Safe Pregnancy by Infectious Disease Control in Kinshasa

描述（由申请人提供）：疟疾、性传播感染（STI）和结核病（TB）在撒哈拉以南非洲的孕妇（PW）中很常见，是导致不良出生结局和孕产妇发病率和死亡率的重要可预防原因。非洲的许多PW寻求产前护理（ANC），但没有得到适当的护理，尽管抗生素或抗疟药的假定治疗（PT）和结核病的预防性治疗可能是有效的。因此，产前检查意味着在资源匮乏的环境中“错失了改善母婴健康的机会”。 我们建议制定两项新的产前干预措施，以防止这些感染，可以在该地区广泛实施。首先，我们将评估阿奇霉素（AZM）在高危PW中的PT。AZM对细菌性STI有效;然而，需要确定具有成本效益的实用PT方案。AZM还具有抗疟疾活性;通过将AZM与磺胺嘧啶-乙胺嘧啶（SP;疟疾的标准治疗PT）联合使用，我们希望提高疗效并延迟抗SP疟疾的发作。第二，我们将测试HIV（+）PW中潜伏性TB感染的短程治疗方案的安全性和依从性。 我们建议在刚果民主共和国金沙萨的两个大型产前保健诊所工作，我们目前正在那里提供产前艾滋病毒筛查和治疗。在这些诊所，我们的团队将同时进行两项随机、安慰剂对照的临床试验：（1）一项四组试验，以确定高危HIV（-）PW在妊娠中期、妊娠晚期、不使用或两次使用AZM（2 g）治疗的疗效（所有群体都接受特殊保护）;和（2）在HIV（+）中进行的单独双臂试验，TB感染的PW，以比较异烟肼300 mg/d治疗9个月的标准方案和异烟肼300 mg/d+利福平600 mg/d治疗3个月的短程方案治疗潜伏期M.肺结核感染。 该项目是在资源贫乏的非洲开发一种综合、实用的方法来管理PW中高度流行的疟疾、性传播感染和结核病的首批尝试之一。它将建立在美国和金沙萨的研究者之间富有成效的合作历史的基础上，特别是在PW的大型纵向队列研究已经成功的Projet SIDA。它还将建立在金沙萨公共卫生学院一个新兴的多学科研究和培训方案的基础上，并加强这一方案。

DESCRIPTION (provided by applicant): Malaria, sexually transmitted infections (STIs), and tuberculosis (TB), are frequent in pregnant women (PW) in sub-Saharan Africa and are important preventable causes of poor birth outcomes and maternal morbidity and mortality. Many PW in Africa seek antenatal care (ANC) but do not receive appropriate care for these infections, although presumptive therapy (PT) with antibiotics or antimalarials and preventive therapy for TB can be effective. The antenatal visit thus represents a "missed opportunity" to improve maternal and infant health in resource-poor settings. We propose to develop two new antenatal interventions against these infections that can be widely implemented in the region. First, we will evaluate PT with azithromycin (AZM) in high-risk PW. AZM is effective against bacterial STIs; however cost-effective, practical PT regimens need to be identified. AZM also has antimalarial activity; by combining AZM with sulfadoxine-pyrimethamine (SP; standard-of-care PT for malaria), we hope to improve effectiveness and delay the onset of SP-resistant malaria. Second, we will test the safety of, and compliance with, a short-course regimen for latent TB infection in HIV (+) PW. We propose to work in two large antenatal care clinics in Kinshasa, Democratic Republic of Congo where we are currently offering antenatal HIV screening and treatment. At these clinics, our team will concurrently conduct two randomized, placebo-controlled clinical trials: (1) a four-arm trial to determine the efficacy of presumptive AZM (2 g) treatment taken by high-risk HIV (-) PW in the second trimester, third trimester, neither or both times (with all groups receiving SP); and (2) a separate two-arm trial in HIV (+), TB-infected PW to compare the safety of (and compliance to) the standard regimen of 9 months of isoniazid 300 mg/d with a short course regimen of 3 months of isoniazid (300 mg/d) plus rifampin (600 mg/d) for latent M. tb infection. This project is one of the first attempts to develop an integrated, practical approach to managing highly prevalent malaria, STIs, and TB in PW in resource-poor Africa. It will build on a productive history of collaboration between investigators in the USA and Kinshasa, especially Projet SIDA, where large longitudinal cohort studies in PW have been successful. It will also build upon, and augment, a burgeoning, multidisciplinary research and training program at the Kinshasa School of Public Health.