Global TB Program Research

Siyakhula

Siyakhula, a collaborative Global TB Program HIV/AIDS training program led by Dr. Anna Mandalakas, supports three public health doctoral trainees in operational, clinical, and translational research focusing on HIV/AIDS and TB in pediatric populations, and two in-country cohorts of predoctoral trainees in applied research methods. Our blended binational approach is primarily driven by Eswatini-based learning forums, augmented by strategic US-based learning opportunities to strengthen operational, clinical, and translational research capacity in Eswatini, while simultaneously producing high-quality researchers who will successfully transition to independence, train the next generation of Emaswati scientists, and lead national efforts to end the dual HIV/TB epidemic. This project is being implemented in partnership with Baylor Children’s Foundation in Eswatini, the Eswatini Ministry of Health, the University of Eswatini, and the University of Texas Health School of Public Health. (NIH Funded 2021-2026)

Read more publications associated with this project.

INSIGHT

As part of the NIH Fogarty International Center LAUNCH Initiative, the INSIGHT consortium is formed between Baylor College of Medicine Global TB Program, with leadership from Dr. Anna Mandalakas, the University of Alabama at Birmingham, the University of Maryland Baltimore, and the University of Pittsburgh. The consortium aims to train the next generation of aspiring global health researchers by giving early-career scientists a mentored research training experience in global health at established biomedical and behavioral research sites across 24 low- and middle-income (LMIC) institutions in 20 countries and their respective international research training sites in Africa, Asia, and the Americas. Trainee research projects are supported by experienced and dedicated mentors with expertise in clinical, public health, laboratory, and implementation research. (NIH Fogarty International Center funded; 2021-2026)

Read more publications associated with this project.

Quantifiable Stool-based TB PCR to Improve Diagnostics and Treatment Monitoring
In 2019, the National Institutes of Health (NIH) awarded Baylor College of Medicine’s Global TB Program funding to support stool diagnostics in Eswatini, Mozambique and Tanzania. The project, led by Dr. Anna Maria Mandalakas, tested new stool-based TB diagnostic tool to improve TB detection in children and people living with HIV. 

The project demonstrated that our novel stool-based test is just as effective as the first-line lab-based test typically performed on sputum, which is coughed up from the lungs and often difficult for children and people with HIV to produce. Our test correctly identified nearly 95% of TB cases among participants we knew had TB. Among participants who were diagnosed with TB based on clinical criteria (such as symptoms, a positive chest X-ray, or exposure to TB, among others) rather than a lab test, our stool-based PCR test provided microbiological confirmation in 17-21% of additional TB cases compared to the recommended diagnostic tests. If incorporated into routine diagnostic evaluation, our test could help to identify individuals with TB who are missed with current routine tests. We also demonstrated that within the first two weeks of treatment, our stool-based test can predict patients who initially had a positive M tuberculosis detection test that will become negative during treatment. Hence, this technique could differentiate people who are likely to respond well to treatment from those for whom first-line treatment will not be effective. This will help to guide precise treatment tailored to the needs of individuals. This study also demonstrated that targeted Next Generation Sequencing can identify drug resistance from stool provided by participants with TB. This technique affords the opportunity to obtain critical diagnostic information for TB patients who struggle to provide respiratory specimens, such as young children and people with HIV. These new tests promise to help identify the 60% of child TB cases and 40% of adult TB cases that are currently missed, improve TB treatment outcomes among vulnerable patients, and help to contain the spread of drug-resistant TB.

Read more publications associated with this project. 

DCLIPT (Developing Clinical Prediction Tools to Define Strategies for Differentiated Service Delivery in Children and Adolescents Living with HIV in sub-Saharan Africa)

The DCLIPT project, funded by NIH and led by Dr. Alexander Kay, aims to improve health outcomes for children and adolescents living with HIV (CALHIV) in sub-Saharan Africa. It focuses on developing clinical prediction tools to better identify those at highest risk for death and viral non-suppression following antiretroviral therapy (ART) initiation. By analyzing data from the Texas Children’s Global (TCH Global) network across multiple African countries, the project is creating models using machine learning to predict these risks. Additionally, DCLIPT will evaluate different tuberculosis preventive treatment (TPT) strategies to determine their effectiveness in reducing TB incidence and mortality among CALHIV. The ultimate goal is to guide more personalized and effective care for this vulnerable population. This project is being implemented in partnership with Baylor Children’s Foundations in Eswatini, Lesotho, and Tanzania. (NIH and CFAR Funded, 2020-2025)

Read more publications associated with this project.

Thrasher Research Fund Projects

Performance of Computer-Aided Detection for Tuberculosis Diagnosis in Children Living with HIV

This is a prospective cohort study of children living with HIV who are evaluated for TB at the Port Moresby General Hospital. Inclusion criteria: all CLHIV <15 years of age consulting in the HIV clinic and completing evaluation for TB at PMGH. Exclusion criteria: if the child or the parent refuses participation (refuses to sign informed consent). The primary outcome is the CAD reading score optimal threshold generated by the ROC (receiver operating characteristic) curve, which will be calculated by plotting the true positive rate against the false positive rate of the CAD reading on a curve for the diagnosis of tuberculosis. This project is led by Dr. Anca Vasiliu.

LISN
Wastewater - Catalyst
TBfreePNG

Evidence demonstrates an elevated risk of tuberculosis (TB) in pregnant and postpartum mothers. Since 2006, the WHO has recommended screening for active TB in pregnant women as part of routine antenatal care in populations with a TB prevalence above 100/100,000. In Papua New Guinea the prevalence of TB is 432/100,000 and climbs to over 1000/100,000 in the National Capital District which contains the capital of Port Moresby, Papua New Guinea. Leveraging a robust family-centered integrated approach, the Global TB Program through the leadership of Dr. Henry Welch and support of Dr. Anca Vasiliu collaborate with partners in Papua New Guinea to support implementation of TBfreePNG. TBfreePNG integrated TB screening, prevention, and diagnosis of pregnant and postpartum mothers and their children over 18 months (Stop TB Partnership TB Reach funded, 2023-2025).

TB REACH: The Butimba Project

One of our team’s signature projects was born with a community-based child TB case-finding intervention complemented by operational research. Funded by the Stop TB Partnership’s TB REACH initiative directly to the Baylor Children’s Foundation-Eswatini, our program was designed to increase early detection of TB cases in Eswatini, a setting with an extremely high HIV burden, through innovative approaches. We demonstrated a 32 percent increase in bacteriologically confirmed child TB detection in year one. We also found that contacts were more two-times more likely to have TB if they were under 5 years old, nearly five times more likely to have TB if they were living with HIV, over seven times more likely to have TB if they were already reporting more than one TB symptom, and almost twice as likely to have TB if they shared a bed or home with the person first diagnosed with TB in the house (known as the index case).

There was a 1.4-fold increased chance of detecting a TB case in households known to be affected by HIV. Most importantly, we demonstrated that contact tracing prioritizing children is not only feasible in a TB/HIV high-burden setting but contributes to overall case detection. Our findings support WHO guidelines prioritizing contact tracing among children and HIV-infected populations while highlighting the potential to integrate TB and HIV case finding.

Read more publications associated with this project.

The Child TB-HIV Project

The Global TB Program has partnered with the School of Medicine and Health Sciences at the University of Papua New Guinea and The Paediatric Society of Papua New Guinea to improve diagnostic and treatment capacity of children and families affected by TB and HIV since 2013 through The Child TB-HIV Project, funded by the Australian Government. Not only does the Global TB Program through the leadership of Dr. Henry Welch helps lead a team that treats over 900 children with TB yearly, but it has also implemented best practices such as the care and treatment of children with MDR-TB, TB-HIV co-infection, the use of GeneXpert, developing TB guidelines, as well as training.

EpiScars (Post-TB epigenetic scars' impact on long-term inflammation, immunity and mortality)

The EpiScars project, funded by the NIH from 2023-2027 and led by Dr. Andrew DiNardo, aims to understand why tuberculosis (TB) survivors face a significantly higher risk of death from conditions like cardiovascular disease, cancer, and recurrent infections, even after being cured of TB. Researchers will follow 300 TB survivors for 36 months to identify specific DNA methylation marks, called EpiScars, that may increase the risk of illness and death. The project will also use advanced single-cell sequencing to explore how certain progenitor cells may contribute to the long-term effects of these epigenetic changes. Additionally, mouse studies will investigate whether manipulating cellular processes, such as the TCA cycle, can help repair these epigenetic scars. The research will take place in Eswatini and the U.S.

Common Epigenetic Post-Infections Premature Aging

The Common Epigenetic Post-Infectious Premature Aging Project, funded by the NIH from 2023-2027 and led by Dr. Andrew DiNardo, seeks to understand why survivors of infections like pneumonia and sepsis face a significantly higher risk of death, with survival rates for severe pneumonia patients as low as 22-30% after two years. The project will study DNA methylation changes that occur after various infections (bacterial and viral pneumonia, tuberculosis, skin infections, and HIV) to determine which alterations are linked to higher mortality within two years. Researchers will use single-cell bioinformatics to explore how these epigenetic changes affect long-term inflammation and immune response. Mouse studies will also investigate metabolic factors that drive these immune and inflammatory disruptions. The research is based in Houston, Texas.