Preventive tuberculosis treatment starts waning after one year in high-burden settings, study finds
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Tuberculosis preventive treatment (TPT) is considered one of the most important public health tools to protect individuals and countries from the deadly infectious disease and is a critical part of the World Health Organization's goal to end the global TB epidemic by 2035. This treatment, which includes antibiotic medicines that can prevent inactive TB infections from developing into active disease, has been shown to be highly effective, but how long this protection lasts—and whether its duration varies by region or community risk level—remains unclear.
To better understand the duration of protection from TPT, researchers at Boston University School of Public Health (BUSPH) and the University of California, Berkeley School of Public Health (UC Berkeley) estimated TB risk among people with TB infections in 24 countries and found that TPT offered strong initial protection, but long-term protection varied depending on the burden of TB disease in each area.
Protection varies with local TB burden
Published in The Lancet Respiratory Medicine, the study found that TPT offered strong protection during the first 12–24 months across settings with all levels of TB burden. In medium- and low-burden settings, this protection lasted for at least eight and 13 years, respectively, and there was no significant difference in long-term TB disease risk between people who did and did not complete the full course of medication.
However, in high-burden settings, the initial protection achieved from TPT began waning after just one year of taking the medication.
These findings suggest that expanding TPT among high-risk groups in less-burdened countries can provide meaningful and long-lasting protection against this disease, but high-burden countries should consider combining TPT with other interventions to achieve the long-term benefits these medications can provide.
"In this study, our results corroborated something that was already well-established—TPT is highly effective at preventing TB progression among close contacts and people who have been infected with TB," says study lead author Lauren Linde, an epidemiology doctoral student at SPH.
"However, our finding that the initial effect of TPT declined so rapidly in very high-burden settings strengthens the case for not placing too much emphasis on TPT in isolation from other interventions that address ongoing community transmission."
The reach of preventive treatment
The study presents the most comprehensive data thus far on the duration of protection from a single course of TPT across multiple settings. Nearly two billion people—a quarter of the world's population—are infected with TB, most of whom live in low- and middle-income countries. While most TB infections remain latent and produce no symptoms, about 5–10% of infections progress to active TB disease. In 2024, 1.2 million people died after developing active TB disease.
Preventive treatment consists of one or more antibiotic medications, such as isoniazid and rifapentine, typically prescribed for four months. In 2024, 5.3 million people received this treatment, and officials at the 2023 United Nations High-Level Meeting on Tuberculosis committed to expanding this treatment to 45 million people across the globe, which would cover 90% of the global population at highest risk of developing TB.
Increasing access to these medications is critical, but understanding the short- and long-term effectiveness of preventive treatment is also essential to achieve the goal of eliminating TB worldwide.
"One of the most encouraging findings is that a single course of preventive treatment was associated with protection lasting well over a decade in settings where TB is relatively uncommon," says study senior and corresponding author Dr. Leonardo Martinez, assistant professor of epidemiology at UC Berkeley. "Expanding access to preventive treatment in these settings could protect more people from developing TB for many years."
Tracking TB risk across 24 countries
For the study, Linde and colleagues used data from 44 cohort studies that traced close contacts of individuals with TB in 24 countries between 1998 and 2023. The analysis included more than 85,000 contacts who tested positive for TB infection at the beginning of the study, among whom 1,080 people developed active TB.
Low-burden countries were defined as those with fewer than 20 new TB disease cases per 100,000 people annually, while medium-burden countries included those with 20–100 new TB cases per 100,000 people annually, and high-burden countries included those with more than 100 new TB cases per 100,000 people annually.
Most cases of active TB disease occurred within the first two years of infection, supporting past research indicating that this period is crucial for people with TB infections to receive treatment.
People in medium- and low-burden settings who completed the medication course developed the strongest protection and had a lower risk of developing TB within the first year of infection compared with people who only partially completed the course—but within two years of infection, the risk among these groups was not meaningfully different. Both groups still showed strong protection for at least eight years.
Reinfection may shorten protection
The researchers say more data is needed to understand why protection waned faster in high-burden settings.
"It is understood that high-burden settings will have higher rates of re-exposure and reinfection, and that is likely driving a large portion of the waning effects we observed," Linde says.
"Once you complete a course of TPT, those antibiotics leave your system and you aren't protected from getting infected again. There is also some conjecture in the literature that TPT might actually be less effective at killing all the TB bacteria among people in higher-burden settings, who may have had multiple exposures and carry a relatively larger baseline bacterial load, but unfortunately our data can't tease apart these possible mechanisms."
Combining treatment with other safeguards
The team hopes this new insight can encourage continued expansion of TPT across the globe and guide high-burden countries to offer this treatment in tandem with other health-protective resources to detect, prevent and treat TB.
"TPT is a critical tool for combating the spread of TB worldwide, and we aim to continue studying how to best target TPT to achieve the greatest impact in reducing TB incidence," Linde says.
Publication details
Lauren R Linde et al, Duration of effectiveness of tuberculosis preventive treatment across various tuberculosis burden settings: a systematic review and individual-participant meta-analysis, The Lancet Respiratory Medicine (2026). DOI: 10.1016/s2213-2600(26)00219-5
Journal information: Lancet Respiratory Medicine
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Infectious diseasesCommon illnesses & PreventionPreventive medicine Provided by Boston University Who's behind this story?
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