Multi-drug resistant TB should be treated as a public health emergency

LONDON Experts gathered in London last week to call for urgent action to tackle the global problem of multi-drug resistant tuberculosis. Resistance to the commonly used anti-TB drugs is increasing rapidly in many countries of the world, particularly the former Soviet Union.Mario Raviglione, co-ordinator of TB Strategy and Operations at the World Health Organisation said: "The situation in countries such as Estonia should be treated as a public health emergency on a par with an Ebola outbreak. In general about 2–3% of TB is multi-drug resistant but this rises to 14% of new cases in Estonia."The meeting, 'TB drug resistance: from molecules to macro-economics', held at the Royal Society of Medicine, gathered together for the first time specialists in many different fields in order to uncover the extent of drug-resistant TB and discuss strategies to deal with it.Tuberculosis kills two million people each year and the number of new cases has increased by 6% over two years. This is despite the fact that drugs to tackle the condition are relatively cheap. Part of the problem is the spread of HIV. Together, HIV and TB form a lethal combination, each speeding the other's progress. The other problem is the growth of drug resistance to the two most powerful anti-TB drugs, isoniazid and rifampicin.Strains of TB that are resistant to a single drug have been documented in every country surveyed and strains that are resistant to all the major drugs have emerged. The treatment of multi-drug resistant TB is complex, time consuming and difficult for both patient and doctor. It requires up to two years of treatment with drugs that can be 100 times more expensive than the standard treatment. For many countries already struggling to implement an effective TB programme this extra cost can be prohibitively expensive. Drug-resistant TB is caused by patients either not completing their six-month course of antibiotics or being given incorrect treatment. Patients may not take all their drugs because of side effects, or not complete the whole course because they start to feel better. Medical ignorance can also be a problem, with doctors prescribing the wrong treatment regimens. In many countries the supply of drugs is not reliable.According to the WHO, poorly supervised or incomplete treatment of TB is worse than no treatment at all. Such patients remain infectious and the bacilli in their lungs may develop resistance to anti-TB drugs. People they infect will have the same drug-resistant strain.It was only during the second half of the 1990s that surveys organised by the WHO and the International Union Against Tuberculosis and Lung Disease revealed the extent of multi-drug resistant TB. The biggest problem is in the countries of the former USSR. In Estonia, for example, 36.9% of new cases of TB are resistant to at least one anti-tuberculosis drug. Other countries with a high prevalence or drug resistance include China, Iran and Russia.There are pockets where the problem is even higher. Vivien Stern, senior research fellow at the International Centre for Prison Studies, King's College London, told the meeting that 10% of the Russian prison population has TB — an astonishing 100,000 out of the prison population of one million. Estimates vary as to the number of those affected with multi-drug resistant TB but levels of 20–40% have been suggested.In Africa, where the rates of TB drug resistance are relatively low at the moment there is a potential for a huge increase because of the growing burden of HIV. Alwyn Mwinga, senior lecturer in the department of medicine at the University of Zambia School of Medicine, told the meeting: "In order to avoid the occurrence of the 'third plague' in Africa, it is vital that efforts to control tuberculosis and HIV infection are regarded as top priority."The increase in global trade, international travel and a rising number of refugees means the problem is not confined to developing countries. Peter Davies, consultant respiratory physician at Aintree University Hospital, Liverpool, said: "Drug resistance is a problem in the developing world but leave it long enough and it will become a problem for the developed world."For example, countries such as Denmark and Israel have seen recent increases in multi-drug resistant TB due mainly to immigration. Figures from the Public Health Laboratory Service show that the number of cases of TB in the UK is at its highest for 18 years although the proportion of multi-drug resistance has remained stable.So what is the solution? Mario Raviglione argues: "If we control TB properly in the first place then multi-drug resistant TB does not emerge. Countries that have tackled TB control adequately for decades, such as Chile and Cuba, do not have a problem."The WHO recommended strategy for curing TB is called DOTS (Directly Observed Treatment, Short-course), which involves a health worker or trained volunteer observing and recording patients taking the full course of the correct dosage of anti-TB medicines. There is no doubt that when DOTS is followed properly it can produce dramatic results — producing cure rates of up to 95% even in the poorest countries.The World Bank has ranked the DOTS strategy as one of the "most cost effective of all health interventions" — a six-month supply of drugs for DOTS costs just US$11 per patient. Despite this, however, the WHO estimates that only 23% of people with infectious TB are treated in DOTS programmes. A major problem is one of drug shortages, often caused by financial constraints, inefficient drug procurement systems and poor management. Hopefully this situation will be improved with the launch of the Global TB Drug Facility on 21 March. The initiative by the WHO and the Stop TB partnership aims to finance and distribute TB drugs to treat up to 45 million patients over the next ten years.Raviglione says that once drug resistance is a problem it should be treated as a public health emergency, with the international community providing whatever support and resources are needed. "First, there needs to be a rapid implementation of DOTS to switch the tap off so more cases don't arise and for those cases that exist there should be implementation of DOTS Plus [a strategy involving the use of second-line anti TB drugs]." The worry for the future is that TB strains will emerge that are resistant to the current second-line drugs. Now that the complete genome sequence of Mycobacterium tuberculosis has been uncovered scientists have fundamental information about each of the possible targets for new antibacterial drugs.Douglas Young, Fleming Professor of Medical Microbiology at Imperial College, London told the meeting: "New drugs can be selected to ensure activity against multi-drug resistant isolates and, by avoiding an intracellular activation step, it may be possible to reduce the rate at which new resistances emerge."The problem is getting pharmaceutical companies to invest in developing such drugs. Peter Davies is not optimistic: "Companies tend to be more interested in developing drugs for the developed world, such as for Alzheimer's disease. I feel the world is uninterested as tuberculosis mostly affects poor people in poor countries, unlike AIDS that also affects people in rich countries. I think we are going to see a lot of deaths in the next ten years."

Multi-drug resistant TB should be treated as a public health emergency

Experts gathered at a conference in London last week called for urgent action to tackle the global problem of multi-drug resistant tuberculosis.

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