Lilian Tina Minja

PhD proposal: Challenges in tuberculosis care for people starting methadone maintenance treatment in Dar es Salaam
Supervisor: Sebastien Gagneux

Propsal abstract
Introduction: Substance use disorders, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and tuberculosis (TB) are three epidemics that are linked together and fuel each other in various ways. The number of people who inject drugs (PWID) in Tanzania is rapidly increasing, with an estimated 40,000 injectors in 2005. PWID are at a high risk of developing TB and HIV/AIDS. The prevalence of latent tuberculosis infection (LTBI) among PWID ranges between 10-59%, whereas the prevalence of active TB in PWID in Tanzania has been estimated at 4% (23 times higher than the general population). The HIV/AIDS prevalence among PWID in Tanzania was reported around 51.1% and HIV infected PWID are known to have a 20 to 37 fold risk of developing active TB compared to HIV negative individuals. A decrease in health seeking behavior among PWIDs together with difficulties in completing medical evaluations as well as adhering to TB treatment further worsens the TB burden among PWID. Thus there is a need for timely prevention, diagnosis and treatment of TB in PWID.

Diagnosis is difficult as PWID have a reduction in cough frequency and severity secondary to the effect of opiates, and HIV infection is associated with a higher proportion of sputum smear-negative and extra pulmonary TB (EPTB). Other comorbidities prevalent in PWID in Tanzania include hepatitis B infection, hepatitis C infection and vitamin D deficiency. The above pose challenges not only in predisposing PWID to develop active TB but also increase the risk of adverse events due to TB treatment.

Main Objectives: This study aims to address challenges in diagnosing and managing LTBI and active TB among PWID starting methadone maintenance treatment (MMT) in Dar es Salaam. We will determine the prevalence of LTBI and active TB and assess the risk of developing hepatotoxicity following initiation of isoniazid prophylactic therapy (IPT) for LTBI and anti TB therapy for active TB among PWID starting MMT. The study will look at underlying risk factors for TB development including vitamin D deficiency as well as explore the barriers and perceptions related to health services provided to PWID.

Specific Objectives:

1. To determine the prevalence of LTBI among PWID starting MMT.
2. To determine the prevalence of active TB among PWID starting MMT.
3. To assess the risk of developing hepatotoxicity following initiation of IPT for LTBI among PWID on MMT.
4. To determine the prevalence of vitamin D deficiency among PWID starting MMT with LTBI and active TB.
5. To explore the barriers in access to health services for PWID and the perception of health care providers and PWID towards each other.

Exploratory objectives:

1. To evaluate different diagnostic tools for determining active TB in PWID starting MMT.
2. To assess the risk of developing hepatotoxicity following initiation of anti TB therapy for active TB among PWID on MMT.

Methodology: This prospective study will be carried out in the Ilala, Kinondoni and Temeke districts of Dar es Salaam, Tanzania. After obtaining informed consent, 400 PWID will be consecutively recruited and screened for LTBI and active TB, HIV status, hepatitis B and C as well as baseline vitamin D levels. In depth interviews and focus group discussions will be used for the qualitative part of the study. Management of LTBI, active TB, HIV/AIDS, hepatitis B and C will follow the Tanzanian national guidelines. Transaminases will be monitored throughout the duration of TB treatment in predefined intervals.

Laboratory procedures: At recruitment, two sputum samples (one spontaneous and one induced) will be collected for Ziehl-Neelsen stain, Xpert MTB/RIF and TB culture from each participant; TB culture from the induced sputum will serve as the reference standard for evaluation of new diagnostics for active TB. Furthermore, chest radiographs will be used for TB screening. LTBI will be determined by Mantoux tuberculin skin test (TST) and QuantiFERON