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Toxoplasma gondii , Plasmodium falciparum , and Trypanosoma cruzi are important human pathogens that cause severe disease in the mother and fetus during pregnancy. Global incidence of congenital complications due to these parasites varies dramatically depending on overall transmission rates and the immune status of the population. A primary means of disease that unifies these three parasites is causing inflammation in and around the placenta, which can increase the ability of the parasite to be transmitted to the fetus. Newly emerging models of placental development have great potential to revolutionize our understanding of parasite–placenta interactions. These include placental organoids and trophoblast stem cells. For each of these parasites we speculate about the importance of congenital transmission in its evolutionary history in light of evolutionary theory of vertical transmission. Congenital infections are a leading preventable cause of pregnancy complications impacting both mother and fetus. Although advancements have been made in understanding various congenital infections, the mechanisms of parasitic infections during pregnancy remain poorly understood. This review covers the global incidence of three parasites capable of congenital transmission – Trypanosoma cruzi, Plasmodium spp. , and Toxoplasma gondii – and the state of research into their transplacental transmission strategies. We highlight technological advancements in placental modeling that offer opportunities to reveal how parasites cause gestational pathology. Additionally, we discuss the likelihood that selective adaptation contributed to the evolution of mechanisms that facilitate placental infection. These insights provide a foundation for understanding the progression and pathology of congenital parasitic diseases and identifying future research directions. [ABSTRACT FROM AUTHOR]

Background: Malaria has a stable perennial transmission across Uganda. Placental malaria is associated with adverse maternal, fetal, and neonatal outcomes. The factors associated with placental malaria are poorly understood in the study setting. The aim of the study was to assess the prevalence of placental malaria and to determine its associated factors among parturient women in Lira District, Uganda. Methods: This was a cross-sectional study among 366 pregnant women who delivered at Lira Regional Referral Hospital. Data were collected from December 2018 to February 2019 using an interviewer-administered questionnaire. The variables were socio-demographic, obstetric characteristics, and malaria preventive practices. Standard Diagnostic Bioline Rapid Diagnostic Tests were used to detect placental malaria present in placental blood. Microscopy was used to quantify the grade of placental malaria parasitaemia. Logistic regression was used to assess factors associated with placental malaria. Results: The mean age of the participants was 25.34 years (standard deviation [SD] 5.73). The prevalence of placental malaria was [4.4% (16/366) 95% CI (2.5 to 7.0)]. Of these, only 7/16 were positive on microscopy, with 2/7 having moderate parasitemia and 5/7 having mild parasitaemia. Women aged less than 20 years [AOR 3.48, 95% CI (1.13 to 10.72)], and those not taking iron supplements during pregnancy [AOR = 3.55, 95% CI (1.02 to 12.31)] were associated with an increased likelihood of having placental malaria. Conclusion: The prevalence of placental malaria was low in this setting. This may have reflected the low malaria transmission rates following intensive indoor residual spraying. Placental malaria infection was associated with younger age and not taking iron supplements during pregnancy. Public health measures need to scale up and emphasise adherence to malaria preventive measures during pregnancy especially among teenage mothers. [ABSTRACT FROM AUTHOR]

Abstract Background Malaria has a stable perennial transmission across Uganda. Placental malaria is associated with adverse maternal, fetal, and neonatal outcomes. The factors associated with placental malaria are poorly understood in the study setting. The aim of the study was to assess the prevalence of placental malaria and to determine its associated factors among parturient women in Lira District, Uganda. Methods This was a cross-sectional study among 366 pregnant women who delivered at Lira Regional Referral Hospital. Data were collected from December 2018 to February 2019 using an interviewer-administered questionnaire. The variables were socio-demographic, obstetric characteristics, and malaria preventive practices. Standard Diagnostic Bioline Rapid Diagnostic Tests were used to detect placental malaria present in placental blood. Microscopy was used to quantify the grade of placental malaria parasitaemia. Logistic regression was used to assess factors associated with placental malaria. Results The mean age of the participants was 25.34 years (standard deviation [SD] 5.73). The prevalence of placental malaria was [4.4% (16/366) 95% CI (2.5 to 7.0)]. Of these, only 7/16 were positive on microscopy, with 2/7 having moderate parasitemia and 5/7 having mild parasitaemia. Women aged less than 20 years [AOR 3.48, 95% CI (1.13 to 10.72)], and those not taking iron supplements during pregnancy [AOR = 3.55, 95% CI (1.02 to 12.31)] were associated with an increased likelihood of having placental malaria. Conclusion The prevalence of placental malaria was low in this setting. This may have reflected the low malaria transmission rates following intensive indoor residual spraying. Placental malaria infection was associated with younger age and not taking iron supplements during pregnancy. Public health measures need to scale up and emphasise adherence to malaria preventive measures during pregnancy especially among teenage mothers.

Introduction: Depending on the microenvironment, γδ T cells may assume characteristics similar to those of Th1, Th2, Th17, regulatory T cells or antigen presenting cells. Despite the wide documentation of the effect of Th1/Th2 balance on pregnancy associated malaria and outcomes, there are no reports on the relationship between γδ T cell phenotype change and Placental Malaria (PM) with pregnancy outcomes. This study sought to investigate the involvement of γδ T cells and its subsets in placental Plasmodium falciparum malaria. Methods: In a case-control study conducted in Yaoundé, Cameroon from March 2022 to May 2023, peripheral, placental and cord blood samples were collected from 50 women at delivery (29 PM negative: PM- and 21 PM positive: PM+; as diagnosed by light microscopy). Hemoglobin levels were measured using hemoglobinometer. PBMCs, IVBMCs and CBMCs were isolated using histopaque-1077 and used to characterize total γδ T cell populations and subsets (Vδ1+, Vδ2+, Vδ1-Vδ2-) by flow cytometry. Results: Placental Plasmodium falciparum infection was associated with significant increase in the frequency of total γδ T cells in IVBMC and of the Vd1+ subset in PBMC and IVBMC, but decreased frequency of the Vδ2+ subset in PBMC and IVBMC. The expression of the activation marker: HLA-DR, and the exhaustion markers (PD1 and TIM3) within total γδ T cells and subsets were significantly up-regulated in PM+ compared to PM- group. The frequency of total γδ T cells in IVBMC, TIM-3 expression within total γδ T cells and subsets in IVBMC, as well as HLA-DR expression within total γδ T cells and Vδ2+ subset in IVBMC were negatively associated with maternal hemoglobin levels. Furthermore, the frequency of total γδ T cells in PBMC and PD1 expression within the Vδ2+ subset in CBMC were negatively associated with birth weight contrary to the frequency of Vδ1-Vδ2- subset in PBMC and HLA-DR expression within the Vδ2+ subset in IVBMC which positively associated with maternal hemoglobin level and birth weight, respectively. Conclusion: The data indicate up-regulation of activated and exhausted γδ T cells in Plasmodium falciparum placental malaria, with effects on pregnancy outcomes including maternal hemoglobin level and birth weight. [ABSTRACT FROM AUTHOR]

Background Malaria in pregnancy leads to placental malaria. The primary pathogenesis of the complex fetal implications in placental malaria is tissue hypoxia due to sequestrations of Plasmodium falciparum-infected erythrocytes in the placenta. However, the pathomechanism of placental Plasmodium vivax infection has not been thoroughly investigated. Hypoxia-inducible factor-1α (HIF-1α) is a key transcriptional mediator of the response to hypoxic conditions, which interacts with the change and imbalances of many chemical mediators, including angiogenic factors, leading to fetal growth abnormality. Methods This study was conducted cross-sectionally in Maumere, Sikka Regency, East Nusa Tenggara Province, previously known as one of the malaria endemic areas with a high incidence of low birth weight (LBW) cases. This study collected peripheral and umbilical blood samples and placental tissues from mothers who delivered their babies with LBW at the TC Hiller Regional Hospital. All of the blood samples were examined for parasites by microscopic and PCR techniques, while the plasma levels of VEGF, PlGF, VEGFR-1, VEGFR-2, and HIF-1α were determined using ELISA. The sequestration of infected erythrocytes and hemozoin was determined from placental histological slides, and the expression of placenta angiogenic factors was observed using the immunofluorescent technique. Results In this study, 33 cases had complete data to be analyzed. Of them, 19 samples were diagnosed as vivax malaria and none of falciparum malaria. There were significant differences in Δ 10th percentile growth curve of baby's body weights and also all angiogenic factors in placental tissues {VEGF, PlGF, and VEGFR-1, VEGFR-2, and HIF-1α} between those infected and not infected cases (p Conclusion This study indicated that Plasmodium vivax sequestration may promote LBW through alterations and imbalances in angiogenic factors led by HIF-1α.

Background Malaria in pregnancy leads to placental malaria. The primary pathogenesis of the complex fetal implications in placental malaria is tissue hypoxia due to sequestrations of Plasmodium falciparum-infected erythrocytes in the placenta. However, the pathomechanism of placental Plasmodium vivax infection has not been thoroughly investigated. Hypoxia-inducible factor-1α (HIF-1α) is a key transcriptional mediator of the response to hypoxic conditions, which interacts with the change and imbalances of many chemical mediators, including angiogenic factors, leading to fetal growth abnormality. Methods This study was conducted cross-sectionally in Maumere, Sikka Regency, East Nusa Tenggara Province, previously known as one of the malaria endemic areas with a high incidence of low birth weight (LBW) cases. This study collected peripheral and umbilical blood samples and placental tissues from mothers who delivered their babies with LBW at the TC Hiller Regional Hospital. All of the blood samples were examined for parasites by microscopic and PCR techniques, while the plasma levels of VEGF, PlGF, VEGFR-1, VEGFR-2, and HIF-1α were determined using ELISA. The sequestration of infected erythrocytes and hemozoin was determined from placental histological slides, and the expression of placenta angiogenic factors was observed using the immunofluorescent technique. Results In this study, 33 cases had complete data to be analyzed. Of them, 19 samples were diagnosed as vivax malaria and none of falciparum malaria. There were significant differences in Δ 10th percentile growth curve of baby's body weights and also all angiogenic factors in placental tissues {VEGF, PlGF, and VEGFR-1, VEGFR-2, and HIF-1α} between those infected and not infected cases (p

IntroductionDepending on the microenvironment, γδ T cells may assume characteristics similar to those of Th1, Th2, Th17, regulatory T cells or antigen presenting cells. Despite the wide documentation of the effect of Th1/Th2 balance on pregnancy associated malaria and outcomes, there are no reports on the relationship between γδ T cell phenotype change and Placental Malaria (PM) with pregnancy outcomes. This study sought to investigate the involvement of γδ T cells and its subsets in placental Plasmodium falciparum malaria.MethodsIn a case-control study conducted in Yaoundé, Cameroon from March 2022 to May 2023, peripheral, placental and cord blood samples were collected from 50 women at delivery (29 PM negative: PM- and 21 PM positive: PM+; as diagnosed by light microscopy). Hemoglobin levels were measured using hemoglobinometer. PBMCs, IVBMCs and CBMCs were isolated using histopaque-1077 and used to characterize total γδ T cell populations and subsets (Vδ1+, Vδ2+, Vδ1-Vδ2-) by flow cytometry.ResultsPlacental Plasmodium falciparum infection was associated with significant increase in the frequency of total γδ T cells in IVBMC and of the Vδ1+ subset in PBMC and IVBMC, but decreased frequency of the Vδ2+ subset in PBMC and IVBMC. The expression of the activation marker: HLA-DR, and the exhaustion markers (PD1 and TIM3) within total γδ T cells and subsets were significantly up-regulated in PM+ compared to PM- group. The frequency of total γδ T cells in IVBMC, TIM-3 expression within total γδ T cells and subsets in IVBMC, as well as HLA-DR expression within total γδ T cells and Vδ2+ subset in IVBMC were negatively associated with maternal hemoglobin levels. Furthermore, the frequency of total γδ T cells in PBMC and PD1 expression within the Vδ2+ subset in CBMC were negatively associated with birth weight contrary to the frequency of Vδ1-Vδ2- subset in PBMC and HLA-DR expression within the Vδ2+ subset in IVBMC which positively associated with maternal hemoglobin level and birth weight, respectively.ConclusionThe data indicate up-regulation of activated and exhausted γδ T cells in Plasmodium falciparum placental malaria, with effects on pregnancy outcomes including maternal hemoglobin level and birth weight.

Abstract 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. Data on the socio-demographic, clinical, obstetric, and malaria prevention practices of pregnant women were collected using interviewer-administered questionnaires and from women’s treatment cards. Malaria was diagnosed by light microscopy, rapid diagnostic test, and multiplex real-time polymerase chain reaction. Risk factors for malaria were evaluated using bivariable and multivariable logistic regression models. A P-value of

Background Malaria in pregnancy leads to placental malaria. The primary pathogenesis of the complex fetal implications in placental malaria is tissue hypoxia due to sequestrations of Plasmodium falciparum-infected erythrocytes in the placenta. However, the pathomechanism of placental Plasmodium vivax infection has not been thoroughly investigated. Hypoxia-inducible factor-1α (HIF-1α) is a key transcriptional mediator of the response to hypoxic conditions, which interacts with the change and imbalances of many chemical mediators, including angiogenic factors, leading to fetal growth abnormality. Methods This study was conducted cross-sectionally in Maumere, Sikka Regency, East Nusa Tenggara Province, previously known as one of the malaria endemic areas with a high incidence of low birth weight (LBW) cases. This study collected peripheral and umbilical blood samples and placental tissues from mothers who delivered their babies with LBW at the TC Hiller Regional Hospital. All of the blood samples were examined for parasites by microscopic and PCR techniques, while the plasma levels of VEGF, PlGF, VEGFR-1, VEGFR-2, and HIF-1α were determined using ELISA. The sequestration of infected erythrocytes and hemozoin was determined from placental histological slides, and the expression of placenta angiogenic factors was observed using the immunofluorescent technique. Results In this study, 33 cases had complete data to be analyzed. Of them, 19 samples were diagnosed as vivax malaria and none of falciparum malaria. There were significant differences in Δ 10th percentile growth curve of baby's body weights and also all angiogenic factors in placental tissues {VEGF, PlGF, and VEGFR-1, VEGFR-2, and HIF-1α} between those infected and not infected cases (p Conclusion This study indicated that Plasmodium vivax sequestration may promote LBW through alterations and imbalances in angiogenic factors led by HIF-1α.

In malaria-endemic areas, pregnant women are more susceptible to Plasmodium falciparum infection, especially primigravidae. During pregnancy, parasites sequester in the placenta and bind to the receptor chondroitin sulfate (CSA). This unique adhesion is mediated by the parasite protein VAR2CSA expressed on the surface of infected erythrocytes (IE). Placental malaria is associated with poor pregnancy outcomes including perinatal mortality, preterm delivery, small for gestational age (SGA) and low birthweight deliveries. Over successive pregnancies, women acquire functional antibodies that inhibit IE adhesion to CSA. Here, we examine the development of anti-adhesion activity and the breadth of anti-adhesion activity as a function of number of previous pregnancies, using samples collected from pregnant women living in an area with high seasonal malaria transmission. Women reached plateau levels of antiadhesion activity and breadth of anti-adhesion activity after 5 pregnancies. We related the level of anti-adhesion activity and reactivity with surface IE to SGA 19/232 pregnancies resulted in SGA, and report that an increase of 10% in median anti-adhesion activity reduced the odds of SGA by 13% and this relationship approached significance. Further, at an anti-adhesion activity level of 43.7%, an increase of 10% in the breadth of activity significantly reduced the odds of SGA by 21.5%. Antibodies that recognize IE surface increased over successive pregnancies, but were not associated with a reduction in SGA. These results can serve as a guideline for assessing vaccine candidates aiming to reduce poor pregnancy outcomes associated with placental malaria. [ABSTRACT FROM AUTHOR]

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. Data on the socio-demographic, clinical, obstetric, and malaria prevention practices of pregnant women were collected using interviewer-administered questionnaires and from women’s treatment cards. Malaria was diagnosed by light microscopy, rapid diagnostic test, and multiplex real-time polymerase chain reaction. Risk factors for malaria were evaluated using bivariable and multivariable logistic regression models. A P-value of<0.05 was considered statistically significant. Results Among the examined parturient women, 14.3% (95% CI 11.4–17.5%) had Plasmodium infections. The prevalence of peripheral, placental, and congenital malaria was 12.2% (95% CI 9.5–15.3%), 10.9% (95% CI 8.2–14.1%), and 3.7% (95% CI 2.3–6.1%), respectively. About 90.6% of peripheral and 92% of placental Plasmodium infections were asymptomatic. Plasmodium infection at parturiency was independently predicted by maternal illiteracy (AOR=2.03, 95% CI 1.11–3.74), primigravidity (AOR=1.88, 95% CI 1.01–3.49), lack of antenatal care follow-up (AOR=2.28, 95% CI 1.04–5.03), and history of symptomatic malaria during pregnancy (AOR=4.2, 95% CI 2.32–7.59). Moreover, the blood group O phenotype was significantly associated with placental malaria among the primiparae. Conclusions Overall, asymptomatic Plasmodium infections were prevalent among parturients in northwest Ethiopia. Maternal illiteracy, primigravidity, lack of antenatal care follow-up, and history of symptomatic malaria during pregnancy were the risk factors for malaria during parturiency. Thus, promotion of a healthy pregnancy through ANC follow-up, strengthening malaria prevention and control practices, and screening of malaria in asymptomatic pregnant women are suggested to reduce its burden in pregnancy [ABSTRACT FROM AUTHOR]

In malaria-endemic areas, pregnant women are more susceptible to Plasmodium falciparum infection, especially primigravidae. During pregnancy, parasites sequester in the placenta and bind to the receptor chondroitin sulfate (CSA). This unique adhesion is mediated by the parasite protein VAR2CSA expressed on the surface of infected erythrocytes (IE). Placental malaria is associated with poor pregnancy outcomes including perinatal mortality, preterm delivery, small for gestational age (SGA) and low birthweight deliveries. Over successive pregnancies, women acquire functional antibodies that inhibit IE adhesion to CSA. Here, we examine the development of anti-adhesion activity and the breadth of anti-adhesion activity as a function of number of previous pregnancies, using samples collected from pregnant women living in an area with high seasonal malaria transmission. Women reached plateau levels of anti-adhesion activity and breadth of anti-adhesion activity after 5 pregnancies. We related the level of anti-adhesion activity and reactivity with surface IE to SGA 19/232 pregnancies resulted in SGA, and report that an increase of 10% in median anti-adhesion activity reduced the odds of SGA by 13% and this relationship approached significance. Further, at an anti-adhesion activity level of 43.7%, an increase of 10% in the breadth of activity significantly reduced the odds of SGA by 21.5%. Antibodies that recognize IE surface increased over successive pregnancies, but were not associated with a reduction in SGA. These results can serve as a guideline for assessing vaccine candidates aiming to reduce poor pregnancy outcomes associated with placental malaria.

BackgroundPlacental malaria (PM) has been associated with a higher risk of malaria during infancy. However, it is unclear whether this association is causal, and is modified by infant sex, and whether intermittent preventive treatment in pregnancy (IPTp) can reduce infant malaria by preventing PM.MethodsData from a birth cohort of 656 infants born to HIV-uninfected mothers randomised to IPTp with dihydroartemisinin-piperaquine (DP) or Sulfadoxine-pyrimethamine (SP) was analysed. PM was categorized as no PM, active PM (presence of parasites), mild-moderate past PM (> 0-20% high powered fields [HPFs] with pigment), or severe past PM (> 20% HPFs with pigment). The association between PM and incidence of malaria in infants stratified by infant sex was examined. Causal mediation analysis was used to test whether IPTp can impact infant malaria incidence via preventing PM.ResultsThere were 1088 malaria episodes diagnosed among infants during 596.6 person years of follow-up. Compared to infants born to mothers with no PM, the incidence of malaria was higher among infants born to mothers with active PM (adjusted incidence rate ratio [aIRR] 1.30, 95% CI 1.00-1.71, p = 0.05) and those born to mothers with severe past PM (aIRR 1.28, 95% CI 0.89-1.83, p = 0.18), but the differences were not statistically significant. However, when stratifying by infant sex, compared to no PM, severe past PM was associated a higher malaria incidence in male (aIRR 2.17, 95% CI 1.45-3.25, p

BackgroundMaternal malarial infection leads to poor perinatal outcomes, including low birth weight from preterm delivery and/or fetal growth restriction, particularly in primigravidas. In placental malaria, Plasmodium falciparum-infected red blood cells cause an inflammatory response that can interfere with maternal-fetal exchange, leading to poor growth. The type I interferon (IFN-I) pathway plays an immunomodulatory role in viral and bacterial infections, usually by suppressing inflammatory responses. However, its role in placental malaria is unknown. This study examines the cytokine responses in placental tissue from subsets of malaria-infected and uninfected women, and attempts to correlate them with particular birth outcomes.Methods40 whole placental biopsy samples were obtained from pregnant women at least 16 years of age recruited to a larger prospective chemoprevention trial against malaria. These were patients at Tororo District Hospital in Uganda, an area of high malaria endemicity where approximately 40% of women have evidence of malaria infection at delivery. They were regularly followed at a local clinic and monitored for fever, with blood smears performed then and at time of delivery to diagnose malaria infection. Placenta biopsies were taken for histological diagnosis of placental malaria, as well as quantitative PCR analysis of genes in the IFN-I pathway (IFN-β, IL-10 and MX-1). Parameters such as infant birth weight and gestational age were also recorded.ResultsHistological analysis revealed placental malaria in 18 samples, while 22 were found to be uninfected. RT-PCR analysis showed a four-fold increase in IFN-β and IL-10 expression in multigravidas with placental malaria when compared to gravidity-matched, uninfected controls. This effect was not observed in primigravidas. Interestingly, linear regression analysis showed a positive association between IFN-β levels and higher birth weights (β = 101.2 g per log2-fold increase in IFN-β expression, p = 0.042). This association was strongest in primigravidas with placental malaria (β = 339.0, p = 0.006).ConclusionsThese results demonstrate differential regulation of the IFN-I pathway in placental malaria according to gravidity, with the greatest anti-inflammatory response seen in multigravidas. The association between IFN-β levels and higher birth weight also suggests a protective role for IFN-I against fetal growth restriction in placental malaria.