BCG vaccination status may predict sputum conversion in patients with pulmonary tuberculosis:a new consideration for an old vaccine?

Failure to convert (persistent sputum and/or culture positivity) while on antituberculosis (anti-TB) treatment at the end of the second month of anti-TB therapy has been reported to be a predictor of treatment failure. Factors that could be associated with persistent bacillary positivity at the end of the second month after initiation of anti-TB treatment were assessed

BCG protects against tuberculosis irrespective of HIV status:a matched case-control study in Mwanza, Tanzania

While BCG vaccine protects against severe tuberculosis (TB) in children, its effect against adult TB is questionable. Furthermore, it is not known if HIV co-infection modifies the effect of BCG. Among 352 pairs of Tanzanian TB cases and matched controls, the BCG scar was associated with a reduced risk of TB (OR 0.3, 95% CI 0.2 to 0.7, p=0.005), irrespective of HIV status (interaction, p=0.623). BCG vaccination considerably reduced the risk of TB, both among individuals with and without HIV infection

Negative Effect of Smoking on the Performance of the QuantiFERON TB Gold in Tube Test.

False negative and indeterminate Interferon Gamma Release Assay (IGRA) results are a well documented problem. Cigarette smoking is known to increase the risk of tuberculosis (TB) and to impair Interferon-gamma (IFN-γ) responses to antigenic challenge, but the impact of smoking on IGRA performance is not known. The aim of this study was to evaluate the effect of smoking on IGRA performance in TB patients in a low and high TB prevalence setting respectively. Patients with confirmed TB from Denmark (DK, n = 34; 20 smokers) and Tanzania (TZ, n = 172; 23 smokers) were tested with the QuantiFERON-TB Gold In tube (QFT). Median IFN-γ level in smokers and non smokers were compared and smoking was analysed as a risk factor for false negative and indeterminate QFT results. Smokers from both DK and TZ had lower IFN-γ antigen responses (median 0.9 vs. 4.2 IU/ml, p = 0.04 and 0.4 vs. 1.6, p < 0.01), less positive (50 vs. 86%, p = 0.03 and 48 vs. 75%, p < 0.01) and more false negative (45 vs. 0%, p < 0.01 and 26 vs. 11%, p = 0.04) QFT results. In Tanzanian patients, logistic regression analysis adjusted for sex, age, HIV and alcohol consumption showed an association of smoking with false negative (OR 17.1, CI: 3.0-99.1, p < 0.01) and indeterminate QFT results (OR 5.1, CI: 1.2-21.3, p = 0.02). Cigarette smoking was associated with false negative and indeterminate IGRA results in both a high and a low TB endemic setting independent of HIV status

The Prevalence of Latent Mycobacterium Tuberculosis Infection Based on an Interferon-γ Release Assay: A Cross-Sectional Survey Among Urban Adults in Mwanza, Tanzania.

One third of the world's population is estimated to be latently infected with Mycobacterium tuberculosis (LTBI). Surveys of LTBI are rarely performed in resource poor TB high endemic countries like Tanzania although low-income countries harbor the largest burden of the worlds LTBI. The primary objective was to estimate the prevalence of LTBI in household contacts of pulmonary TB cases and a group of apparently healthy neighborhood controls in an urban setting of such a country. Secondly we assessed potential impact of LTBI on inflammation by quantitating circulating levels of an acute phase reactant: alpha-1-acid glycoprotein (AGP) in neighborhood controls. The study was nested within the framework of two nutrition studies among TB patients in Mwanza, Tanzania. Household contacts- and neighborhood controls were invited to participate. The study involved a questionnaire, BMI determination and blood samples to measure AGP, HIV testing and a Quantiferon Gold In tube (QFN-IT) test to detect signs of LTBI. 245 household contacts and 192 neighborhood controls had available QFN-IT data. Among household contacts, the proportion of QFT-IT positive was 59% compared to 41% in the neighborhood controls (p = 0.001). In a linear regression model adjusted for sex, age, CD4 and HIV, a QFT-IT positive test was associated with a 10% higher level of alpha-1-acid glycoprotein(AGP) (10(B) 1.10, 95% CI 1.01; 1.20, p = 0.03), compared to individuals with a QFT-IT negative test. LTBI is highly prevalent among apparently healthy urban Tanzanians even without known exposure to TB in the household. LTBI was found to be associated with elevated levels of AGP. The implications of this observation merit further studies

Diabetes is a Risk Factor for Pulmonary Tuberculosis: A Case-Control Study from Mwanza, Tanzania.

Diabetes 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. A 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. Among 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. Diabetes 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

CD4 lymphocyte dynamics in Tanzanian pulmonary tuberculosis patients with and without hiv co-infection

The interaction of HIV and tuberculosis (TB) on CD4 levels over time is complex and has been divergently reported. CD4 counts were assessed from time of diagnosis till the end of TB treatment in a cohort of pulmonary TB patients with and without HIV co-infection and compared with cross-sectional data on age- and sex-matched non-TB controls from the same area. Of 1,605 study participants, 1,250 were PTB patients and 355 were non-TB controls. At baseline, HIV was associated with 246 (95% CI: 203; 279) cells per μL lower CD4 counts. All PTB patients had 100 cells per μL lower CD4 counts than the healthy controls. The CD4 levels were largely unchanged during a five-month of TB treatment. HIV infected patients not receiving ART at any time and those already on ART at baseline had no increase in CD4 counts after 5 months of TB treatment, whereas those prescribed ART between baseline and 2 months, and between 2 and 5 months increased by 69 (22;117) and 110 (52; 168) CD4 cells per μL after 5 months. The increase in circulating CD4 levels observed in PTB in patients is acquired after 2 months of treatment irrespective of HIV status. Initiation of ART is the strongest factor correlated with CD4 increase during TB treatment.\ud \ud \u

Infrequent detection of Pneumocystis jirovecii by PCR in oral wash specimens from TB patients with or without HIV and healthy contacts in Tanzania

\ud In tuberculosis (TB) endemic parts of the world, patients with pulmonary symptoms are managed as "smear-negative TB patients" if they do not improve on a two-week presumptive, broad-spectrum course of antibiotic treatment even if they are TB microscopy smear negative. These patients are frequently HIV positive and have a higher mortality than smear-positive TB patients. Lack of access to diagnose Pneumocystis jirovecii pneumonia might be a contributing reason. We therefore assessed the prevalence of P. jirovecii by PCR in oral wash specimens among TB patients and healthy individuals in an HIV- and TB-endemic area of sub-Saharan Africa. A prospective study of 384 patients initiating treatment for sputum smear-positive and smear-negative TB and 100 healthy household contacts and neighbourhood controls. DNA from oral wash specimens was examined by PCR for P. jirovecii. All patients delivered sputum for TB microscopy and culture. Healthy contacts and community controls were clinically assessed and all study subjects were HIV tested and had CD4 cell counts determined. Clinical status and mortality was assessed after a follow-up period of 5 months. 384 patients and 100 controls were included, 53% and 8% HIV positive respectively. A total number of 65 patients and controls (13.6%) were at definitive risk for PCP based on CD4 counts <200 cells per mm3 and no specific PCP prophylaxis. Only a single patient (0.3% of the patients) was PCR positive for P. jirovecii. None of the healthy household contacts or neighbourhood controls had PCR-detectable P. jirovecii DNA in their oral wash specimens regardless of HIV-status. The prevalence of P. jirovecii as detected by PCR on oral wash specimens was very low among TB patients with or without HIV and healthy individuals in Tanzania. Colonisation by P. jirovecii was not detected among healthy controls. The present findings may encourage diagnostic use of this non-invasive method

First-in-Man Open Clinical Trial of a Combined rdESAT-6 and rCFP-10 Tuberculosis Specific Skin Test Reagent

Tuberculin is still the only available skin test reagent for the diagnosis of mycobacterial infection. The product has a remarkable sensitivity, but poor specificity. Previous studies, including two human phase I clinical trials, have indicated that rdESAT-6 has a potential as an improved skin test reagent. Animal studies have shown that the sensitivity may be increased by inclusion of the genetically related CFP-10 antigen in the preparation without loosing specificity.In this study a Lactococcus fermented, recombinant skin test reagent consisting of a 1ratio1 wt/wt of rdESAT-6 and CFP-10 was manufactured according to GMP standards and tested for the first time in 42 healthy adult volunteers. The two doses of 0.01 microg or 0.1 microg were injected intradermally by the Mantoux technique with 6 or 12 weeks interval. No serious adverse events and only mild adverse reactions were reported. The reagent elicited a positive skin test reaction after the first injection in one participant, who most likely was latently infected with M. tuberculosis as indicated by an appreciable IFN gamma response just below the Quantiferon(R) cut-off level at the screening visit. None of the remaining participants in the four groups had any skin test reactions and sensitisation by the reagent could therefore be excluded.The investigational skin test reagent rdESAT-6 and CFP-10 appeared safe and non-sensitising in this first-in-man clinical trial in human volunteers and can now be tested in larger clinical trials involving individuals with latent M. tuberculosis infection or active TB disease.ClinicalTrials.gov NCT00793702

Diabetes prevalence by HbA1c and oral glucose tolerance test among HIV-infected and uninfected Tanzanian adults.

BACKGROUND: The burden of diabetes is increasing in sub-Saharan Africa, including among people living with HIV. We assessed the prevalence of diabetes and the roles of HIV, antiretroviral therapy (ART) and traditional risk factors among adults in Tanzania. METHODS: We analysed diabetes-relevant baseline data from 1,947 adult participants in the CICADA study in Mwanza, Tanzania: 655 HIV-uninfected, 956 HIV-infected ART-naïve, and 336 HIV-infected persons on ART. WHO guidelines for haemoglobin A1c (HbA1c) and oral glucose tolerance test (OGTT) were used to define diabetes and prediabetes. Risk factors were evaluated using multinomial logistic regression analysis. Relative risk ratios (RRR) were generated comparing participants with diabetes and prediabetes against the reference of those with no diabetes. RESULTS: Mean age was 41 (SD 12) years; 59% were women. The prevalence of diabetes was 13% by HbA1c and 6% by OGTT, with partial overlap among participants identified by the two tests. Relative to HIV-uninfected, HIV-infected ART-naïve persons had increased relative risks of diabetes (HbA1c: RRR = 1.95, 95% CI 1.25-3.03; OGTT: RRR = 1.90, 95% CI 0.96-3.73) and prediabetes (HbA1c: RRR = 2.89, 95% CI 1.93-4.34; OGTT: RRR = 1.61, 95% CI 1.22-2.13). HIV-infected participants on ART showed increased risk of prediabetes (RRR 1.80, 95% CI 1.09, 2.94) by HbA1c, but not diabetes. CD4 count < 200 cell/μL at recruitment increased risk and physical activity decreased risk of diabetes by both HbA1c and OGTT. CONCLUSIONS: The prevalence of diabetes was high, especially among HIV-infected ART-naïve adults. Being more physically active was associated with lower risk of diabetes. HbA1c and OGTT identified different participants as having diabetes or prediabetes. Overall, the finding of high burden of diabetes among HIV-infected persons suggests that health systems should consider integrating diabetes screening and treatment in HIV clinics to optimize the care of HIV patients and improve their health outcomes

Incidence, risk factors and mortality of tuberculosis in Danish HIV patients 1995-2007

<p>Abstract</p> <p>Background</p> <p>Human Immunodeficiency Virus (HIV) infection predisposes to tuberculosis (TB). We described incidence, risk factors and prognosis of TB in HIV-1 infected patients during pre (1995-1996), early (1997-1999), and late Highly Active Antiretroviral Therapy (HAART) (2000-2007) periods.</p> <p>Methods</p> <p>We included patients from a population-based, multicenter, nationwide cohort. We calculated incidence rates (IRs) and mortality rates (MRs). Cox's regression analysis was used to estimate risk factors for TB infection with HAART initiation included as time updated variable. Kaplan-Meier was used to estimate mortality after TB.</p> <p>Results</p> <p>Among 2,668 patients identified, 120 patients developed TB during the follow-up period. The overall IR was 8.2 cases of TB/1,000 person-years of follow-up (PYR). IRs decreased during the pre-, early and late-HAART periods (37.1/1000 PYR, 12.9/1000 PYR and 6.5/1000 PYR respectively). African and Asian origin, low CD4 cell count and heterosexual and injection drug user route of HIV transmission were risk factors for TB and start of HAART reduced the risk substantially. The overall MR in TB patients was 34.4 deaths per 1,000 PYR (95% Confidence Interval: 22.0-54.0) and was highest in the first two years after the diagnosis of TB.</p> <p>Conclusions</p> <p>Incidence of TB still associated with conventional risk factors as country of birth, low CD4 count and route of HIV infection while HAART reduces the risk substantially. The mortality in this patient population is high in the first two years after TB diagnosis.</p