Pregnancy Associated Immune Responses to Tuberculosis and HIV in India and South Africa (PARTHISA)

Dr. Jyoti Mathad is Co-PI of this study. 

Purpose: Tuberculosis (TB) is a leading cause of maternal mortality, especially among HIV-infected women. Women are most likely to develop active TB during and immediately after pregnancy. The immunologic conditions responsible for this phenomenon are not understood. Though evidence points to expansion of systemic T reg cell during pregnancy, preliminary analysis of data from the PRACHITi study shows that CD4+ T cells and Tregs decrease in pregnancy, suggesting either that Treg expansion only occurs locally in the placenta or that other cells, such as monocytes, are responsible for the Th1 suppression. The purpose of this study is to expand the PRACHITi study by collecting additional peripheral and placental samples to assess the role of monocytes and NK cells in the pathogenesis of TB in pregnancy. By including a new RePORT site in South Africa, we will ensure sufficient samples from both HIV-infected and HIV-uninfected women.

Design: A prospective longitudinal cohort study of HIV-infected and HIV-uninfected mother-infant pairs with active TB and without active TB in South Africa and India. Pregnant women will be enrolled from the antenatal clinics, TB clinics, and hospital wards at Sassoon Hospital in Pune, India, and at Chris Hani Baragwanath Academic Hospital (CBAH) in South Africa, up to 24 weeks of gestation. (We will enroll women with active TB upto 3 weeks postpartum.)They will have additional visits at second trimester (if enrolled in first trimester), third trimester, delivery, 6 weeks, 3, and 6 months postpartum. Postpartum maternal visits will be paired with infant visits. For those without TB, we will screen for active TB and collect maternal blood samples for cytokine assays, flow cytometry, and gene transcription studies at each visit, Those with active TB will be followed up upto 24 weeks after completion of TB treatment.If any women who develop active TB during study priod will be requested to enroll in active TB arm. At delivery, we will collect placenta and cord blood samples. At postpartum visits we will collect breast milk samples.

Participant Population: This study will follow 6 cohorts of HIV-infected and HIV-uninfected pregnant women: 

1. Cohort A1: HIV-infected women diagnosed with drug-sensitive or drug-resistant active TB that became clinically apparent while pregnant or within 3 weeks postpartum;  
2. Cohort A2: HIV-uninfected women diagnosed with drug-sensitive or drug-resistant active TB that became clinically apparent while pregnant or within 3 weeks postpartum; 
3. Cohort B1: HIV-infected pregnant women up to 24 weeks of gestational age with a positive IGRA but no evidence of active TB;
4. Cohort B2: HIV-uninfected pregnant women  up to 24 weeks of gestational age with a positive IGRA but no evidence of active TB;
5. Cohort C: HIV-infected pregnant women up to 24 weeks of gestational age with a negative IGRA
6. Cohort D: HIV-uninfected pregnant women  up to 24 weeks of gestational age with a negative IGRA

Infants of mothers enrolled in the study will be followed clinically with the same follow-up schedule as their mothers.

Study Sites: 

• BJ Medical College (BJMC)/Sassoon General Hospital in Pune, India- (Cohorts A and B)
• Chris Hani Baragwanath Academic Hospital (CBAH), Soweto, South Africa-Cohort A, B, C and D

Study Duration: Mother-infant pairs in Cohorts A will be followed up to 24 weeks after TB treatment is stopped. Mother-infant pairs in cohorts B C and D will be followed from enrollment during pregnancy through at least 6 months postpartum. 

Primary Objectives:

1. To compare MTB-specific immune markers and cell populations in HIV-infected and HIV-uninfected pregnant women by stage of pregnancy - after delivery - by TB infection and TB disease status 
2. To compare placental cell populations in pregnant women with active TB, latent TB and no evidence of TB infection or disease.