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PARTNERSHIPS FOR ENHANCED ENGAGEMENT IN RESEARCH (PEER) HEALTH
Cycle 1

 
Principal Investigator: Andani Eka Putra, Andalas University
NIH-Supported Collaborator: Megan Murray, Harvard Medical School
Title of NIH Award: Epidemiology and Transmission Dynamics of MRD/XDR Tuberculosis
Project Dates: October 2013 - April 2017

Project Overview
 
Multidrug-resistant tuberculosis (MDR-TB) has hampered global efforts to control and manage tuberculosis infections. Indonesia ranks 8th globally among high MDR-TB burden countries, with WHO estimating about 2% of new and 17% of retreatment cases testing positive for multi-drug resistance. The US Global Health Initiative strategy for Indonesia aimed to diagnose one million TB patients and treat 5,100 MDR-TB patients by 2015. Despite progress made with the Indonesia National TB Program, significant gaps remain in understanding how and under what circumstances resistant Mtb emerges and is transmitted. This project aimed to elucidate the host, microbial, and environmental factors underlying the emergence and transmission of MDR and XDR-TB in Indonesia, obtain an unbiased prevalence of MDR, and describe the distribution and patterns of drug resistance mutations.
 
This observational prospective cohort study enrolled 2,400 incident cases of suspect pulmonary tuberculosis from government-operated community health centers, lung clinics, or hospitals within Padang, Pariaman Regency, and Pariaman City districts. Participants were followed up by healthcare professionals as per routine national protocol. Those testing positive for RIF-resistance had samples cultured, tested for antibiotic resistance, and sent for whole genome sequencing. The study results aimed to help the NTP and USAID accurately assess the burden of MDR and the need for new TB diagnostics and second-line drugs within Indonesia.
 
Final Summary of Project Activities
 
The research team engaged extensively with various government levels to ensure the study aligned with the existing TB eradication program in West Sumatra. They obtained necessary permissions, conducted training sessions for TB officers, and procured essential equipment, including the GeneXpert machine. Field preparations involved training officers on study procedures, including obtaining participant consent, conducting interviews, collecting sputum samples, and managing data. Initially, the study focused on Padang, Padang Pariaman, and Pariaman City districts, but due to low initial sample collection, Pesisir Selatan District was added in 2015.
 
Throughout the study, 2,436 new sputum samples were collected, with 2,425 testing positive on GeneXpert. Among these, 32 cases were identified as rifampicin (RIF) resistant, accounting for 1.32% of the samples. The samples underwent laboratory procedures, including decontamination, DNA extraction, and whole genome sequencing using Illumina technology, with bioinformatics analysis conducted at Toyama University, Japan. The team maintained rigorous sample and data collection protocols, ensuring proper storage and transport. Results were submitted to the Department of Health for follow-up and treatment, providing updated information on TB patients and supporting the national TB program. Additionally, the team found a positive response to their training and engagement efforts, as demonstrated by the high-quality data collected and the support from local health offices.
 
The project faced challenges, particularly in collecting adequate samples and questionnaires, a common issue in community-based research. The team extended the research period to address these challenges and improve enumerator management. By October 2017, all procedures were completed. Moving forward, the team plans to publish their findings in international journals. This community-based study ensured rapid identification and treatment of MDR-TB, contributing valuable data for improving TB diagnosis and management in Indonesia. The study's results, according to the PI,  will be published in the Gene Bank, while the team continues to support TB health programs by providing updated information and recommendations for optimizing diagnostics and treatment strategies.
 

 
Health Cycle 1 Recipients