Tuberculosis Misdiagnosis: A Global Crisis
Tuberculosis (TB) remains the world's leading infectious disease killer, responsible for an estimated 1.23 million deaths in 2024 and affecting approximately 10 million people annually.
Recent research has drawn attention to significant challenges in TB diagnostic accuracy globally, while a new testing technology has been developed that may address some of these issues.
Global Misdiagnosis Estimates
A study published in Nature Medicine analyzed 2023 data from 111 low- and middle-income countries to estimate rates of incorrect TB diagnoses. Researchers led by Nicolas Menzies of the Harvard T.H. Chan School of Public Health used World Health Organization (WHO) data to calculate numbers of false negatives and false positives.
Their estimates indicate that:
- Approximately 1 million people who seek medical care for TB-like symptoms have the disease but are not diagnosed (false negatives)
- An estimated 2 million or more people annually are erroneously diagnosed with TB when they have a different condition (false positives)
"Up to a quarter, or potentially more, of individuals diagnosed and treated for TB each year might not have the disease."
Menzies noted that some of these patients could have other conditions such as pneumonia, lung cancer, or chronic obstructive pulmonary disease, which he termed a "blind spot" in the TB field.
Causes of Diagnostic Errors
Menzies attributed high rates of misdiagnosis to imperfect diagnostic tests and human error. TB diagnosis often relies on sputum analysis, with newer PCR machine analysis offering higher accuracy than traditional microscopic methods.
However, over a third of diagnoses in low- and middle-income countries are made without a positive test result, based instead on a clinician's assessment of symptoms like persistent cough, weight loss, and night sweats.
Dr. Marcel Behr, a professor of medicine at McGill University, noted that many health workers who practiced in an era with limited TB diagnostics may still rely on their intuition over improved test results.
Consequences of Misdiagnosis
Menzies highlighted risks associated with incorrect TB diagnoses. While failures to diagnose TB early carry well-recognized risks for individual treatment and bacterial spread, the downsides of incorrect TB diagnoses include:
- Costs associated with treatment and missed work
- Side effects from TB drugs, such as liver damage
- Social stigma faced by TB patients
- Delayed or absent treatment for the patient's actual medical condition
In a study conducted in Brazil with the Ministry of Health, patients initially misdiagnosed with TB were nearly twice as likely to die in the follow-up period compared to those whose TB diagnosis was accurate from the outset.
New Diagnostic Technology
A new TB test, the MiniDock MTB, has been developed by Chinese company Pluslife. The device processes a sample of phlegm or a tongue swab by heating, spinning, and scanning for TB bacterium DNA.
Key specifications:
- Device cost: $300
- Per-test cost: $3–$4
- A study in the New England Journal of Medicine involving nearly 1,400 patients across seven countries found the test meets WHO accuracy targets using phlegm or tongue swabs
- The WHO recommended the test in September 2024
- Traditional testing relies on microscopic examination of phlegm, which requires samples that some patients cannot produce
Limitations of the New Test
"The test may not detect early-stage TB with low bacterial load."
Lucica Ditiu of Stop TB Partnership noted the test also cannot differentiate between drug-susceptible and drug-resistant TB, which requires additional testing for treatment decisions.
Expert Perspectives on Misdiagnosis Data
Dr. Marcel Behr praised the Nature Medicine study for its attention to incorrect TB diagnoses and its rigorous approach, noting that false positives have been understudied.
Conversely, Dr. Lucica Ditiu expressed concern that the study's emphasis on false positives could negatively impact TB statistics, potentially causing governments and global health funders to reallocate resources. She also noted it could make clinicians hesitant to diagnose the disease, particularly in remote areas with underfunded medical facilities.
Ditiu emphasized the need for better diagnostic tools rather than discouraging clinical diagnoses.