Pregnant women as a sentinel group for malaria surveillance in an era of changing malaria transmission (MiPMoz)

 描述(申请人提供)：尽管疟疾造成了重大的疾病负担，但在大多数流行环境中，对孕期疟疾缺乏持续监测。在过去十年间疟疾急剧下降之后，在莫桑比克孕妇中观察到的与疟疾有关的有害影响有所增加[2]，这表明需要密切监测传播情况，以便迅速查明不良后果的反弹，特别是在开展消除疟疾活动的地区。此外，一些证据表明，抗VAR2CSA的免疫球蛋白(VAR2CSA是一种寄生虫抗原，介导恶性疟原虫在胎盘中的隔离)是孕期累积接触恶性疟原虫的标志，可以提供疟疾传播的估计。我们假设，孕期疟疾和妊娠特异性免疫的动态反映了通过地点和时间传播的强度的变化，不仅在孕妇之间，而且在潜在的社区中。这项研究的目的是提供对孕妇到保健机构就诊的价值的流行病学、分子和免疫学见解，以估计疟疾负担及其在不同疟疾传播水平情况下的不利后果，最终希望开发新的工具，在疟疾流行国家监测疟疾。为了解决这一问题，我们将在马普托省三个疟疾传播水平不同的卫生机构进行为期三年的p研究，以确定疟疾传播、寄生虫学结果与孕妇在第一次产前就诊、分娩和就诊期间感染疟疾的临床影响之间的关系(目标1.1)。此外，我们将建立一个样本库生物库，以便今后调查影响孕期疟疾疾病的宿主和寄生虫因素(目标1.2)。我们还将确定从孕妇和儿童就诊时获得的疟疾估计数(目标2.1)与VAR2CSA血清流行率(目标2.2)之间的关系。在社区大规模用药后，将在马古德的孕妇中评估阻断疟疾传播对妊娠特异性血清学(AIM 2.3)的影响。最后，Manhiça卫生研究中心(目标3)的科学能力将通过以下方面的培训来发展：a)疟疾数据的流行病学研究和管理；b)用于检测疟疾寄生虫的分子工具和用于快速绘制耐药性图谱的抗疟疾耐药性分子标记；以及c)将妊娠特异性免疫作为评估疟疾传播的创新工具。这项研究将有助于促进孕期疟疾研究议程，提高我们对孕期疟疾易感性决定因素的科学知识，并证明在消除疟疾的背景下，一种易于实施的新一代血清学工具用于疟疾监测的可行性和价值。

 DESCRIPTION (provided by applicant): Continued monitoring of malaria in pregnancy is lacking in most endemic settings, in spite of its significant disease burden. Increases in malaria-related harmful effects observed among Mozambican pregnant women after drastic malaria declines during the last decade [2] suggest that closely monitoring of the transmission is needed to quickly identify rebounds in adverse outcomes, especially in areas embarking in malaria elimination activities. Moreover, several evidences point to IgGs against VAR2CSA (the parasite antigen that mediates sequestration of P. falciparum in the placenta) as a marker of cumulative exposure to P. falciparum during pregnancy that can provide estimates of malaria transmission. We hypothesize that dynamics of malaria in pregnancy and pregnancy-specific immunity reflect changes in the intensity of transmission through location and time, not only among pregnant women but also in the underlying community. The goal of this study is to provide epidemiological, molecular and immunological insights of the value of pregnant women attending health facilities to generate estimates of malaria burden and its adverse consequences in situation of varying levels of malaria transmission, with the ultimate hope of developing new tools for the monitoring of malaria in endemic countries. To address this, we will conduct a three-year p study at three health facilities with different levels of malaria transmissin in Maputo Province to determine the relationship between malaria transmission, parasitological outcomes and the clinical impact of malaria infection in pregnant women at their first antenatal visit, delivery and during sick visits (Aim 1.1). Moreover, we will create a sample repository biobank for future investigations on host and parasite factors influencing malaria disease during pregnancy (Aim 1.2). We will also determine the relationship between malaria estimates obtained from pregnant women, children at hospital visits, (Aim 2.1) and seroprevalences against VAR2CSA (Aim 2.2). The impact of interrupting malaria transmission on pregnancy-specific serology (Aim 2.3) will be assessed in pregnant women from Magude after mass drug administration in the community. Finally, scientific capacity in the Manhiça Health Research Center (Aim 3) will be developed through training on a) epidemiological research and management of malaria data; b) molecular tools for detection of malaria parasites and molecular markers of antimalarial resistance for rapid mapping of drug resistance; and c) pregnancy- specific immunity as an innovative tool to assess malaria transmission. This study will contribute to promote a pregnancy malaria research agenda by improving our scientific knowledge on determinants of malaria susceptibility during pregnancy and demonstrating the feasibility and value of an easy-to-implement new generation serological tool for malaria surveillance in malaria elimination contexts.