Possible risk factors of progression to overt disease among individuals with latent tuberculosis infection in Sudan

Latent TB infections (LTBI) constitute a pool fornew TB cases, ~5% of LTBI individuals progress to overt disease during their lifetime. Simple and cheap progression risk factors are needed to triage individuals for treatment. In aprospective case control study and following informed consent, apparently healthy 98 household contacts (HHCs) and 186 community contacts (CCs) were enrolled. Tuberculin skin test (TST), whole blood stimulation/IFN-γ release assays and IL-4/IL-4δ2 mRNA copies were studied. Two hundred eighty-four volunteers were enrolled, five percent (5/98) of HHCs developed smear positive pulmonary TB compared to none in the CCs (p=0.004). The mean TST induration of the newly diagnosed TB patients was 16±2 mm at recruitment and the lapse of time to development of overt disease was 12±10 months. The majority of newly diagnosed TB patients had IFN-γ production levels below the cutoff level for LBTI diagnosis. A third of the HHCs and CCs had high IFN-γ levels, but none developed overt disease. The ratio of IL-4/IL-4δ2 mRNA copies in the newly diagnosed TB patients was significantly higher than that of the CCs (p0.0002). TST induration of ≥15was identified as a suitable simple and cheap test to triage individuals with LBTI for treatment.