Latent and subclinical tuberculosis in HIV infected patients: a cross-sectional study.

BACKGROUND: HIV and tuberculosis (TB) are commonly associated. Identifying latent and asymptomatic tuberculosis infection in HIV-positive patients is important in preventing death and morbidity associated with active TB. METHODS: Cross-sectional study of one time use of an interferon-gamma release assay (T-SPOT.TB - immunospot) to detect tuberculosis infection in patients in a UK inner city HIV clinic with a large sub-Saharan population. RESULTS: 542 patient samples from 520 patients who disclosed their symptoms of TB were tested. Median follow-up was 35 months (range 27-69). More than half (55%) originated from countries with medium or high tuberculosis burden and 57% were women. Antiretroviral therapy was used by 67%; median CD4 count at test was 458 cells/µl. A negative test was found in 452 samples and an indeterminate results in 40 (7.4%) but neither were associated with a low CD4 count. A positive test was found in 10% (50/502) individuals. All patients with positive tests were referred to the TB specialist, 47 (94%) had a chest radiograph and 46 (92%) attended the TB clinic. Two had culture-positive TB and a third individual with features of active TB was treated. 40 started and 38 completed preventive treatment. One patient who completed preventive treatment with isoniazid monotherapy subsequently developed isoniazid-resistant pulmonary tuberculosis. No patient with a negative test has developed TB. CONCLUSIONS: We found an overall prevalence of latent TB infection of 10% through screening for TB in those with HIV infection and without symptoms, and a further 1% with active disease, a yield greater than typically found in contact tracing. Acceptability of preventive treatment was high with 85% of those with latent TB infection eventually completing their TB chemotherapy regimens. IGRA-based TB screening among HIV-infected individuals was feasible in the clinical setting and assisted with appropriate management (including preventive treatment and therapy for active disease). Follow-up of TB incidence in this group is needed to assess the long-term effects of preventive treatment.

1alpha,25-dihydroxyvitamin D3 inhibits matrix metalloproteinases induced by Mycobacterium tuberculosis infection.

Matrix metalloproteinases (MMP) can degrade all components of pulmonary extracellular matrix. Mycobacterium tuberculosis induces production of a number of these enzymes by human macrophages, and these are implicated in the pathogenesis of pulmonary cavitation in tuberculosis. The active metabolite of vitamin D, 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], has previously been reported to inhibit secretion of MMP-9 in human monocytes (MN), but its influence on the secretion and gene expression of MMP and tissue inhibitors of MMP (TIMP) in M. tuberculosis-infected cells has not previously been investigated. We therefore determined the effects of 1alpha,25(OH)(2)D(3) on expression, secretion and activity of a number of MMP and TIMP in M. tuberculosis-infected human leucocytes; we also investigated the effect of 1alpha,25(OH)(2)D(3) on the secretion of interleukin-10 (IL-10) and prostaglandin E(2) (PGE(2)), both transcriptional regulators of MMP expression. We found that M. tuberculosis induced expression of MMP-1, MMP-7 and MMP-10 in MN and MMP-1 and MMP-10 in peripheral blood mononuclear cells (PBMC). 1alpha,25(OH)(2)D(3) significantly attenuated M. tuberculosis-induced increases in expression of MMP-7 and MMP-10, and suppressed secretion of MMP-7 by M. tuberculosis-infected PBMC. MMP-9 gene expression, secretion and activity were significantly inhibited by 1alpha,25(OH)(2)D(3) irrespective of infection. In contrast, the effects of 1alpha,25(OH)(2)D(3) on the expression of TIMP-1, TIMP-2 and TIMP-3 and secretion of TIMP-1 and TIMP-2 were small and variable. 1alpha,25(OH)(2)D(3) also induced secretion of IL-10 and PGE(2) from M. tuberculosis-infected PBMC. These findings represent a novel immunomodulatory role for 1alpha,25(OH)(2)D(3) in M. tuberculosis infection.