Academic journal article Bulletin of the World Health Organization

Barriers to Reaching the Targets for Tuberculosis Control: Multidrug-Resistant tuberculosis/Obstacles a la Realisation Des Objectifs De la Lutte Antituberculeuse: Tuberculoses multiresistantes/La Tuberculosis Multirresistente, Un Obstaculo Para Alcanzar Las Metas De la Lucha Antituberculosa

Academic journal article Bulletin of the World Health Organization

Barriers to Reaching the Targets for Tuberculosis Control: Multidrug-Resistant tuberculosis/Obstacles a la Realisation Des Objectifs De la Lutte Antituberculeuse: Tuberculoses multiresistantes/La Tuberculosis Multirresistente, Un Obstaculo Para Alcanzar Las Metas De la Lucha Antituberculosa

Article excerpt

Introduction

"The existence, in the lungs, of those peculiar productions to which the name of Tubercles has been restricted by modern anatomists, is the cause, and constitutes the true anatomical character, of Consumption" (Bishop, 1918). (1)

In 2004 it was estimated that 4.3% of all new and previously treated tuberculosis (TB) cases worldwide were multidrug-resistant (MDR-TB). (2)

The United States Centers for Disease Control and Prevention (CDC) and WHO published, in 2006, the results of a worldwide survey (3) examining resistance to second-line anti-TB drugs, showing that 2% of Mycobacterium tuberculosis isolates were extensively resistant (XDR-TB), that is strains resistant to at least rifampicin and isoniazid, a fluoroquinolone and one or more of the following injectable drugs: kanamycin, amikacin, capreomycin. In the Republic of Korea and Latvia, the proportion of XDR-TB cases among MDR-TB cases was as high as 15% and 19%, respectively, over the period 2000-2004. Patients with XDR-TB were 64% more likely to die or have treatment failure than patients with MDR-TB. (3) In the United States of America, the cure rate of XDR-TB patients was 31%, which is only slightly greater than the estimated proportion of spontaneously healed tuberculosis. (4) Highly drug-resistant TB in a setting in rural South Africa with a high prevalence of HIV infection was reported in 2006, with 98% mortality within 30 days of seeking care. (5,6)

From a short-term perspective it is difficult to estimate the global trend in drug resistance, but in the period since 1943 there is hardly any doubt that resistance has increased. For patients with drug-resistant TB this means that they might be in a similar situation as in the pre-chemotherapy era, when individuals with TB were "consumed" by the disease.

Background

The first anti-TB drug, streptomycin, was isolated in 1943 and its therapeutic introduction saved many lives. However, early trials in United Kingdom and the USA showed that resistance to streptomycin developed during mono-therapy and that patients' symptoms deteriorated. (7,8) The concept of combined chemotherapy was based on this observation. By 1950, the success of combined drug chemotherapy for TB was established. (9) In the following decades more drugs were introduced for the TB treatment, and unfortunately further resistance developed. (10)

In 1960, the British Medical Research Council developed fully-supervised chemotherapy to ensure patient adherence to the prescribed treatment regimen, which was proved to prevent development of multidrug resistance. (11) It was not, however, until the 1980s that the International Union Against Tuberculosis and Lung Disease (IUATLD) gradually implemented this fully-supervised chemotherapy under programmatic conditions in the United Republic of Tanzania and other African countries. (12)

In the 1990s, WHO developed the DOTS strategy as a package of five elements aimed at achieving at least 70% detection and 85% cure rate. This strategy, which is now a fundamental pillar of the new Stop TB strategy announced in 2006, (13) has been widely accepted. Out of a total of 211 countries and territories, 200 report annually to WHO on their progress achieved in TB control. By the end of 2004, 83% of the world's population lived in countries or parts of countries covered by DOTS.

Treatment success in 2003 by a cohort of 1.7 million patients was 82% on average, very close to the global target of 85% set for 2005. However, treatment success was below average in the African Region (72%), which can be partly attributed to HIV co-infection, and in the European Region (75%), partly due to drug resistance. (14)

Almost 40 years after introduction of directly observed combination chemotherapy for TB, and with the accumulated knowledge of the mechanisms leading to development of drug resistance, the latter still remains one of the main barriers to TB control. …

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