WHO and the emergence of XDR-TB
A Clinical Infectious Diseases (CID) journal news release, related to an article to be published 1 December 2007, was misleading in stating that: "In South Africa, the 2001 implementation of the WHO's anti-TB program may have inadvertently helped to create a new strain of extensively drug-resistant tuberculosis (XDR-TB)". As a result, several news articles have misreported WHO's guidance on the design of TB treatment programmes.
WHO does not implement programmes. WHO formulates norms and standards and technically supports Member States who are responsible for ensuring the proper implementation of programmes.
Since the early 1990s, WHO has produced a series of guidelines for effective treatment of drug-susceptible and drug-resistant TB, including recommendations regarding the need for drug resistance surveillance and drug susceptibility testing for good clinical and epidemiological practice.
The authors of the CID article call for enhanced drug resistance surveillance to combat the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), and this is fully consistent with WHO guidance over the last 12 years.
WHO AND THE DEVELOPMENT OF MDR-TB AND XDR-TB GUIDELINES
(Recommendations regarding the fundamental role of drug resistance surveillance and drug susceptibly testing in TB treatment and control)
Since the early 1990s WHO has produced a series of guidelines for effective treatment of drug susceptible TB and drug-resistant TB, and has supported national efforts to adopt and adapt these guidelines based on requests from Member States:
- In 1994, the WHO Framework for effective TB control which recommended the five core elements for TB treatment and control (later known as DOTS*) recommended the establishment of microscopy service and "if additional resources are made available, establish culture and susceptibility testing in order to monitor drug resistance".
- In 1994, WHO and the International Union Against Tuberculosis and Lung Disease launched the Global Project on Anti-Tuberculosis Drug Resistance Surveillance, which has produced three reports (1997, 2000, 2004) of national survey results, with a fourth report to be published in 2008. This project is supported by a global network of 'Supranational Reference Laboratories' to support and improve the quality of drug susceptibility testing and surveillance.
- Two years later, in 1996, Guidelines for the management of drug-resistant tuberculosis developed further the recommendations for drug susceptibility testing: "The specialized unit must have the services of a laboratory able to carry out culture and reliable tests for drug resistance (to the essential drugs and also to second-line drugs). The quality of the susceptibility tests carried out in this laboratory should be regularly checked by another reference laboratory at national or supranational level."
- In April 1998, experts in drug-resistant tuberculosis met for the first time to develop international guidelines on the programmatic approach to drug-resistant TB management. A report Basis for the development of an evidence-based case-management strategy for MDR-TB within the WHO's DOTS strategy, was published in which it was recommended that "surveillance must be an integral part of MDR-TB control: support should be garnered to enhance the ability of the supranational reference laboratory network system to conduct ongoing surveillance; further laboratory collaboration between resource-rich regions and MDRTB "hot zones" should be fostered; results from surveillance must guide MDR-TB treatment strategies and must inform approaches to prevention of further drug resistance".
- The document also contained the report of a subsequent meeting held in Geneva in July 1998 which included a discussion on standardized versus individualized regimens for MDR-TB. The conclusions stated: "DOTS-Plus is a management initiative designed to address MDR-TB that consists of (i) DOTS, the WHO's TB control strategy and (ii) pilot treatment protocols based on individualized or standardized treatment regimens of second-line drugs". The annex of this document contained two generic protocols, one for a standard regimen; and one for an individualized regimen. This document became the guide that WHO made available to all countries on MDR-TB treatment.
- In January 1999, those principles were reiterated by experts in the Coordination of DOTS-Plus pilot projects for the management of MDR-TB report at the first meeting of what subsequently became known as the Stop TB Partnership's Working Group on MDR-TB.
- In September 1999, a scientific panel meeting was held which resulted in the publication, the following year, of the first set of comprehensive guidelines including recommendations with respect to laboratory requirements for drug susceptibility testing, Guidelines for establishing DOTS-Plus pilot projects for the management of MDR-TB.
- In 2000, the Green Light Committee (GLC) for access to second line drugs was developed and WHO started serving as the secretariat for the committee. The committee approves piloting and scale up of MDR-TB treatment programmes, based on WHO guidelines, and ensures access to necessary technical assistance. Over 40 countries have GLC approved projects to date.
- In 2001, the first attempt to standardize international methodology for second-line drug susceptibility testing was presented in the WHO guidelines for drug susceptibility testing for second-line anti-TB drugs for DOTS-Plus (subsequently updated).
- The Stop TB Strategy, launched in March 2006, included the prevention and control of MDR-TB within its six key components.
- In May 2006, findings from a series of projects clearly demonstrated that MDR-TB can be effectively treated in low-income countries. The updated guidelines, Guidelines for the programmatic management of drug-resistant tuberculosis, encompassed those findings and lessons learnt from 46 projects, and have been implemented in 29 countries since 2000.
- In October 2006, a Global Task Force on XDR-TB was formed to respond to specific concerns over XDR-TB. The Task Force concluded with a series of recommendations to national programmes including: strengthen basic activities to control TB and HIV/AIDS to avoid additional emergence of MDR-TB and XDR-TB; scale up the programmatic management of MDR-TB and XDR-TB; strengthen laboratory services for adequate and timely diagnosis of MDR-TB and XDR-TB; expand surveillance of MDR-TB and XDR-TB; and foster sound infection control measures to avoid MDR-TB and XDR-TB transmission.