Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Instituto Gulbenkian de Ciência, Oeiras, Portugal.
PLoS Negl Trop Dis. 2021 Apr 29;15(4):e0009390. doi: 10.1371/journal.pntd.0009390. eCollection 2021 Apr.
Malaria in Brazil represents one of the highest percentages of Latin America cases, where approximately 84% of infections are attributed to Plasmodium (P.) vivax. Despite the high incidence, many aspects of gestational malaria resulting from P. vivax infections remain poorly studied. As such, we aimed to evaluate the consequences of P. vivax infections during gestation on the health of mothers and their neonates in an endemic area of the Amazon.
We have conducted an observational cohort study in Brazilian Amazon between January 2013 and April 2015. 600 pregnant women were enrolled and followed until delivery. After applying exclusion criteria, 329 mother-child pairs were included in the analysis. Clinical data regarding maternal infection, newborn's anthropometric measures, placental histopathological characteristics, and angiogenic and inflammatory factors were evaluated. The presence of plasma IgG against the P. vivax (Pv) MSP119 protein was used as marker of exposure and possible associations with pregnancy outcomes were analyzed. Multivariate logistic regression analysis revealed that P. vivax infections during the first trimester of pregnancy are associated with adverse gestational outcomes such as premature birth (adjusted odds ratio [aOR] 8.12, 95% confidence interval [95%CI] 2.69-24.54, p < 0.0001) and reduced head circumference (aOR 3.58, 95%CI 1.29-9.97, p = 0.01). Histopathology analysis showed marked differences between placentas from P. vivax-infected and non-infected pregnant women, especially regarding placental monocytes infiltrate. Placental levels of vasomodulatory factors such as angiopoietin-2 (ANG-2) and complement proteins such as C5a were also altered at delivery. Plasma levels of anti-PvMSP119 IgG in infected pregnant women were shown to be a reliable exposure marker; yet, with no association with improved pregnancy outcomes.
This study indicates that P. vivax malaria during the first trimester of pregnancy represents a higher likelihood of subsequent poor pregnancy outcomes associated with marked placental histologic modification and angiogenic/inflammatory imbalance. Additionally, our findings support the idea that antibodies against PvMSP119 are not protective against poor pregnancy outcomes induced by P. vivax infections.
巴西的疟疾是拉丁美洲发病率最高的地区之一，其中约 84%的感染归因于间日疟原虫（Plasmodium vivax）。尽管发病率很高，但由于间日疟原虫感染导致的妊娠疟疾的许多方面仍研究甚少。因此，我们旨在评估在亚马逊地区的疟疾流行地区，间日疟原虫感染对母亲及其新生儿健康的影响。
我们在 2013 年 1 月至 2015 年 4 月期间在巴西亚马逊地区进行了一项观察性队列研究。共纳入 600 名孕妇，并在分娩前进行随访。应用排除标准后，329 对母婴被纳入分析。评估了母体感染、新生儿人体测量学指标、胎盘组织病理学特征以及血管生成和炎症因子的情况。用血浆 IgG 针对间日疟原虫（Pv）MSP119 蛋白的存在作为暴露的标志物，并分析了其与妊娠结局的可能相关性。多变量逻辑回归分析表明，妊娠早期的间日疟原虫感染与早产（调整优势比[aOR]8.12，95%置信区间[95%CI]2.69-24.54，p<0.0001）和头围减少（aOR 3.58，95%CI 1.29-9.97，p=0.01）等不良妊娠结局相关。组织病理学分析显示，间日疟原虫感染孕妇与未感染孕妇的胎盘有明显差异，特别是胎盘单核细胞浸润。血管调节因子如血管生成素-2（ANG-2）和补体蛋白如 C5a 的胎盘水平在分娩时也发生改变。感染孕妇的血浆抗-PvMSP119 IgG 水平被证明是一种可靠的暴露标志物，但与改善妊娠结局无关。
本研究表明，妊娠早期的间日疟原虫疟疾与随后发生的与明显的胎盘组织学改变和血管生成/炎症失衡相关的不良妊娠结局的可能性更高。此外，我们的研究结果支持这样的观点，即针对 PvMSP119 的抗体并不能预防由间日疟原虫感染引起的不良妊娠结局。
