Past Placental Malaria Research Articles

Placental Malaria and Its Relationship with Neonatal Birth Weight among Primigravidae: An Analytical Cross-sectional Study.

Malaria can be fatal during pregnancy, posing a serious risk to both mothers and fetuses, especially in sub-Saharan Africa. Primigravidae are particularly susceptible to placental malaria in areas with high rates of transmission due to insufficient immunity. This study aimed to determine the prevalence of placental malaria infection, risk factors, types of Plasmodium causing malaria during pregnancy, and its relationship with neonatal birth weight among primigravidae. This was an analytical cross-sectional study involving 357 primigravidae who delivered at Abubakar Tafawa Balewa University Teaching Hospital, Bauchi, Nigeria. Placental blocks were taken from the pericentric area of the maternal surface of the placenta, and the birth weights of the neonates were recorded. The samples were fixed in 10% neutral-buffered formalin, and histopathological analysis was performed. The primary outcome measure was to determine the relationship between placental malaria and neonatal birth weight. Demographics and outcomes were analyzed using standard statistical tests. Multivariable regression models accounting for potential confounders were created for the primary and secondary outcomes with adjusted odds ratios as the measures of effect. The prevalence of placental malaria was 38.4%. Among the participants with positive placenta malaria parasitemia, 49.6%, 36.5%, and 13.9% had chronic, acute, and past placental malaria infections, respectively. Only Plasmodium falciparum was found in the placenta. According to the bivariate analysis, unbooked status (p = 0.001), non-use of intermittent preventive therapy for malaria (p < 0.001), and village dwelling (p = 0.020) were significantly associated with placental malaria. However, on multivariable logistic regression, only non-uptake of intermittent preventive therapy for malaria was independently associated with placental malaria (adjusted odds ratio, 2.2, 95% confidence interval: 1.20, 4.1, p = 0.011). There was a significant difference in the mean birth weight between those with placental malaria and those without placental malaria (2.8 ± 0.5 kg vs. 3.2 ± 0.4 kg, p = 0.001). Additionally, placental malaria was significantly associated with low birth weight among the primigravidae (p < 0.001). In Nigeria, there is a strong correlation between low birth weight and placental malaria in Primidravidae. Placental malaria was found to be independently correlated with non-uptake of intermittent preventive therapy for malaria.

Associations between prenatal malaria exposure, maternal antibodies at birth, and malaria susceptibility during the first year of life in Burkina Faso.

In this study, we investigated how different categories of prenatal malaria exposure (PME) influence levels of maternal antibodies in cord blood samples and the subsequent risk of malaria in early childhood in a birth cohort study (N = 661) nested within the COSMIC clinical trial (NCT01941264) in Burkina Faso. Plasmodium falciparum infections during pregnancy and infants' clinical malaria episodes detected during the first year of life were recorded. The levels of maternal IgG and IgG1-4 to 15 P. falciparum antigens were measured in cord blood by quantitative suspension array technology. Results showed a significant variation in the magnitude of maternal antibody levels in cord blood, depending on the PME category, with past placental malaria (PM) more frequently associated with significant increases of IgG and/or subclass levels across three groups of antigens defined as pre-erythrocytic, erythrocytic, and markers of PM, as compared to those from the cord of non-exposed control infants. High levels of antibodies to certain erythrocytic antigens (i.e., IgG to EBA140 and EBA175, IgG1 to EBA175 and MSP142, and IgG3 to EBA140 and MSP5) were independent predictors of protection from clinical malaria during the first year of life. By contrast, high levels of IgG, IgG1, and IgG2 to the VAR2CSA DBL1-2 and IgG4 to DBL3-4 were significantly associated with an increased risk of clinical malaria. These findings indicate that PME categories have different effects on the levels of maternal-derived antibodies to malaria antigens in children at birth, and this might drive heterogeneity to clinical malaria susceptibility in early childhood.

Age-modified factors associated with placental malaria in rural Burkina Faso

BackgroundMalaria in pregnancy can result in placental infection with fetal implications. This study aimed at assessing placental malaria (PM) prevalence and its associated factors in a cohort of pregnant women with peripheral malaria and their offspring.MethodThe data were collected in the framework of a clinical trial on treatments for malaria in pregnant women . Placental malaria (PM) was diagnosed by histopathological detection of parasites and/or malaria pigment on placenta biopsies taken at delivery. Factors associated with PM were assessed using logistic regression.ResultsOut of 745 biopsies examined, PM was diagnosed in 86.8 % of women. Acute, chronic and past PM were retrieved in 11 (1.5 %), 170 (22.8 %), and 466 (62.6 %) women, respectively. A modifying effect was observed in the association of gravidity or anemia at the study start with pooled PM (presence of parasites and/or malaria pigment). In women under 30, gravidity ≤ 2 was associated with an increased prevalence of pooled PM but in women aged 30 years or more, gravidity was no more associated with pooled PM (OR 6.81, 95 % CI 3.18 – 14.60; and OR 0.52, 95 % CI 0.10 – 2.76, respectively). Anemia was associated with pooled PM in women under 30 (OR 1.96, 95 % CI 1.03 – 3.72) but not in women aged 30 years or more (OR 0.68, 95 % CI 0.31 – 1.49). Similarly, the association of gravidity with past-chronic PM depended also on age. A higher prevalence of active PM was observed in women under 30 presenting with symptomatic malaria (OR 3.79, 95 % CI 1.55 – 9.27), while there was no significant increase in the prevalence of active PM (presence of parasites only) in women with symptomatic malaria when aged 30 years or more (OR 0.42, 95 % CI 0.10 – 1.75). In women with chronic PM, the prevalence of low birth weight or prematurity was the highest (31.2 %) as compared with past PM or no PM.ConclusionDespite the rapid diagnosis and efficacious treatment of peripheral infection, the prevalence of placental malaria remained high in women with P. falciparum peripheral infection in Nanoro, especially in younger women This underlines the importance of preventive measures in this specific group.

Histopathological lesions and exposure to Plasmodium falciparum infections in the placenta increases the risk of preeclampsia among pregnant women

Preeclampsia (PE) is a placental disorder with different phenotypic presentations. In malaria-endemic regions, high incidence of PE is reported, with debilitating foeto-maternal effects, particularly among primigravid women. However, the relationship between placental pathology and Plasmodium falciparum infection in the placenta with PE is underexplored. Placentas from 134 pregnant women were examined after delivery for pathological lesions and placental malaria (PM). They comprised of 69 women without PE (non-PE group) and 65 women diagnosed with PE (PE group). The presence of placental pathology increased the risk of PE, with particular reference to syncytial knots. Placental malaria was 64 (48.1%) and 21 (15.8%) respectively for active and past infections and these proportions were significantly higher in the PE group compared to the non-PE group. Further multivariate analyses showed placental pathology (adjusted (aOR) 3.0, 95% CI = 1.2–7.5), active PM (aOR 6.7, 95% CI = 2.3–19.1), past PM (aOR 12.4, 95% CI = 3.0–51.0) and primigravidity (aOR 6.6, 95% CI 2.4–18.2) to be associated with PE. Our findings suggest that placental histological changes and PM are independent risk factors for PE particularly in primigravida. These findings might improve the management of PE in malaria-endemic regions.

Modulation of innate immune responses at birth by prenatal malaria exposure and association with malaria risk during the first year of life

BackgroundFactors driving inter-individual differences in immune responses upon different types of prenatal malaria exposure (PME) and subsequent risk of malaria in infancy remain poorly understood. In this study, we examined the impact of four types of PME (i.e., maternal peripheral infection and placental acute, chronic, and past infections) on both spontaneous and toll-like receptors (TLRs)-mediated cytokine production in cord blood and how these innate immune responses modulate the risk of malaria during the first year of life.MethodsWe conducted a birth cohort study of 313 mother-child pairs nested within the COSMIC clinical trial (NCT01941264), which was assessing malaria preventive interventions during pregnancy in Burkina Faso. Malaria infections during pregnancy and infants’ clinical malaria episodes detected during the first year of life were recorded. Supernatant concentrations of 30 cytokines, chemokines, and growth factors induced by stimulation of cord blood with agonists of TLRs 3, 7/8, and 9 were measured by quantitative suspension array technology. Crude concentrations and ratios of TLR-mediated cytokine responses relative to background control were analyzed.ResultsSpontaneous production of innate immune biomarkers was significantly reduced in cord blood of infants exposed to malaria, with variation among PME groups, as compared to those from the non-exposed control group. However, following TLR7/8 stimulation, which showed higher induction of cytokines/chemokines/growth factors than TLRs 3 and 9, cord blood cells of infants with evidence of past placental malaria were hyper-responsive in comparison to those of infants not-exposed. In addition, certain biomarkers, which levels were significantly modified depending on the PME category, were independent predictors of either malaria risk (GM-CSF TLR7/8 crude) or protection (IL-12 TLR7/8 ratio and IP-10 TLR3 crude, IL-1RA TLR7/8 ratio) during the first year of life.ConclusionsThese findings indicate that past placental malaria has a profound effect on fetal immune system and that the differential alterations of innate immune responses by PME categories might drive heterogeneity between individuals to clinical malaria susceptibility during the first year of life.

High titres of immunoglobulin g class 1 antibodies to duffy binding-like (DBL) 5 during the third trimester of pregnancy are associated with past placental malaria at delivery in an area of high seasonal transmission in Burkina Faso.

Objective: In malaria endemic area, women acquire throughout successive pregnancies, increasing protection against Plasmodium falciparum malaria infections by having increased levels of antibodies to the Variant 2 Cell Surface antigen- Chondroitin Sulphate A. Primigravidae are more susceptible to placental malaria due to the lack of these specific antibodies to placental malaria-antigens. However, it is currently difficult to diagnose placental malaria by a noninvasive method prior to delivery. The objective of this study was to assess whether VAR2CSA specific antibody levels from peripheral blood obtained during the third trimester of pregnancy, could predict placental infection at delivery. Methods: A total of 263 pregnant women participating to the COSMIC study (NCT01941264) were included in this study. Peripheral blood samples were collected at the third antenatal care visit performed during the third trimester of pregnancy. Placental infec-tions were determined by histology. Antibody levels (total IgG, IgG1 and IgG3) to VAR2CSA subdomains DBL5 and ID1-ID2a in serum samples were quantified using En-zyme Linked ImmunoSorbent Assay. Results: Placental malaria was estimated at 54.9% among pregnant women enrolled in the study. More than half of the study population had a past placental infection. Among factors investigated, in univariate analyses ITN use, gravidity, season of delivery, number of IPTp-SP doses, gestational age and peripheral malaria status at the 3rd ANC visit significantly affected DBL5 and ID1ID2a specific antibody titres. In multivariate analyses, ITN use (OR=5.17, 95% CI: (1.36 - 19.61), p = 0.016) was associated with the risk of placental malaria at delivery, while older women were at lower risk (OR = 0.45, 95% CI: (0.23-0.88), p=0.021). Importantly, higher levels of IgG1 anti-DBL5 at the 3rd trimester (OR=11.96, 95% CI: (3.69-38.77), p<0.001) were significantly associated with placental malaria. Conclusions: Findings of this study indicate that high levels of DBL5 IgG1 at the third tri-mester of pregnancy could predict placental malaria, which was mostly past infections in our study population. The assessment of this exposition marker during pregnancy could alterna-tively be used as an optional biomarker for PM diagnosis.

Placental malaria and neonatal anti-tetanus antibody status: any association?

Background. Neonatal tetanus(NT) has remained an important cause of neonatal morbidity and mortality in the tropics where high prevalence of placental malaria coexists. The current strategy for the control of NT involves stimulating production of protective level of anti-tetanus antibody in the mother, through tetanus toxoid immunization, and transferring same through the placental to the foetus. Placental malaria is known to alter the morphology and functions of the placenta, but the effect on transfer of anti-tetanus antibody specifically, remains unsettled. We studied the influence of placental malaria on transplacental transfer of anti-tetanus antibodies among mother-infant pairs at the University of Maiduguri Teaching Hospital North-Eastern Nigeria. Method. Maternal and cord blood samples were collected from 162 mother-baby pair and analysed for anti-tetanus antibody levels using ELISA. Placental biopsy was also taken from each mother-baby pair and placental malaria diagnosed histologically. Results. One hundred and sixteen (71.6%) of the 162 mother-infant pairs were positive for placental malaria out of which 59(50.9%) had chronic-active, 44 (37.9%) acute and 13 (11.2%) had past placental malaria. Forty-one (25.3%) babies were classified as seronegative for tetanus antibodies of whom 32 were delivered to mothers who were positive for placental malaria. Fifty-six (34.5%) mother-infant pairs had poor placental transfer for tetanus antibodies as signified by cord-maternal ratio of Conclusion. Placental malaria has remained a very common medical condition in Maiduguri among pregnant women and may partly account for the high level of neonatal tetanus prevalent in the area.

ABO blood group system and placental malaria in an area of unstable malaria transmission in eastern Sudan

BackgroundUnderstanding the pathogenesis of malaria in pregnancy and its consequences for both the mother and the baby is fundamental for improving malaria control in pregnant women.AimThe study aimed to investigate the role of ABO blood groups on pregnancy outcomes in an area of unstable malaria transmission in eastern Sudan.MethodsA total of 293 women delivering in New Half teaching hospital, eastern Sudan during the period October 2006–March 2007 have been analyzed. ABO blood groups were determined and placental histopathology examinations for malaria were performed. Birth and placental weight were recorded and maternal haemoglobin was measured.Results114 (39.7%), 61 (22.1%) and 118 (38.2%) women were primiparae, secundiparae and multiparae, respectively. The ABO blood group distribution was 82(A), 59 (B), 24 (AB) and 128 (O). Placental histopathology showed acute placental malaria infections in 6 (2%), chronic infections in 6 (2%), 82 (28.0%) of the placentae showed past infection and 199 (68.0%) showed no infection. There was no association between the age (OR = 1.02, 95% CI = 0.45–2.2; P = 0.9), parity (OR = 0.6, 95% CI = 0.3–1.2; P = 0.1) and placental malaria infections. In all parity blood group O was associated with a higher risk of past (OR = 1.9, 95% CI = 1.1–3.2; P = 0.01) placental malaria infection. This was also true when primiparae were considered separately (OR = 2.6, 95% CI = 1.05–6.5, P = 0.03).Among women with all placental infections/past placental infection, the mean haemoglobin was higher in women with the blood group O, but the mean birth weight, foeto-placental weight ratio was not different between these groups and the non-O group.ConclusionThese results indicate that women of eastern Sudan are at risk for placental malaria infection irrespective to their age or parity. Those women with blood group O were at higher risk of past placental malaria infection.

Maternal HIV Infection and Placental Malaria Reduce Transplacental Antibody Transfer and Tetanus Antibody Levels in Newborns in Kenya

In clinical trials, maternal tetanus toxoid (TT) vaccination is effective in protecting newborns against tetanus infection, but inadequate placental transfer of tetanus antibodies may contribute to lower-than-expected rates of protection in routine practice. We studied the effect of placental malaria and maternal human immunodeficiency virus (HIV) infection on placental transfer of antibodies to tetanus. A total of 704 maternal-cord paired serum samples were tested by ELISA for antibodies to tetanus. The HIV status of all women was determined by an immunoglobulin G antibody-capture particle-adherence test, and placental malaria was determined by placental biopsy. Maternal history of TT vaccination was recorded. Tetanus antibody levels were reduced by 52% (95% confidence interval [CI], 30%-67%) in newborns of HIV-infected women and by 48% (95% CI, 26%-62%) in newborns whose mothers had active-chronic or past placental malaria. Thirty-seven mothers (5.3%) and 55 newborns (7.8%) had tetanus antibody levels <0.1 IU/mL (i.e., were seronegative). Mothers' self-reported history of lack of tetanus immunization was the strongest predictor of seronegativity and of tetanus antibody levels in maternal and cord serum. Malarial and HIV infections may hinder efforts to eliminate maternal and neonatal tetanus, making implementation of the current policy for mass vaccination of women of childbearing age an urgent priority.

The association of anti-phospholipid antibodies with parity in placental malaria

Anti-phospholipid antibodies (aPL) are autoantibodies associated with both infections and the pathogenesis of certain pregnancy complications. In the latter, but not the former, aPL are dependent on a co-factor, beta(2) glycoprotein I (beta2GPI), which can also be used as an antigen for detection of such aPL in pregnancy. A cross-sectional study was carried out on serum samples from Kumasi, Ghana, to determine the occurrence and beta2GPI-dependence of aPL in placental malaria. Anti-cardiolipin, anti-phosphatidylserine and anti-beta2GPI enzyme-linked immunosorbent assays (ELISAs) were performed on sera from 103 HIV-non-infected gravid women. Placental malaria, both active and past infection, was diagnosed in 33/103 (32%) based on placental histology. In multiparae, beta2GPI-independent IgM antibodies to cardiolipin (P = 0.018) and phosphatidylserine (P = 0.009) were observed, which were most pronounced in past placental malaria infection. In primiparae, no association emerged between aPL and placental malaria. Trends for improved clinical parameters were identified in infected women with levels of anti-cardiolipin beyond the 99th multiple of the median for a healthy, non-malarious population. This study in placental malaria reports parity associations of beta2GPI-independent aPL profiles, and does not support a role for beta2GPI-dependent aPL. It is of significance in the context of the known parity differences in pregnancy malaria immunity.

Malaria in pregnancy: adverse effects on haemoglobin levels and birthweight in primigravidae and multigravidae.

In areas of endemic transmission, malaria in pregnancy is associated with severe maternal anaemia and low birthweight babies. The prevalence of infection is highest in primigravidae (PG), and hence control efforts are usually geared towards this high risk group. Using a sensitive measure of placental infection, we investigated the relationship between active-acute, active-chronic and past placental infection with maternal anaemia and low birthweight in women of all gravidities. Between January 1996 and July 1997, 912 women delivering in Kilifi District Hospital, Kenya, were recruited. Haemoglobin and peripheral malaria slides were taken prior to delivery, placental biopsies and smears were taken at the time of delivery and birthweight and maternal height and weight were measured soon after birth. Information was obtained on socio-economic and educational status. The association between placental malaria, severe anaemia and low birthweight was investigated for women of different gravidities. By placental histology, the prevalence of active or past malaria in all gravidities was high, ranging from 64% in PG to 30% in gravidities 5 and above. In gravidities 1-4, active malaria infection was associated with severe maternal anaemia, adjusted OR 2.21 (95% CI 1.36, 3.61). There was a significant interaction between chronic or past malaria and severe anaemia in their effects on birthweight, whereby the risk of low birthweight was very high in women with both chronic or past placental malaria and severe anaemia: OR 4.53 (1.19, 17.2) in PG; 13.5 (4.57, 40) in gravidities 2-4. In this area of moderate malaria transmission, women of all parities have substantially increased risk of low birthweight and severe anaemia as a result of malaria infection in pregnancy. The risk of low birthweight is likely to be particularly high in areas with a high prevalence of severe anaemia.