Tuberculosis (TB) remains a major global health challenge, causing approximately 1.25 million deaths and 10.8 million illnesses annually.
The Indo-Pacific region accounts for over half of the global TB burden, prompting intensified efforts in vaccine research, treatment strategies, and regional collaborations. Researchers are exploring new vaccine candidates, improving existing ones through advanced delivery methods, and developing controlled human infection models, while international bodies and national governments, including Australia, focus on addressing the disease's socio-economic determinants and strengthening health systems.
Global and Regional Burden
TB is identified as a leading infectious cause of death worldwide. In 2023, approximately 1,400 people developed TB in Australia, with 67 deaths reported between 2021 and 2023. Rates among Aboriginal and Torres Strait Islander peoples are significantly higher, reported to be between four and six times that of non-Indigenous Australian-born Australians.
The Indo-Pacific region bears a substantial portion of the global TB burden. Papua New Guinea records one of the highest TB incidence rates globally, and TB cases in the broader Pacific region increased by 33 percent in 2024.
The prevalence of TB is linked to socio-economic conditions such as poverty, overcrowding, undernutrition, and fragile health systems.
Challenges in Prevention and Treatment
Current tools for combating TB present several significant challenges:
- Vaccination: The Bacille Calmette-Guérin (BCG) vaccine offers protection to young children against severe, disseminated forms of TB. However, its effectiveness in adolescents and adults, who are primary transmitters of pulmonary TB, is limited and inconsistent.
- Drug-Resistant TB (DR-TB): DR-TB is an increasing concern, developing when treatment is incomplete or interrupted. In 2023, over 400,000 people globally developed DR-TB, with significant numbers in Asia and the Pacific, including 170,000 cases in the WHO South-East Asia Region and 74,000 in the Western Pacific Region. Papua New Guinea alone records approximately 2,400 DR-TB cases annually.
- Treatment Regimens: Treatment for drug-sensitive TB typically involves daily antibiotics for four to nine months. DR-TB can require up to 20 months of treatment, often accompanied by severe side effects and lower success rates.
- Financial Barriers: Around half of TB patients worldwide incur catastrophic costs, defined as exceeding one-fifth of their annual household income, for diagnosis and treatment. This figure rises to approximately 80 percent for those undergoing DR-TB treatments.
- Access to Newer Therapies: While newer diagnostics and shorter, safer treatment regimens have emerged, many existing tools are considered outdated. Therapies developed over the past decade have reduced treatment times and toxicity, but their access remains uneven in many countries due to financing, procurement systems, and diagnostic limitations. Funding for TB research and development has also been reported as insufficient.
Advances in Vaccine Research
Researchers are pursuing multiple innovative avenues to improve TB vaccination and develop new tools to combat the disease.
Immune Response Evaluation
Immunologist Erica Andersen-Nissen leads a team at the Cape Town Lab, which assesses immune responses, particularly T cells, in HIV and TB vaccine trial participants. Their work includes identifying changes in "helper" T cells after BCG revaccination in teenagers and pinpointing polyfunctional CD4 T cells and donor-unrestricted T cells as potentially important for protective TB vaccine responses.
Correlates of Protection
Biostatisticians analyze immune data to define "correlates of protection," comparing responses between protected and unprotected trial participants. One trial evaluating BCG revaccination showed 45% effectiveness in preventing sustained conversion of IGRA tests in teenagers, a proxy for TB infection. Methodologies developed for HIV and COVID-19 vaccine trials are being adapted for TB, considering participants' potential prior exposure to M. tb or BCG.
M72 Vaccine Candidate
Andersen-Nissen's team is generating immune data from a Phase 2b trial of the M72 vaccine, which statisticians are currently evaluating. Detailed mechanistic insights into M72's potential effectiveness are being sought through large-scale single-cell analysis of trial samples.
Improved BCG Delivery
Associate Professor Andreas Kupz's research focuses on improving the existing BCG vaccine, citing its complex protein composition. Australian research indicates that mucosal delivery (e.g., inhalation) of modified BCG strains activates progenitor cells and prompts T cells to establish local residency within the lungs, which has shown superior protection in animal models compared to traditional intradermal vaccination. Previous studies demonstrated significant protection from intravenous BCG in non-human primates, although this method is considered impractical for mass vaccination. Clinical trials are underway at Oxford University to evaluate the safety, immunogenicity, and optimal dosage of licensed BCG delivered into human lungs. Researchers are also developing modified BCG strains that aim to offer improved immunity without increased virulence.
Controlled Human Infection Models (CHIMs)
Kublin and collaborators are investigating the use of CHIMs for TB vaccine and drug research. This involves intentionally infecting human volunteers who can be effectively treated. An advanced CHIM is being developed with Harvard University, utilizing an engineered M. tb strain containing "kill switches" designed to cause the bacteria to self-destruct without specific drugs, potentially advancing studies within approximately two years.
Biostatistics and Training
Biostatistician Edlefsen contributes to IMPAc-TB, a project focused on elucidating protective immune responses against M. tb, and trains future TB biostatisticians through the African Tuberculosis Biostatistics Training Program.
Implementation and Broader Factors
While a new TB vaccine is estimated to be at least five years from deployment, the World Health Organization (WHO) is advising countries to begin developing implementation plans. Research into vaccine acceptability notes enthusiasm in communities most affected by TB.
The COVID-19 pandemic reversed a trend of declining TB deaths globally, particularly affecting lower and middle-income countries. TB is recognized as a disease exacerbated by poverty and vulnerability. Australia collaborates with Indo-Pacific governments on TB prevention and response through partnerships with universities, civil society, medical research institutes, and TB Alliance. Australia also advocates for TB elimination efforts in the region through its position on the board of the Global Fund to Fight AIDS, Tuberculosis and Malaria.
Investment in TB research and development is identified as important for enhancing tools for neighboring countries and reducing long-term strain on health systems.
Continued progress against TB requires sustained political commitment and investment to strengthen patient support systems and accelerate the development of new tools. Factors such as climate change, which can disrupt treatment, displace communities into crowded conditions, and increase food insecurity, add urgency to these efforts. Integrating TB treatments into climate-resilient health systems across the Indo-Pacific is identified as necessary.