The Silent Spread: How Half of the World’s TB Cases Fly under the Radar

Asymptomatic tuberculosis may play a key role in global transmission. Discover its hidden impact and the challenges of detection and control.

After a brief hiatus, tuberculosis (TB) recently surpassed COVID-19 to reclaim the title of the world’s deadliest infectious disease—a title it has held throughout most of human history. Global TB control has been hindered by imperfect diagnostic tests, lack of an effective vaccine, and complex treatment regimens. Funding cuts to the WHO and USAID further threaten to unravel decades of progress in the fight against TB.

The hidden face of an ancient disease

In 2023, TB caused over 10 million cases globally. Although we typically picture TB patients as individuals who are visibly ill and coughing, recent evidence disputes this notion, demonstrating that roughly 63% of people with bacteriologically confirmed TB report no cough, and 28% report no symptoms at all. Other studies suggest that asymptomatic TB might be responsible for up to 68% of global TB transmission. This creates a massive blind spot for TB control efforts. Most TB screening programs rely on people feeling unwell to present to health care facilities for TB testing. But what happens when over half of all cases don’t have the most common symptom for TB?

Roughly 63% of people with bacteriologically confirmed TB report no cough, and 28% report no symptoms at all

Recent scientific advances have revealed that symptom-based screening is missing a notable proportion of TB patients. These "silent spreaders" may be unwittingly transmitting the disease to friends, family members, and others in their communities. Last year, TB experts developed a framework called the International Consensus for Early TB (ICE-TB) to classify early TB states based on the presence of symptoms, macroscopic pathology and likely infectiousness. The WHO has further acknowledged this issue by refining the definition of asymptomatic TB to inform programmatic management. These efforts have provided some much-needed clarity to asymptomatic TB phenotypes and highlight the need for intensified research.

Symptom-based screening is missing a notable proportion of TB patients. These "silent spreaders" may be unwittingly transmitting the disease to friends, family members, and others in their communities

However, most research on asymptomatic TB has come from prevalence survey data which rely on patients presenting with common TB symptoms or a positive chest x-ray before further diagnostic testing is performed. This data overlooks an important asymptomatic TB phenotype, which is characterized by people who have detectable TB bacteria in their sputum yet show no visible abnormalities on chest X-rays. Studies that employ universal testing have discovered that between 3-52% of all TB cases present with a negative chest X-ray despite being bacteriologically confirmed by PCR or culture. While the exact prevalence of this phenotype is unknown, it may play an important role in perpetuating transmission.

How big is the elephant in the room?

Recognition of this hidden phenotype may have major implications:

1. Underestimated burden: Global TB estimates rely heavily on prevalence surveys that typically use chest X-rays or presence of symptoms as screening tools. If they're missing this phenotype entirely, we may be significantly underestimating the true burden of TB.
2. Clinical management: We don't know if people with this form of TB require treatment. If so, would they require the same treatment as other TB patients? Or would a regimen like those approved for TPT be enough?
3. Research gaps: We also don't understand how much these patients contribute to transmission, the progression rates (or if they can clear the infection, pointing at some kind of temporary colonization) or the immunological profile of individuals with this phenotype.

In collaboration with a group of international TB experts, we wrote a Comment in the Lancet Respiratory Medicine to raise awareness on the importance of this early TB phenotype and highlight the research gaps that might contribute to better TB control and patient management. The growing recognition of asymptomatic TB—particularly this overlooked phenotype—is fundamentally shifting our understanding of a centuries-old epidemic. Available evidence suggests that this hidden form of TB warrants urgent attention, and may represent an additional source of infectious TB that has slipped between the cracks of passive case finding and imperfect diagnostics for centuries.