The truth (and false positives) of TB diagnosis : NPR

A woman diagnosed with tuberculosis receives treatment at Barawe General Hospital in Somalia.

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Tuberculosis has gained the unwanted distinction of being the world’s number one deadly infectious disease – a role it took over from COVID in 2023. Tuberculosis has claimed the lives of 1.23 million people in 2024 and sickens around 10 million people each year.

Research now casts doubt on the true number of TB cases.

A new study published in Natural medicine found that many TB diagnoses may be incorrect – and that this could have significant implications for patient care and well-being.

The study analyzed data from 111 low- and middle-income countries in 2023. Since no one knows the true number of TB patients, Nicolas Menzies – co-author of the paper and associate professor of global health at the Harvard TH Chan School of Public Health – says he and his colleagues used data on the number of TB cases submitted to the World Health Organization and came up with a formula to estimate false negatives and false positives. No matter how you break the numbers down, he says, the main conclusion is the same: There are a lot of incorrect diagnoses.

Menzies and colleagues estimate that among those who seek medical attention for symptoms that may indicate TB infection, about one million people have the disease but do not receive that diagnosis. These are false negatives. On the other hand, the estimated number of false positives was even worse: Every year, 2 million or more people are wrongly told they have TB when they actually have something else.

“Of all the people who are diagnosed and treated for TB each year, perhaps a quarter of them – and maybe even more – may not have TB,” says Menzies. He says in the most severe cases, these patients could suffer from a life-threatening illness like pneumonia, lung cancer or chronic obstructive pulmonary disease. He says this type of misdiagnosis is a “dead spot” in the world of tuberculosis.

The study was both praised – and criticized – by outside experts.

Paying attention to incorrect TB diagnoses is an important step, says Dr. Marcel Behr, professor of medicine at McGill University and founding director of the McGill International Tuberculosis Centre. “The question of whether we have false positives has been little studied,” he says, adding that he was impressed by the “rigorous approach” of the research.

But for Dr Lucica Ditiu, pulmonologist at the head of the Stop TB Partnership, this emphasis on false positives could backfire. She fears the study will cast doubt on TB statistics, prompting governments and global health funders to move their dollars elsewhere. Ditiu also worries that misdiagnosis could make clinicians reluctant to diagnose the disease for fear of making a mistake.

The reason for diagnostic errors

Why are there so many false positives and missed cases?

Menzies’ theory: imperfect diagnostic tests – and human error.

There are various ways to diagnose TB, but most tests rely on sputum (mucus coughed up by a patient) which is then analyzed for signs of TB bacteria. The accuracy rate varies widely, with the new PCR analysis machine being much more precise than traditional methods of examining a sample under a microscope.

However, a significant number of diagnoses are made without a positive test result. Well over a third of diagnoses in low- and middle-income countries are the result of a doctor, nurse or other clinician examining a patient’s symptoms — such as persistent cough, weight loss, night sweats — and then following guidelines to make their best medical guess.

Menzies believes these clinical assessments, while well-intentioned, are responsible for many cases where people are told they have TB when they actually have something else.

Behr – who runs a tuberculosis diagnostic lab – has a theory about what’s going on.

He believes that many health workers “grew up in an era where there were no good TB diagnoses” and are used to trusting their instincts for test results. He admits that it “takes a little time for doctors to adapt” and adopt the improved tests.

Ditiu hopes the impact of this study will be to improve access to testing – and the tests themselves – and not dissuade clinicians from making a diagnosis, particularly in remote areas where medical facilities are underfunded.

“If the point of the paper is to say we need better tools, better diagnostics, I think that’s absolutely correct,” she says. “If it is to say: Oh my God, the clinical diagnosis is so badso it’s very damaging. Because the reality of the world, like it or not, is that our biggest problem with TB is that we have a very large number of people who are not diagnosed at all, in any form. »

The consequences?

Whatever the future of TB diagnosis, Menzies believes an important message from his study concerns the dangers of misdiagnosis.

Failure to diagnose tuberculosis early can be problematic, both for the treatment of the individual and for the safety of those who may contract the bacterial infection. These risks have received a lot of attention, he notes. In contrast, he says, the downsides of falsely telling someone they have tuberculosis have received less attention.

He can list a long list of reasons why this is so problematic: treatment costs and time off work, drug side effects – particularly liver damage caused by powerful anti-TB drugs – and the stigma that TB patients face.

And another major problem: the patient is not treated in time for what he has.

In Brazil, Menzies partnered with the Ministry of Health to conduct a study of patients who were diagnosed with tuberculosis and then had their diagnosis changed. These patients were nearly twice as likely to die during the follow-up period than patients whose TB diagnosis was accurate at baseline.

“I always sigh when I read, you know, stories like, ‘Analysts were surprised by a discovery.’ But it’s actually something that surprised us,” says Menzies.

His conclusion? “Some people who have received false-positive diagnoses actually have quite serious illnesses that would benefit from prompt diagnosis and treatment.”

This discovery led Menzies to take incorrect diagnoses of tuberculosis much more seriously. Behr hopes that Menzies’ new study – quantifying these incorrect diagnoses on a global scale – will do the same in the field of tuberculosis more broadly. Behr says it’s a topic that has been discussed quietly and “needs to turn up the volume a little bit.”