Tuberculosis is a public health problem responsible for thousands of deaths worldwide, especially in high-burden countries such as Brazil. In this context, the identification and management of latent Mycobacterium tuberculosis infection (LTBI) constitute central strategies for preventing progression to active tuberculosis and reducing community transmission. Latent M. tuberculosis infection is characterized by the presence of the bacillus in the body without clinical manifestations of active disease. Despite being asymptomatic, a substantial proportion of infected individuals may progress to active tuberculosis, particularly in situations of immunosuppression, HIV coinfection, or malnutrition, making early diagnosis a key component of prevention and control strategies. Currently, the diagnosis of LTBI relies on indirect methods based on the host immune response, such as the tuberculin skin test (TST) and interferon-gamma release assays (IGRA). Although widely used, these tests exhibit variable sensitivity and specificity, in addition to technical, immunological, and operational limitations. Factors such as immunosuppression, extreme age, comorbidities, nutritional status, variability in TST administration and interpretation, the booster effect, and cross-reactivity with the Bacillus Calmette–Guérin (BCG) vaccine interfere with test results, favoring the occurrence of false-negative and false-positive outcomes. This study aimed to critically analyze the diagnostic limitations of latent Mycobacterium tuberculosis infection and discuss their impacts on the prevention of active tuberculosis through a narrative literature review. National and international technical documents and guidelines were selected, as well as scientific articles published between 2014 and 2025, available in the SciELO and BVS databases. The Brazilian Ministry of Health Tuberculosis Control Recommendations Manual and the 2024 Global Tuberculosis Report were also included. Duplicate studies, rare case reports, and articles not directly related to the topic were excluded. The analysis demonstrated that weaknesses in diagnostic methods hinder the accurate identification of infected individuals, particularly among vulnerable populations such as people living with HIV, young children, patients receiving immunosuppressive therapies, and household contacts of bacilliferous cases. These limitations compromise contact tracing, risk stratification, and appropriate indication of preventive therapy, potentially resulting in both missed prevention opportunities and unnecessary treatment in low-risk individuals. It is concluded that diagnostic limitations of LTBI represent a significant barrier to the effective prevention of active tuberculosis. Careful interpretation of available tests, considering the clinical and epidemiological context, as well as strengthening Primary Health Care as a strategic axis of tuberculosis control actions, is essential. Furthermore, investments in research and in the development of more sensitive and specific diagnostic methods are necessary to improve tuberculosis prevention strategies.
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Karam et al. (2026) studied this question.
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