co-Trimoxazole in Zambian Infants (TZI)

描述（由申请人提供）：目前世界卫生组织指南建议，出生时暴露于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预防，为期一年，而无需确认H1 V感染。然而，70-90%的暴露婴儿不会成为艾滋病毒阳性，但仍将采取预防措施一年。赞比亚婴儿复方新诺明（TZI）是一项为期三年的前瞻性研究，旨在衡量世卫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-MALARIA是TZI中的一项巢式病例对照研究，重点是TMP-SMZ对婴儿疟疾发病率、耐药性及其对婴儿期疟疾免疫力获得的影响。TZI-MALARIA提出了三个问题：1）TMP-SMZ暴露是否会降低预防期间无症状寄生虫血症和临床疟疾的发生率？2)在TMP-SMZ预防性治疗停止后的几个月内，既往接受预防性治疗者的无症状寄生虫血症和临床疟疾发生率是否高于预期？3)TMP-SMZ暴露是否会增加对磺胺嘧啶-乙胺嘧啶（一种与TMP-SMZ交叉耐受的主要抗疟药）的耐药性？这些问题的答案将通过比较疟疾流行期间和之后的累积疟疾发病率，并对SP耐药标记物进行遗传分析，作为两组婴儿之间的比较：病例-婴儿出生时暴露于艾滋病毒并接受预防（但后来在12个月时被证明HIV阴性）;对照组-时间和地理位置匹配的HIV未暴露、HIV阴性婴儿，未接受TMP-SMZ预防。TZI-MALARIA是K23五年职业发展计划的核心活动。该计划整合了课堂作业，指导研究，实际实地经验，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母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.