Immune correlates of acute Mycobacterium tuberculosis infection in household contacts in Kampala, Uganda

Abstract

To determine immunologic and epidemiologic correlates of acute Mycobacterium tuberculosis infection in household contacts of infectious tuberculosis cases, we performed a prospective, community-based cohort study of index cases and their household contacts in Kampala, Uganda. Contacts were evaluated for tuberculin skin test (TST) conversion over two years. Interferon-gamma expression was measured using a whole blood assay after stimulating with M. tuberculosis culture-filtrate. In 222 contacts with a TST less than 5 mm at baseline, the one-year rate of TST conversion was 27%. The TST conversion was associated with the infectiousness of the index case and proximity of contact. Interferon-gamma levels at baseline were greater among TST converters compared with those who did not convert. The risk of TST conversion increased four-fold as the baseline interferon-gamma increased 10-fold, but only in contacts with BCG vaccination. In household contacts of tuberculosis, interferon-gamma responses to non-specific mycobacterial antigens may be used to make an early diagnosis of tuberculosis infection, especially in resource-limited settings where bacille Calmette-Guérin vaccination is commonly used.

Figure 1

Study profile for the household contact study in Kampala, Uganda, 1995–1999. IFNγ = interferon-γ.

Figure 2

Change in tuberculin skin test (TST) in 64 household contacts in Kampala, Uganda, 1995–1999. Each horizontal bar represents a household contact who met the definition of converter. The left end of the bar marks the initial TST and the right end of the bar marks the TST at the time of conversion. The length of the bar represents the size of the TST conversion.

Figure 3

Changes in interferon-γ responses relative to baseline levels in 34 tuberculin skin test converters according to initial quartiles of interferon-γ (white bars) and bacille Calmette-Guérin vaccination status (gray bars).