Portal de Periódicos da CAPES

Can We Accurately Diagnose Tuberculosis Infection in Children?

2011; Lippincott Williams & Wilkins; Volume: 30; Issue: 9 Linguagem: Inglês

10.1097/inf.0b013e318221c94e

1532-0987

Anna M. Mandalakas, Anne Detjen, Anneke C. Hesseling,

Pneumonia and Respiratory Infections

To the Editors: Although it is a preventable disease, tuberculosis (TB) kills nearly one-half million children each year. Some countries with a high burden of TB do not prioritize child contact tracing and chemoprophylaxis, even in young children who have a high risk of disease progression and death after exposure. Interferon-gamma release assays (IGRAs) were developed to improve the detection of Mycobacterium tuberculosis (M.tb) infection. Accurate detection of M.tb infection should support targeting of vulnerable children for preventive strategies. In the August 2011 issue of the journal, Machingaidze et al1 reviewed the utility of a single commercially available IGRA in the detection of M.tb infection in children. Their review concisely illustrates that the QuantiFERON-TB (Cellestis, Australia) is not superior to the tuberculin skin test for the diagnosis of TB disease. This is not surprising, given that IGRAs are tests of infection. However, tests of M.tb infection are frequently used as adjunctive tests when diagnosing TB disease in children. It is, therefore, important that clinicians recognize the limitations of IGRA use in this context. Most notably, a negative IGRA does not rule out disease. The preferential use of IGRAs over the tuberculin skin test should also be considered in the light of their added cost in addition to operational benefits and challenges within each health care setting. To address these considerations, systematic reviews and individual studies should also report on operational aspects of IGRA use including failed assays, indeterminate values, missed return visits, and inadequate phlebotomy. The authors highlight the paucity and variability of available data assessing the use of IGRAs for the diagnosis of M.tb infection. Data are most limited in children with the highest risk of disease progression including young and HIV-infected children and those living in high-burden settings. In these children, the ELISPOT-based T-Spot.TB assay (Oxford Immunotec, Oxford, United Kingdom) may be more sensitive.2 Because there is no standard for the detection of M.tb infection, the authors reviewed studies using active TB as a surrogate measure. Nevertheless, existing evidence suggests that accurately quantified TB exposure may serve as a more robust surrogate measure of infection2–5 and may reflect an immunologic state consistent with infection rather than disease. Unfortunately, to date, researchers in the field have quantified exposure using heterogeneous methods, making pooled analysis challenging. To more accurately assess IGRA performance for M.tb infection in children, future studies should ideally use standardized, rigorous, and child-specific measures of M.tb exposure that support future pooled analysis of study outcomes from diverse settings and populations. The most important potential application for IGRAs is the identification of children who are at risk for progressing to future disease after infection. Definitive data on this question remain lacking in children. Longitudinal studies incorporating serial measures and capturing unbiased ascertainment of incident TB among children with well-defined M.tb exposure and isoniazid preventive therapy use are essential. IGRAs are important immune-epidemiological tools that can support much needed research regarding the transmission and prevention of childhood TB. Tools for the accurate identification of children at highest risk of disease progression may significantly reduce the cost of life-saving preventive therapy in children. Anna M. Mandalakas, MD Department of Pediatrics Case Western Reserve University Cleveland, OH Desmond Tutu TB Centre Department of Paediatrics and Child Health Stellenbosch University Anne K. Detjen, MD The International Union Against Tuberculosis and Lung Disease New York, NY Anneke C. Hesseling, MD, PhD Desmond Tutu TB Centre Department of Paediatrics and Child Health Stellenbosch University Tygerberg, South Africa