Effect of IPTP Regimens on Malaria-Related Immunity

IPTP 方案对疟疾相关免疫的影响

• 批准号: 6969064
• 负责人: PATRICK E DUFFY
• 金额: $ 19.67万
• 依托单位: SEATTLE BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6969064
• 关键词: Africa; antimalarial agents; chemoprevention; clinical trials; cooperative study; cord blood; drug adverse effect; hospital utilization; human pregnant subject; human therapy evaluation; inflammation; longitudinal human study; malaria; microorganism disease chemotherapy; patient oriented research; pediatric pharmacology; postnatal growth disorder; pregnancy infection; women' s health

Pregnancy malaria is thought to kill hundreds of thousands of African infants each year, but the impact of pregnancy malaria on infant health and malaria susceptibility has been poorly studied. Our longitudinal cohort studies in mother-infant pairs indicate that placental malaria increases the frequency of parasitemia during infancy, delays infant development, and increases the frequency of hospitalization during early life, and that proinflammatory molecule levels in cord blood are independently associated with delayed anthropometric development during infancy. This proposed Project will examine the impact of pregnancy malaria on malaria susceptibility and clinical outcomes during infancy and early childhood, in the context of a randomized trial of four Intermittent Preventive Treatment (IPTp) regimens against pregnancy malaria. This research is based on the following hypotheses: sulfadoxinepyrimethamine (SP) alone will be less effective than other IPTp regimens for preventing placental infection and inflammation; infants born to mothers receiving SP will be parasitemic at an earlier age and with greater frequency than other infants; infants born to mothers receiving SP will experience increased rates of hospitalization and malaria-related hospitalization compared to other infants; compared to other infants, infants born to mothers receiving SP will suffer delayed growth during infancy. Randomized IPTp trials offer a unique opportunity to study the impact of pregnancy malaria on infant outcomes, by clearly stratifying women into groups with different levels of exposure defined in the course of the trial. Based on our hypotheses and Preliminary Results, we expect the following outcomes: placental malaria and fetal inflammatory responses will be more common in the SP group, and placental malaria will increase risk of parasitemia and hospitalization during infancy, while both placental malaria and cord inflammation will be related to delayed anthropometric development of the infant. These studies will establish the mechanisms underlying increased infant mortality related to pregnancy malaria, and may illuminate long-term effects of in utero inflammation on health and development during early childhood.

据认为，妊娠期疟疾每年导致数十万非洲婴儿死亡，但对妊娠期疟疾对婴儿健康和疟疾易感性的影响的研究很少。我们在母婴对中进行的纵向队列研究表明，胎盘疟疾增加了婴儿期寄生虫血症的频率，延迟了婴儿发育，并增加了生命早期住院的频率，并且脐带血中的促炎分子水平与婴儿期人体测量发育延迟独立相关。这个拟议的项目将在一项针对妊娠疟疾的四种间歇性预防治疗（IPTp）方案的随机试验的背景下，研究妊娠疟疾对婴儿和幼儿期疟疾易感性和临床结果的影响。本研究基于以下假设：单独使用磺胺多辛乙胺嘧啶（SP）在预防胎盘感染和炎症方面的效果不如其他IPTp方案；接受SP的母亲所生的婴儿会在更早的年龄和更频繁地感染寄生虫