No abstract

BackgroundDiabetes and TB are associated, and diabetes is increasingly common in low-income countries where tuberculosis (TB) is highly endemic. However, the role of diabetes for TB has not been assessed in populations where HIV is prevalent.MethodsA case-control study was conducted in an urban population in Tanzania among culture-confirmed pulmonary TB patients and non-TB neighbourhood controls. Participants were tested for diabetes according to WHO guidelines and serum concentrations of acute phase reactants were measured. The association between diabetes and TB, and the role of HIV as an effect modifier, were examined using logistic regression. Since blood glucose levels increase during the acute phase response, we adjusted for elevated serum acute phase reactants.ResultsAmong 803 cases and 350 controls the mean (SD) age was 34.8 (11.9) and 33.8 (12.0) years, and the prevalence of diabetes was 16.7% (95% CI: 14.2; 19.4) and 9.4% (6.6; 13.0), respectively. Diabetes was associated with TB (OR 2.2, 95% CI: 1.5; 3.4, p<0.001). However, the association depended on HIV status (interaction, p = 0.01) due to a stronger association among HIV uninfected (OR 4.2, 95% CI: 1.5; 11.6, p = 0.01) compared to HIV infected (OR 0.1, 95% CI: 0.01; 1.8, p = 0.13) after adjusting for age, sex, demographic factors and elevated serum acute phase reactants.ConclusionDiabetes is a risk factor for TB in HIV uninfected, whereas the association in HIV infected patients needs further study. The increasing diabetes prevalence may be a threat to TB control.

Abstractobjective Strong evidence suggests diabetes may be associated with tuberculosis (TB) and could influence TB treatment outcomes. We assessed the role of diabetes on sputum culture conversion and mortality among patients undergoing TB treatment.methods A total of 1250 Tanzanian TB patients were followed prospectively during TB treatment with sputum culture after 2 and 5 months. Survival status was assessed at least 1 year after initiation of treatment. At baseline, all participants underwent testing for diabetes and HIV, and the serum concentration of the acute phase reactant alpha-1 glycoprotein (AGP) was determined.results There were no differences between participants with and without diabetes regarding the proportion of positive cultures at 2 (3.8% vs. 5.8%) and 5 (1.3% vs. 0.9%) months (P > 0.46). However, among patients with a positive TB culture, relatively more patients with diabetes died before the 5-month follow-up. Within the initial 100 days of TB treatment, diabetes was associated with a fivefold increased risk of mortality (RR 5.09, 95% CI 2.36; 11.02, P < 0.001) among HIV uninfected, and a twofold increase among HIV co-infected patient (RR 2.33 95% CI 1.20; 4.53, P = 0.012), while diabetes was not associated with long-term mortality. Further adjustment with AGP did not change the estimates.conclusion Diabetes considerably increases risk of early mortality during TB treatment. The effect may not be explained by increased severity of TB, but could be due to impaired TB treatment response. Research is needed to clarify the mechanism and to assess whether glycaemic control improves survival.

BackgroundThe performance of the tuberculosis specific Interferon Gamma Release Assays (IGRAs) has not been sufficiently documented in tuberculosis- and HIV-endemic settings. This study evaluated the sensitivity of the QuantiFERON TB-Gold In-Tube (QFT-IT) in patients with culture confirmed pulmonary tuberculosis (PTB) in a TB- and HIV-endemic population and the effect of HIV-infection and CD4 cell count on test performance.Methodology/Principal Findings161 patients with sputum culture confirmed PTB were subjected to HIV- and QFT-IT testing and measurement of CD4 cell count. The QFT-IT was positive in 74% (119/161; 95% CI: 67–81%). Sensitivity was higher in HIV-negative (75/93) than in HIV-positive (44/68) patients (81% vs. 65%, p = 0.02) and increased with CD4 cell count in HIV-positive patients (test for trend p = 0.03). 23 patients (14%) had an indeterminate result and this proportion decreased with increasing CD4 cell count in HIV-positive patients (test for trend p = 0.03). Low CD4 cell count (<300 cells/µl) did not account for all QFT-IT indeterminate nor all negative results. Sensitivity when excluding indeterminate results was 86% (95% CI: 81–92%) and did not differ between HIV-negative and HIV–positive patients (88 vs. 83%, p = 0.39).Conclusions/SignificanceSensitivity of the QFT-IT for diagnosing active PTB infection was reasonable when excluding indeterminate results and in HIV-negative patients. However, since the test missed more than 10% of patients, its potential as a rule-out test for active TB disease is limited. Furthermore, test performance is impaired by low CD4 cell count in HIV-positive patients and possibly by other factors as well in both HIV-positive and HIV-negative patients. This might limit the potential of the test in populations where HIV-infection is prevalent.

Background Antigen specific release of IP-10 is an established marker for infection with M.tuberculosis . Compared to IFN-γ, IP-10 is released in 100-fold higher concentrations enabling the development of novel assays for detection. Dried blood spots are a convenient sample for high throughput newborn screening. Aim To develop a robust and sensitive ELISA-based assay for IP-10 detection in plasma, dried blood spots (DBS) and dried plasma spots (DPS); to validate the ELISA in clinically relevant samples; and to assess the performance of the assay for detection of Cytomegalovirus (CMV) and M.tuberculosis specific immune responses. Method We raised mice and rat monoclonal antibodies against human IP-10 and developed an ELISA. The assay was validated and applied to the detection of CMV and M.tuberculosis specific responses in 18 patients with immune reactivity towards M.tuberculosis and 32 healthy controls of which 22 had immune reactivity towards CMV and none towards M.tuberculosis . We compared the performance of this new assay to IFN-γ. Results The ELISA was reliable for IP-10 detection in both plasma and filter paper samples. The linear range of the ELISA was 2.5–600 pg/ml. IFN-γ was not readily detectable in DPS samples. IP-10 was stabile in filter paper samples for at least 4 weeks at 37°C. The correlation between IP-10 detected in plasma, DPS and DBS samples was excellent (r 2 >0.97). Conclusions This newly developed assay is reliable for IP-10 quantification in plasma, DBS and DPS samples from antigen stimulated and non-stimulated whole blood. The filter paper assays enable easy sample acquisition and transport at ambient temperature e.g. via the postal system. The system can potentially simplify diagnostic assays for M.tuberculosis and CMV infection.

Undernutrition is common among tuberculosis (TB) patients. The objective of this study was to assess the effect of multi-micronutrient supplementation during TB treatment on weight, body composition, and handgrip strength. A total of 865 patients with smear-positive (PTB+) or -negative (PTB-) pulmonary TB were randomly allocated to receive a daily biscuit with or without multi-micronutrients for 60 d during the intensive phase of TB treatment. Weight, arm fat area, arm muscle area, and handgrip strength were assessed at baseline and after 2 and 5 mo. At 2 mo, the multi-micronutrient supplementation led to a higher handgrip gain (1.22 kg; 95% CI = 0.50, 1.94; P = 0.001) but had no effects on other outcomes. The effects of multi-micronutrient supplementation were modified by HIV infection (P-interaction = 0.002). Among HIV- patients, multi-micronutrient supplementation increased weight gain by 590 g (95% CI = -40, 1210; P = 0.07) and handgrip strength by 1.6 kg (95% CI = 0.78, 2.47; P < 0.001), whereas among HIV+ patients, it reduced weight gain by 1440 g (95% CI = 290, 2590; P = 0.002) and had no effect on handgrip strength (0.07 kg; 95% CI = -1.30, 1.46; P = 0.91). The reduced weight gain among HIV+ patients receiving multi-micronutrient supplementation seemed to be explained by a higher proportion of patients reporting fever. At 5 mo, the effects on weight were sustained, whereas there was no effect on handgrip strength. In conclusion, multi-micronutrient supplementation given as a biscuit is beneficial among HIV- PTB patients and may be recommended to TB programs. More research is needed to develop an effective supplement for HIV+ PTB patients.

No abstract

Diabetes is associated with lower levels of Mtb antigen-specific IFN-γ, and the validity of IFN- γ tests for LTBI may be questionable in individuals with diabetes.