Widespread TB Misdiagnoses Revealed: A New Look at the World's Leading Infectious Killer

Tuberculosis (TB), the world's leading infectious disease killer, caused 1.23 million deaths in 2024 and affects approximately 10 million people annually. New research published in Nature Medicine now suggests that many TB diagnoses may be incorrect, with significant implications for patient care.

Study Uncovers Widespread Misdiagnoses

A groundbreaking study, analyzing 2023 data from 111 low- and middle-income countries, has estimated substantial numbers of incorrect TB diagnoses. Nicolas Menzies, a co-author and associate professor at the Harvard T.H. Chan School of Public Health, and his colleagues developed a formula using World Health Organization (WHO) data to estimate both false negatives and false positives.

Their estimates indicate a critical dual challenge:

• 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).

Menzies stated that up to a quarter, or potentially more, of individuals diagnosed and treated for TB each year might not have the disease.

He highlighted that in serious cases, these misdiagnosed patients could have other potentially fatal conditions such as pneumonia, lung cancer, or chronic obstructive pulmonary disease. Menzies termed this crucial oversight a "blind spot" in the TB field.

Mixed Reactions from Experts

Dr. Marcel Behr, a professor of medicine at McGill University, lauded the study for drawing attention to incorrect TB diagnoses and for its rigorous approach, particularly noting that the issue of false positives has been understudied.

Conversely, Dr. Lucica Ditiu, head of Stop TB Partnership, voiced concern. She feared that the study's emphasis on false positives could negatively impact TB statistics, potentially causing governments and global health funders to reallocate resources. Ditiu also worried it could make clinicians hesitant to diagnose the disease, especially in remote areas with underfunded medical facilities.

Ditiu emphasized the need for better diagnostic tools rather than discouraging clinical diagnoses.

Root Causes of Misdiagnosis

Menzies attributes the high rates of misdiagnoses 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, a significant portion of diagnoses—over a third in low- and middle-income countries—are made without a positive test result. These diagnoses are based on a clinician's assessment of symptoms like persistent cough, weight loss, and night sweats. Menzies suggests these clinical assessments contribute to many false positive cases.

Dr. Behr theorizes that many health workers, having practiced in an era with limited TB diagnostics, may still rely on their intuition over improved test results. He noted that adapting to better tests takes time for medical professionals.

Grave Consequences of Incorrect Diagnoses

Menzies highlighted the perils of misdiagnosis. While the risks of failing to diagnose TB early (for individual treatment and bacterial spread) are well-recognized, the downsides of an incorrect TB diagnosis have received less attention. These downsides include:

• Significant costs associated with treatment and missed work.
• Severe side effects from strong TB drugs, such as liver damage.
• The profound 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, Menzies observed a critical finding:

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.

This finding underscores that some individuals with false positive TB diagnoses have serious underlying conditions that would benefit from prompt and accurate treatment. Behr hopes this study will increase awareness and action regarding incorrect TB diagnoses on a broader scale.