TWN Info Service on Health Issues (November 06/5)

8 November 2006

WHO cannot delegate leadership responsibility to tackle TB crisis

At the launch of its report on the ‘Development of New Drugs for TB Chemotherapy’ on 30 October, (http://www.accessmed-msf.org/documents/TBPipeline.pdf) Medecin Sans Frontier (MSF) says that the WHO policy is not able to deal with the current TB crisis. MSF calls for the WHO to take on its leadership responsibility to deal with the problem instead of relying on philantrophy.

This comes in the wake of the plans announced by the WHO’s Global Task Force on XDR-TB (extensively drug-resistant tuberculosis) at its first meeting, in early October to work with national and international partners to respond to the health emergency. (http://www.who.int/mediacentre/news/notes/2006/np29/en/index.html).

The following article is reproduced with the permission of South-North Development Monitor (SUNS) # 6131, 1 November 2006.

With best wishes
Evelyne Hong
TWN

Health: WHO policy inadequate to deal with TB catastrophe

By Kanaga Raja, Geneva, 31 October 2006

Medecins Sans Frontieres (MSF) has sounded alarm bells about the current tuberculosis crisis which has reached emergency proportions, and which the standard World Health Organisation (WHO) policy is unable to cope with.

MSF International President Dr Rowan Gillies told a press briefing Monday that TB has been a health catastrophe, with the rapid rise of multi-drug resistant TB and grossly insufficient research and development for new drugs. He called on the WHO to take on its leadership responsibility, saying that it was not enough to rely on philanthropic organizations.

According to MSF, the recent outbreak of extensive drug-resistant tuberculosis (XDR-TB) represents an emergency requiring the WHO to devise drastically new approaches, as relying on standard WHO TB strategies will be fatal.

To respond to the XDR-TB outbreak, WHO will need to get newer drugs to patients as soon as possible by ensuring accelerated development of new drugs already in clinical trials. Existing TB drugs and diagnostics are not adequate.

An MSF report, "Development of New Drugs for TB Chemotherapy", launched at the press conference, finds that none of the TB drugs currently in development, however promising, will be able to drastically improve TB treatment in the near future. The WHO must take the lead in ensuring that there is major re-prioritization and increased funding of TB research.

(The full MSF report can be found at http://www.accessmed-msf.org/documents/TBPipeline.pdf)

With 9 million people developing active tuberculosis every year and 1.7 million deaths annually, TB is far from under control. HIV infection dramatically increases the risk of developing active tuberculosis and is driving the TB epidemic in Africa. The situation is exacerbated by the increasing emergence of extensively drug-resistant TB.

Directly Observed Therapy (DOT), as promoted by the WHO to improve compliance for the difficult and long-lasting regimen, is demanding for patients, labour intensive for health staff and is compromised in settings where health services are poorly accessible, said MSF.

Analysing the current TB drug pipeline, the MSF report noted that there are simply not enough promising compounds in the pipeline compared to the pipeline for other diseases that predominantly affect the wealthy countries. Also, many of the compounds in the pipeline today are derivatives of existing ones.

The report also noted that most of the funding to neglected disease research and development is still philanthropic, with governments only contributing 16% to product development partnerships' engagement in drug development.

At the Monday press briefing, Gillies said that TB has been a health catastrophe for a number of years. It has been very difficult to treat in the Western world - treatment takes about six months and diagnostic tests are not very good. When it comes to the developing world, it is much more difficult. The diagnostic tests that are available today are well over 100 years old.

On top of that, there is multi-drug resistant TB, which is resistant to a number of drugs. Instead of the normal six-month treatment, multi-drug resistant TB takes about 18-20 months to treat. Also, the drugs used to treat this form of TB are quite toxic and often they don't succeed anyway, he added.

Gillies attributed the present situation to the fact that there has been very little research and development on TB in the last 40-50 years. The drug pipeline was completely closed down in the last 30-40 years mainly because TB patients do not live in countries that are a reasonable market for pharmaceutical research.

Gillies however noted that there has been an increase in research and development in the last few years mainly through philanthropic organizations such as the Global Alliance for TB Drug Development (largely funded by the Bill and Melinda Gates Foundation), and the drug pipeline has been restarted. But he said that we are still a long way to treating normal TB and even further away to treating multi-drug resistant TB.

MSF is asking for leadership from the WHO in the major health crises of today, especially TB. Gilles stressed that the WHO cannot delegate this responsibility but it has to take it onto itself, especially when it comes to R&D into new tools and medications. ''This is what we desperately need,'' Gillies said.

Dr Tido von Schoen-Angerer, Director of the MSF Campaign for Access to Essential Medicines, said that there are only a few promising drugs currently in the pipeline. There are only six drugs for TB in clinical development whereas there are around 150 for cardiovascular diseases.

There must be more investment in R&D for TB, and this cannot only be through philanthropic effort. Stronger engagement is required by governments.

According to MSF, with 450,000 new cases of drug-resistant TB globally each year, resistance to drugs is a problem that is growing at a rapid pace. Multi-drug resistant tuberculosis (MDR-TB) is a form of tuberculosis resistant to at least the two principal first-line drugs rifampicin and isoniazid.

The Global XDR-TB Task Force convened by the WHO in October 2006 has defined extensively drug-resistant tuberculosis (XDR-TB) as a form of tuberculosis resistant not only to rifampicin and isoniazid, but also to certain second-line drugs (at least one fluoroquinolone and one of the three injectable drugs kanamycin, amikacin or capreomycin).

MSF said that XDR-TB is particularly alarming in the context of HIV, as people who are co-infected with HIV/AIDS could die before test results can confirm their drug resistance. Using standard drugs to treat XDR-TB without knowing whether there is drug resistance could effectively condemn a patient to death.

According to Dr Francoise Louis, MSF TB and HIV/AIDS advisor: ''Business as usual would be a disaster when it comes to treating XDR-TB. XDR-TB has the potential to be devastating in places where HIV/AIDS is widespread. But trying to treat XDR-TB with the tools we have today would be like trying to put out a forest fire with a garden hose.''

To respond to the XDR-TB outbreak, said MSF, the WHO will need to get newer drugs to patients as soon as possible by working with regulatory agencies and pharmaceutical companies to ensure fast-track clinical development and availability of new drugs for ''compassionate use''.

The WHO will also need to push to accelerate the development of more easy-to-use tests. This will require the WHO to take a lead and not simply delegate responsibility to product development partnerships.

According to MSF, the emergence of XDR-TB is a reflection of how the WHO approach to TB has failed, particularly by neglecting R&D into urgently needed new drugs and diagnostics that could help reduce the nearly two million TB deaths each year.

The drugs in today's standard TB treatment were developed in the 1950s and 1960s and the most commonly used TB test was developed over a century ago and manages to detect TB in only about half of the cases. In addition, existing TB drugs and tests are even less adapted for use in people who also have HIV/AIDS.

According to MSF, it is seeing an increasing number of cases of multi-drug resistant TB (MDR-TB) among the 17,000 patients it treats in over 94 projects in 44 countries.

A MSF survey of 326 TB patients in its TB project in Abkhazia (Georgia) found that 68 patients (20%) had MDR-TB, among whom 15 patients (22%) were resistant to two or more second-line drugs and 2 patients (3% of the MDR patients) were resistant to three or more of the second-line drugs, and thus have XDR-TB.

A survey among suspected TB patients in the rural district of KwaZulu Natal in South Africa between January 2005 and March 2006 revealed that 221 (41%) of 544 patients that tested culture positive for M.tuberculosis were infected by multi-drug resistant strains.

53 patients out of 221 (24% of MDR or 10% of all culture positive patients) were infected with XDR strains. 51% of the XDR patients had no prior TB treatment, suggesting that they had been newly infected by XDR-TB strains, and that resistance did not develop during treatment. 52 of the 53 XDR-TB patients died.

The combination of XDR-TB and HIV infection leads patients to develop a highly aggressive form of tuberculosis that causes death in a very short time, MSF said.

MSF also said that patients undergoing treatment for MDR-TB face long and arduous treatment lasting up to two years, much of which is often spent hospitalized in isolated wards. The drugs are very toxic, cause a wide range of side effects and are very expensive, costing up to $15,000 per treatment course.

The emergence and rapid spread of XDR-TB in high HIV prevalence settings represent a major threat to global health. The phenomenon is a demonstration of the limitations of TB control programmes, which have been relying on outdated tools for TB diagnosis and treatment, MSF said.

The immediate responses of the public health community must not focus solely on strengthening control programmes. It is also urgent to mobilize all necessary resources for the rapid delivery of new drugs and diagnostic tools.

It is also crucial that the drug pipeline be filled with compounds that act through novel mechanisms that are able to target novel molecular targets, in order to avoid cross-resistance with drugs currently in use, said MSF.

Currently, there are a few new promising candidate drugs in the clinical phase of development. There is an urgent need for innovative thinking in the field of clinical trials for new TB drugs, in order to speed up the development of these new drugs and accelerate their delivery to patients.

Also, rapid, reliable and field adapted diagnostic tools for TB and drug resistant forms of TB are an integral part of treatment strategies and urgently need to be developed, MSF said.