Prospective study of malaria in pregnancy, placental and congenital malaria in Northwest Colombia.

BACKGROUND: Pregnancy Associated Malaria (PAM) include malaria in pregnancy (MiP), placental malaria (PM), and congenital malaria (CM). The evidence available in Colombia on PAM focuses on one of the presentations (MiP, PM or CM), and no study longitudinally analyses the infection from the pregnant woman, passing through the placenta, until culminating in the newborn. This study determined the frequency of MiP, PM, and CM caused by Plasmodium vivax, Plasmodium falciparum, or mixed infections, according to Thick Blood Smear (TBS) and quantitative Polymerase Chain Reaction (qPCR). Identifying associated factors of PAM and clinical-epidemiological outcomes in northwestern Colombia. METHODS: Prospective study of 431 pregnant women, their placenta, and newborns registered in the data bank of the research Group "Salud y Comunidad César Uribe Piedrahíta" which collected information between 2014 and 2020 in endemic municipalities of the departments of Córdoba and Antioquia. The frequency of infection was determined with 95% confidence intervals. Comparisons were made with the Chi-square test, Student t-test, prevalence ratios, and control for confounding variables by log-binomial regression. RESULTS: The frequency of MiP was 22.3% (4.6% using TBS), PM 24.8% (1.4% using TBS), and CM 11.8% (0% using TBS). Using TBS predominated P. vivax. Using qPCR the proportions of P. vivax and P. falciparum were similar for MiP and PM, but P. falciparum predominated in CM. The frequency was higher in nulliparous, and women with previous malaria. The main clinical effects of PAM were anaemia, low birth weight, and abnormal APGAR score. CONCLUSIONS: The magnitude of infections was not detected with TBS because most cases were submicroscopic (TBS-negative, qPCR-positive). This confirmed the importance of improving the molecular detection of cases. PAM continue being underestimated in the country due to that in Colombia the control programme is based on TBS, despite its outcomes on maternal, and congenital health.

Sickle cell disease and pregnancy profile of complicated malaria in 982 pregnancies in Kinshasa.

INTRODUCTION: Malaria is associated with high morbidity during pregnancy. Homozygous sickle cell pregnant women are even more exposed during complicated malaria. The objective of the study was to evaluate the maternal and fetal morbidity of homozygous sickle cell pregnant pregnant women with complicated malaria. METHODS: We conducted a retrospective case-control study of 982 pregnancies in sickle cell pregnant women, during which a group of sickle cell pregnant women who received antimalarial chemoprophylaxis was compared to another group without chemoprophylaxis. We analyzed the clinical evolution of pregnant women (VOCs and transfusions, pregnancy weight gain) and parasite (parasite density at the time of diagnosis of complicated malaria and during treatment for three days). We analyzed the parameters of newborns at birth (age of pregnancy at the time of delivery, birth weight, weight of the placenta and histopathological examination of the placenta. RESULTS: Out of 982 pregnancies, 15% of pregnant women suffered from complicated malaria, 57% suffered from uncomplicated malaria and 28% did not suffer from malaria. Pregnancy weight gain, birth weight, was better in the group of pregnant women who received chemoprophylaxis and the placenta had less histological lesions. Parasite density was low. There was a significant positive correlation between parasite density and the number of CVOs and transfusions and between parasite density and histological lesions of the placenta and low birth weight. CONCLUSION: Complicated malaria is associated with high maternal and fetal morbidity in sickle cell patients. Malaria chemoprophylaxis can reduce maternal and fetal complications and parasite density during malaria infection.

Revisión sistemática de la exactitud diagnóstica de la gota gruesa en comparación con la reacción en cadena de la polimerasa para malaria asociada al embarazo, 2010-2022 / Systematic review of the diagnostic accuracy of thick smear compared to polymerase chain reaction for pregnancy-associated malaria, 2010-2022

RESUMEN Objetivos. Evaluar la exactitud de gota gruesa (GG) frente a la reacción en cadena de la polimerasa (PCR) cuantitativa para la malaria asociada al embarazo (MAE). Materiales y métodos. Se realizó una revisión sistemática de pruebas diagnósticas en nueve bases de datos. Se evaluó la calidad metodológica con QUADAS. Se estimó sensibilidad, especificidad, cociente de probabilidad positivo (CPP) y negativo (CPN), razón de odds diagnóstica (ORD) y área bajo la curva ROC. Se determinó la heterogeneidad con el estadístico Q de Der Simonian-Laird y la incertidumbre con el porcentaje de peso de cada estudio sobre el resultado global. Resultados. Se incluyeron diez estudios con 5691 gestantes, 1415 placentas y 84 neonatos. En los estudios con nPCR (PCR anidada) y qPCR (PCR cuantitativa) como estándar, los resultados de exactitud diagnóstica fueron estadísticamente similares, con sensibilidad muy baja (50 y 54%, respectivamente), alta especificidad (99% en ambos casos), alto CPP y deficiente CPN. Usando nPCR la OR diagnóstica fue 162 (IC95%=66-401) y el área bajo la curva ROC fue 95%, mientras que con qPCR fueron 231 (IC95%=27-1951) y 78%, respectivamente. Conclusiones. Mediante un protocolo exhaustivo se demostró el bajo desarrollo de investigaciones sobre la exactitud diagnóstica de la GG en MAE. Se demostró que la microscopía tiene un desempeño deficiente para el diagnóstico de infecciones asintomáticas o de baja parasitemia, lo que afianza la importancia de implementar otro tipo de técnicas en el seguimiento y control de las infecciones por malaria en las gestantes, con el fin de lograr el control y posible eliminación de la MAE.

ABSTRACT Objective. To evaluate the accuracy of thick smear (TS) versus quantitative polymerase chain reaction (PCR) for pregnancy-associated malaria (PAM). Materials and methods. We carried out a systematic review of diagnostic tests in nine databases. Methodological quality was evaluated with QUADAS. Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the ROC curve were estimated. Heterogeneity was determined with the Der Simonian-Laird Q method and uncertainty with the weighted percentage of each study on the overall result. Results. We included 10 studies with 5691 pregnant women, 1415 placentas and 84 neonates. In the studies with nested PCR (nPCR) and quantitative PCR (qPCR) as the standard, the diagnostic accuracy results were statistically similar, with very low sensitivity (50 and 54%, respectively), high specificity (99% in both cases), high PLR and poor NLR. When nPCR was used, the DOR was 162 (95%CI=66-401) and the area under the ROC curve was 95%, while with qPCR it was 231 (95%CI=27-1951) and 78%, respectively. Conclusions. We demonstrated that research on the diagnostic accuracy of TS in PAM is limited. Microscopy showed poor performance in the diagnosis of asymptomatic or low parasitemia infections, which reinforces the importance of implementing other types of techniques for the follow-up and control of malaria infections in pregnant women, in order to achieve the control and possible elimination of PAM.

Immunohistopathological changes in the placenta of malaria-infected women in unstable transmission setting of Aligarh.

INTRODUCTION: Pregnant women are more susceptible to malaria due to a combination of physiological and immunological changes. The infection may even affect the growth and survival of the foetus, which mainly occur when parasite enters the placenta. The sequestration of infected erythrocytes may trigger the host response, leading to placental inflammation and altered development, affecting the structure and nutrient transport of placenta. These factors collectively impair placental functions and affect foetal growth. METHODS: Pregnant women with peripheral parasitaemia for P. falciparum and P. vivax (20 each) were included in the present study, along with 15 age-matched uninfected healthy pregnant women. Placentae were analysed for the presence of local parasitaemia along with pathological lesions caused due to the parasite. Immunohistochemical staining for CD20, CD45 and CD68 cells was performed for examining the specific leucocytes in the intervillous space of the placenta. RESULTS: Of the 20 individuals with P. falciparum, only seven placentae showed parasitaemia, whereas individuals with P. vivax showed no placental infection. The pathological changes observed in the P. falciparum-infected placenta include syncytial knotting, excess fibrinoid deposition, syncytiotrophoblast necrosis, syncytial rupture, thickening of trophoblast basement membrane and increased collagen deposition. Immunohistochemical staining showed a significant increase in B cells (CD20), leucocytes (CD45) and monocytes and macrophages (CD68) in the P. falciparum-infected placenta (p < 0.0001). DISCUSSION: The result implies that P. falciparum is responsible for pathological alterations in placenta, affecting the nutrient transport across placenta and foetal growth. The immune cells also migrate to the placenta and accumulate in the intervillous space to show humoral and cell-mediated immunity against the parasite.

Congenital malaria: Frequency and epidemiology in Colombia, 2009-2020.

Congenital Malaria (CM) is an underestimated and under-researched problem in Colombia, despite its severe clinical, epidemiological, economic, and public health consequences. The objective was to determine the general frequency of CM, the specific frequency of CM by diagnostic test and plasmodial species, and identify its associated factors. A retrospective study was carried out using the records of 567 newborns. qPCR and Thick Blood Smear (TBS) were performed. The frequency of infection was determined with a 95% confidence interval. Associated factors were identified by non-parametric tests and odds ratios; the confusion was controlled with a logistic regression model. All cases corresponded to submicroscopic CM (negative with TBS and positive with PCR), and the frequency was 12.2% (95%CI = 9.4-14.9). The detection was statistically higher in the umbilical cord with 16,2% (95%CI = 12.4-19.9) versus peripheral blood of the newborn with 2.2% (95%CI = 0.7-4.9). CM was statistically higher in newborn whose mothers had malaria in the last year, gestational and placental malaria. The median birth weight in newborn infected with CM was lower compared to the one of healthy neonates. Because the control program in Colombia is based on TBS, it must be improved with the inclusion of other tests that allow the detection of submicroscopic CM. In addition, the program has other limitations such as do not have specific actions for pregnant women and have a passive surveillance system. These difficulties do not allow to show the magnitude of CM, its consequences on neonatal and infant health, constituting a serious problem of health injustice.

Trends of malaria infection in pregnancy in Ghana over the past two decades: a review.

BACKGROUND: There has been a global decline in malaria transmission over the past decade. However, not much is known of the impact of this observation on the burden of malaria infection in pregnancy in endemic regions including Ghana. A narrative review was undertaken to help describe trends in malaria infection in pregnancy in Ghana. Among others, such information is important in showing any progress made in malaria in pregnancy control. METHODS: To describe trends in pregnancy-associated malaria infection in Ghana, a search and review of literature reporting data on the prevalence of asymptomatic Plasmodium falciparum infection in pregnancy was conducted. RESULTS: Thirty-six (36) studies, conducted over 1994-2019, were included in the review. In the northern savannah zone with largely seasonal malaria transmission, prevalence appeared to reduce from about 50-60% in 1994-2010 to 13-26% by 2019. In the middle transitional/forest zone, where transmission is perennial with peaks in the rainy season, prevalence apparently reduced from 60% in the late 1990 s to about 5-20% by 2018. In the coastal savannah area, there was apparent reduction from 28 to 35% in 2003-2010 to 5-11% by 2018-2019. The burden of malaria infection in pregnancy continues to be highest among teenagers and younger-aged pregnant women and paucigravidae. CONCLUSIONS: There appears to be a decline in asymptomatic parasite prevalence in pregnancy in Ghana though this has not been uniform across the different transmission zones. The greatest declines were noticeably in urban settings. Submicroscopic parasitaemia remains a challenge for control efforts. Further studies are needed to evaluate the impact of the reduced parasite prevalence on maternal anaemia and low birthweight and to assess the local burden of submicroscopic parasitaemia in relation to pregnancy outcomes.

Natural Acquired Immunity to Malaria Antigens among Pregnant Women with Hemoglobin C Trait.

Hemoglobin C is the second most common structural hemoglobinopathy in Africa, and carriers have a reduced risk of severe malaria. However, the effect of HbAC on the antibody response to malaria antigens in pregnancy has not been studied. Here, we measured PfEMP1-specific antibodies in plasma samples from 74 Beninese pregnant women with either HbAA or HbAC. IgG-mediated inhibition of VAR2CSA+ infected erythrocytes adhesion to chondroitin sulfate A (CSA) was also tested. PfEMP1-specific IgG levels to VAR2CSA were significantly lower in HbAC women, suggesting less exposure to VAR2CSA. In contrast, the percentage of VAR2CSA+-infected erythrocytes adhesion to CSA was not different between HbAA and HbAC women. Moreover, IgG levels to PfEMP1 variants associated with severe malaria were not significantly different between groups. The findings indicate similar exposure to Plasmodium falciparum parasites expressing PfEMP1 variants causing severe malaria, and justify more comprehensive studies of hemoglobinopathy-related qualitative and quantitative differences in PfEMP1-specific antibody responses.

Retrospective study of toxoplasmosis prevalence in pregnant women in Benin and its relation with malaria.

BACKGROUND: Globally distributed with variable prevalence depending on geography, toxoplasmosis is a zoonosis caused by an obligate intracellular protozoan parasite, Toxoplasma gondii. This disease is usually benign but poses a risk for immunocompromised people and for newborns of mothers with a primary infection during pregnancy because of the risk of congenital toxoplasmosis (CT). CT can cause severe damage to fetuses-newborns. To our knowledge, no study has been conducted in sub-Saharan Africa on toxoplasmosis seroprevalence, seroconversion and CT in a large longitudinal cohort and furthermore, no observation has been made of potential relationships with malaria. METHODS: We performed a retrospective toxoplasmosis serological study using available samples from a large cohort of 1,037 pregnant women who were enrolled in a malaria follow-up during the 2008-2010 period in a rural area in Benin. We also used some existing data to investigate potential relationships between the maternal toxoplasmosis serological status and recorded malaria infections. RESULTS: Toxoplasmosis seroprevalence, seroconversion and CT rates were 52.6%, 3.4% and 0.2%, respectively, reflecting the population situation of toxoplasmosis, without targeted medical intervention. The education level influences the toxoplasmosis serological status of women, with women with little or no formal education have greater immunity than others. Surprisingly, toxoplasmosis seropositive pregnant women tended to present lower malaria infection during pregnancy (number) or at delivery (presence) and to have lower IgG levels to Plasmodium falciparum Apical Membrane Antigen 1, compared to toxoplasmosis seronegative women. CONCLUSIONS: The high toxoplasmosis seroprevalence indicates that prevention against this parasite remains important to deploy and must be accessible and understandable to and for all individuals (educated and non-educated). A potential protective role against malaria conferred by a preexisting toxoplasmosis infection needs to be explored more precisely to examine the environmental, parasitic and/or immune aspects.

Placental malaria caused by Plasmodium vivax or P. falciparum in Colombia: Histopathology and mediators in placental processes.

Knowledge about the relation of histopathological characteristics and mediators of physiological processes in the placenta malaria (PM) is poor, and that PM caused by Plasmodium vivax is almost null. The objective was to compare histopathological characteristics, cytokines and mediators of physiological processes in PM depending on the parasitic species, through a cross-sectional study in three groups: negative-PM, vivax-PM, falciparum-PM from Northwestern Colombia. The diagnosis of PM was made with thick blood smear, qPCR, and histopathology. Immuno-histochemical was made with EnVision system (Dako) and Zeiss Axio Imager M2 with light microscope. Cells in apoptosis were studied with the TUNEL technique. To measure the expression level of cytokines and mediators qRT-PCR was used. We included 179 placentas without PM and 87 with PM (53% P. vivax and 47% P. falciparum). At delivery, anemia was 25% in negative-PM, 60% in vivax-PM, and 44% in falciparum-PM group. The neonatal weight had an intense difference between groups with 3292±394g in negative-PM, 2,841±239 in vivax-PM, and 2,957±352 in falciparum-PM. The histopathological characteristics and CD+ cells in placenta with statistical differences (Dunn´s test) between negative-PM vs vivax-PM (P. falciparum was similar to P. vivax) were infarction, fibrinoid deposits, calcification, cells in apoptosis, immune infiltrates in decidua and intervillous space, CD4+, CD8+, CD14+, CD56+, CD68+. The expression levels of mediators in the placenta with statistical differences (Dunn´s test) between negative-PM vs vivax-PM (P. falciparum was similar to P. vivax) were Fas, FasL, HIF1α, Cox1, Cox2, VEGF, IL4, IL10, IFNγ, TNF, TGFß, FOXP3, and CTLA4. PM with P. falciparum and P. vivax, damages this organ and causes significant alteration of various physiological processes, which cause maternal anemia and a reduction in neonatal weight in degrees that are statistically and clinically significant. It is necessary that the search for plasmodial infection in pregnant and placenta goes from passive to active surveillance with adequate diagnostic capacity.

Molecular detection of Toxoplasma gondii in placentas of women who received therapy during gestation in a toxoplasmosis outbreak.

Toxoplasmosis is a disease caused by T. gondii, a protozoa which affects humans and animals and is widely distributed worldwide. In humans, there is great concern due to the serious consequences that can occur in the infection of pregnant women and the newborn. The early diagnosis of gestational toxoplasmosis is important for treatment to be carried out in order to prevent vertical transmission or reduce damage. The diagnosis can be made through the detection of antibodies in pregnant women or neonates and PCR of amniotic fluid. Previous studies have also reported PCR of the placenta as a good diagnostic test. Our study evaluated the detection of T. gondii DNA in placenta samples from parturients seen at the University Hospital of Santa Maria, Southern Brazil and treated during the pregnancy. We performed PCR in forty samples and five were positive, representing 12.5%. When correlating the treatment time and the detection of DNA in the placentas, no significant result was found. The prevalence of positive samples was lower than in other studies in the literature. The data reaffirm the importance of carrying out the analysis of the placenta.

The association between acute fatty liver disease and nitric oxide during malaria in pregnancy.

BACKGROUND: Liver disease is a common feature of malaria in pregnancy, but its pathogenesis remains unclear. METHODS: To understand the pathogenesis of liver disease during malaria in pregnancy, comparative proteomic analysis of the liver in a mouse model of malaria in pregnancy was performed. RESULTS: Decreased levels of mitochondrial and peroxisomal proteins were observed in the livers of pregnant mice infected with the lethal rodent malaria parasite Plasmodium berghei strain NK65. By contrast, increased levels of perilipin-2, amyloid A-1, and interferon (IFN)-γ signalling pathway-related proteins were observed in the livers of infected pregnant mice, suggesting that IFN-γ signalling may contribute to the development of liver disease during malaria in pregnancy. IFN-γ signalling is a potential trigger of inducible nitric oxide synthase (iNOS) expression. Liver disease associated with microvesicular fatty infiltration and elevated liver enzymes in pregnant wild-type mice infected with malaria parasites was improved by iNOS deficiency. CONCLUSIONS: In this study, a causative role of iNOS in liver disease associated with microvesicular fatty infiltration during malaria in pregnancy was demonstrated. These findings provide important insight for understanding the role of iNOS-mediated metabolic responses and the pathogenesis of high-risk liver diseases in pregnancy, such as acute fatty liver.

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

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

The Angiopoietin-Tie2 axis contributes to placental vascular disruption and adverse birth outcomes in malaria in pregnancy.

BACKGROUND: Malaria during pregnancy is a major contributor to the global burden of adverse birth outcomes including fetal growth restriction, preterm birth, and fetal loss. Recent evidence supports a role for angiogenic dysregulation and perturbations to placental vascular development in the pathobiology of malaria in pregnancy. The Angiopoietin-Tie2 axis is critical for placental vascularization and remodeling. We hypothesized that disruption of this pathway would contribute to malaria-induced adverse birth outcomes. METHODS: Using samples from a previously conducted prospective cohort study of pregnant women in Malawi, we measured circulating levels of angiopoietin-1 (Angpt-1) and Angpt-2 by Luminex (n=1392). We used a preclinical model of malaria in pregnancy (Plasmodium berghei ANKA [PbA] in pregnant BALB/c mice), genetic disruption of Angpt-1 (Angpt1+/- mice), and micro-CT analysis of placental vasculature to test the hypothesis that disruptions to the Angpt-Tie2 axis by malaria during pregnancy would result in aberrant placental vasculature and adverse birth outcomes. FINDINGS: Decreased circulating levels of Angpt-1 and an increased ratio of Angpt-2/Angpt-1 across pregnancy were associated with malaria in pregnancy. In the preclinical model, PbA infection recapitulated disruptions to the Angiopoietin-Tie2 axis resulting in reduced fetal growth and viability. Malaria decreased placental Angpt-1 and Tie2 expression and acted synergistically with reduced Angpt-1 in heterozygous dams (Angpt1+/-), to worsen birth outcomes by impeding vascular remodeling required for placental function. INTERPRETATION: Collectively, these data support a mechanistic role for the Angpt-Tie2 axis in malaria in pregnancy, including a potential protective role for Angpt-1 in mitigating infection-associated adverse birth outcomes. FUNDING: This work was supported by the Canadian Institutes of Health Research (CIHR), Canada Research Chair, and Toronto General Research Institute Postdoctoral Fellowship Award. The parent trial was supported by the European & Developing Countries Clinical Trials Partnership and the Malaria in Pregnancy Consortium, which was funded by the Bill & Melinda Gates Foundation. The funders had no role in design, analysis, or reporting of these studies.

Maternal nematode infection upregulates expression of Th2/Treg and diapedesis related genes in the neonatal brain.

Intestinal nematode infections common during pregnancy have recently been shown to have impacts that extend to their uninfected offspring including altered brain gene expression. If maternal immune signals reach the neonatal brain, they might alter neuroimmune development. We explored expression of genes associated with four distinct types of T cells (Th1, Th2, Th17, Treg) and with leukocyte transendothelial migration and endocytosis transport across the blood-brain barrier (BBB) in the postnatal brain of offspring of nematode-infected mice, through secondary analysis of a whole brain gene expression database. Th1/Th17 expression was lowered by maternal infection as evidenced by down-regulated expression of IL1ß, Th1 receptors and related proteins, and of IL22 and several Th17 genes associated with immunopathology. In contrast, Th2/Treg related pathways were upregulated as shown by higher expression of IL4 and TGF-ß family genes. Maternal infection also upregulated expression of pathways and integrin genes involved in transport of leukocytes in between endothelial cells but downregulated endosome vesicle formation related genes that are necessary for endocytosis of immunoglobulins across the BBB. Taken together, pup brain gene expression indicates that maternal nematode infection enhanced movement of leukocytes across the neonatal BBB and promoted a Th2/Treg environment that presumably minimizes the proinflammatory Th1 response in the pup brain.

Toxoplasma gondii GRA28 Is Required for Placenta-Specific Induction of the Regulatory Chemokine CCL22 in Human and Mouse.

Toxoplasma gondii is an intracellular protozoan pathogen of humans that can cross the placenta and result in adverse pregnancy outcomes and long-term birth defects. The mechanisms used by T. gondii to cross the placenta are unknown, but complex interactions with the host immune response are likely to play a role in dictating infection outcomes during pregnancy. Prior work showed that T. gondii infection dramatically and specifically increases the secretion of the immunomodulatory chemokine CCL22 in human placental cells during infection. Given the important role of this chemokine during pregnancy, we hypothesized that CCL22 induction was driven by a specific T. gondii-secreted effector. Using a combination of bioinformatics and molecular genetics, we have now identified T. gondii GRA28 as the gene product required for CCL22 induction. GRA28 is secreted into the host cell, where it localizes to the nucleus, and deletion of the GRA28 gene results in reduced CCL22 placental cells as well as a human monocyte cell line. The impact of GRA28 on CCL22 production is also conserved in mouse immune and placental cells both in vitro and in vivo. Moreover, parasites lacking GRA28 are impaired in their ability to disseminate throughout the animal, suggesting a link between CCL22 induction and the ability of the parasite to cause disease. Overall, these data demonstrate a clear function for GRA28 in altering the immunomodulatory landscape during infection of both placental and peripheral immune cells and show a clear impact of this immunomodulation on infection outcome. IMPORTANCE Toxoplasma gondii is a globally ubiquitous pathogen that can cause severe disease in HIV/AIDS patients and can also cross the placenta and infect the developing fetus. We have found that placental and immune cells infected with T. gondii secrete significant amounts of a chemokine (called CCL22) that is critical for immune tolerance during pregnancy. In order to better understand whether this is a response by the host or a process that is driven by the parasite, we have identified a T. gondii gene that is absolutely required to induce CCL22 production in human cells, indicating that CCL22 production is a process driven almost entirely by the parasite rather than the host. Consistent with its role in immune tolerance, we also found that T. gondii parasites lacking this gene are less able to proliferate and disseminate throughout the host. Taken together, these data illustrate a direct relationship between CCL22 levels in the infected host and a key parasite effector and provide an interesting example of how T. gondii can directly modulate host signaling pathways in order to facilitate its growth and dissemination.

Risk factors for Plasmodium falciparum infection in pregnant women in Burkina Faso: a community-based cross-sectional survey.

BACKGROUND: Malaria in pregnancy remains a public health problem in sub-Saharan Africa. Identifying risk factors for malaria in pregnancy could assist in developing interventions to reduce the risk of malaria in Burkina Faso and other countries in the region. METHODS: Two cross-sectional surveys were carried out to measure Plasmodium falciparum infection using microscopy in pregnant women in Saponé Health District, central Burkina Faso. Data were collected on individual, household and environmental variables and their association with P. falciparum infection assessed using multivariable analysis. RESULTS: A total of 356 pregnant women were enrolled in the surveys, 174 during the dry season and 182 during the wet season. The mean number of doses of sulfadoxine-pyrimethamine for Intermittent Preventive Treatment in pregnancy (IPTp-SP) was 0.4 doses during the first trimester, 1.1 doses at the second and 2.3 doses at the third. Overall prevalence of P. falciparum infection by microscopy was 15.7%; 17.8% in the dry season and 13.7% in the wet season. 88.2% of pregnant women reported sleeping under an insecticide-treated net (ITN) on the previous night. The odds of P. falciparum infection was 65% lower in women who reported using an ITN compared to those that did not use an ITN (Odds ratio, OR = 0.35, 95% CI 0.14-0.86, p = 0.02). IPTp-SP was also associated with reduced P. falciparum infection, with each additional dose of IPTp-SP reducing the odds of infection by 44% (OR = 0.56, 95% CI 0.39-0.79, p = 0.001). Literate women had a 2.54 times higher odds of P. falciparum infection compared to illiterate women (95% CI 1.31-4.91, p = 0.006). CONCLUSIONS: The prevalence of P. falciparum infection among pregnant women remains high in Burkina Faso, although use of IPTp-SP and ITNs were found to reduce the odds of infection. Despite this, compliance with IPTp-SP remains far from that recommended by the National Malaria Control Programme and World Health Organization. Behaviour change communication should be strengthened to encourage compliance with protective malaria control tools during pregnancy.

Effector Vγ9Vδ2 T cell response to congenital Toxoplasma gondii infection.

A major γδ T cell population in human adult blood are the Vγ9Vδ2 T cells that are activated and expanded in a TCR-dependent manner by microbe-derived and endogenously derived phosphorylated prenyl metabolites (phosphoantigens). Vγ9Vδ2 T cells are also abundant in human fetal peripheral blood, but compared with their adult counterparts they have a distinct developmental origin, are hyporesponsive toward in vitro phosphoantigen exposure, and do not possess a cytotoxic effector phenotype. In order to obtain insight into the role of Vγ9Vδ2 T cells in the human fetus, we investigated their response to in utero infection with the phosphoantigen-producing parasite Toxoplasma gondii (T. gondii). Vγ9Vδ2 T cells expanded strongly when faced with congenital T. gondii infection, which was associated with differentiation toward potent cytotoxic effector cells. The Vγ9Vδ2 T cell expansion in utero resulted in a fetal footprint with public germline-encoded clonotypes in the Vγ9Vδ2 TCR repertoire 2 months after birth. Overall, our data indicate that the human fetus, from early gestation onward, possesses public Vγ9Vδ2 T cells that acquire effector functions following parasite infections.

Seroprevalence and associated risk factors of Toxoplasma gondii infection among pregnant mother in Makassar, Indonesia.

The protozoan parasite, Toxoplasma gondii is estimated to infect one-third of the world's population. Infection in pregnant women can cause severe conditions for their babies. Until now, there is no data regarding Toxoplasma infection from Makassar pregnant mothers. This study aims to obtain information on Toxoplasma specific antibodies and to measure the risk factor associate with parasite infection. This cross-sectional study conducted in 9 of 47 primary health centres (Puskesmas) in Makassar. Blood samples and questionnaires were collected from 184 pregnant women aged 15-42 years old from September to October 2020. ELISA technique was used to examine the IgG and IgM antibodies. Univariable and multivariable analyses were carried out to measure factors that independently associate with Toxoplasma antibody positivity. Our result showed the range of Toxoplasma IgM and IgG are 0.06-1.01 and 0.09-3.01, respectively. While no one of our participants has an acute Toxoplasma gondii infection (IgM positive), we found 32,6% pregnant mothers are exposed to parasite (positive IgG). Contact with cats [OR(95%CI): 10.45(3.77-28.99)], consume chicken satay [OR(95%CI): 9.72(3.71-25.48)] and consume un-boiled water/ filtered water [OR(95%CI): 5.98(1.77-20.23)] are independently associate with positive Toxoplasma IgG antibody. Based on the result, we conclude that pregnant women in Makassar are exposed to T. gondii and the oocyst and tissue cyst of parasite contaminates food and water in Makassar.

Detection and genetic characterisation of Toxoplasma gondii circulating in free-range chickens, pigs and seropositive pregnant women in Benue state, Nigeria.

Toxoplasma gondii parasites present strong but geographically varied signatures of population structure. Populations sampled from Europe and North America have commonly been defined by over-representation of a small number of clonal types, in contrast to greater diversity in South America. The occurrence and extent of genetic diversity in African T. gondii populations remains understudied, undermining assessments of risk and transmission. The present study was designed to establish the occurrence, genotype and phylogeny of T. gondii in meat samples collected from livestock produced for human consumption (free-range chickens, n = 173; pigs, n = 211), comparing with T. gondii detected in blood samples collected from seropositive pregnant women (n = 91) in Benue state, Nigeria. The presence of T. gondii DNA was determined using a published nested polymerase chain reaction, targeting the 529 bp multicopy gene element. Samples with the highest parasite load (assessed using quantitative PCR) were selected for PCR-restriction fragment length polymorphism (PCR-RFLP) targeting the surface antigen 3 (SAG3), SAG2 (5' and 3'), beta-tubulin (BTUB) and dense granule protein 6 (GRA6) loci, and the apicoplast genome (Apico). Toxoplasma gondii DNA was detected in all three of the populations sampled, presenting 30.6, 31.3 and 25.3% occurrence in free-range chickens, pigs and seropositive pregnant women, respectively. Quantitative-PCR indicated low parasite occurrence in most positive samples, limiting some further molecular analyses. PCR-RFLP results suggested that T. gondii circulating in the sampled populations presented with a type II genetic background, although all included a hybrid type I/II or II/III haplotype. Concatenation of aligned RFLP amplicon sequences revealed limited diversity with nine haplotypes and little indication of host species-specific or spatially distributed sub-populations. Samples collected from humans shared haplotypes with free-range chickens and/or pigs. Africa remains under-explored for T. gondii genetic diversity and this study provides the first detailed definition of haplotypes circulating in human and animal populations in Nigeria.

Asymptomatic malaria and anaemia among pregnant women during high and low malaria transmission seasons in Burkina Faso: household-based cross-sectional surveys in Burkina Faso, 2013 and 2017.

BACKGROUND: Malaria in endemic countries is often asymptomatic during pregnancy, but it has substantial consequences for both the mother and her unborn baby. During pregnancy, anaemia is an important consequence of malaria infection. In Burkina Faso, the intensity of malaria varies according to the season, albeit the prevalence of malaria and anaemia as well as their risk factors, during high and low malaria transmission seasons is underexplored at the household level. METHODS: Data of 1751 pregnant women from October 2013 to March 2014 and 1931 pregnant women from April 2017 to June 2017 were drawn from two cross-sectional household surveys conducted in 24 health districts of Burkina Faso. Pregnant women were tested for malaria in their household after consenting. Asymptomatic carriage was defined as a positive result from malaria rapid diagnostic tests in the absence of clinical symptoms of malaria. Anaemia was defined as haemoglobin level less than 11 g/dL in the first and third trimester and less than 10.5 g/dL in the second trimester of pregnancy. RESULTS: Prevalence of asymptomatic malaria in pregnancy was estimated at 23.9% (95% CI 20.2-28.0) during the high transmission season (October-November) in 2013. During the low transmission season, it was 12.7% (95% CI 10.9-14.7) between December and March in 2013-2014 and halved (6.4%; 95% CI 5.3-7.6) between April and June 2017. Anaemia prevalence was estimated at 59.4% (95% CI 54.8-63.8) during the high transmission season in 2013. During the low transmission season, it was 50.6% (95% CI 47.7-53.4) between December and March 2013-2014 and 65.0% (95% CI 62.8-67.2) between April and June, 2017. CONCLUSION: This study revealed that the prevalence of malaria asymptomatic carriage and anaemia among pregnant women at the community level remain high throughout the year. Thus, more efforts are needed to increase prevention measures such as IPTp-SP coverage in order to reduce anaemia and contribute to preventing low birth weight and poor pregnancy outcomes.