Identification of immunological biomarkers which may differentiate latent tuberculosis from exposure to environmental nontuberculous mycobacteria in children.

A positive gamma interferon (IFN-γ) response to Mycobacterium tuberculosis early secretory antigenic target-6 (ESAT-6)/culture filtrate protein-10 (CFP-10) has been taken to indicate latent tuberculosis (TB) infection, but it may also be due to exposure to environmental nontuberculous mycobacteria in which ESAT-6 homologues are present. We assessed the immune responses to M. tuberculosis ESAT-6 and cross-reactive responses to ESAT-6 homologues of Mycobacterium avium and Mycobacterium kansasii. Archived culture supernatant samples from children at 3 years post-BCG vaccination were tested for cytokine/chemokine responses to M. tuberculosis antigens. Furthermore, the IFN-γ responses to M. tuberculosis antigens were followed up for 40 children at 8 years post-BCG vaccination, and 15 TB patients were recruited as a control group for the M. tuberculosis ESAT-6 response in Malawi. IFN-γ enzyme-linked immunosorbent assays (ELISAs) on supernatants from diluted whole-blood assays, IFN-γ enzyme-linked immunosorbent spot (ELISpot) assays, QuantiFERON TB Gold-In Tube tests, and multiplex bead assays were performed. More than 45% of the responders to M. tuberculosis ESAT-6 showed IFN-γ responses to M. avium and M. kansasii ESAT-6. In response to M. tuberculosis ESAT-6/CFP-10, interleukin 5 (IL-5), IL-9, IL-13, and IL-17 differentiated the stronger IFN-γ responders to M. tuberculosis ESAT-6 from those who preferentially responded to M. kansasii and M. avium ESAT-6. A cytokine/chemokine signature of IL-5, IL-9, IL-13, and IL-17 was identified as a putative immunological biosignature to differentiate latent TB infection from exposure to M. avium and M. kansasii in Malawian children, indicating that this signature might be particularly informative in areas where both TB and exposure to environmental nontuberculous mycobacteria are endemic.

High accuracy of home-based community rapid HIV testing in rural Malawi.

OBJECTIVE: To assess the performance of rapid HIV antibody tests when used as part of a home-based community wide counseling and testing strategy in northern Malawi. DESIGN: A cross-sectional population survey of HIV infection, 2007 to 2008. METHODS: Adults aged 15 years or older in a demographic surveillance area were counseled and then offered an HIV test at their home by government-certified counselors. Two initial rapid tests (Determine and Uni-Gold) were performed on all samples and a third, tie-breaker test (SD Bioline) used to resolve discordant results. All people who wanted to know were posttest-counseled and informed of their results with referral to local clinical services if found to be HIV-positive. Laboratory quality control comprised retesting all positive and every tenth negative venous blood sample collected. RESULTS: A total of 10,819 adults provided venous blood samples for HIV testing, of whom 7.5% (813) were HIV-positive. The accuracy of the parallel testing strategy used was high with 99.6% sensitivity, 100.0% specificity, 99.9% positive predictive value, and 99.9% negative predictive value. CONCLUSION: Face-to-face rapid testing by health personnel with minimum training at the client's home performs well when used on a wide scale in the community setting.