Pregnancy triggers immunological changes aimed to tolerate the fetus, but its impact on B lymphocytes is poorly understood. In addition, exposure to the Plasmodium parasite is associated with altered distribution of peripheral memory B cell (MBC) subsets. To study the combined impact of high malaria exposure and pregnancy in B cell subpopulations, we analyzed PBMCs from pregnant and nonpregnant individuals from a malaria-nonendemic country (Spain) and from a high malaria-endemic country (Papua New Guinea). In the malaria-naive cohorts, pregnancy was associated with a significant expansion of all switched (IgD−) MBC and a decrease of naive B cells. Malaria-exposed women had more atypical MBC and fewer marginal zone–like MBC, and their levels correlated with both Plasmodium vivax– and Plasmodium falciparum–specific plasma IgG levels. Classical but not atypical MBC were increased in P. falciparum infections. Moreover, active atypical MBC positively correlated with proinflammatory cytokine plasma concentrations and had lower surface IgG levels than the average. Decreased plasma eotaxin (CCL11) levels were associated with pregnancy and malaria exposure and also correlated with B cell subset frequencies. Additionally, active atypical and active classical MBC expressed higher levels of eotaxin receptor CCR3 than the other B cell subsets, suggesting a chemotactic effect of eotaxin on these B cell subsets. These findings are important to understand immunity to infections like malaria that result in negative outcomes for both the mother and the newborn and may have important implications on vaccine development.

The prevalences of T. vaginalis, C. trachomatis and N. gonorrhoeae were high among pregnant women in coastal PNG. The poor performance of clinically based syndromic diagnosis suggests that alternative strategies are urgently required to improve detection and reduce the burden of sexually transmitted infections and their associated adverse pregnancy outcomes in this population.

BackgroundMalaria places a significant burden on the limited resources of many low income countries. Knowing more about why and where people seek treatment will enable policy makers to better allocate the limited resources. This study aims to better understand what influences treatment-seeking behaviour for malaria in one such low-income country context, Papua New Guinea (PNG).MethodsTwo culturally, linguistically and demographically different regions in PNG were selected as study sites. A cross sectional household survey was undertaken in both sites resulting in the collection of data on 928 individuals who reported suffering from malaria in the previous four weeks. A probit model was then used to identify the factors determining whether or not people sought treatment for presumptive malaria. Multinomial logit models also assisted in identifying the factors that determined where people sought treatments.ResultsResults in this study build upon findings from other studies. For example, while distance in PNG has previously been seen as the primary factor in influencing whether any sort of treatment will be sought, in this study cultural influences and whether it was the first, second or even third treatment for a particular episode of malaria were also important. In addition, although formal health care facilities were the most popular treatment sources, it was also found that traditional healers were a common choice. In turn, the reasons why participants chose a particular type of treatment differed according to the whether they were seeking an initial or subsequent treatments.ConclusionsSimply bringing health services closer to where people live may not always result in a greater use of formal health care facilities. Policy makers in PNG need to consider within-country variation in treatment-seeking behaviour, the important role of traditional healers and also ensure that the community fully understands the potential implications of not seeking treatment for illnesses such as malaria at a formal health care facility.

BackgroundMalaria in early pregnancy is difficult to study but has recently been associated with fetal growth restriction (FGR). The pathogenic mechanisms underlying malarial FGR are poorly characterized, but may include impaired placental development. We used in vitro methods that model migration and invasion of placental trophoblast into the uterine wall to investigate whether soluble factors released into maternal blood in malaria infection might impair placental development. Because trophoblast invasion is enhanced by a number of hormones and chemokines, and is inhibited by pro-inflammatory cytokines, many of which are dysregulated in malaria in pregnancy, we further compared concentrations of these factors in blood between malaria-infected and uninfected pregnancies.Methodology/Principal FindingsWe measured trophoblast invasion, migration and viability in response to treatment with serum or plasma from two independent cohorts of Papua New Guinean women infected with Plasmodium falciparum or Plasmodium vivax in early pregnancy. Compared to uninfected women, serum and plasma from women with P. falciparum reduced trophoblast invasion (P = .06) and migration (P = .004). P. vivax infection did not alter trophoblast migration (P = .64). The P. falciparum-specific negative effect on placental development was independent of trophoblast viability, but associated with high-density infections. Serum from P. falciparum infected women tended to have lower levels of trophoblast invasion promoting hormones and factors and higher levels of invasion-inhibitory inflammatory factors.Conclusion/SignificanceWe demonstrate that in vitro models of placental development can be adapted to indirectly study the impact of malaria in early pregnancy. These infections could result in impaired trophoblast invasion with reduced transformation of maternal spiral arteries due to maternal hormonal and inflammatory disturbances, which may contribute to FGR by limiting the delivery of maternal blood to the placenta. Future prevention strategies for malaria in pregnancy should include protection in the first half of pregnancy.

Intra-country differences need to be considered in estimating household costs for both outpatient and inpatient malaria treatment. Our findings suggest that it is important to recognize the impact of both direct and indirect costs on individuals' capacity to afford treatment. Certain indirect costs are difficult to measure accurately, particularly respondents' interpretations of their productive versus non-productive time. Despite this, exploring intra-country cost variation can provide important information to health policy makers.

Abstract. We conducted a prospective longitudinal study of fetal size in rural Papua New Guinea (PNG) involving 439 ultrasound-dated singleton pregnancies with no obvious risk factors for growth restriction. Sonographically estimated fetal weights (EFWs; N = 788) and birth weights (N = 376) were included in a second-order polynomial regression model (optimal fit) to generate fetal weight centiles. Means for specific fetal biometric measurements were also estimated. Fetal weight centiles from a healthy PNG cohort were consistently lower than those derived from Caucasian and Congolese populations, which overestimated the proportion of fetuses measuring small for gestational age (SGA; 10th centile). Tanzanian and global reference centiles (Caucasian weight reference adapted to our PNG cohort) were more similar to those observed in our cohort, but the global reference underestimated SGA. Individual biometric measurements did not differ significantly from other cohorts. In rural PNG, a locally derived nomogram may be most appropriate for detection of SGA fetuses.

Immunopathology of placental malaria is most significant in women in their first pregnancy especially in endemic areas, due to a lack of protective immunity to Plasmodium falciparum, which is acquired in successive pregnancies. In some studies (but not all), grand multigravidae (defined as 5 or more pregnancies, G5–7) are more susceptible to poor birth outcomes associated with malaria compared to earlier gravidities. By comparing peripheral cellular responses in primigravidae (G1), women in their second to fourth pregnancy (G2–4) and grand multigravidae we sought to identify key components of the dysregulated immune response. PBMC were exposed to CS2-infected erythrocytes (IE) opsonised with autologous plasma or unopsonised IE, and cytokine and chemokine secretion was measured. Higher levels of opsonising antibody were present in plasma derived from multigravid compared to primigravid women. Significant differences in the levels of cytokines and chemokines secreted in response to IE were observed. Less IL-10, IL-1β, IL-6 and TNF but more CXCL8, CCL8, IFNγ and CXCL10 were detected in G5–7 compared to G2–4 women. Our study provides fresh insight into the modulation of peripheral blood cell function and effects on the balance between host protection and immunopathology during placental malaria infection.

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