co-Trimoxazole in Zambian Infants (TZI)

描述(由申请人提供)：目前世界卫生组织的指南建议，出生时接触艾滋病毒的婴儿应接受复方新诺明(TMZ-SMZ)作为预防肺孢子虫肺炎的经验性药物，为期一年，无需确认H1V感染。然而，70%-90%的受感染婴儿不会成为艾滋病毒阳性，但仍将推定接受一年的预防性治疗。赞比亚婴儿中的复方新诺明(TZI)是一项为期三年的前瞻性研究，衡量世界卫生组织关于常见儿科传染病的建议对人群水平的影响。TZI由美国国际开发署资助，自2003年7月1日以来一直在积极招募患者。TZI-疟疾是TZI内的一项嵌套病例对照研究，重点关注TMP-SMZ对婴儿疟疾发病率、耐药性的影响，以及它对婴儿疟疾免疫获得的影响。TZI-疟疾提出三个问题：1)接触TMP-SMZ是否会降低预防期间的无症状寄生虫血症和临床疟疾的发生率？2)在停止TMP-SMZ预防后的几个月里，以前接受预防的人是否会经历比预期更高的无症状寄生虫血症和临床疟疾的发生率？3)TMP-SMZ暴露是否会增加对磺胺多辛-乙胺嘧啶的耐药率？这些问题将通过比较疟疾在预防期间和预防后的累积率，并对SP耐药标记进行遗传分析，作为两组婴儿之间的比较：病例-出生时接触艾滋病毒并接受预防(但后来被证明在12个月时艾滋病毒阴性)的婴儿；以及对照--时间和地理上匹配的未接触艾滋病毒的、艾滋病毒阴性的婴儿，没有接受TMP-SMZ预防。Zzi疟疾是K23职业发展五年计划的核心活动。这项计划整合了课堂作业、指导研究、实践实地经验、额外的项目开发、教学和其他活动，这些活动来自波士顿大学公共卫生学院和我的上级组织国际卫生与发展中心的学术环境。

DESCRIPTION (provided by applicant): Current World Health Organization guidelines recommend that infants exposed to HIV at birth should receive cotrimoxazole (TMZ-SMZ) as empiric prophylaxis against Pneumocystis pneumonia for one year without confirmation of H1V infection. However, 70-90% of exposed infants will not become HIV positive but would still take prophylaxis presumptively for one year. CoTrimoxazole in Zambian Infants (TZI) is a three year prospective study measuring population level effects of the WHO's proposal on common pediatric infectious diseases. TZI is funded by USAID and has been actively recruiting patients since July 1, 2003. TZI-MALARIA is a nested case control study within TZI focusing on TMP-SMZ's impact on infant malaria rates, drug resistance, and its effect on the acquistion of malaria immunity during infancy. TZI-MALARIA asks three questions: 1) Will TMP-SMZ exposure reduce rates of asymptomatic parasitemia and clinical malaria during the period of prophylaxis? 2) Will former recipients ofprophylaxis experience higher than expected rates of asymptomatic parasitemia and clinical malaria in the monthsfollowing the cessation of TMP-SMZ prophylaxis? 3) Will TMP-SMZ exposure increase rates of resistance to sulfadoxine-pyrimethamine, a leading antimalarial that is cross-tolerant with TMP-SMZ? These questions will be answered by comparing cumulative rates of malaria during and after the period of prophyalxis, and conducting genetic analsis for SP-resistance markers as a comparison between two groups of infants: Cases - infants exposed to HIV at birth and receiving prophylaxis (but later proven HIV negative at 12 months); and Controls - temporally and geographically matched HIV-unexposed, HIV negative infants, not receiving TMP-SMZ prophylaxis. TZI-MALARIA constitutes the core activity of a five year K23 career development plan. This program integrates class work, mentored research, practical field experience, additional project development, teaching, and other activities derived from the academic environment of Boston University's School of Public Health and my parent organization, the Center for International Health and Development.