Respiratory review

The challenge of diagnosing tuberculosis in children: a perspective from a high incidence area

In vitro interferon-γ (IFN-γ) assays have emerged as novel alternatives to the tuberculin skin test (TST) for the diagnosis of latent tuberculosis (TB) infection. These assays have been evaluated in low incidence countries, mainly in adults, and have been shown to be more specific than TST. Because few studies have been done in high incidence countries, and because paediatric data are limited, we compared a whole-blood IFN-γ assay with TST among hospitalized Indian children.

Between July 2004 and June 2005, a total of 105 consecutively admitted children (median age 6 years; 82% had BCG scars) in whom TB was suspected or had history of contact with an index case were recruited at a rural hospital in India. All children underwent TST, and the QuantiFERON-TB-Gold In Tube (QFT) assay.

The overall prevalence of TB infection was similar with both tests. With a TST cut-off point of ≥10 mm, 10 of 105 (9.5%; 95% CI 3.8, 15.2) children were TST positive. With a cut-off point of IFN-γ ≥ 0.35 IU/ml, 11 of 105 (10.5%; 95% CI 4.5, 16.4) were QFT positive. The concordance between TST and QFT was substantial (agreement 95.2%; kappa [κ] 0.73; 95% CI for κ 0.53, 0.92). Agreement between TST and QFT results was 100% (κ 1.0) in BCG scar-negative children as compared to 94% (κ 0.63) in scar-positive children. BCG was not associated with the results of either TST or QFT (P > 0.05 for both tests). The number of children with bacteriologically confirmed active TB was too small to permit the estimation of sensitivity of the tests.

In a rural, predominantly BCG-vaccinated paediatric population in India, the TST and QFT assay produced comparable results. BCG vaccination did not significantly affect either TST or QFT results. Larger studies are needed to compare the sensitivity of the IFN-γ assay with that of the TST in children with bacteriologically and/or clinically confirmed TB.

Part of the reason for failing to bring about a more rapid reduction in tuberculosis incidence worldwide is the lack of effective involvement of all practitioners—public and private—in the provision of high quality tuberculosis care. While health-care providers who are part of national tuberculosis programmes have been trained and are expected to have adopted proper diagnosis, treatment, and public-health practices, the same is not likely to be true for non-programme providers. Studies of the performance of the private sector conducted in several different parts of the world suggest that poor quality care is common. The basic principles of care for people with, or suspected of having, tuberculosis are the same worldwide: a diagnosis should be established promptly; standardised treatment regimens should be used with appropriate treatment support and supervision; response to treatment should be monitored; and essential public-health responsibilities must be carried out. Prompt and accurate diagnosis, and effective treatment are essential for good patient care and tuberculosis control. All providers who undertake evaluation and treatment of patients with tuberculosis must recognise that not only are they delivering care to an individual, but they are also assuming an important public-health function. The International Standards for Tuberculosis Care (ISTC) describe a widely endorsed level of care that all practitioners should seek to achieve in managing individuals who have, or are suspected of having, tuberculosis. The document is intended to engage all care providers in delivering high quality care for patients of all ages, including those with smear-positive, smear-negative, and extra-pulmonary tuberculosis, tuberculosis caused by drug-resistant Mycobacterium tuberculosis complex, and tuberculosis combined with HIV infection.