Tuberculin skin testing in HIV-infected patients in Campo Grande, Mato Grosso do Sul State, Brazil

A cross-sectional study on HIV/AIDS was carried out in 108 outpatients from the university hospital of the Federal University of Mato Grosso do Sul, Campo Grande, Brazil, from July to December 2008, to investigate latent tuberculosis infection using the tuberculin skin test (TST). The prevalence of positive results was 13.9 percent. The CD4+ T cell count (p = 0.091) and the diagnosis time (p = 0.010) were statistically significant when compared with TST positivity. In the cohort of HIV/AIDS patients who had latent tuberculosis infection, the median diagnosis time was eight years. Undetectable viral load presented significant association (p = 0.046) with tuberculosis infection. The fact that numerous individuals with HIV/AIDS infection presented a negative reaction to the tuberculin skin test is probably related to alterations in the cellular immune response induced by HIV infection. The tuberculin test is a useful tool for the detection of latent tuberculosis infection and should be performed in all HIV/AIDS individuals at the time of the diagnosis and on a yearly basis, if negative. Both the early identification of the tuberculosis infection by the tuberculin skin test at the moment of immunological restoration and chemoprophylaxis in infected individuals are mechanisms to control HIV/AIDS and tuberculosis coinfection.

Genetic polymorphisms in vitamin D receptor, vitamin D-binding protein, Toll-like receptor 2, nitric oxide synthase 2, and interferon-γ genes and its association with susceptibility to tuberculosis: [review]

Mycobacterium tuberculosis kills more people than any other single pathogen, with an estimated one-third of the world's population being infected. Among those infected, only 10 percent will develop the disease. There are several demonstrations that susceptibility to tuberculosis is linked to host genetic factors in twins, family and associated-based case control studies. In the past years, there has been dramatic improvement in our understanding of the role of innate and adaptive immunity in the human host defense to tuberculosis. To date, attention has been paid to the role of genetic host and parasitic factors in tuberculosis pathogenesis mainly regarding innate and adaptive immune responses and their complex interactions. Many studies have focused on the candidate genes for tuberculosis susceptibility ranging from those expressed in several cells from the innate or adaptive immune system such as Toll-like receptors, cytokines (TNF-α, TGF-β, IFN-γ, IL-1b, IL-1RA, IL-12, IL-10), nitric oxide synthase and vitamin D, both nuclear receptors and their carrier, the vitamin D-binding protein (VDBP). The identification of possible genes that can promote resistance or susceptibility to tuberculosis could be the first step to understanding disease pathogenesis and can help to identify new tools for treatment and vaccine development. Thus, in this mini-review, we summarize the current state of investigation on some of the genetic determinants, such as the candidate polymorphisms of vitamin D, VDBP, Toll-like receptor, nitric oxide synthase 2 and interferon-γ genes, to generate resistance or susceptibility to M. tuberculosis infection.

Effect of the injection of an extract of Ascaris suum on macrophage activation during the early phase of Mycobacterium bovis BCG infection in C57Bl/6 mice

Injection of an Ascaris suum extract (Asc) affects both the humoral and cellular immune responses to unrelated antigens when it is co-administered with these antigens. In the present study we evaluated the effect of Asc on macrophage activation in the early phase of Mycobacterium bovis BCG (Pasteur strain TMCC 1173) infection in C57Bl/6 mice. C57Bl/6 mice were injected intraperitoneally (ip) with 0.1 mg BCG (BCG group) or BCG plus 1 mg Asc (BCG + Asc group). The peritoneal exudates were obtained at 2, 7 and 14 days after infection. The numbers of IFN-g-secreting cells were assessed by the ELISPOT assay. Nitric oxide (NO) production was measured by the Griess method and by the evaluation of NADPH diaphorase activity in the peritoneal exudates. The administration of Asc extract increased NADPH diaphorase activity (2 days: control = 0, BCG = 7 per cent, BCG + Asc = 13 per cent, and Asc = 4 per cent; 7 days: control = 4, BCG = 13 per cent, BCG + Asc = 21 per cent, and Asc = 4.5 per cent) and TNF-a levels (mean + or - SD; 2 days: control = 0, BCG = 169 + or - 13, BCG + Asc = 202 + or - 37, and Asc = 0; 7 days: control = 0, BCG = 545 + or - 15.5, BCG + Asc = 2206 + or - 160.6, and Asc = 126 + or - 26; 14 days: control = 10 + or - 1.45, BCG = 9 + or - 1.15, BCG + Asc = 126 + or - 18, and Asc = 880 + or - 47.67 pg/ml) in the early phase of BCG infection. Low levels of NO production were detected at 2 and 7 days after BCG infection, increasing at 14 days (mean + or - SD; 2 days: control = 0, BCG = 3.7 + or - 1.59, BCG + Asc = 0.82 + or - 0.005, Asc = 0.48 + or - 0.33; 7 days: control = 0, BCG = 2.78 + or - 1.54, BCG + Asc = 3.07 + or - 1.05, Asc = 0; 14 days: control = 0, BCG = 9.05 + or - 0.53, BCG + Asc = 9.61 + or - 0.81, Asc = 10.5 + or - 0.2 (2 x 106) cells/ml). Furthermore, we also observed that Asc co-injection induced a decrease of BCG-colony-forming units (CFU) in the spleens of BCG-infected mice during the first week of infection (mean + or - SD; 2 days: BCG = 1.13 + or - 0.07 and BCG + Asc = 0.798 + or - 0.305; 7 days: BCG = 1.375 + or - 0.194 and BCG + Asc = 0.548 + or - 0.0226; 14 days: BCG = 0.473 + or - 0.184 and BCG + Asc = 0.675 + or - 0.065 (x 102) CFU). The present data suggest that Asc induces the enhancement of the immune response in the early phase of BCG infection.