16 September 2006
1. Background to the Global TB Challenge
TB is a world-wide problem. However with the exception of the Russian Federation 21 of the 22 countries that have a high burden of TB (defined as countries which cumulatively contribute 80% of the TB burden of the world) are from the developing world - with 9 countries from Africa on the list. These countries are (starting with countries that contributes the most) are: India, China, Indonesia, Nigeria, South Africa, Bangladesh, Pakistan, Ethiopia, Philippines, Kenya, DR Congo, Vietnam, Tanzania, Uganda, Brazil, Afghanistan, Thailand, Mozambique, Zimbabwe, Myanmar, and Cambodia.
Despite the huge burden of disease from TB, no new drugs or diagnostics have been developed in the past 30 years. According to the Global Alliance for TB Drug Development, despite the large market: "only 5% of the 16 million people currently sick with TB can pay for treatment - a lack of buying power that has dissuaded investors for decades". The Alliance also notes that most of the basic science behind the current drugs used for the treatment of TB is 50 years old. Clearly, pharmaceutical companies, because they cannot generate profits from research and development in TB drugs have not invested in the search for new TB drugs.
As a result of lack of new drugs as well as patients defaulting treatment, many patients develop multi-drug resistance to the currently available drugs. Whilst treatment for TB costs R400 per patient for the drugs used, drug costs (excluding hospitalization and loss of earnings etc) for the treatment of multi-drug resistant TB is R24 000. Again quoting the alliance, these drugs are "often toxic and ineffective….many MDR-TB cases defy a cure".
2. TB and Extreme Drug Resistant TB in South Africa
The Department of Health has had a national TB Control Programme in place since 1994/5 and adopted the World Health Organisation Strategy of Directly Observed Treatment - short course (DOTS) in 1999. Despite these measures the number of cases, the cure rate and the defaulter rates remain high.
In March 2006, in line with a WHO/AFRO decision of African Health Ministers, a TB Crisis Management Plan was launched by the Minister of Health. The Plan focuses in the first instance on 4 districts which have a quarter of the national TB case load. These districts are: Amatole and Nelson Mandela Metro in the Eastern Cape; Ethwkweni metro in KwaZulu-Natal; and the Johannesburg metro in Gauteng. The mainstay of the Plan is social mobilization to ensure that TB is de-stigmatised, that people seek treatment early; and that patients complete treatment.
About a year ago a medical officer working at the Church of Scotland Hospital in KwaZulu-Natal noticed that many patients with TB were not responding to treatment for multi-drug resistant TB. The Department of Health asked the University of KwaZulu-Natal to investigate the matter and a study was initiated. In a one-year period 53 patients were classified to have extreme-drug resistant TB. Extreme drug resistant TB is classified as cases that are resistant to 3 or more of the 6 second-line of TB drugs.
Experts are not clear about why such a large number of XDR-TB was found at the Church of Scotland Hospital. Scientists from the MRC and the University of KwaZulu-Natal have proposed that a study of 10 KwaZulu-Natal public hospitals, chosen at random, be conducted to investigate how widespread the problem is. This survey should be completed by the end of December this year. They also proposed to the Department that similar surveys be conducted in all other provinces.
According to a 6 September 2006 WHO report posted on the WHO website, XDR-TB has been "identified in all regions of the world but is most frequent in the countries of the former Soviet Union and in Asia". The report also suggests that the US has a 4% prevalence rate and that Latvia has a 19% prevalence of XDR-TB.
The WHO report further cites the "recent outbreak of XDR-TB in an HIV-positive population in KwaZulu-Natal in South Africa ….characterized by alarmingly high mortality rates".
What is clear is that XDR-TB is no more infectious than TB and is certainly not as infectious as SARS - despite media reports that suggest that anyone who walks next to a person with XDR-TB will also 'catch it'! Experts also note that it is possible that MDR-TB maybe transmitted from person to person under certain conditions (for example should people live in overcrowded homes or be in overcrowded and poorly ventilated clinics and hospitals).
It is clear that clinics and hospitals need to review and strengthen their infection control practices as a matter of urgency. This includes ensuring proper ventilation and separation of suspect TB cases as early as possible from other patients to prevent person-to person transmission.
In terms of the treatment of XDR-TB, experts have proposed a return to two drugs that were first used decades ago viz., capreomycin and para amino salicylic acid. With the advent of newer drugs, which were found to be more efficacious and with fewer side effects, these drugs were not used in the treatment of TB. Experts have also informed the Department that a return to the use of capreomycin and para amino salicylic acid needs to be done carefully given that they are toxic and that if patients default on these drugs and if the bacilli become resistant to them then no other drugs would be available to treat these patients. This implies that it may be necessary to hospitalize patients diagnosed with XDR-TB for a period of 24 months.
The drug para amino salicylic acid is currently registered in South Africa and arrangements are currently being made to obtain supplies. Capreomycin is currently not registered because of change of ownership of the drug but it's registration is currently being processed by the Medicines Control Council.
In a further effort to understand XDR-TB as well as its treatment the Minister of Health will be hosting two meetings with TB experts and representatives if the pharmaceutical and medical diagnostics industries. The meeting of experts is scheduled to take place on Tuesday, 19 September 2006. The aim of the meeting with representatives of the pharmaceutical and medical diagnostics industries is to assess progress in the research and development of new TB diagnostics and new drugs.
Once the Department has gathered additional information about the nature, spread and treatment of XDR-TB (including technical support from the World Health Organisation), further plans for strengthening TB control interventions will be developed and implemented as a matter of urgency.
3. Conclusions