Tuberculosis has sadly reclaimed its title as the leading infectious disease killer globally, surpassing COVID-19 in 2023. In 2024, it was responsible for the deaths of about 1.23 million individuals and affects approximately 10 million each year.
Recent research is bringing into question the accuracy of TB diagnoses.
A study published in Nature Medicine suggests that many tuberculosis cases might be misdiagnosed, which could have serious consequences for patient care.
This study examined data from 111 low- and middle-income countries in 2023. Given the uncertainty regarding the actual number of TB cases, co-author Nicolas Menzies, who is an associate professor of global health at Harvard, explained that his team used statistics on diagnosed cases shared with the World Health Organization to create a method for estimating both false positives and negatives. Regardless of how you interpret the numbers, it appears that a significant portion of diagnoses are incorrect.
Menzies estimates that around a million individuals who show TB symptoms receive treatment without a proper diagnosis, labeling them as false negatives. Conversely, more than 2 million people are mistakenly told they have TB when they actually have another condition.
“Among those diagnosed with TB each year, potentially a quarter, or even more, may not have the disease,” Menzies notes. In the worst cases, patients might have severe conditions like pneumonia or lung cancer. He points out that this kind of misdiagnosis has largely been overlooked in the TB field.
The study has received mixed reactions from experts.
Dr. Marcel Behr, a professor at McGill University and former director of the McGill International TB Centre, commended the research for shedding light on misdiagnoses, a subject that has not been thoroughly explored. He found the approach to be rigorous.
On the other hand, Dr. Lucica Ditiu from the Stop TB Partnership expressed concerns that heightened focus on false positives might detract from TB statistics, possibly causing governments to redirect funding elsewhere. She also fears that this emphasis could lead clinicians to hesitate when making diagnoses.
Causes of Misdiagnoses
What leads to such a high rate of false positives and undiagnosed cases?
Menzies attributes this to imperfect diagnostic tools and human errors.
TB can be diagnosed using several methods, mainly focusing on sputum analysis to detect the bacteria. The reliability of these tests varies, with advanced PCR techniques being significantly more reliable compared to older methods. However, many diagnoses don’t rely on positive test results. In fact, more than a third of diagnoses in low- and middle-income countries are made based on clinical judgment, where healthcare workers assess symptoms like persistent cough and night sweats.
Menzies argues that while these clinical assessments have good intentions, they are often the source of misdiagnosed TB cases.
Behr, who runs a diagnostic lab, believes that many health practitioners rely heavily on their instincts, a habit formed during periods when there were not as many reliable TB tests available. He admits that adapting to improved diagnostic tools takes time.
Ditiu hopes this study will lead to better access to diagnostic tools rather than having clinicians shy away from making diagnoses, especially in underserved areas.
“If the intention is to advocate for enhanced diagnostic tools, that’s spot on,” she states. “But if it implies that clinical diagnosis is fundamentally flawed, then that’s quite damaging. The reality is we still have a significant number of unidentified TB cases.”
Potential Consequences
No matter what the future holds for TB diagnosis, Menzies believes there’s a crucial takeaway concerning the risks tied to misdiagnosis.
Not diagnosing TB early can have serious ramifications—both for the treatment of the individual and for public health. While the importance of catching TB early has garnered considerable attention, the impact of falsely diagnosing someone with TB has been less explored.
Menzies lists several issues that arise from this misdiagnosis: costs of unnecessary treatment, lost work time, side effects from TB medications, and social stigma directed at patients. Perhaps most critically, individuals are not receiving timely treatment for whatever ailments they might actually have.
In Brazil, Menzies collaborated with the Ministry of Health to study patients initially diagnosed with TB who were then re-diagnosed later. Those individuals were nearly twice as likely to die compared to those whose original TB diagnosis was accurate.
He expresses genuine surprise at this finding: “You often read reports stating that analysts were shocked by an outcome. In our case, we were indeed surprised.” His conclusion is telling: “Some who receive false positives may actually have serious conditions that require immediate attention.”
This has caused Menzies to take the issue of incorrect TB diagnoses more seriously. Behr is hopeful that Menzies’ findings will bring this pressing issue to the forefront of the TB community, emphasizing that it’s been a conversation that needs to gain more visibility.
