UPDATES FROM THE 8TH REPORT INTERNATIONAL ANNUAL MEET-ING AT SALVADOR, BRAZIL – TO REFLECT AND MOVE FORWARD AGAINST TUBERCULOSIS USING COLLABORATIVE RESEARCH

By: Adhella Menur, Lidya Chaidir

If you read last year’s newsletter about the 7th Re-PORT Annual Meeting in Goa, India (INA-RESPOND Newsletter Sept 2023), we now bring you an update on the 8th RePORT Annual Meeting held in Salvador, Brazil.

To refresh your memory, RePORT (Regional Prospective Observational Research in Tuberculosis (TB)) is an international consortium established by the National Institute of Allergy and Infectious Diseases (NIAID) in 2013 (https://reportinternational.org/). Member countries include Indonesia (coordinated by INA-RESPOND), India, South Africa, Brazil, China, the Philippines, South Korea, and Uganda. The consortium’s inter-national activities are managed by the RePORT International Coordinating Center (TB-RICC), chaired by Dr. Jerrold Elner. The project is structured into two phases: Phase I (2013-2023, now completed) and Phase II (2019-present). The Re-PORT consortia are linked by a common data and specimen collection protocol, supporting local TB data and specimen repositories and research efforts in each participating country. RePORT Inter-national follows a standardized common protocol for two study cohorts—Cohort A for active TB and Cohort B for household contacts—with countries choosing to conduct one or both based on available resources.

INA-RESPOND participated in Phase I, specifically Cohort A, through the TRIPOD study (Tuberculosis Research of INA-RESPOND On Drug Resistance, NCT02758236, 2017-2020). The RePORT International annual meetings provide a platform for participating countries to coordinate, share TB research updates, present junior investigator projects, and engage in high-level discussions. This year, the meeting was held over four days in Salva-dor, Brazil, starting with a data pre-meeting on August 20th, followed by the main meeting from August 21st to 23rd, 2024. INA-RESPOND was represented by Adhella Menur, a TRIPOD researcher, and Lidya Chaidir as a Junior Investigator.

The data pre-meeting brought exciting updates. Following the complex process of Phase I data harmonization across participating countries, the Global Data Harmonization team advanced to visualizing and analyzing the data. In this RePORT data harmonization project, the TRIPOD study contributed 312 bacteriologically TB-confirmed subjects. RePORT International has partnered with Frontiers Science Foundation for data management, developing a centralized database and creating portal dashboards for data visualization, monitoring, and tracking cross-network study progress. One key initiative is the portal dashboard named RADar (RePORT Specimen and Data Availability Dashboard), an interactive tool that allows users to explore aggregate counts and summaries of available data and specimens across RePORT. RADar aims to facilitate new concept proposals by enhancing Re-PORT’s visibility and making investigators—both internal and external—more aware of the resources available within the network. Alex Benns from Frontiers Science presented a live demo of RADar, expressing enthusiasm about finalizing this tool in collaboration with RePORT member countries.

During the data pre-meeting, each RePORT coun-try member presented how specimens and data are stored and linked at their respective sites. Re-PORT International also sought to understand the challenges each country faced. Adhel shared the complexities of biorepository management within INA-RESPOND, which handles thousands of specimens from sites across Indonesia, all centralized at the INA-RESPOND Reference Laboratory in Tangerang District Hospital. Fortunately, smooth operations were ensured through clear procedures and strong coordination between clinical researchers, laboratory staff, the data team, and the IT team. The key link between specimens and clinical data is the unique identifier assigned to each participant. However, INA-RESPOND currently uses a simple Excel-based system for biorepository management. RePORT International plans to support INARESPOND by implementing FreezerPro, a cutting-edge laboratory management software. FreezerPro offers user-friendly tools for labeling, tracking, and managing samples with precision, improving overall efficiency and accuracy.

The following three days of the main meeting were packed with updates from RePORT International, new insights into TB science, Junior Investigator presentations, and capacity-building discussions. Dr. Bruno Andrade, the Principal Investigator from Brazil, opened the session with enthusiasm, highlighting his excitement for a productive and enjoyable meeting. He emphasized RePORT Brazil’s success in building networks, conducting extensive research, and publishing widely, attributing this to strong engagement with the Ministry of Health and TB-RiCC. RePORT Brazil also runs a career development program that offers funding to support young researchers who significantly contribute to their research achievements. Fatimah Jones from NIAID delivered sponsor updates, underscoring the importance of RePORT International as a research collaboration aimed at ending TB. She outlined NIAID’s four priority areas in TB research: (1) advancing fundamental TB knowledge, (2) improving TB diagnosis, (3) developing better treatment and prevention strategies, and (4) accelerating vaccine development. She also emphasized RePORT’s vision to strengthen the clinical and research capacities of regional networks, while fostering young and mid-career investigators and cultivating future RePORT leaders in partner countries.

The TB science update sessions featured key topics like the progression to active TB, treatment responses, and subclinical TB. One standout presentation was from Sarah Fortune of Harvard University, who discussed human-focused biological discovery in TB research. She explained that Mycobacterium tuberculosis (MTB) evolves under drug and host pressures, presenting findings from her study (Liu Q et al., Science 2022, doi: 10.1126/science.abq2787) on the transcriptional regulator Rv1830, or resR, as a frequent target of positive (adaptive) selection. resR mutants do not show canonical drug resistance or drug tolerance but instead shorten the post-antibiotic effect, allowing MTB to resume growth faster after drug exposure. This “phenotype antibiotic resilience” can contribute to treatment failure and the acquisition of canonical drug resistance. She emphasized the enormous opportunity within the RePORT International consortium to share data, samples, and assays, as differences across regions could reveal critical variations in pathogenic strategies. She encouraged the consortium to explore MTB strains in each country. Adhel and Lidya nodded to this idea since they had discussed it before, particularly the prospect of studying TRIPOD MTB strains and their geographical distribution in blind-spot regions like Medan, Denpasar, and Makassar. They considered spoligotyping as a cost-effective alternative to whole genome sequencing for this purpose. The homework clearly consists of finding funding to support this project.

This year, INA-RESPOND proudly sent Lidya Chaidir, a highly regarded TB researcher in Indonesia, as a Junior Investigator. Lidya has been assisting the INA-RESPOND Reference Laboratory, mainly working with Gustiani on extracting MTB DNA and performing targeted sequencing to analyze molecular drug resistance. Lidya’s abstract, titled “Discordant rifampicin susceptibility results between Xpert MTB/RIF and phenotypic drug susceptibility testing: Experience from a prospective study of adult pulmonary tuberculosis patients in Indonesia,” was one of only six abstracts selected from 27 submissions across RePORT member countries. The abstract highlighted despite the widespread use of Xpert MTB/RIF in Indonesia, there is a lack of performance
data and epidemiological information on rpoB mutations, highlighting a need for further research. Lidya envisioned further testing to increase scientific value, such as minimum inhibitory
concentrations (MIC) tests using MYCOTB MIC plate, at least on isolates with disputed and unreported mutations. Other accepted abstracts included: 1). Effects of missed anti-tuberculosis therapy doses on treatment outcome – RePORT Brazil, 2). Predictive metabolite signatures for risk of progression to active TB from QuantiFERON supernatants of household contacts of TB patients – RePORT India, 3). Insights into post-TB lung disease severity through PET-CT Imaging, lung function testing, and immune characterization – RePORT South Africa, 4). Subclinical TB in adults with household exposure to recently diagnosed pulmonary TB patients – RePORT South Africa, and 5). Transcriptomic and proteomic biomarkers for subclinical TB – RePORT South Africa.

Each RePORT country member was provided 10 minutes to present their achievements, activities, and challenges. Adhel, on behalf of Prof. Dr. Erlina Burhan, Sp. P (K), and INA-RESPOND, presented updates on RePORT Indonesia. The highlight was the approval of the Material Transfer Agreement (MTA) for shipping specimens for the RePORT International Biomarker study after nearly a year of effort. Adhel appreciated the hard work of Hanum and the INA-RESPOND team, as well as the support from Sheetal Verma and the RePORT Biomarker team for this achievement. She also mentioned the upcoming TRIPOD publication on treatment outcomes and ongoing MTB laboratory capacity building. The biggest challenge for INA-RESPOND remains the lack of active funding for TB research. INA-RESPOND is also under significant reorganization in the Ministry of Health. Adhel emphasized INA-RESPOND’s interest in pursuing external funding and collaboration opportunities. In response, the TB-RiCC leadership held a close gathering with Adhel and Lidya to brainstorm ways to boost opportunities for RePORT Indonesia, focusing on finding funding and assisting in writing research grants. They plan further discussions with INA-RESPOND and Indonesia TB researchers during the November UNION meeting in Bali, Indonesia.

Dr. Bob Bollinger from the capacity-strengthening working group provided updates on last year’s achievements, including the development and launch of TB courses and the enrollment of four RICC post-doctoral fellows from RePORT Brazil and India. He announced the next new recruitment for the post-doctoral fellowship program and shared his excitement about expanding access to TB courses through a QR code initiative, which everyone can access. The RePORT Scientific Review Committee also provided updates on their work, informed attendees about projects in the queue, and encouraged investigators to submit research proposals.

Dr. Jerrold Ellner concluded the meeting by celebrating its success, noting the high participation, engagement of external speakers, and excellent Junior Investigator presentations. He praised the demonstration of the RADar, research updates, and the community engagement plan. The inclusion of a TB survivor (a Brazilian clinician who worked in the ICU) talks and the environmentally friendly, paperless format, supported by an Annual Meeting website, were well-received. Reflecting on RePORT International’s journey, Dr. Ellner thanked country members and supporting teams. He announced an upcoming supplement in the Clinical Infectious Diseases journal titled “Advancing TB research: enhancing treatment outcomes, predicting disease progression, and understanding subclinical TB.” This will include an article about RePORT International milestones and prospects. The challenges ahead include promoting RePORT data and biospecimens, collaborating with other TB networks, seeking external funding, and moving toward interventional research.

RePORT Indonesia, through INA-RESPOND, is committed to advancing TB research through collaborative efforts.

This meeting was truly memorable for me. First, I had the opportunity to travel with Lidya Chaidir, who I deeply admire. She is a role model for any woman interested in science, particularly in TB research. Second, I met and befriended Evangeline Ann Daniel, a junior investigator from RePORT India. She is such a lovely person and a passionate young TB researcher. A highlight of the meeting was when the three of us had the opportunity to chat with Prof. Bavesh Kana during lunch. Prof. Kana works at the University of the Witwatersrand in Johannesburg, South Africa. He shared inspiring stories about how he began his career, building his research lab from scratch, persistently seeking grants, and doing research creatively. Out of over 700 applicants worldwide, he received a prestigious grant from the Howard Hughes Medical Institute. He also translated his research into products used for quality assurance of TB diagnostic tools, which are now used in over 20 countries, including Indonesia.

Despite being such a renowned researcher, his humbleness and openness truly inspired me. He encouraged us to be resilient and never give up, no matter the challenges we face. He shared a piece of wisdom from his mentor: “Whatever happens in life, just dance with it!”

Thank you, INA-RESPOND, for this incredible opportunity – Adhel.