As the world industrialises and becomes more high-tech, tuberculosis (TB) has become a somewhat forgotten disease - with there being a general assumption that it has been consigned to the history books. However, from a global perspective it remains a major healthcare problem. Given the scale of international travel coupled with the infectious nature of the disease there are worrying signs that TB is making a comeback around the world and that complacency could be the biggest problem in dealing with its resurgence.
TB is an infectious disease caused by Mycobacterium tuberculosis. The disease is characterized by the development of granulomas (granular tumours) in the infected tissues, particularly the lungs. The disease is spread when an infected person coughs or sneezes and someone else inhales the droplets. These bacteria can settle in the lungs, grow and spread in the body leading to further organ damage. TB develops in people whose immune systems do not successfully deal with the primary infection. The disease may occur within weeks after the primary infection, or it may remain dormant for years before causing disease.
It is important that the disease is treated promptly because of the infection pattern. If left untreated, each person with active TB will infect on average between 10 and 15 people every year. Factors that contribute to the spread of TB include the frequency of contact with people who have the disease, and living in crowded or unsanitary accommodation.
Uneven global impact
As with a number of other healthcare challenges TB falls into the class of diseases that predominantly affect developing regions of the world. Although around 2 million people died as a result of TB in 2002, figures from WHO on TB incidence and mortality reveal the contrast in how it affects industrialised and developing regions. For example, in 2002, Europe accounted for 4% of global deaths associated with TB, but in Africa the corresponding figure was just over 30% and in South-East Asia it was 34%. Even in terms of cases, Europe only accounted for 5% of global TB cases, but in Africa the figure was 24% and in South-East Asia it was 33%.
Sadly this ‘uneven impact’ has meant that TB has often slipped from being a major healthcare priority - and this is confirmed by the general lack of understanding of the disease amongst the public. It would be unfair to assume that all major healthcare agencies have reduced their efforts in the area of TB, but there is a need to raise the profile of their efforts and to educate the public and healthcare professionals so that they recognise the seriousness of any resurgence in TB. Many healthcare agencies have also called on their governments to invest more in measures to tackle TB and for the pharmaceutical industry to include it in their R&D programmes.
Same disease, new problems
One of the problems in effectively dealing with TB is that the antibiotic drugs that were previously used are becoming less effective. Strains of TB bacilli that are resistant to single types of drugs have been reported in most countries and there are even some that are resistant to all major anti-TB drugs. As with other forms of antibiotic resistance exhibited by bacteria, poorly supervised or incomplete treatment of TB have all contributed to the problem. In most cases, treatment options for drug-resistant TB do exist but they are expensive, time-consuming and there is inevitably a greater risk to patients because of the toxic nature of the drugs employed. WHO have estimated that the cost of treating these forms of TB can be 100 times more than for the treatment of drug-susceptible TB.
There are also worrying trends in the way that TB is now affecting people worldwide. In particular, healthcare agencies such as WHO have noted that HIV and TB form a lethal combination. TB has become a leading cause of death among people who are HIV-positive and it now accounts for about 13% of AIDS deaths worldwide.
Raising the profile
The power of a dedicated approach in tackling TB has been shown by the WHO-approved DOTS ("directly-observed treatment, short-course") programme. DOTS involves political commitment as well as healthcare support and provision of treatment. In the absence of HIV or multidrug-resistance, WHO has estimated that even in the poorest countries cure rates of up to 95% can be achieve for TB.
Prioritising DOTS in India is particularly important since the country is estimated to shoulder 30% of the global burden of TB. In 1998, only 2% of the Indian population were covered by DOTS, but by the end of 2002 around half the population were covered. The programme is continuing with the hope that DOTS can cover the whole country.
There is no doubt that Indian DOTS has been a success and the commitment involved has been impressive, involving the training of over 10,000 doctors, 2000 laboratory technicians, and 100,000 allied health workers. A recent analysis of the impact of the programme found that 80% of TB cases were successfully treated. Furthermore, whereas death rates among infectious patients treated within the programme were 4%, they were over seven times higher in the non-DOTS programme.
The next generation
There is growing pressure on the pharmaceutical industry to help develop a new generation of TB drugs. TB is often described as a ‘neglected disease’ as more than 40 years are said to have elapsed since the last novel treatment was launched.
However this situation may be slowly changing, particularly because of the efforts to set up Public-Private Partnerships (PPP). Through their wide experience of drug development, pharmaceutical companies have an important role to play in ensuring that PPPs have sufficient long–term financing and appropriately manage their resources. An example of this approach is the not-for-profit Global Alliance for TB Drug Development (TB Alliance). The TB Alliance involves a number of international public and private partners, including some from the pharmaceutical industry such as Novartis India. In June 2005, the TB Alliance announced the start of phase I clinical trials for the lead TB drug in its pipeline, PA-824. In 2002, the TB Alliance obtained exclusive worldwide rights to PA-824 and its derivatives from the US biotech firm Chiron. Chiron's commitment to make the TB technology available royalty-free in endemic countries can be seen as a further indication of how the industry’s position over neglected diseases is shifting.
Another welcome development has been the decision by AstraZeneca to open a research centre in Bangalore focused on the discovery of new treatments for TB and other neglected diseases. The centre employs 100 scientists, who collaborate with their international colleagues involved in genomics and infection research. The AstraZeneca Research Foundation India is also funding research projects at various academic centres around the country.
The risk of complacency
Although there are new problems to resolve, TB is still considered a treatable disease, but it does not always receive the priority status it deserves from governments. In many areas of the world, particularly in industrialised countries, a degree of complacency appears to have set in that is hampering efforts by organisations to eradicate TB. Every year, The Stop TB Partnership, which is a partnership hosted by WHO, has been promoting World TB Day to try and raise the profile of TB and to encourage governments to cooperate to halt its spread. In 2004, World TB Day was held in New Delhi. The event involved delegations from 22 highest TB burden countries, as well as political representatives of the G8 countries. As has been seen for other diseases, international approaches provide the best means to effectively prevent and treat TB - and to make sure that the dangers it poses cannot be forgotten.
(The author is with Chiltern International, a Clinical Research Organisation based in Slough)