BackgroundExtrapulmonary tuberculosis is likely a marker of underlying immune compromise. Our objective was to determine race and sex differences in extrapulmonary tuberculosis risk in order to identify the optimal population in which to assess for host factors associated with extrapulmonary tuberculosis.MethodsWe performed an observational study of all tuberculosis cases reported to the Tennessee Department of Health, January 1, 2000 to December 31, 2006. We compared the incidence of extrapulmonary tuberculosis by race and sex. We also examined risk factors associated with extrapulmonary disease among all persons with tuberculosis.ResultsExtrapulmonary tuberculosis incidence per 100,000 population was 5.93 in black men, 3.21 in black women, 1.01 in non-black men, and 0.58 in non-black women. Among those with tuberculosis, black women were most likely to have extrapulmonary disease (38.6%), followed by black men (28.1%), non-black women (24.6%) and non-black men (21.1%). In multivariate logistic regression among persons with tuberculosis, black women (OR 1.82 (95% CI 1.24-2.65), p = 0.002), black men (OR 1.54 (95% CI 1.13-2.09, p = 0.006), foreign birth (OR 1.55 (95% CI 1.12-2.14), p = 0.009), and HIV infection (OR 1.45 (95% CI 0.99-2.11), p = 0.06) were associated with extrapulmonary tuberculosis.ConclusionsBlack men and black women had the highest incidence of extrapulmonary tuberculosis, and high odds of extrapulmonary disease among persons with tuberculosis. These data suggest that factors in addition to tuberculosis exposure contribute to extrapulmonary tuberculosis risk in blacks.

No abstract

Objective To characterize risk factors for non-completion of treatment for latent tuberculosis infection (LTBI). Secondarily, to assess the impact of LTBI treatment regimen on subsequent risk of tuberculosis. Methods Close contacts of adults (≥15 years) with pulmonary tuberculosis were prospectively enrolled in a multi-center study in the U.S. and Canada from January 2002–December 2006. Close contacts to TB patients were screened and cross-matched with tuberculosis registries to identify those who developed active tuberculosis. Results Of the 3,238 contacts screened, 1,714 (53%) were diagnosed with LTBI. Preventive therapy was recommended in 1,371 (80%); 1,147 contacts (84%) initiated therapy, of whom 723 (63%) completed treatment. In multivariate analysis, study site, initial interview sites other than a home or healthcare setting, and treatment with isoniazid were significantly associated with LTBI treatment non-completion. Fourteen tuberculosis cases were identified in contacts, all of whom initiated isoniazid. There were two cases among persons who received six or more months of isoniazid (66 cases/100,000 person-years), and nine cases among persons who received 0–5 months (median 2 months) of isoniazid (792 cases/100,000 person-years; p<0.001); data on duration of isoniazid for three cases were not available. Conclusion Only 53% (723 of 1,371) of close contacts for whom preventive therapy was recommended actually completed treatment. Close contacts of TB patients were significantly less likely to complete LTBI treatment if they took isoniazid. Less than six months of isoniazid therapy was associated with increased risk of active TB.

No abstract

Young children and people living with HIV continue to be at highest risk for TB meningitis. Early diagnosis remains challenging, especially since conventional diagnostic tests have sub-optimal sensitivity and specificity. Recently, nucleic acid amplification testing emerged as the preferred diagnostic modality due to its rapid turnaround time and high specificity. Several recent studies have assessed the optimal treatment for TB meningitis. While the benefit of treatment intensification, by increasing rifampin dosing or adding a fluoroquinolone, is unclear, a growing body of evidence suggests that steroids confer a survival advantage, particularly in patients with mild disease. Additionally, TB meningitis management is further complicated by high rates of HIV co-infection. Recent data suggest that unlike other forms of TB, early initiation of antiretroviral therapy in patients with TB meningitis is associated with higher rates of adverse reactions, without improved survival. TB meningitis continues to be a significant problem worldwide. Despite recent advances, more studies are warranted to improve early disease detection and optimize therapy.

Purpose Previous studies suggest that disease-modifying anti-rheumatic drugs (DMARDs) increase tuberculosis (TB) risk. The accuracy of pharmacy and coded-diagnosis information to identify persons with TB is unclear. Methods Within a cohort of rheumatoid arthritis (RA) patients (2000–2005) enrolled in Tennessee Medicaid, we identified those with potential TB using ICD9-CM diagnosis codes and/or pharmacy claims. Using the Tennessee TB registry as the gold standard for identification of TB, we estimated the sensitivity, specificity, predictive values and the respective 95% confidence intervals for each TB case-ascertainment strategy. Results Ten of 18,094 RA patients had confirmed TB during 61,461 person-years of follow-up (16.3 per 100,000 person-years). The sensitivity and positive predictive value (PPV) and respective 95% confidence intervals were low for confirmed TB based on ICD9-CM codes alone (60.0% (26.2–87.8) and 1.3% (0.5–2.9)), pharmacy data alone (20% (2.5–55.6) and 4.1% (0.5–14.3)), and both (20% (2.5–55.6) and 25.0% (3.2–65.1)). Conclusions Algorithms that use administrative data alone to identify TB have a poor positive predictive value that results in a high false positive rate of TB detection.

Background Independent of HIV infection, extrapulmonary TB (EPTB) risk is increased in women, persons of black race or foreign birth, and by genetic variants in vitamin D receptor (VDR), interleukin-1 beta (IL-1β), and toll-like receptor (TLR)-2; functional correlates are unclear. We evaluated macrophage expression of VDR, TLR2, cathelicidin, and TNF-α, and production of IL-1β in HIV-seronegative persons with previous EPTB, previous pulmonary TB, latent M. tuberculosis infection, and uninfected TB contacts. Persons with previous pleural TB were excluded due to enhanced immune responses at the site of disease. Methods Macrophages were stimulated with TLR-2 agonist M. tuberculosis lipoprotein (LpqH), live and gamma-irradiated M. tuberculosis . Results M. tuberculosis – infected macrophages from persons with previous EPTB had increased VDR expression (29.17 relative value unit increase in median expression vs. uninfected contacts, after adjusting for foreign-born status; P = 0.02). Macrophages from persons with previous EPTB had a 38.88 μg/mL increase in median IL-1β production after stimulation with LpqH compared to uninfected contacts ( P = 0.01); the effect was similar (44.99 μg/mL) but not statistically significant after controlling for foreign-born status. Median 25-hydroxyvitamin D levels were low but not significantly different between groups. Conclusions There was increased macrophage expression of VDR after stimulation with live M. tuberculosis in persons with previous extrapulmonary TB. If post-treatment VDR expression reflects expression prior to disease, it may identify persons at risk for extrapulmonary TB. Electronic supplementary material The online version of this article (10.1186/s12879-019-3958-7) contains supplementary material, which is available to authorized users.

Objective 25-hydroxyvitamin D [25(OH)D] levels after recovery from tuberculosis (TB) may reflect pre-morbid levels and therefore provide insight into pathogenesis. We assessed 25(OH)D levels after recovery from TB disease, and compared to levels in persons without TB disease. Methods Case-control study. Cases were persons who had recovered from culture-confirmed Mycobacterium tuberculosis disease. Controls were persons without TB disease. Total 25(OH)D was measured from stored plasma specimens using liquid chromatography-mass spectrometry. Results 29 persons with prior TB disease and 36 controls were included. Median 25(OH)D levels were 24.7 ng/mL (IQR, 18.3–34.1) in prior TB disease, and 33.6 ng/mL (IQR, 26.2–42.4) in controls (Mann-Whitney; P=0.01). Multivariable linear regression analysis showed that black race (adjusted mean difference [β]=−8.3 ng/mL; 95% CI −14.5, −2.2; P<0.01), enrollment in winter (β=−10.4 ng/mL; 95% CI −17.0, −3.8; P<0.01) and prior TB disease (β=−5.8 ng/mL; 95% CI −11.4, −0.3; P=0.05) were associated with lower 25(OH)D levels. Conclusions Persons who had recovered from TB disease had lower 25(OH)D levels compared to controls without TB disease, after adjusting for important confounders. Larger, longitudinal studies are needed to further characterize the possible role of low 25(OH)D in the pathogenesis of TB disease and TB recurrence after recovery.