H. L. Rieder

Global Surveillance for Antituberculosis-Drug Resistance, 1994–1997

BACKGROUND Drug-resistant tuberculosis threatens efforts to control the disease. This report describes the prevalence of resistance to four first-line drugs in 35 countries participating in the World Health Organization-International Union against Tuberculosis and Lung Disease Global Project on Anti-Tuberculosis Drug Resistance Surveillance between 1994 and 1997. METHODS The data are from cross-sectional surveys and surveillance reports. Participating countries followed guidelines to ensure the use of representative samples, accurate histories of treatment, standardized laboratory methods, and common definitions. A network of reference laboratories provided quality assurance. The median number of patients studied in each country or region was 555 (range, 59 to 14,344). RESULTS Among patients with no prior treatment, a median of 9.9 percent of Mycobacterium tuberculosis strains were resistant to at least one drug (range, 2 to 41 percent); resistance to isoniazid (7.3 percent) or streptomycin (6.5 percent) was more common than resistance to rifampin (1.8 percent) or ethambutol (1.0 percent). The prevalence of primary multidrug resistance was 1.4 percent (range, 0 to 14.4 percent). Among patients with histories of treatment for one month or more [corrected], the prevalence of resistance to any of the four drugs was 36.0 percent (range, 5.3 to 100 percent), and the prevalence of multidrug resistance was 13 percent (range, 0 to 54 percent). The overall prevalences were 12.6 percent for resistance to any of the four drugs [corrected] (range, 2.3 to 42.4 percent) and 2.2 percent for multidrug resistance (range, 0 to 22.1 percent). Particularly high prevalences of multidrug resistance were found in the former Soviet Union, Asia, the Dominican Republic, and Argentina. CONCLUSIONS Resistance to antituberculosis drugs was found in all 35 countries and regions surveyed, suggesting that it is a global problem.

Global trends in resistance to antituberculosis drugs.

Background Data on global trends in resistance to antituberculosis drugs are lacking. Methods We expanded the survey conducted by the World Health Organization and the International Union against Tuberculosis and Lung Disease to assess trends in resistance to antituberculosis drugs in countries on six continents. We obtained data using standard protocols from ongoing surveillance or from surveys of representative samples of all patients with tuberculosis. The standard sampling techniques distinguished between new and previously treated patients, and laboratory performance was checked by means of an international program of quality assurance. Results Between 1996 and 1999, patients in 58 geographic sites were surveyed; 28 sites provided data for at least two years. For patients with newly diagnosed tuberculosis, the frequency of resistance to at least one antituberculosis drug ranged from 1.7 percent in Uruguay to 36.9 percent in Estonia (median, 10.7 percent). The prevalence increased in Estonia, from 28....

LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement

Tuberculosis control relies on the identification and preventive treatment of individuals who are latently infected with Mycobacterium tuberculosis. However, direct identification of latent tuberculosis infection is not possible. The diagnostic tests used to identify individuals latently infected with M. tuberculosis, the in vivo tuberculin skin test and the ex vivo interferon-γ release assays (IGRAs), are designed to identify an adaptive immune response against, but not necessarily a latent infection with, M. tuberculosis. The proportion of individuals who truly remain infected with M. tuberculosis after tuberculin skin test or IGRA conversion is unknown. It is also uncertain how long adaptive immune responses towards mycobacterial antigens persist in the absence of live mycobacteria. Clinical management and public healthcare policies for preventive chemotherapy against tuberculosis could be improved, if we were to gain a better understanding on M. tuberculosis latency and reactivation. This statement by the TBNET summarises knowledge and limitations of the currently available tests used in adults and children for the diagnosis of latent tuberculosis infection. In summary, the main issue regarding testing is to restrict it to those who are known to be at higher risk of developing tuberculosis and who are willing to accept preventive chemotherapy.

The risk of tuberculosis related to tumour necrosis factor antagonist therapies : a TBNET consensus statement

Anti-tumour necrosis factor (TNF) monoclonal antibodies or soluble TNF receptors have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. Individuals who are treated with TNF antagonists are at an increased risk of reactivating latent infections, especially tuberculosis (TB). Following TNF antagonist therapy, the relative risk for TB is increased up to 25 times, depending on the clinical setting and the TNF antagonist used. Interferon-&ggr; release assays or, as an alternative in individuals without a history of bacille Calmette–Guérin vaccination, tuberculin skin testing is recommended to screen all adult candidates for TNF antagonist treatment for the presence of latent infection with Mycobacterium tuberculosis. Moreover, paediatric practice suggests concomitant use of both the tuberculin skin test and an interferon-&ggr; release assay, as there are insufficient data in children to recommend one test over the other. Consequently, targeted preventive chemotherapy is highly recommended for all individuals with persistent M. tuberculosis-specific immune responses undergoing TNF antagonist therapy as it significantly reduces the risk of progression to TB. This TBNET consensus statement summarises current knowledge and expert opinions and provides evidence-based recommendations to reduce the TB risk among candidates for TNF antagonist therapy.

European framework for tuberculosis control and elimination in countries with a low incidence

As countries approach the elimination phase of tuberculosis, specific problems and challenges emerge, due to the steadily declining incidence in the native population, the gradually increasing importance of the importation of latent tuberculosis infection and tuberculosis from other countries and the emergence of groups at particularly high risk of tuberculosis. Therefore, a Working Group of the World Health Organization (WHO), the International Union Against Tuberculosis and Lung Disease (IUATLD) and the Royal Netherlands Tuberculosis Association (KNCV) have developed a new framework for low incidence countries based on concepts and definitions consistent with those of previous recommendations from WHO/IUATLD Working Groups. In low-incidence countries, a broader spectrum of interventions is available and feasible, including: 1) a general approach to tuberculosis which ensures rapid detection and treatment of all the cases and prevention of unnecessary deaths; 2) an overall control strategy aimed at reducing the incidence of tuberculosis infection (risk-group management and prevention of transmission of infection in institutional settings) and 3) a tuberculosis elimination strategy aimed at reducing the prevalence of tuberculosis infection (outbreak management and provision of preventive therapy for specified groups and individuals). Government and private sector commitment towards elimination, effective case detection among symptomatic individuals together with active case finding in special groups, standard treatment of disease and infection, access to tuberculosis diagnostic and treatment services, prevention (e.g. through screening and bacille Calmette-Guéria immunization in specified groups), surveillance and treatment outcome monitoring are prerequisites to implementing the policy package recommended in this new framework document.

Standardized tuberculosis treatment outcome monitoring in Europe

Consensus-based recommendations have been developed by a Working Group of the World Health Organisation (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD) on uniform reporting of tuberculosis (TB) treatment outcome data in countries in Europe. The main purpose of treatment monitoring is to find out how many of the potential infectious TB patients notified were declared cured at the end of treatment. Following the uniform case definitions as defined in 1996, emphasis is placed on cohort analysis of definite cases of pulmonary TB. The Working Group recommends using a minimal set of six mutually exclusive categories of treatment outcome: cure, treatment completed, failure, death, treatment interrupted, and transfer out. More detailed subsets may be chosen. Treatment outcome is expressed as a percentage of the total number of cases notified. Analysis should be separate for new and retreatment cases. Treatment outcome data have to be collected at the local level and passed on to regional and national authorities on an ongoing basis. Evaluation of treatment results becomes, preferably, an inbuilt component of national monitoring of programme performance. Because of the long duration of treatment, it is recommended that analysis is carried out in the first quarter of the calendar year that follows a full year after the last patient was enrolled. Feedback is essential. Treatment outcome results should become an inseparable part of the annual report on tuberculosis.

Guidelines for conducting tuberculin skin test surveys in high prevalence countries.

This Supplement provides an update on guidelines first published in 1996 on conducting a tuberculin skin test survey and analyzing the resulting data. The updated guidelines add experiences gained from community surveys, revisit the proposed sampling strategies, and provide additional information on ethical considerations.

Tuberculosis control in Europe and international migration

This is a consensus-based position paper of a Task Force, comprising representatives of nongovernmental and governmental organizations in the European Region of the International Union Against Tuberculosis and Lung Disease and the World Health Organization, on tuberculosis control in the countries of Europe and international migration. Tuberculosis among the foreign population entering European countries represents an increasing and important proportion of all tuberculosis cases reported in these countries. Adequate surveillance systems allow the identification of population segments at an excess risk of tuberculosis compared to the general population. Among groups of foreigners with a risk considerably exceeding that of the general population, screening for tuberculosis and infection with M. tuberculosis yields a large number of persons in many countries who can benefit from curative and preventive interventions. The Task Force recommends that European countries: 1) have notification systems based on both mandatory laboratory and physician reports of tuberculosis cases, to allow identification of population segments at an excess incidence of tuberculosis compared to the general population; 2) consider screening of high incidence and prevalence groups among the entering foreign population for tuberculosis and infection with M. tuberculosis amenable to curative and preventive i intervention; 3) utilize existing governmental and nongovernmental organizations to provide culturally and socially sensitive services to ensure proper follow-up and implementation of interventions; 4) provide comprehensive curative and preventive services to treat tuberculosis; and 5) evaluate efficiency and efficacy of screening procedures on an ongoing basis.

Methodological issues in the estimation of the tuberculosis problem from tuberculin surveys.

SETTING National tuberculin skin test surveys. OBJECTIVES To review the operating characteristics of the tuberculin skin test, to ascertain the validity of estimating prevalence and risk of infection from tuberculin skin test surveys under various conditions, and to review constraints in the estimation of the magnitude of the tuberculosis problem in the community from such surveys. METHODS This report utilizes hypothetical and selected real data obtained in regional and national surveys at various points in time to exemplify methodological issues. RESULTS Risk of infection, the essence to be abstracted from tuberculin skin test surveys, theoretically allows for a comparison of the extent of transmission of tubercle bacilli in various populations. However, the conduct of tuberculin skin test surveys and the analysis and interpretation of their results are not free from important technical problems. Accurate estimation of infection prevalence is particularly vulnerable to the great variability of the tests specificity under various circumstances. Furthermore, the annual risk of infection has averaging characteristics that preclude a rapid assessment of changes in transmission patterns. Finally, estimates of infection risk do not necessarily provide a standardized parameter to derive incidence of infectious cases, because of variations in the quality of intervention and varying risks of progression from latent infection to overt tuberculosis. CONCLUSIONS While tuberculin skin test surveys provide the currently most widely used means of assessing tuberculosis transmission patterns over prolonged periods of time in a community, results from such surveys must be interpreted with caution when accurate estimates of the tuberculosis problem are sought.

Operational research in low-income countries: what, why, and how?

Operational research is increasingly being discussed at institutional meetings, donor forums, and scientific conferences, but limited published information exists on its role from a disease-control and programme perspective. We suggest a definition of operational research, clarify its relevance to infectious-disease control programmes, and describe some of the enabling factors and challenges for its integration into programme settings. Particularly in areas where the disease burden is high and resources and time are limited, investment in operational research and promotion of a culture of inquiry are needed so that health care can become more efficient. Thus, research capacity needs to be developed, specific resources allocated, and different stakeholders (academic institutions, national programme managers, and non-governmental organisations) brought together in promoting operational research.