Working Group Finds Its Ideas Relevant to and Supported by TB Community at Paris Conference
By Paul Nunn, Coordinator, TB/HIV and Drug Resistance, World Health Organization, Geneva
The Drug Resistance Working Group organized two “pre-consultation” meetings in Paris on October 18th to take advantage of the 39th World Union Conference on Lung Health taking place at the same time.
Participants were interested by the similarity of events that gives rise to resistance across diseases - TB is not different. They expressed concern at how use of drugs for other conditions might be exacerbating drug resistance in TB, including the formation of extensively drug resistant TB (XDR-TB). Examples of this include widespread empirical use of fluoroquinolones for conditions such as community-acquired pneumonia and chronic diarrhea, especially in individuals with HIV infection. These were possible drivers of the recent XDR-TB outbreak in KwaZulu Natal, South Africa.
Participants also voiced concerns about TB drug quality which many felt is another of the key drivers of drug resistance. There is some evidence for concern from the 1990s, when several fixed dose combinations of rifampicin, isoniazid and ethambutol and pyrazinamide were found to have insufficient quantities of bio-available rifampicin. Ensuring the quality of medicines is crucial for the prevention of resistance.
While prequalification by WHO and its partners has been developed for ARVs, it has not been well applied to TB drugs, especially the 2nd line drugs used to treat MDR-TB. Ensuring that practitioners prescribe correctly is a challenge for the generally weak regulation systems that exist in high TB burden countries. Both these issues are expected to be major areas of discussion at the upcoming meeting on "Global Tuberculosis Control and Patient Care: a Ministerial meeting of high MDR and XDR-TB burden countries" in Beijing, China, April 1-3, that is being organized by the World Health Organization, the Ministry of Health of the Peoples Republic of China and the Bill & Melinda Gates Foundation. Analytical work currently underway in preparation for the meeting will model future scenarios for MDR and XDR-TB with a stagnant global response, compared to one with greater investment, and will also look at the financial and economic costs of drug-resistant TB.
Participants in the CGD consultations agreed that the increase in antimicrobial resistance serves as a clear call for more widespread, accurate and timely drug resistance surveillance. While TB drug resistance surveillance appears to be rather more advanced than that for other diseases; in fact, all diseases, TB included, need much better systematic surveillance. As technologies develop, they open up the possibility of synergies between diseases - for TB, HIV and many bacteria, resistance can now be detected by genetic-based tests, which, in the case of TB at least, significantly shorten the time required for diagnosis. A recommendation might be to create molecular diagnostics laboratories that could serve as a common platform for diagnosing resistance across several major diseases.
Consistent with the DRWG’s interest in this area, there are new signs of interest in laboratory capacity-strengthening from donors. For example, WHO and the International AIDS Society are collaborating to establish the HIV Resnet, a global HIV drug resistance surveillance network. Additionally, a small group of malaria experts has been working to consider how a global network (called the proposed World Antimalarial Resistance Network (WARN)) might operate, to bring together clinical, molecular, in vitro and pharmacological data on drug efficacy and drug resistance to malaria. The expert group wants to develop WARN in a manner that builds local capacity in data analysis and presentation in developing countries and facilitates widespread access to information.
In the TB realm, a Global Laboratory Initiative (GLI) was proposed to and endorsed by the Stop TB Coordinating Board in October 2007, and has recently been upgraded to the status of a Working Group within the Stop TB Partnership. The Partnership is actively seeking integration of improved micro-biological laboratory services including resistance testing and smear microscopy into a broader strategy of laboratory strengthening in hospital and primary care. This will require a broad approach to reforming the laboratory system, focusing particularly on microbiological capacity for monitoring drug resistance (including other antibiotics beyond TB).
Additionally, the World Bank announced (at the Paris meeting) a regional laboratory strengthening effort of US$ 140 million, which will seek Board approval during the second half of 2009. Promoting a global public goods approach, this initiative’s primary proposed objective is to improve access, quality and efficiency of TB diagnostic services, (which remains heavily neglected), using an integrated approach to laboratory strengthening. Cross-disease efforts to strengthen laboratories are still not the norm, but there seems to be an increased interest in this area and growing recognition of potential economies of scale and greater health benefits as cross-disease resistance spreads.
