Malarial Immunity in Pregnant Cameroonian Women

描述(由申请人提供)：项目摘要：恶性疟疾是孕妇的一个主要健康问题，因为它增加了产妇死亡率和不良的妊娠结局。此外，母亲在怀孕期间患疟疾的婴儿比母亲没有疟疾的婴儿患严重疟疾、贫血、哮喘和在出生后第一年死亡的风险更高。我们的长期目标是改善撒哈拉以南非洲妇女和儿童的健康。因此，喀麦隆雅温得大学和夏威夷大学的科学家们建议回答有关目前推荐的孕期疟疾预防战略的关键问题，即使用磺胺多辛-乙胺(IPT-SP)进行间歇预防性治疗。具体地说，我们试图确定在怀孕第二和/或第三个月期间给予IPT-SP是否影响1)抑制胎盘寄生虫隔离的抗体(Ab)的获得，2)与低出生体重儿相关的胎盘病理，3)抗疟疾免疫球蛋白通过胎盘转移到候选疫苗抗原，4)宫内启动胎儿T和B细胞，以及5)婴儿在出生第一年期间感染恶性疟原虫的数量和严重程度，以及他们获得免疫力的比率。研究将在雅温德市进行，那里的传播率为每月约1次传染性叮咬，以及在农村地区，那里的个人每晚收到约0.7次传染性叮咬。拟议的研究将首次评估居住在中非/西非和疟疾传播率较低地区的孕妇的IPT-SP。这也将是第一次研究IPT-SP对疟疾抗原VAR2csa抗体产生的影响，以及这与卢婴儿相关的胎盘病理的关系。最后，这项研究将首次确定IPT-SP是否会降低婴儿在出生时的保护性免疫水平，以及这如何影响出生一岁的婴儿的疟疾发作和抗体反应。相关性：拟议的研究将有助于确定世界卫生组织目前建议的预防发展中国家孕妇疟疾的方法的优点和缺点。这项研究的新信息应有助于改善对非洲母亲及其子女的保健。

DESCRIPTION (provided by applicant): Project Summary: Plasmodium falciparum malaria is a major health problem for pregnant women since it increases maternal mortality and poor pregnancy outcomes. In addition, infants whose mothers have malaria during pregnancy are at an increased risk of developing severe malaria, anemia, asthma and dying during the first year of life than those whose mothers remain malaria-free. Our long-term goal is to improve the health of women and children living in sub-Saharan Africa. Accordingly, scientists at the University of Yaounde, Cameroon and University of Hawaii propose to answer key questions about the current recommended strategy for prevention of malaria during pregnancy, namely intermittent preventive treatment using sulfadoxine-pyrimethamine (IPT-SP). Specifically, we seek to determine if IPT-SP administered during the 2nd and/or 3rd trimester influences 1) the acquisition of antibodies (Ab) that inhibit parasite sequestration in the placenta, 2) placental pathology associated with low birthweight babies, 3) transplacental transfer of antimalarial IgG to vaccine-candidate antigens, 4) in utero priming of fetal T and B cells, and 5) the number and severity of P. falciparum infections infants have, as well as their rate of acquisition of immunity, during the first year of life. Studies will be conducted in the city of Yaounde where transmission is ~1 infectious bite per month and in rural villages where individuals receive ~0.7 infectious bites per night. The proposed studies will be the first to evaluate IPT-SP in pregnant women living in Central/West Africa and in an area where transmission of malaria is low. It will also be the first to study the effect of IPT-SP on production of Ab to the malaria antigen VAR2csa and how this relates to placental pathology associated with LEW babies. Finally, the study will be the first to determine if IPT-SP reduces the level of protective immunity infants have at birth and how this influences malaria episodes and Ab responses in infants during the 1st year of life. Relevance: The proposed study will help determine the strengths and weaknesses of the method currently recommended by the World Health Organization for prevention of malaria in pregnant women living in developing countries. New information from this study should lead to improved health care for African mothers and their children.