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.