Effects of Pregnancy-associated Malaria on T Cell Cytokines in Cameroonian Women.

Although Th17 cells subsets improve immunity against extra and intracellular pathogens, and in modulating Th1 and other immune responses, its role on pregnancy-associated malaria (PAM) is unknown. This study aims to investigate the effects of PAM on Th1 (IFN-γ, TNF-α), IL-10 family (IL-10, IL-19, IL-22), Th17 (IL-17A, IL-23) cytokines and on CXCL-10 chemokine profiles in pregnant women. Between 2010 and 2011, venous blood specimens from 107 volunteer pregnant Cameroonian women was used to determine parasitaemia microscopically and haemoglobin levels using HemoCue analyzer. Plasma levels of the biomarkers were determined by ELISA. Parasitaemia was higher in women with low haemoglobin levels, parity and mother's age. IL-10 and CXCL-10 plasma levels were higher in the malaria infected and in anaemic women while IFN-γ and IL-17A levels were higher in malaria non-infected and in non-anaemic women. Parasitaemia correlated positively with IL-10 and CXCL-10 levels but inversely with IFN-γ and IL-17A. Haemoglobin levels were higher in women with low IL-10 and CXCL-10 levels, and in group with high IFN-γ, IL-17A and IL-23 levels. Only IL-10 levels associated negatively with parity. Positive correlations were observed between Th17 (IL-17A) and Th1 (IFN-γ, TNF-α), IL-10 family (IL-19 and IL-22) and Th17 (IL-23) cytokines. Multivariate analysis showed association between: mother's age and IFN-γ levels, parasitaemia and IL-10 and CXCL-10 levels and haemoglobin levels, gestational age and IL-17A levels. In conclusion, during PAM, CXCL-10 and IL-10 responses are implicated in the pathogenesis while Th17 and Th1 immune responses, via IL-17A and IFN-γ might play protective roles.

Gravidity-dependent production of antibodies that inhibit binding of Plasmodium falciparum-infected erythrocytes to placental chondroitin sulfate proteoglycan during pregnancy.

During pregnancy, Plasmodium falciparum-infected erythrocytes sequester in the placenta by adhering to chondroitin 4-sulfate, creating a risk factor for both the mother and the fetus. The primigravidae are at higher risk for placental malaria than the multigravidae. This difference in susceptibility has been attributed to the lack of antibodies that block the adhesion of infected erythrocytes to placental chondroitin 4-sulfate in primigravid women. However, recent results show that many primigravidae at term have antibody levels similar to those of multigravidae, and thus the significance of antiadhesion antibodies in providing protection against malaria during pregnancy remains unclear. In this study, we analyzed plasma samples from women of various gravidities at different gestational stages for antiadhesion antibodies. The majority of women, regardless of gravidity, had similar levels of antibodies at term. Most primigravidae had low levels of or no antiadhesion antibodies prior to ~20 weeks of pregnancy and then produced antibodies. Multigravidae also lacked antibodies until ~12 weeks of pregnancy, but thereafter they efficiently produced antibodies. In pregnant women who had placental infection at term, higher levels of antiadhesion antibodies correlated with lower levels of placental parasitemia. The difference in kinetics of antibody production between primigravidae and multigravidae correlated with the prevalence of malaria in these groups, suggesting that antibodies are produced during pregnancy in response to placental infection. The early onset of efficient antibody response in multigravidae and the delayed production to antibodies in primigravidae appear to account for the gravidity-dependent differential susceptibilities of pregnant women to placental malaria.

Acquisition and decay of antibodies to pregnancy-associated variant antigens on the surface of Plasmodium falciparum-infected erythrocytes that protect against placental parasitemia.

Otherwise clinically immune women in areas endemic for malaria are highly susceptible to Plasmodium falciparum malaria during their first pregnancy. Pregnancy-associated malaria (PAM) is characterized by placental accumulation of infected erythrocytes that adhere to chondroitin sulfate A (CSA). Susceptibility to PAM decreases with increasing parity, apparently due to acquisition of antibodies directed against the variant surface antigens (VSAs) that mediate the adhesion to CSA (VSA(CSA)). This study found that levels of VSA(CSA)-specific antibodies depend on endemicity, that anti-VSA(CSA) IgG is acquired during gestation week 20, and that plasma levels of the antibodies decline during the postpartum period. There is evidence that VSA(CSA)-specific antibodies are linked to placental infection and that high antibody levels contribute to the control of placental infection by inhibiting parasite adhesion to CSA. Data suggest that VSA(CSA) is a target for vaccination against PAM.

The epidemiology of Plasmodium falciparum malaria in two Cameroonian villages: Simbok and Etoa.

In support of ongoing immunologic studies on immunity to Plasmodium falciparum, demographic, entomologic, parasitologic, and clinical studies were conducted in two Cameroonian villages located 3 km apart. Simbok (population = 907) has pools of water present year round that provide breeding sites for Anopheles gambiae, whereas Etoa (population = 485) has swampy areas that dry up annually in which A. funestus breed. Results showed that individuals in Simbok receive an estimated 1.9 and 1.2 infectious bites per night in the wet and dry season, respectively, whereas individuals in Etoa receive 2.4 and 0.4 infectious bites per night, respectively. Although transmission patterns differ, the rate of acquisition of immunity to malaria appears to be similar in both villages. A prevalence of 50-75% was found in children < 10 years old, variable levels in children 11-15 years old, and 31% in adults. Thus, as reported in other parts of Africa, individuals exposed to continuous transmission of P. falciparum slowly acquired significant, but not complete, immunity.

Detection of the Plasmodium falciparum antigen histidine-rich protein 2 in blood of pregnant women: implications for diagnosing placental malaria.

Pregnant women have an increased susceptibility to infection by Plasmodium falciparum. Parasites may be present in the placenta yet not detectable in peripheral blood smears by routine light microscopy. In order to determine how frequently misdiagnosis occurs, peripheral blood and placental samples were collected from 1,077 Cameroonian women at the time of giving birth and examined for the presence of malarial parasites by using light microscopy. Results showed that 20.1% of the women who had placental malaria were peripheral blood smear negative. Thus, malarial infection was not detected by microscopic examination of peripheral blood smears from approximately one out of five malaria-infected women. Since P. falciparum parasites secrete histidine-rich protein 2 (HRP-2), we sought to determine if detecting HRP-2 in either peripheral plasma or whole blood might be used to diagnose the presence of parasites "hidden" in the placenta. Samples of peripheral plasma from 127 women with different levels of placental malarial infection were assayed by HRP-2-specific enzyme-linked immunosorbent assay. HRP-2 was detected in 88% of the women with placental malaria who tested negative by blood smear. Additionally, whole blood was obtained from 181 women and tested for HRP-2 with a rapid, chromatographic strip test (ICT). The ICT test accurately detected malarial infection in 89.1% of P. falciparum-infected women. Furthermore, 94% of women with malaria were accurately diagnosed by using a combination of microscopy and the ICT test. Thus, detection of HRP-2 in conjunction with microscopy should improve diagnosis of malaria in pregnant women.