Tuberculosis (TB)

A “to do” list on MDR-TB

Global experts on tuberculosis (TB ) say that fighting multidrug-resistant TB (MDR -TB ) is complicated. They point out the ease with which one person can transmit the disease, and the difficulties of countries in stopping transmission. They look around the world, especially at developing countries, and see only a handful of places where the spread of the MDR -TB epidemic across an entire nation has been reversed. So they are scared.

And yet these experts also strongly believe that controlling MDR -TB can be done.

At Basabelo TB Hospital in Maseru, Lesotho, Dr Askar Yedilayev inspects the mouth of a patient who is infected with MDR-TB.
WHO/Dominic Chavez
At Basabelo TB Hospital in Maseru, Lesotho, Dr Askar Yedilayev inspects the mouth of a patient who is infected with MDR-TB.

How? Here is some of their advice. Their opinions comprise a useful pocket guide, collected through interviews and observations. And while numbers are assigned to items, these are not ranked in order of importance. Collectively, these items should contain some common sense, some acquired wisdom and maybe a few kernels of insight.

1. Turn off the tap

Dr Mario Raviglione, Director of the Stop TB Department at the World Health Organization (WHO), has been saying this for years, and it bears repeating. The only way to stop MDR-TB is to build a strong basic TB control programme so that those who become ill with TB do not develop MDR-TB. And at the same time, officials also need to build strong MDR-TB treatment programmes so that those infected do not spread the infection and that their infection doesn’t turn into extensively drug-resistant TB (XDR-TB).

2. Help is near – partners, too

WHO and its partners have scores of experts who can offer technical assistance to countries as they build their response to MDR-TB. In 2000, they also initiated the Green Light Committee, which allows access to high-quality second-line drugs to treat MDR-TB. Since 2003, the Global Fund to Fight AIDS, Tuberculosis and Malaria has committed US$ 2.4 billion to TB control programmes. Still, funding gaps persist. The 22 high-burden TB countries had a combined funding gap of hundreds of millions of dollars in 2008. Dr Raviglione said the organizations are “aware of those gaps and working closely with governments, the Global Fund, UNITAID and other funding agencies to mobilize needed funds.”

Finally, several nongovernmental organizations have years of experience in building MDR-TB programmes. Two examples are the Foundation for Innovative New Diagnostics (FIND), who are experts in setting up laboratories; and Partners In Health, who are experts in initiating treatment programmes.

3. Look at the examples from other countries

Three countries are worth a look. In just four years (2002–2005), China greatly expanded its TB control programme, delivering treatment of ordinary TB free of charge to 1.2 million people. It also greatly expanded surveillance of cases, which sharply increased the numbers of reported cases of TB. In 2002, China’s public health system treated 170,000 TB patients; by 2005, 500,000 were enrolled in treatment programmes annually. China is now entering a new phase by turning towards control of MDR-TB and assuming global leadership on many fronts: increasing funding by millions of dollars for scientific TB research; and hosting a WHO ministerial meeting in Beijing of the world’s high-burden MDR-TB countries.

The Russian Federation, in battling its high numbers of MDR-TB cases, has moved aggressively to build new laboratories, train a range of health workers and revamp health systems in prisons, including the installation of infection-control ventilation systems. Towards this end, the Government secured a US $150 million loan from the World Bank and an US $80 million grant from the Global Fund. It also has submitted multiple applications for second-line drugs with the Green Light Committee and, by the end of 2008, had more than 1,700 patients receiving drugs through the GLC process, or roughly 40% of the global total of GLC patients.

Peru has mobilized a community-based response to MDR-TB countrywide, achieving cure rates as high as 83% among patients. At first, the country relied heavily on outside expertise; it now funds nearly the entire MDR-TB control programme. Now confident in its strategy, Peru offers technical assistance to other Latin American countries.

4. Strengthen laboratories

Laboratories are the backbones of any successful TB control programme, and WHO experts say many more are needed. “We need to get laboratories nearer to the patients,” said Dr Paul Nunn, Coordinator of TB/HIV and Drug Resistance at WHO’s Stop TB Department. The goal, he said, will be to have one laboratory capable of growing cultures of sputum samples for every 5 million people, and one laboratory capable of detecting drug resistance strains for every 10 million. That means adding 2000 laboratories around the world. The number of laboratories, Nunn said, has not kept pace with population increases or the spread of TB. One example, Kenya, had one national referral laboratory serving 12 million people at independence in 1963; today, this same laboratory serves 35 million people. Plans are under way to build four new laboratories.

5. Expand research

The Bill & Melinda Gates Foundation has committed roughly US$ 500 million to date on TB research. Dr Peter M. Small, Senior Program Officer for TB, calls the lack of good diagnostic tools and anti-TB drugs an outrage. “We are combating a disease that kills someone every 20 seconds, with a 125-year-old diagnostic test that fails to diagnose half the number of cases, with an 85-year-old vaccine that does not protect adults and with 40-year-old drug regimens that you have to take for six months,” he said.

Dr Jim Yong Kim, Professor of Medicine and Social Medicine at Harvard Medical School, has experience in fighting MDR-TB since 1995, when a friend had died of drug-resistant TB in a slum outside Lima, Peru. He said he hoped researchers would discover many new drugs to fight TB. “It’s not just one or two new drugs, we need four or five new drugs immediately. People aren’t sounding the alarm loud enough. Every time we look, the problem is worse then we thought. Now it is coming together with HIV in sub-Saharan Africa and it could be the most frightening thing we are ever going to see,” he said.

One hope is that emerging economies in countries such as Brazil, China, India, the Russian Federation and South Africa, start ambitious TB research programmes. “These countries all have significant research capacity, which for the most part is not turned towards TB,’’ said WHO’s Dr Nunn.

6. Train more health workers

Training more health workers means ongoing training for a range of health workers – from doctors to community health workers – with limited formal education. Typical topics include MDR-TB diagnosis and treatment; case discussions; infection control; referral system plans; and, in areas with HIV-TB coinfection, the co-management of drugs for both diseases.

HIV -TB coinfection issues are highly complicated and little understood, making it difficult to train health workers. “We need more extensive training of health workers because it’s so difficult,” said Dr Hind Satti, Director of Partners In Health Lesotho’s MDR-TB control programme. “We’re finding higher rates of sideeffects among patients than anywhere else in the world – and we think it is due to coinfection.”

7. Protect health workers (and everyone else )

Controlling TB infections in health settings is particularly important because so few hospitals in developing countries have infection-control ventilation systems. Without these systems, everyone in the hospital, from health workers to visitors, is at risk. “Virtually every health care facility in the developing world and in much of the industrialized world is in need of drastic improvement in airborne infection control,” Dr Nunn said. “It is a serious risk in many parts of the world just to go into a hospital. It almost brings you back to the palace of diseases of Florence Nightingale at Scutari.”

[Florence Nightingale was the Superintendent of Nurses at Scutari Hospital in Turkey during the Crimean War (1854–1856), where the monthly rate of mortality among British soldiers in the first winter reached 40%. Many died from sicknesses acquired in hospitals, not from war injuries. Nurse Nightingale improved hygiene practices and, 18 months later, the mortality rate had reduced to 2%.].

8. Ensure access to high-quality drugs

In many countries, first-line and second-line anti-TB drugs can be bought over-the-counter. This concerns those who run TB control programmes because misuse of these drugs may generate further drug resistance and possibly extensively drug-resistant TB (XDR-TB). Another concern is that counterfeit or poor-quality anti-TB drugs are available on the open market. Ministers have three options: lobby for legislation that prohibits the sale of anti-TB drugs without a doctor’s prescription; accredit doctors who are trained to treat MDR-TB; and apply to the Green Light Committee for access to quality-assured secondline medication. “The Green Light Committee has a key role to play,” said Dr Marcos Espinal, Executive Secretary of the Stop TB Partnership, who worked on the establishment of this mechanism.

9. Know your epidemic

No MDR-TB epidemic in any one country is identical. MDR-TB in eastern and southern Africa is interwoven with the AIDS epidemic, creating a raft of issues that are non-existent in regions with low HIV prevalence. In many countries of the former Soviet Union, rates of MDR-TB among new TB cases are higher than anywhere else in the world. This demands a different type of response. One of the first steps is to study a country’s MDR-TB epidemic and tailor the response to the local situation.

10. Make no excuses – commit funding

A common error, say many TB specialists, is that governments do not appropriate enough funds to put together a comprehensive response. Another common mistake is that countries delay starting MDR-TB programmes until the entire system is ready to go. “One example is laboratory capacity,” said Carole Mitnick, Assistant Professor of Global Health and Social Medicine at Harvard Medical School. “While I’m in complete agreement with the need to build laboratory capacity locally, I don’t agree it is a prerequisite to get treatment started. There are laboratories available elsewhere.”

The bottom line, she said, is simple: “Don’t make excuses. Start as soon as possible.”

Dr Michael E. Kimerling, former director of the Gorgas TB Initiative at the University of Alabama at Birmingham and now Senior Program Officer for TB at the Bill & Melinda Gates Foundation, said the consequences of inaction are dire. “If you ignore the problem, TB doesn’t go away, it gets worse,” he said. “Look at what happened after the breakup of the Soviet Union and the economic collapse then. If this current global economic crisis results in programmes falling apart, it’s very predictable what you are going to get – more drug resistance and more deaths.”