined in mother-newborn pairs to determine their effect on the congenital transmission of Trypanosoma cruzi. Parasitemia was qualitatively assessed in mothers and newborns by the microhematocrit test; parasite load was determined in the placental tissues of transmitting and non-transmitting mothers by the detection of T. cruzi DNA and by histology. Compared to transmitter mothers, the frequency and prevalence of parasitemia were found to be increased in non-transmitter mothers; however, the frequency and prevalence of parasite load were higher among the transmitter mothers than among their non-transmitter counterparts. Additionally, serum levels of interferon (IFN)-γ were measured by an enzyme-linked immunosorbent assay (ELISA) in peripheral, placental, and cord blood samples. Median values of IFN-γ were significantly increased in the cord blood of uninfected newborns. The median IFN-γ values of transmitter and non-transmitter mothers were not significantly different; however, non-transmitter mothers had the highest total IFN-γ production among the group of mothers. Collectively, the results of this study suggest that the anti-T. cruzi immune response occurring in the placenta and cord is under the influence of the cytokines from the mother's blood and results in the control of parasitemia in uninfected newborns.

Prevalence of Risk Factors Associated with Placental Malaria in Observational Study in Kator Primary Health Center South Sudan

Introduction: Civil unrest, public health system fragility and community mass relocation had played major roles in development of Placental Malaria Parasitization. This study aimed to measure and identifies risk factors associated with placental malaria infections in Kator primary health center. Methods and Materials: 115 enrolled pregnant women in cross-section survey after signing consent form using observational technique tools in one year period. ABO, peripheral blood antigen detection for malaria parasites using RDT kits and quantitative questionnaire information were obtained at recruitment phase while second peripheral blood for placental malaria parasites species applying RDT, placental weight and baby weight were measured after delivery as phase two. SPSS version 26 was applied with 0.005% P-value and CI 95%. Results: Out of 115 recruited pregnant women only (86.0%) 99 reached delivery room. With 29 primigravidae, 23 secundigravidae and 47 multigravidae; primigravida OR 95%CI 2.4 (1.73-5.64) P-vale 0.00013 and secundigravida with OR 95% CI1.8 (1.23-2.93) P-value 0.00072 and multigravida with OR 95% CI 1.5 (0.91-3.45) P-value 0.83. untreated bed net with OR 95% CI 1.4 (1.12-3.08) P-value 0.00053 and shared bed net at night with OR 95% CI 7.4(5.18-17.32) P-value 0.00027. Low birth weight, low placental weight and blood group O were not associated with placental malaria. Overall Placental Malaria prevalent was 26.3%. Conclusion: in this study, elevated placental malaria was recorded in Kator area of South Sudan. Doubling efforts to reduce placental malaria infections and its adverse clinical complications a new strategy to control the syndromic effects of the disease is required.

Evaluating circulating soluble markers of endothelial dysfunction and risk factors associated with PE: A multicentre longitudinal case control study in northern Ghana

Serpin E1/PAI-1, N-terminal pro-brain natriuretic peptide (NTpro-BNP) and neuropilin-1 are markers which have been associated with endothelial dysfunction. However, data on the levels of these markers in PE is limited. The limited data on the pathophysiology of PE in relation to these markers necessitated the study.This was a multicentre case-control study conducted at the Obstetrics and Gynaecology Department of the Tamale Teaching Hospital, the Bawku Presbyterian Hospital and the Bolgatanga Regional Hospital. Out of 520 consenting pregnant women, 127 pregnant women met the inclusion criteria (53 with PE and 74 controls) and were included in this study. Venous, placental, cord and peripheral blood were collected for biomarker assay, haematological parameters and placental parasite determination. Placental tissue sections were obtained for placental malaria and histopathological lesions associated with hypoperfusion. Maternal heart rate and foetal umbilical artery Doppler impedance indices; resistance index (RI) and systolic diastolic (SD) ratio were determined to confirm utero-placental hypoperfusion.Significantly higher proportions of foeto-maternal complications; eclampsia, low birth weight (LBW), neonatal intensive care unit admissions (NICU), intrauterine growth restriction (IUGR), caesarian deliveries and early gestational age at delivery were associated with PE. Women with PE had lower concentrations of platelet (p = 0.02) whereas red cell distribution width (RDW) was markedly elevated (p = 0.01). NTPro-BNP concentration was markedly elevated (p = 0.01) in women with PE whereas neuropilin-1 concentration was lower (p = 0.03) compared to the non-PE group. Maternal heart rate was elevated in women with PE and Doppler resistance indices (RI and SD) were significantly elevated in foetuses of PE women than foetuses of the controls. Placental mal-perfusion lesions were higher in women with PE compared to the non-PE group.Women with PE had increased risk of adverse foeto-maternal complications, significantly associated with placental mal-perfusion lesions, had reduced platelet concentration and elevated RDW-CV levels. NTPro-BNP, RI and SD are elevated in women with PE whereas neuropilin-1 concentration is reduced. Significant changes in these pathological variables in PE women is indicative of significant derangement in endothelial function culminating in adverse maternal and perinatal outcomes of pregnancy.

Placental Parasitic Infections and Pregnancy Outcomes Among Women Delivering at a Tertiary Hospital in Northern Tanzania.

Placental parasitic infections continue to be a public health problem despite numerous interventions put in place. Placental parasitic infections reported are Toxoplasma, Trypanosome, Borrelia, Schistosoma, Hookworm and Plasmodia. The infections persist to cause poor pregnancy outcomes such as maternal anaemia, low birth weight and stillbirth. This study aimed to determine the prevalence and pregnancy outcomes associated with placental parasitic infections at a tertiary hospital in northern Tanzania. A cross sectional study was conducted at Kilimanjaro Christian Medical Centre between June and July 2016. Pregnant women were interviewed before delivery and additional information obtained from their medical files. Blood samples as well as placental material were collected from each mother. Malaria was tested using a malaria rapid diagnostic test (mRDT). A total of 80 placental slide sections were made following histological protocols. After staining, slide sections were examined for the presence of parasites microscopically. Pearson's Chi-square and Fisher's exact tests were used to test for differences between groups. Placental malaria parasites were found on histological examination of 8(10%) mothers' placental sections, none of whom had a positive mRDT. Education status was significantly associated with placental malaria (p=0.035). Stillbirth, maternal anaemia and pre-eclampsia were significantly associated with placenta malaria (p<0.05). Placental malaria was found to be prevalent in the studied population and was associated with stillbirth, maternal anaemia and pre-eclampsia. Efforts for developing malaria tests that will detect subclinical infections are needed in order to identify infections early and offer prompt treatment to prevent poor pregnant outcomes.

The Rate of Asymptomatic Plasmodium Parasitemia and Placental Parasitization in Urban and Rural Areas of Cross River State, Nigeria

Background: Malaria in pregnancy contributes to feto-maternal morbidity and mortality even in asymptomatic forms of the disease especially in malaria endemic regions such as Nigeria. Objective: To determine the rate of asymptomatic malaria parasitemia and placental parasitization among the rural and urban pregnant women and its feto-maternal effects in Cross River State, Nigeria. Methodology: This was a prospective study of 440 pregnant women in rural and urban settings. Participants completed structured questionnaire and also have their blood samples and placentas examined for presence of malaria parasites by microscopy and histology respectively. Maternal hemoglobin concentration, birth weight, neonatal length, Apgar score and other anthropometric measurements were obtained to assess feto-maternal effect of asymptomatic malaria parasitemia and placental parasitisation in pregnancy. Data were analyzed using SPSS version 21.0 and level of significance was set as 0.05. ResultsThe prevalence of asymptomatic malaria parasitemia was 40.2% while malaria placental parasitization was 70.2%. Based on residential status, 49.5% of rural residents had malaria parasitemia which is significantly higher than their urban resident counterparts 30.9% (p=0.000). The prevalence of placental parasitization was significantly higher among rural residents 80.9% than their urban resident counterparts 59.5% (p=0.000). Concerning obstetric outcome of patients with positive malaria placental parasitisation, preterm delivery, low 5th minutes Apgar score (&lt;7), low birth weight (&lt;2.5kg) and low neonatal length were significantly higher in pregnancy with positive placental parasitisation than in women with negative placental malaria parasitisation. Also, preterm delivery, anemia, low 5th minutes Apgar score (&lt;7) and low birth weight (&lt;2.5kg) were significantly higher in pregnancy with positive malaria parasitemia than women with negative malaria parasitemia. ConclusionAsymptomatic malaria parasitemia (40.2%) and malaria placental parasitization (70.2%) in this study is high and contributes to poor obstetric outcomes mostly in the rural areas. Rural pregnant women have the highest burden than the urban women. Promotion of the use of ITNs, IPT during pregnancy and other malaria preventive measures are necessary especially in rural areas where malaria burden is highest.

Blood Group ABO, Placental Malaria Parasitization and Pregnancy Outcome in Munuki Primary health Centre in South Sudan

Several studies in Malaria endemic areas have reported conflicting observations on Blood Group ABO association with placental Malaria and pregnancy outcome. The purpose of this study is to determine the association between Placental Malaria and Blood Group O in the Munuki Primary Health Care Centre in South Sudan. Material and Methods: This was a prospective study. Each pregnant lady was enrolled after signing of informed consent and meeting study entry criteria. In all 589 pregnant women were evaluated. For each done were; ABO phenotype ones, at the enrolment and testing for malaria in and twice in the cause of pregnancy. Peripheral blood malaria parasites testing were by using RDT test to describe the type of plasmodium species. Results: The 589 enrolled were as follows; 154 (32.6%), 124 (26.3%) and 182 (38.6%) primigravidae, secundigravidae and multigravidae, respectively. The ABO distribution was; 124 (A), 59 (B), 14 (AB) and 257 (O). Negative peripheral Malaria parasites for pregnant women at ANC have higher positive Peripheral Malaria at DR with OR 2.93 CI (1.78__4.88) and ANC positive Malaria cases had higher chances of become positive during delivery OR 0.43 CI (0.30___0.62). Blood group O and peripheral malaria at DR with OR 1.17 CI (0.92___1.48) and Other Blood group at DR with OR 0.84 CI (0.67___1.06). Blood group O participants had higher P. Falciparum 60 /106 accounts for 56.6%. These results revealed significance interaction effect of Placental Malaria Parasites in Blood group O in Munuki Primary Health Center in Juba-South Sudan. This study recommends usage of protective measures against malaria during pregnancy.

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

The use of standard antimalarial drugs, such asdihydroartemisinin-piperaquine (DHP) for the treatment of malaria during pregnancy is limited due to the risk of teratogenicity. The alternative is therefore required although fewexist. 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. 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. 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. A combination of A.paniculata tablet (AS201-01) with DHP has the potential to reduce the toxicity of DHP in malaria treatment.

Parasite infestation influences life history but not boldness behavior in placental live-bearing fish

Parasites can negatively affect the reproductive success of hosts. Placental species may be particularly susceptible, because parasite-induced stress during pregnancy could potentially influence embryo development. Here, we examine the consequences of a trematode infestation (black spot disease, BSD) for fetal development and adult behavior in 19 natural populations of the placental live-bearing fish species Poeciliopsis retropinna (Poeciliidae) in Costa Rica. First, we observed substantial variation in parasite infestation among populations which correlated with a number of local environmental conditions (elevation, river width, depth, and flow velocity). Furthermore, we observed substantial variation in parasite infestation among females within populations associated with maternal age and size. We found that the infestation rate significantly influenced embryonic development, with more heavily parasitized females producing smaller and worse-conditioned offspring at birth, possibly, because a costly immune response during pregnancy limits, either directly or indirectly, nourishment to developing embryos. Finally, a behavioral experiment in the field showed that the infestation rate did not affect an individual’s boldness. Our study indicates that in placental live-bearing fish parasite infestation leads to reduced embryo provisioning during pregnancy, resulting in a smaller offspring size and quality at birth potentially with negative implications for offspring fitness.

The efficacy of intermittent preventive therapy in the eradication of peripheral and placental parasitemia in a malaria-endemic environment, as seen in a tertiary hospital in Abuja, Nigeria.

To determine whether intermittent preventive therapy in pregnancy (IPTp) eradicates peripheral and placental malaria and improves birth weight. A cross-sectional study was conducted of 426 pregnant mothers on IPTp with sulphadoxine-pyrimethamine against malaria who presented in labor, at National Hospital Abuja, Nigeria between January and June 2017. The hospital is within the malaria-endemic zone of West Africa. Consenting pregnant women with uncomplicated singleton term pregnancy who had antenatal care in the hospital and lived in the study area for at least 6months were consecutively recruited. Peripheral and placental blood were collected and examined for malaria parasite by microscopy. Babies were weighed at birth. The prevalence of peripheral malaria parasitemia and placental parasitization were 12.9% (95% confidence interval [CI] 10.0-16.6) and 9.4% (95% CI 7.0-12.7), respectively. Parasite density in both peripheral parasitemia and placental parasitization was low among the women that took IPTp, decreasing with increasing doses, with no parasitemia or parasitization in women that took up to three doses. Birth weight was lower in babies of mothers with plasmodium infestation than in those without infestation (P<0.001, P=0.024). IPTp reduces both peripheral parasitemia and placental parasitization, with the capacity to eliminate or prevent them. IPTp also reduces low birth weight.

Functional Antibodies against Placental Malaria Parasites Are Variant Dependent and Differ by Geographic Region.

During pregnancy, Plasmodium falciparum-infected erythrocytes (IE) accumulate in the intervillous spaces of the placenta by binding to chondroitin sulfate A (CSA) and elicit inflammatory responses that are associated with poor pregnancy outcomes. Primigravidae lack immunity to IE that sequester in the placenta and thus are susceptible to placental malaria (PM). Women become resistant to PM over successive pregnancies as antibodies to placental IE are acquired. Here, we assayed plasma collected at delivery from Malian and Tanzanian women of different parities for total antibody levels against recombinant VAR2CSA antigens (FCR3 allele), and for surface reactivity and binding inhibition and opsonizing functional activities against IE using two CSA-binding laboratory isolates (FCR3 and NF54). Overall, antibody reactivity to VAR2CSA recombinant proteins and to CSA-binding IE was higher in multigravidae than in primigravidae. However, plasma from Malian gravid women reacted more strongly with FCR3 whereas Tanzanian plasma preferentially reacted with NF54. Further, acquisition of functional antibodies was variant dependent: binding inhibition of P. falciparum strain NF54 (P < 0.001) but not of the strain FCR3 increased significantly with parity, while only opsonizing activity against FCR3 (P < 0.001) increased significantly with parity. In addition, opsonizing and binding inhibition activities of plasma of multigravidae were significantly correlated in assays of FCR3 (r = 0.4, P = 0.01) but not of NF54 isolates; functional activities did not correlate in plasma from primigravidae. These data suggest that IE surface-expressed epitopes involved in each functional activity differ among P. falciparum strains. Consequently, geographic bias in circulating strains may impact antibody functions. Our study has implications for the development of PM vaccines aiming to achieve broad protection against various parasite strains.

A randomized controlled trial of azithromycin and sulphadoxine–pyrimethamine as prophylaxis against malaria in pregnancy among human immunodeficiency virus–positive women

Malaria and human immunodeficiency virus (HIV) infections in pregnancy are important and major contributing factors to maternal morbidity and mortality in sub-Saharan Africa. Prevention of malaria in HIV-positive pregnant woman will reduce the burden of malaria-HIV comorbidity. The objective of this study was to compare effects and safety of azithromycin (AZ) with sulphadoxine-pyrimethamine (SP) for intermittent preventive therapy for malaria in HIV-positive pregnant women. We performed a randomized, controlled, open-label pregnancy trial of 140 HIV-positive pregnant patients attending antenatal clinics at the University College Hospital and Adeoyo Maternity Teaching Hospital, Ibadan, Nigeria. Participants were enrolled from a gestational age of 16 weeks and randomized to receive AZ or SP. The primary outcome was peripheral parasitaemia at delivery. Secondary outcomes were drug tolerability, foetal outcome and birthweight. The χ2 test (or Fisher's exact test, as appropriate) and Student's t test were used in the per-protocol analysis. The level of statistical significance was p<0.05. A total of 123 participants (87.9%) completed the study: 60 participants received AZ and 63 received SP. The incidence of malaria parasitaemia at delivery in the AZ group was 6 (10.0%), compared with 7 (11.1%) in the SP group (relative risk 0.89 [95% confidence interval 0.28 to 2.82], p=0.84). Placental parasitization was demonstrated in 1 (1.6%) participant in the SP group compared with 3 (5.0%) in the AZ group (p=0.36). The findings suggest that AZ is comparable to SP in malaria prevention and safety in HIV-positive pregnant women.

Fetal and Maternal Innate Immunity Receptors Have Opposing Effects on the Severity of Experimental Malaria in Pregnancy: Beneficial Roles for Fetus-Derived Toll-Like Receptor 4 and Type I Interferon Receptor 1.

ABSTRACTMalaria in pregnancy (MiP) is a distinctive clinical form of Plasmodium infection and is a cause of placental insufficiency leading to poor pregnancy outcomes. Maternal innate immunity responses play a decisive role in the development of placental inflammation, but the action of fetus-derived factors in MiP outcomes has been overlooked. We investigated the role of the Tlr4 and Ifnar1 genes, taking advantage of heterogenic mating strategies to dissect the effects mediated by maternally and fetally derived Toll-like receptor 4 (TLR4) or type I interferon receptor 1 (IFNAR1). Using a mouse infection system displaying severe MiP outcomes, we found that the expressions of TLR4 and IFNAR1 in the maternal compartment take part in deleterious MiP outcomes, but their fetal counterparts patently counteract these effects. We uncovered that fetal TLR4 contributes to the in vitro uptake of infected erythrocytes by trophoblasts and to the innate immune response in the placenta, offering robust protection of fetus viability, but had no sensible impact on the placental parasite burden. In contrast, we observed that the expression of IFNAR1 in the fetal compartment was associated with a reduced placental parasite burden but had little beneficial effect on fetus outcomes. Furthermore, the downregulation of Ifnar1 expression in infected placentas and in trophoblasts exposed to infected erythrocytes indicated that the interferon-IFNAR1 pathway is involved in the trophoblast response to infection. This work unravels that maternal and fetal counterparts of innate immune pathways drive opposing responses in murine placental malaria and implicates the activation of innate receptors in fetal trophoblast cells in the control of placental infection and in the protection of the fetus.

Placental Malaria Parasitization at Delivery: Experience at a Nigerian Tertiary Hospital

Background: In malaria endemic areas, pregnant women are constantly at risk of repeated malaria infestation which if left untreated, poses a significant threat to the health and survival of the mother and her baby. Objective: This study determined the prevalence and risk factors for placental malaria parasitaemia among parturients at the Federal Medical Centre, Yenagoa, Nigeria. Methodology: A prospective cross-sectional analytical study of 205 parturients recruited consecutively at presentation for delivery. An interviewer-administered questionnaire was used to collect data. After delivery, placental blood was collected for microscopy to detect malaria parasites. Data was analysed using SPSS version 22. Results: The prevalence of placental malaria parasitaemia was 13.7%. Maternal age &lt;25 years (P&lt;0.001), low educational status (P = 0.03), low parity (P = 0.03), unbooked status (P &lt; 0.001) and non-use of intermittent preventive treatment (P &lt;0.001) were significantly associated with placental malaria parasitaemia. Receiving three or more doses of sulphadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy was by far, more protective for placental malaria than receiving 2 doses (odds ratio = 0.25). Plasmodium falciparum was the only parasite species detected. Conclusion: Malaria still ravages our obstetric population and the significant contributors include low maternal age, low educational status, low parity, unbooked status and non-use of intermittent preventive treatment in pregnancy. Women should be encouraged to utilize antenatal care. There should be a prompt adoption of the recent WHO recommendations regarding malaria prophylaxis in pregnancy in all obstetric units and the medication should be given as Directly Observed Therapy.

Matched Placental and Circulating Plasmodium falciparum Parasites are Genetically Homologous at the var2csa ID1-DBL2X Locus by Deep Sequencing.

In pregnancy-associated malaria, infected erythrocytes accumulate in the placenta. It is unclear if in polyclonal infections this results in distinct peripheral and placental parasite populations. We used long amplicon deep sequencing of Plasmodium falciparum var2csa ID1-DBL2X from 15 matched peripheral and placental samples collected at delivery from a high transmission area to determine genetic homology. Despite substantial sequence variation and detecting 23 haplotypes, the matched pairs mostly contained the same genetic variants, with 11 pairs sharing 100% of their variants, whereas others showed some heterogeneity. Thus, at delivery, peripheral and placental parasites appear to intermix and placental genotypes can be inferred through peripheral sampling.

Relationships between infection with Plasmodium falciparum during pregnancy, measures of placental malaria, and adverse birth outcomes

BackgroundMalaria in pregnancy has been associated with maternal morbidity, placental malaria, and adverse birth outcomes. However, data are limited on the relationships between longitudinal measures of malaria during pregnancy, measures of placental malaria, and birth outcomes.MethodsThis is a nested observational study of data from a randomized controlled trial of intermittent preventive therapy during pregnancy among 282 participants with assessment of placental malaria and delivery outcomes. HIV-uninfected pregnant women were enrolled at 12–20 weeks of gestation. Symptomatic malaria during pregnancy was measured using passive surveillance and monthly detection of asymptomatic parasitaemia using loop-mediated isothermal amplification (LAMP). Placental malaria was defined as either the presence of parasites in placental blood by microscopy, detection of parasites in placental blood by LAMP, or histopathologic evidence of parasites or pigment. Adverse birth outcomes assessed included low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA) infants.ResultsThe 282 women were divided into three groups representing increasing malaria burden during pregnancy. Fifty-two (18.4%) had no episodes of symptomatic malaria or asymptomatic parasitaemia during the pregnancy, 157 (55.7%) had low malaria burden (0–1 episodes of symptomatic malaria and < 50% of samples LAMP+), and 73 (25.9%) had high malaria burden during pregnancy (≥ 2 episodes of symptomatic malaria or ≥ 50% of samples LAMP+). Women with high malaria burden had increased risks of placental malaria by blood microscopy and LAMP [aRR 14.2 (1.80–111.6) and 4.06 (1.73–9.51), respectively], compared to the other two groups combined. Compared with women with no malaria exposure during pregnancy, the risk of placental malaria by histopathology was higher among low and high burden groups [aRR = 3.27 (1.32–8.12) and aRR = 7.07 (2.84–17.6), respectively]. Detection of placental parasites by any method was significantly associated with PTB [aRR 5.64 (1.46–21.8)], and with a trend towards increased risk for LBW and SGA irrespective of the level of malaria burden during pregnancy.ConclusionHigher malaria burden during pregnancy was associated with placental malaria and together with the detection of parasites in the placenta were associated with increased risk for adverse birth outcomes.Trial Registration Current Controlled Trials Identifier NCT02163447

Microscopic detection of hemozoin in peripheral leukocytes fails to indicate plasmodial placental infection in pregnant women.

Malaria in pregnancy very often includes gestational (parasites in maternal peripheral blood) and placental (parasites in placental blood) infection, but the later condition can only be detected after delivery. High frequency of placental plasmodial infection has been confirmed in many countries and is associated with negative birth outcomes. With the hypothesis that placental infection is accompanied by hemozoin circulation in maternal peripheral blood, an exploratory study was conducted to evaluate the association between peripheral leukocytes with hemozoin and placental infection by Plasmodium vivax or Plasmodium falciparum in parturient women. A descriptive, transversal and exploratory (pilot type) study was carried out with women from two malaria-endemic localities of northwest Colombia. A total of 25 parturient women with confirmed placental infection and 25 without placental infection were included. Two independent readers measured the number of leukocytes with hemozoin in thick smears of maternal peripheral blood. Plasmodial infection in maternal peripheral blood and placental blood was detected by thick smear and quantitative polymerase chain reaction (qPCR). Four parturient women had leukocytes with hemozoin in peripheral blood; three of them had placental plasmodial infection and one was negative for placental infection. No statistically significant association between leukocytes with hemozoin in peripheral blood and placental infection was observed. With this limited sample size, detection of leukocytes with hemozoin by thick smear of maternal peripheral blood did not indicate presence of placental infection.

Parasite dynamics in the peripheral blood and the placenta during pregnancy-associated malaria infection.

BackgroundMalaria infections during pregnancy lead to sequestration of parasite infected red blood cells in the placenta. Placental infection can result in adverse outcomes for mothers and infants. Despite many studies, it remains unclear which peripheral blood infections during pregnancy lead to development of placental malaria. Understanding the timing of peripheral infections that lead to placental malaria and the ability of intermittent preventive treatment with sulfadoxine–pyrimethamine (SP-IPT) and artemisinin-based combination therapy to clear infections will enable the rational design of new interventions to decrease the burden of malaria in pregnancy.MethodsMicrosatellite markers were used to genotype peripheral and placental malaria infections in an observational cohort in Blantyre, Malawi. Genotypes were compared to determine the timing of infections that sequester in the placenta. The effects of SP-IPT and artemether–lumefantrine as curative treatment were also evaluated by assessing the occurrence of peripheral infections or matching genotypes between peripheral and placental parasites following treatment.ResultsGenotypes from 92 peripheral samples prior to delivery, 26 peripheral samples at delivery, and 29 placental samples were compared. Thirty percent of women with genotyped parasites in their placentas that had peripheral infections detected during pregnancy had matching peripheral-placental genotypes. Matching genotypes were not associated with gestational age and occurred from 13 to 39 weeks. Among women with more than one genotyped peripheral infection during pregnancy, 80 % had persistent infection with the same genotype while the remaining were new infections. Among infections treated with SP or artemether–lumefantrine, 28/84 (33 %) and 9/56 (16 %) had infection detected after treatment, respectively. Recrudescent infections were detected after both treatments and occurred up to 76 days after treatment. Women treated with SP-IPT and artemether–lumefantrine had genotypes matching treated infections detected in the placenta.ConclusionsPlacental malaria can occur at any time during pregnancy. In the context of late enrollment in antenatal care, interventions that protect all women of childbearing age and throughout pregnancy are needed. Currently used medications do not always clear peripheral or placental infections. The ability of anti-malarial drugs to prevent or clear placental infections should be considered in the development of future interventions.

Designing a VAR2CSA-based vaccine to prevent placental malaria

Placental malaria (PM) due to Plasmodium falciparum is a major cause of maternal, fetal and infant mortality, but the mechanisms of pathogenesis and protective immunity are relatively well-understood for this condition, providing a path for vaccine development. P. falciparum parasites bind to chondroitin sulfate A (CSA) to sequester in the placenta, and women become resistant over 1–2 pregnancies as they acquire antibodies that block adhesion to CSA. The protein VAR2CSA, a member of the PfEMP1 variant surface antigen family, mediates parasite adhesion to CSA, and is the leading target for a vaccine to prevent PM. Obstacles to PM vaccine development include the large size (∼350kD), high cysteine content, and sequence variation of VAR2CSA. A number of approaches have been taken to identify the combination of VAR2CSA domains and alleles that can induce broadly active antibodies that block adhesion of heterologous parasite isolates to CSA. This review summarizes these approaches, which have examined VAR2CSA fragments for binding activity, antigenicity with naturally acquired antibodies, and immunogenicity in animals for inducing anti-adhesion or surface-reactive antibodies. Two products are expected to enter human clinical studies in the near future based on N-terminal VAR2CSA fragments that have high binding affinity for CSA, and additional proteins preferentially expressed by placental parasites are also being examined for their potential contribution to a PM vaccine.

Placental infections with histologically confirmed Plasmodium falciparum are associated with adverse birth outcomes in India: a cross-sectional study.

BackgroundFew studies have assessed placental malaria infections from low transmission areas by histopathology to define their impact and underlying mechanisms.MethodsPeripheral smears and rapid diagnostic tests (RDTs), placental smears and histological samples, birth weight and gestational age were collected from 2,282 deliveries in three hospitals during a one-year (2006–2007) continuous cross-sectional survey in Madhya Pradesh. Placental histopathology included all 50 cases positive by microscopy or RDT plus 456 randomly selected samples of women negative for malaria by microscopy or RDT. Histological examination included parasites, inflammatory cells, pigment in fibrin, and morphological changes.ResultsThere were 52 histology-positive cases; 38 (73.1%) active (acute and chronic) and 14 past infections. Intervillous parasitaemia was low (60% had < 1% parasitaemia) and monocytosis mostly mild (63%). Compared with uninfected placentas, acute Plasmodium falciparum infections were associated with stillbirth (RR 3.8, 95% CI 1.2-12.1), lower maternal haemoglobin (mean difference: 1.5 g/dL, 95% CI 0.5-2.5), lower birth weight (mean difference 451 g, 95% CI 169–609) and shorter gestation (mean difference 0.8 weeks, 95% CI 0.2-1.4). Chronic or past infections were not associated with these outcomes. Among the 11 peripheral Plasmodium vivax cases, placental parasites were absent, but they were associated with increased placental polymorphonuclear cells.ConclusionsMalaria associated stillbirth and low birth weight in women with low protective immunity may result, at least in part, from a shortened gestation triggered by acute infection, stressing the importance of early malaria detection.

Immune responses during gestational malaria: a review of the current knowledge and future trend of research.

Women pregnant with their first child are susceptible to severe P. falciparum disease from placental malaria because they lack immunity to placenta-specific cytoadherence proteins. In subsequent pregnancies, as immunity against placental parasites is acquired, there is a reduced risk of adverse effects of malaria on the mother and fetus and asymptomatic parasitaemia is common. In the case of vivax malaria, with increasing reports of severe cases in Asia and South America, the effects of infection by this species during pregnancy remain to be elucidated. This review summarized the main aspects involved in the acquisition of specific antimalarial immune responses during pregnancy with emphasis in research carried out in America and Asia, in order to offer a framework of interpretation for studies on pregnant women with malaria which are recently being produced in these regions. The authors conclude that (1) Effective humoral responses during gestational malaria are mainly directed against variant surface antigens codified by genes of the var2Csa family of P. falciparum; (2) Acquisition of immunity against these variant antigens depends on the degree and intensity of transmission, and the chance increases with age and successive pregnancies; (3) Antibody development is guided by specific cellular immune responses in cases of placental and maternal infection, and (4) The study of the significance of acquisition of specific immunity against both P. falciparum and P. vivax in America, should be performed.