Baseline characteristics of mothers at delivery.

<p>Baseline characteristics of mothers at delivery.</p

Impact of malaria on birth weight at term according to gravidity.

<p>Tukey boxplots show the effect of gravidity on the weight of newborns from malaria-infected women (A), and on newborns from women infected according with <i>Plasmodium</i> species (B). The bottom and the top of the box are the first and third quartiles, the line inside the box is the median, and the whiskers represent the lowest and the highest data within 1.5 IQR of the first and upper quartiles. The line indicates the cut-off of low birth weight. Differences between each group were examined with Mann-Whitney or Kruskal-Wallis test with a Dunn’s post hoc test. (A) P—NI x Infec (p<0.0001); M—NI x Infec (p<0.0001); NI- P x M (p<0.0001); and Infec—P x M (p = 0.0004). (B) P—NI x Pv (p = 0.0001); NI x Pf (p = 0.0003); M—NI x Pv (p = 0.0009); NI x Pf (p<0.0001); NI x Mix (p = 0.003); Pv x Pf (p = 0.025); Pv—P x M (p = 0.0009). P, primigravida; M, multigravida; NI, non-infected pregnant women; Infec, infected pregnant women; Pv, <i>P</i>. <i>vivax</i>-infection; Pf, <i>P</i>. <i>falciparum</i>-infection; Mix, mixed-infection.</p

Clinical outcomes of newborns at birth.

<p>Clinical outcomes of newborns at birth.</p

Time-series of gestational malaria cases between 2006–2014.

<p>(A) Number of gestational malaria cases per species, (B) mean birth weight of newborns from non-infected and infected women during pregnancy.</p

Map showing the geographic location of Cruzeiro do Sul, Acre State, Brazilian Amazon.

<p>Cruzeiro do Sul has an estimated population of 82,075 inhabitants. The map also indicates Rio Branco, the capital of Acre state.</p

Forest plot of the odds ratio for weight reduction in newborns from women infected during pregnancy compared to babies from non-infected women, according to <i>Plasmodium</i> species.

<p>Each model adjusting for maternal age, gravidity and years of formal education (less than 4 years); mixed infection (<i>P</i>. <i>vivax</i> and <i>P</i>. <i>falciparum</i>-infection). p values were estimated through logistic regression methods. n, number of events; N, total number in each group; CI, confidence interval; SGA, small for gestational age; LBW, low birth weight.</p

Forest plot of the odds ratio for prematurity in newborns from women infected during pregnancy compared to babies from non-infected women, according to <i>Plasmodium</i> species.

<p>Each model adjusting for maternal age, gravidity and years of formal education (less than 4 years). Mixed infection (<i>P</i>. <i>vivax</i> and <i>P</i>. <i>falciparum</i>-infection). p values were estimated through logistic regression methods. n, number of events; N, total number in each group; CI, confidence interval. Prematurity was defined as birth <37 weeks’ gestation; very preterm birth was defined as birth between ≥28 and <32 weeks’ gestation, and late preterm birth was defined as birth between ≥32 and <37 weeks’ gestation.</p

Flowchart detailing exclusion criteria applied to the evaluation of the enrolled maternal-child pairs.

<p><i>P</i>. <i>vivax infected mothers—one or more infections only by P</i>. <i>vivax; P</i>. <i>falciparum infected mothers—one or more infections only by P</i>. <i>falciparum;</i> Mixed infection—<i>P</i>. <i>vivax</i>- and <i>P</i>. <i>falciparum</i>-infection occurring at the same time and/or at different times during pregnancy.</p

Malaria during pregnancy and newborn outcome in an unstable transmission area in Brazil: A population-based record linkage study

<div><p>Background</p><p>Malaria in pregnancy (MiP) is one of the major causes of mortality and morbidity in tropical regions, causing maternal anemia, intrauterine growth retardation, preterm birth, and low birth weight (LBW). The integration of the information systems on pregnancy and malaria could prove to be a useful method of improved decision making for better maternal-child health.</p><p>Methods</p><p>A population-based observational study acquired information retrospectively from all live births that occurred between 2006 and 2014 in Cruzeiro do Sul (Acre, Brazil). Social and clinical data of the mother and newborn was extracted from the Information System of Live Births. Malaria episodes information was obtained from the Brazilian Epidemiological Surveillance Information System Malaria. A deterministic record linkage was performed to assess malaria impact on pregnancy.</p><p>Results</p><p>The studied population presented a malaria incidence of 8.9% (1283 pregnant women infected), of which 63.9% infected by <i>Plasmodium (P</i>.<i>) vivax</i>. Reduction of newborn birth weight at term (small for gestational age (SGA) and LBW) has been found associated with <i>P</i>. <i>vivax</i> infection during pregnancy (SGA—OR 1.24, 95% CI 1.02–1.52, p = 0.035; term LBW—OR 1.39, 95% CI 1.03–1.88, p = 0.033). Additionally, <i>P</i>. <i>falciparum</i> infection during pregnancy has been found to be associated with preterm births (OR 1.54, 95% CI 1.09–2.18, p = 0.016), which is related with late preterm births (OR 1.59, 95% CI 1.11–2.27, p = 0.011).</p><p>Conclusions</p><p>Despite the decrease of malaria cases during the evaluation period and regardless of <i>Plasmodium</i> species, we present evidence of the deleterious effects of MiP in a low transmission area in the Amazonian region.</p></div

Polymorphisms in <i>Plasmodium vivax</i> Circumsporozoite Protein (CSP) Influence Parasite Burden and Cytokine Balance in a Pre-Amazon Endemic Area from Brazil

<div><p>Mechanisms involved in severe <i>P</i>. <i>vivax</i> malaria remain unclear. Parasite polymorphisms, parasite load and host cytokine profile may influence the course of infection. In this study, we investigated the influence of circumsporozoite protein (CSP) polymorphisms on parasite load and cytokine profile in patients with vivax malaria. A cross-sectional study was carried out in three cities: São Luís, Cedral and Buriticupu, Maranhão state, Brazil, areas of high prevalence of <i>P</i>. <i>vivax</i>. Interleukin (IL)-2, IL-4, IL-10, IL-6, IL-17, tumor necrosis factor alpha (TNF-α, interferon gamma (IFN-γ and transforming growth factor beta (TGF-β were quantified in blood plasma of patients and in supernatants from peripheral blood mononuclear cell (PBMC) cultures. Furthermore, the levels of cytokines and parasite load were correlated with VK210, VK247 and <i>P</i>. <i>vivax</i>-like CSP variants. Patients infected with <i>P</i>. <i>vivax</i> showed increased IL-10 and IL-6 levels, which correlated with the parasite load, however, in multiple comparisons, only IL-10 kept this association. A regulatory cytokine profile prevailed in plasma, while an inflammatory profile prevailed in PBMC culture supernatants and these patterns were related to CSP polymorphisms. VK247 infected patients showed higher parasitaemia and IL-6 concentrations, which were not associated to IL-10 anti-inflammatory effect. By contrast, in VK210 patients, these two cytokines showed a strong positive correlation and the parasite load was lower. Patients with the VK210 variant showed a regulatory cytokine profile in plasma, while those infected with the VK247 variant have a predominantly inflammatory cytokine profile and higher parasite loads, which altogether may result in more complications in infection. In conclusion, we propose that CSP polymorphisms is associated to the increase of non-regulated inflammatory immune responses, which in turn may be associated with the outcome of infection.</p></div