Clinical presentation, demographics and outcome of Tuberculosis (TB) in a low incidence area: a 4-year study in Geneva, Switzerland

<p>Abstract</p> <p>Background</p> <p>The incidence of tuberculosis (TB) in developed countries has decreased since the 1990s, reflecting worldwide efforts to identify and treat TB according to WHO recommendations. However TB remains an important public health problem in industrialized countries with a high proportion of cases occurring among subjects originating from high prevalence countries. The aim of this study was to describe clinical and social characteristics of patients with TB and their outcome in a low incidence area with a high immigration rate.</p> <p>Methods</p> <p>Four-year retrospective study based on a computerized database and subsequent review of medical records of all patients with TB followed at the outpatient section of the Division of Pulmonary Diseases, Geneva University Hospital, Switzerland.</p> <p>Results</p> <p>252 patients (84% foreigners, 25% asylum seekers) aged 38 ± 19 yrs were studied (11% co-infected with HIV). TB was intrapulmonary (TBP) in 158 cases (63%), extrapulmonary (TBE) in 137 (54%), and both in 43 cases (17%). TBP was smear (S)+/culture (C)+ in 59%, S-/C+ in 37%, S-/C- in 4%. Smoking was significantly associated with cavitary disease.</p> <p>Time from onset of symptoms to diagnosis was 2.1 ± 3.1 months. Initially, 10% were asymptomatic; 35% had no general symptoms. Despite systematic sputum analysis (induced or spontaneous), TBP was confirmed only by bronchoscopy in 38 subjects (24% of TBP). Side effects requiring changes in treatment occurred in 38 cases (11%).</p> <p>Treatment was completed in 210 (83%) patients. In 42 cases, follow up was unsuccessful; causes were: failure (n = 2; 0.8%), defaulters (n = 8; 3%), transfer out (n = 28; 11%) and death (n = 4; 1.6%). Relapse rate was 0.24 per 100 patient-years. Considering S+ TBP only, success rate was 87%.</p> <p>Conclusion</p> <p>TB in our area is predominantly a disease of young foreign-born subjects. Smoking appears as a possible risk factor for cavitary TBP. Time to diagnosis remains long. Compliance to treatment is satisfactory. Success rate for S+ TBP is within WHO objectives.</p

Tuberculosis contact investigation with a new, specific blood test in a low-incidence population containing a high proportion of BCG-vaccinated persons

BACKGROUND: BCG-vaccination can confound tuberculin skin test (TST) reactions in the diagnosis of latent tuberculosis infection. METHODS: We compared the TST with a Mycobacterium tuberculosis specific whole blood interferon-gamma assay (QuantiFERON(®)-TB-Gold In Tube; QFT-G) during ongoing investigations among close contacts of sputum smear positive source cases in Hamburg, Germany. RESULTS: During a 6-month period, 309 contacts (mean age 28.5 ± 10.5 years) from a total of 15 source cases underwent both TST and QFT-G testing. Of those, 157 (50.8%) had received BCG vaccination and 84 (27.2%) had migrated to Germany from a total of 25 different high prevalence countries (i.e. >20 cases/100,000). For the TST, the positive response rate was 44.3% (137/309), whilst only 31 (10%) showed a positive QFT-G result. The overall agreement between the TST and the QFT-G was low (κ = 0.2, with 95% CI 0.14.-0.23), and positive TST reactions were closely associated with prior BCG vaccination (OR 24.7; 95% CI 11.7–52.5). In contrast, there was good agreement between TST and QFT-G in non-vaccinated persons (κ = 0.58, with 95% CI 0.4–0.68), increasing to 0.68 (95% CI 0.46–0.81), if a 10-mm cut off for the TST was used instead of the standard 5 mm recommended in Germany. CONCLUSION: The QFT-G assay was unaffected by BCG vaccination status, unlike the TST. In close contacts who were BCG-vaccinated, the QFT-G assay appeared to be a more specific indicator of latent tuberculosis infection than the TST, and similarly sensitive in unvaccinated contacts. In BCG-vaccinated close contacts, measurement of IFN-gamma responses of lymphocytes stimulated with M. tuberculosis-specific antigen should be recommended as a basis for the decision on whether to perform subsequent chest X-ray examinations or to start treatment for latent tuberculosis infection

Reference values for methacholine reactivity (SAPALDIA study)

BACKGROUND: The distribution of airway responsiveness in a general population of non-smokers without respiratory symptoms has not been established, limiting its use in clinical and epidemiological practice. We derived reference equations depending on individual characteristics (i.e., sex, age, baseline lung function) for relevant percentiles of the methacholine two-point dose-response slope. METHODS: In a reference sample of 1567 adults of the SAPALDIA cross-sectional survey (1991), defined by excluding subjects with respiratory conditions, responsiveness during methacholine challenge was quantified by calculating the two-point dose-response slope (O'Connor). Weighted L1-regression was used to estimate reference equations for the 95(th ), 90(th ), 75(th )and 50(th )percentiles of the two-point slope. RESULTS: Reference equations for the 95(th ), 90(th ), 75(th )and 50(th )percentiles of the two-point slope were estimated using a model of the form a + b* Age + c* FEV(1 )+ d* (FEV(1))(2 ), where FEV(1 )corresponds to the pre-test (or baseline) level of FEV(1). For the central half of the FEV(1 )distribution, we used a quadratic model to describe the dependence of methacholine slope on baseline FEV(1). For the first and last quartiles of FEV(1), a linear relation with FEV(1 )was assumed (i.e., d was set to 0). Sex was not a predictor term in this model. A negative linear association with slope was found for age. We provide an Excel file allowing calculation of the percentile of methacholine slope of a subject after introducing age – pre-test FEV(1 )– and results of methacholine challenge of the subject. CONCLUSION: The present study provides equations for four relevant percentiles of methacholine two-point slope depending on age and baseline FEV(1 )as basic predictors in an adult reference population of non-obstructive and non-atopic persons. These equations may help clinicians and epidemiologists to better characterize individual or population airway responsiveness

T-cell-based diagnosis of tuberculosis infection in children in Lithuania: a country of high incidence despite a high coverage with bacille Calmette-Guerin vaccination

<p>Abstract</p> <p>Background</p> <p>Lithuania is a country with a high incidence of tuberculosis (TB), despite a high coverage with bacille Calmette-Guerin (BCG) vaccination. Until now the only method used to detect latent TB infection was the tuberculin skin test (TST). However, TST may have a cross reactivity to the BCG vaccine and to environmental mycobacteria. The aim of this study was to conduct assessments of the diagnostic accuracy of the T-cell based test (T SPOT TB) for TB in children who had previously been BCG vaccinated and compare these with the results of the TST.</p> <p>Methods</p> <p>Between January 2005 and February 2007, children with bacteriologically confirmed TB, children having contacts with a case of infectious pulmonary TB and children without any known risk for TB were tested with both the TST and T SPOT TB.</p> <p>Results</p> <p>The TST and T SPOT TB tests were positive for all patients in the „culture-confirmed TB“ group. Whereas, in the „high risk for TB“ group, the TST was positive for 60%, but the T SPOT TB test, only for 17.8%. Meanwhile the results for the „low risk for TB“ group were 65.4% and 9.6%, respectively. A correlation between the TST and T SPOT TB was obtained in the "culture-confirmed TB" group where the TST ≥15 mm (r = 0.35, p < 0.001).</p> <p>Conclusion</p> <p>The T-cell based method is more objective than the TST for identifying latent TB infection in children who had been previously BCG vaccinated. This method could be useful in countries like Lithuania where there is a high incidence of TB despite a high coverage with BCG vaccination. It may also help to avoid unnecessary chemoprophylaxis when TST reactions are false-positive.</p

Treatment outcome of new pulmonary tuberculosis in Guangzhou, China 1993–2002: a register-based cohort study

<p>Abstract</p> <p>Background</p> <p>Completion of treatment for tuberculosis (TB) is of utmost priority for TB control programs. The aims of this study were to evaluate the treatment outcome of TB cases registered in Guangzhou during the period 1993–2002, and to identify factors associated with treatment success.</p> <p>Methods</p> <p>Two (of eight) districts in Guangzhou were selected randomly as objects of study and their surveillance database was analyzed to assess the treatment outcome and identify factors associated with treatment success for TB cases registered in Guangzhou. Six treatment outcome criteria were assessed based on guidelines set by the World Health Organization (WHO). Logistic regression was used to estimate risk factors for treatment outcome.</p> <p>Results</p> <p>A total of 6743 pulmonary tuberculosis cases (4903 males, 1840 females) were included in this study. The treatment success rate (including cured and complete treatment) was 88% (95%CI 87%–89%). One hundred and eight-six (2.8%) patients died and 401 (5.9%) patients defaulted treatment. In multivariate analysis, treatment success was found to be associated with young age, lack of cavitation and compliance with treatment.</p> <p>Conclusion</p> <p>The total treatment success rate in the current study was similar to the WHO target for all smear positive cases, while the failure rate and the default rate in 2002 were slightly higher. Good care of elderly patients, early diagnosis of cavitation and compliance with treatment could improve the success rate of TB treatment.</p

Screening for latent tuberculosis infection among undocumented immigrants in Swiss healthcare centres; a descriptive exploratory study

BACKGROUND: Migration is one of the major causes of tuberculosis in developed countries. Undocumented patients are usually not screened at the border and are not covered by a health insurance increasing their risk of developing the disease unnoticed. Urban health centres could help identify this population at risk. The objective of this study is to assess the prevalence of latent tuberculosis infection (LTBI) and adherence to preventive treatment in a population of undocumented immigrant patients. METHODS: All consecutive undocumented patients that visited two urban healthcare centres for vulnerable populations in Lausanne, Switzerland for the first time were offered tuberculosis screening with an interferon-gamma assay. Preventive treatment was offered if indicated. Adherence to treatment was evaluated monthly over a nine month period. RESULTS: Of the 161 participants, 131 (81.4%) agreed to screening and 125 had complete examinations. Twenty-four of the 125 patients (19.2%; CI95% 12.7;27.2) had positive interferon-gamma assay results, two of which had active tuberculosis. Only five patients with LTBI completed full preventive treatments. Five others initiated the treatment but did not follow through. CONCLUSION: Screening for tuberculosis infection in this hard-to-reach population is feasible in dedicated urban clinics, and the prevalence of LTBI is high in this vulnerable population. However, the low adherence to treatment is an important public health concern, and new strategies are needed to address this problem

Inter-rater agreement in the assessment of abnormal chest X-ray findings for tuberculosis between two Asian countries

<p>Abstract</p> <p>Background</p> <p>Inter-rater agreement in the interpretation of chest X-ray (CXR) films is crucial for clinical and epidemiological studies of tuberculosis. We compared the readings of CXR films used for a survey of tuberculosis between raters from two Asian countries.</p> <p>Methods</p> <p>Of the 11,624 people enrolled in a prevalence survey in Hanoi, Viet Nam, in 2003, we studied 258 individuals whose CXR films did not exclude the possibility of active tuberculosis. Follow-up films obtained from accessible individuals in 2006 were also analyzed. Two Japanese and two Vietnamese raters read the CXR films based on a coding system proposed by Den Boon et al. and another system newly developed in this study. Inter-rater agreement was evaluated by kappa statistics. Marginal homogeneity was evaluated by the generalized estimating equation (GEE).</p> <p>Results</p> <p>CXR findings suspected of tuberculosis differed between the four raters. The frequencies of infiltrates and fibrosis/scarring detected on the films significantly differed between the raters from the two countries (<it>P </it>< 0.0001 and <it>P </it>= 0.0082, respectively, by GEE). The definition of findings such as primary cavity, used in the coding systems also affected the degree of agreement.</p> <p>Conclusions</p> <p>CXR findings were inconsistent between the raters with different backgrounds. High inter-rater agreement is a component necessary for an optimal CXR coding system, particularly in international studies. An analysis of reading results and a thorough discussion to achieve a consensus would be necessary to achieve further consistency and high quality of reading.</p

Selectivity of the photosensitiser Tookad® for photodynamic therapy evaluated in the Syrian golden hamster cheek pouch tumour model

The response to photodynamic therapy (PDT) with the photosensitiser (PS) Tookad was measured in the Syrian hamster cheek pouch model on normal mucosae and chemically induced squamous cell carcinoma. This PS is a palladium-bacteriopheophorbide presenting absorption peaks at 538 and 762 nm. The light dose, drug dose and drug injection-light irradiation times (DLI), ranging between 100 and 300 J cm(-2), 1-5 mg kg(-1) and 10-240 min respectively, were varied and the response to PDT was analysed by staging the macroscopic response and by the histological examination of the sections of the irradiated cheek pouch. A fast time decay of the tissular response with drug dose of 1-5 mg kg(-1) was observed for DLI ranging from 10 to 240 min and for light doses of 100-300 J cm(-2) delivered at a light dose rate of 150 mW cm(-2). A significantly higher level of tissular response was observed for squamous cell carcinoma compared to normal tissue. Nevertheless, the threshold level of the drug-light dose for a detectable response was not significantly different in the tumoral vs normal tissue. The highest response at the shortest DLIs and the absence of measurable response at DLI larger than 240 min at light dose of 300 J cm(-2) and drug dose of 5 mg kg(-1) reveals the predominantly vascular effect of Tookad. This observation suggests that Tookad could be effective in PDT of vascularised lesions

Treatment outcome of new culture positive pulmonary tuberculosis in Norway

BACKGROUND: The key elements in tuberculosis (TB) control are to cure the individual patient, interrupt transmission of TB to others and prevent the tubercle bacilli from becoming drug resistant. Incomplete treatment may result in excretion of bacteria that may also acquire drug resistance and cause increased morbidity and mortality. Treatment outcome results serves as a tool to control the quality of TB treatment provided by the health care system. The aims of this study were to evaluate the treatment outcome for new cases of culture positive pulmonary TB registered in Norway during the period 1996–2002 and to identify factors associated with non-successful treatment. METHODS: This was a register-based cohort study. Treatment outcome was assessed according to sex, birthplace, age group, isoniazid (INH) susceptibility, mode of detection and treatment periods (1996–1997, 1998–1999 and 2000–2002). Logistic regression was also used to estimate the odds ratio for treatment success vs. non-success with 95% confidence interval (CI), taking the above variables into account. RESULTS: Among the 655 patients included, the total treatment success rate was 83% (95% CI 80%–86%). The success rates for those born in Norway and abroad were 79% (95% CI 74%–84%) and 86% (95% CI 83%–89%) respectively. There was no difference in success rates by sex and treatment periods. Twenty-two patients (3%) defaulted treatment, 58 (9%) died and 26 (4%) transferred out. The default rate was higher among foreign-born and male patients, whereas almost all who died were born in Norway. The majority of the transferred out group left the country, but seven were expelled from the country. In the multivariate analysis, only high age and initial INH resistance remained as significant risk factors for non-successful treatment. CONCLUSION: Although the TB treatment success rate in Norway has increased compared to previous studies and although it has reached a reasonable target for treatment outcome in low-incidence countries, the total success rate for 1996–2002 was still slightly below the WHO target of success rate of 85%. Early diagnosis of TB in elderly patients to reduce the death rate, abstaining from expulsion of patients on treatment and further measures to prevent default could improve the success rate further