Improving the TB case management: The International Standards for Tuberculosis Care.

Tuberculosis (TB) is currently the leading cause of death from a curable infectious disease. The World Health Organization (WHO) estimates that 8.9 million new TB cases occurred in 2004 (of which 3.9 million were sputum smear positive), although only about half of the estimated number were reported by public health systems. Whilst the highest TB incidence rate is in sub-Saharan Africa (estimated to be 356 new cases per 100,000 population per yr), in most countries of the former Soviet Union the estimated incidence rate exceeds 100 new cases per 100,000 population per yr. Although the rate of increase in the TB incidence rate is decreasing, the global TB notification grew by 1% between 2003 and 2004, the last year for which data are available. This continued increase is largely the result of the striking increase in cases in sub-Saharan Africa and, to a lesser extent, in the former USSR. Whilst the worsening of the TB incidence in Africa is due to the HIVepidemic compounded by an insufficient health infrastructure, it is due to different causes in Eastern Europe, including economic decline, increased poverty, social disruption and sub-standard health services. In addition, as a result of these factors, .10% of new TB cases in the Baltic states and in some parts of Russia are multidrug-resistant (MDR-TB), i.e. resistant to at least isoniazid and rifampicin. In the European region, 445,000 new TB cases and nearly 70,000 deaths were estimated to have resulted from TB in 2004. In the Eastern part of the region, the levels of directly observed treatment, short-course (DOTS) strategy coverage and case detection are the lowest among the world regions, and the overall treatment success rate is the second lowest (75%) after Africa

What Research Is Needed to Stop TB? Introducing the TB Research Movement

Christian Lienhardt and colleagues describe the development of the TB Research Movement, which aims to create a framework for concrete actions to harmonize and synergize TB research efforts globally

Has the DOTS Strategy Improved Case Finding or Treatment Success? An Empirical Assessment

Background: Nearly fifteen years after the start of WHO's DOTS strategy, tuberculosis remains a major global health problem. Given the lack of empirical evidence that DOTS reduces tuberculosis burden, considerable debate has arisen about its place in the future of global tuberculosis control efforts. An independent evaluation of DOTS, one of the most widely-implemented and longest-running interventions in global health, is a prerequisite for meaningful improvements to tuberculosis control efforts, including WHO's new Stop TB Strategy. We investigate the impact of the expansion of the DOTS strategy on tuberculosis case finding and treatment success, using only empirical data. Methods and Findings: We study the effect of DOTS using time-series cross-sectional methods. We first estimate the impact of DOTS expansion on case detection, using reported case notification data and controlling for other determinants of change in notifications, including HIV prevalence, GDP, and country-specific effects. We then estimate the effect of DOTS expansion on treatment success. DOTS programme variables had no statistically significant impact on case detection in a wide range of models and specifications. DOTS population coverage had a significant effect on overall treatment success rates, such that countries with full DOTS coverage benefit from at least an 18% increase in treatment success (95% CI: 5–31%). Conclusions: The DOTS technical package improved overall treatment success. By contrast, DOTS expansion had no effect on case detection. This finding is less optimistic than previous analyses. Better epidemiological and programme data would facilitate future monitoring and evaluation efforts

Clinical and operational value of the extensively drug-resistant tuberculosis definition.

Currently, no information is available on the effect of resistance/susceptibility to first-line drugs different from isoniazid and rifampicin in determining the outcome of extensively drug-resistant tuberculosis (XDR-TB) patients, and whether being XDR-TB is a more accurate indicator of poor clinical outcome than being resistant to all first-line anti-tuberculosis (TB) drugs. To investigate this issue, a large series of multidrug-resistant TB (MDR-TB) and XDR-TB cases diagnosed in Estonia, Germany, Italy and the Russian Federation during the period 1999-2006 were analysed. Drug-susceptibility testing for first- and second-line anti-TB drugs, quality assurance and treatment delivery was performed according to World Health Organization recommendations in all study sites. Out of 4,583 culture-positive TB cases analysed, 361 (7.9%) were MDR and 64 (1.4%) were XDR. XDR-TB cases had a relative risk (RR) of 1.58 to have an unfavourable outcome compared with MDR-TB cases resistant to all first-line drugs (isoniazid, rifampicin ethambutol, streptomycin and, when tested, pyrazinamide), and an RR of 2.61 compared with "other" MDR-TB cases (those susceptible to at least one first-line anti-TB drug among ethambutol, pyrazinamide and streptomycin, regardless of resistance to the second-line drugs not defining XDR-TB). The emergence of extensively drug-resistant tuberculosis confirms that problems in tuberculosis management are still present in Europe. While waiting for new tools which will facilitate management of extensively drug-resistant tuberculosis, accessibility to quality diagnostic and treatment services should be urgently ensured and adequate public health policies should be rapidly implemented to prevent further development of drug resistance

Immunodiagnosis of tuberculosis: new questions, new tools conference 2008

Human infection with Mycobacterium tuberculosis exists as a spectrum of conditions ranging from asymptomatic infection to active disease. Novel, accurate tuberculosis immunodiagnostics have been introduced over the last decade, but it remains challenging to timely diagnose active disease and to accurately distinguish asymptomatic M. tuberculosis infection from immune memory resulting from a prior infection eradicated by the host response. The conference titled Immunodiagnosis of Tuberculosis: New Questions, New Tools, which was held on September 21-23, 2008 in Virginia Beach, Virginia, United States, brought together basic scientists and clinical experts to discuss recent progress in tuberculosis research and diagnosis. Global analyses of M. tuberculosis biology and the host immune response, with emphasis on systems approaches to the study of host-pathogen interactions, were presented. Moreover, conference participants discussed new tests in the pipeline and reviewed new technologies leading to novel assay formats. The discussion included technologies ranging from simple, inexpensive point-of-care tests to automated molecular platforms for detection of multiple infections based on the “lab on a chip” concept. It was also recognized that the utility of any new diagnostic relies on laboratory capacity, accessibility, costs, and test deployment. The conference included lessons from the field. For example, the application of existing technologies to neglected areas, such as diagnosis in children and HIV+ populations, was discussed

Risk factors for pulmonary tuberculosis: a clinic-based case control study in The Gambia

BACKGROUND: The tuberculosis (TB) epidemic in Africa is on the rise, even in low-HIV prevalence settings. Few studies have attempted to identify possible reasons for this. We aimed to identify risk factors for pulmonary tuberculosis in those attending a general outpatients clinic in The Gambia, a sub-Saharan African country with relatively low HIV prevalence in the community and in TB patients. METHODS: We conducted a case control study at the Medical Research Council Outpatients' clinic in The Gambia. Pulmonary TB cases were at least 15 years old, controls were age and sex matched clinic attendees. Participants were interviewed using a structured questionnaire. RESULTS: 100 sputum smear positive TB cases and 200 clinic controls were recruited. HIV prevalence was 6.1% in cases and 3.3% in controls. Multivariable assessment of host factors showed that risk of TB was increased among the Jola ethnic group and smokers, and decreased in those in a professional occupation. Assessment of environmental factors showed an increased risk with household crowding, history of household exposure to a known TB case, and absence of a ceiling in the house. In a combined multivariable host-environment model, the risk of TB increased with crowding, exposure to a known TB case, as well as amongst the Jola ethnic group. CONCLUSION: In The Gambia, household crowding and past household exposure to a known TB case are the standout risk factors for TB disease. Further research is needed to identify why risk of TB seems to differ according to ethnicity

Reversion of the ELISPOT test after treatment in Gambian tuberculosis cases

BACKGROUND: New tools are required to improve tuberculosis (TB) diagnosis and treatment, including enhanced ability to compare new treatment strategies. The ELISPOT assay uses Mycobacterium tuberculosis-specific antigens to produce a precise quantitative readout of the immune response to pathogen. We hypothesized that TB patients in The Gambia would have reduced ELISPOT counts after successful treatment. METHODS: We recruited Gambian adults with sputum smear and culture positive tuberculosis for ELISPOT assay and HIV test, and followed them up one year later to repeat testing and document treatment outcome. We used ESAT-6, CFP-10 and Purified Protein Derivative (PPD) as stimulatory antigens. We confirmed the reliability of our assay in 23 volunteers through 2 tests one week apart, comparing within and between subject variation. RESULTS: We performed an ELISPOT test at diagnosis and 12 months later in 89 patients. At recruitment, 70/85 HIV-negative patients (82%) were ESAT-6 or CFP-10 (EC) ELISPOT positive, 77 (90%) were PPD ELISPOT positive. Eighty-two cases (96%) successfully completed treatment: 44 (55%; p < 0.001) were EC ELISPOT negative at 12 months, 17 (21%; p = 0.051) were PPD ELISPOT negative. Sixty (73%) cured cases had a CFP-10 ELISPOT count decrease, 64 (78%) had an ESAT-6 ELISPOT count decrease, 58 (70%) had a PPD ELISPOT count decrease. There was a mean decline of 25, 44 and 47 SFU/2 × 10(5 )cells for CFP-10, ESAT-6 and PPD respectively (p < 0.001 for all). Three of 4 HIV positive patients were cured, all 3 underwent ELISPOT reversion; all 4 not cured subjects (3 HIV-negative, 1 HIV positive) were ESAT-6, CFP-10 and PPD ELISPOT positive at 12 months. CONCLUSION: Successful tuberculosis treatment is accompanied by a significant reduction in the M. tuberculosis-specific antigen ELISPOT count. The ELISPOT has potential as a proxy measure of TB treatment outcome. Further investigation into the decay kinetics of T-cells with treatment is warranted