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Caring about tuberculosis: IUATLD's continuing contributions

2003; Wiley; Volume: 8; Issue: 2 Linguagem: Inglês

10.1046/j.1440-1843.2003.00458.x

1440-1843

Paula I. Fujiwara, John F. Murray,

Pneumocystis jirovecii pneumonia detection and treatment

Few people know that the global burden of tuberculosis is steadily worsening, and that urgent action is desperately needed. Here are the facts: in 1999, there were an estimated 8.4 million new cases, up from 8.0 million in 1997; if present trends continue, 10.2 million new cases are expected in 2005,1 and as has been true for a long time, 95% of all new cases of tuberculosis in the world and 98% of deaths will continue to occur in low-income countries. These are deplorable figures, which reflect as much (or more) on the failure of the society we live in as on the inherent pathogenicity and virulence of Mycobacterium tuberculosis. Tuberculosis is not especially difficult to diagnose; effective and inexpensive drugs to treat it have been available for over 40 years; when medications are properly prescribed, made available, and taken, the disease can be cured in over 95% of all afflicted patients; and, in certain high-risk persons, progression from latent infection to clinically active disease can even be prevented. Complacency, failure to face reality, and lack of will, have all contributed to the current deteriorating global situation. One organization, however, has remained resolutely on the frontlines in the battle against tuberculosis for over 70 years: the International Union Against Tuberculosis and Lung Disease (IUATLD)*. Alone for much of this period, the IUATLD has now been joined by several dedicated partners in a collaborative multifaceted effort to combat tuberculosis and its pathogenic allies, HIV infection and poverty, throughout the world. The purpose of this editorial is to review briefly the historical underpinnings of the IUATLD and its early successes against tuberculosis, and then to describe the powerful global coalitions that have coalesced and how they are furthering the ongoing struggle. The IUATLD is one of the oldest non-profit non-governmental voluntary health associations in the world. Like most contemporary organizations committed to the battle against lung disease, the IUATLD was founded to fight tuberculosis, which at the beginning of the twentieth century was still the most common cause of death in many industrialized countries of the world. Accordingly, to confront the social and medical problems posed by this ubiquitous scourge, several national tuberculosis associations were established in North America, Europe, and Asia. In 1902, during the Berlin International Tuberculosis Congress, the participants decided to create a Central Bureau of Tuberculosis for the purpose of organizing international congresses, which were then held approximately every 4 years until the First World War. After the war, the effort to promote global collaboration for a unified campaign against the disease resumed and was finally consummated in 1920 when delegates from 31 countries met in Paris to celebrate the inauguration of the International Union Against Tuberculosis (IUAT). Then in 1986, in recognition of the fact that its mandate had gradually expanded to include lung diseases other than tuberculosis, the IUAT lengthened its name to IUATLD.2 Throughout IUATLD's long existence, tuberculosis has been the major focus of its pursuits, but both the activities themselves, as well as the places they are carried out, have changed. During its early years, IUATLD organized conferences and disseminated information about tuberculosis among its affiliated associations, which were mainly from wealthy countries. But during the 1950s and 1960s, concepts about tuberculosis had to be dramatically revised after the discovery and widespread usage of effective antituberculosis chemotherapy in industrialized nations; mortality decreased abruptly, and the incidence of the disease, which had been declining, decreased more rapidly than before. In addition, chemoprophylaxis with isoniazid was found to be beneficial in certain populations. To expand this knowledge, IUATLD added research to its portfolio of activities with a study of isoniazid prophylaxis in 28 000 persons with radiographically detectable fibrotic lesions compatible with tuberculosis; the results showed that 52 weeks of treatment prevented the most cases of tuberculosis, but that 24 weeks prevented more cases of tuberculosis per case of isoniazid-induced hepatitis.3 By the early 1970s, it had become clear that tuberculosis was steadily declining in rich countries, but worsening in poor ones, where mortality had decreased, but the number of chronic infectious cases, often patients who were excreting drug-resistant M. tuberculosis, had actually increased. These contrasting results were compared with the effects of no antituberculosis treatment, and led to the conclusion that, from a public health point of view, a bad tuberculosis control program was worse than no program at all.4 Many experts despaired of ever controlling the disease in poverty-stricken regions of the world. These disquieting results did not daunt IUATLD. Under the inspired leadership of Dr Karel Styblo, the redoubtable director of Scientific Activities, the IUATLD introduced a novel comprehensive tuberculosis control program in some of the poorest nations in the world, beginning in Tanzania, and later in Malawi, Mozambique, Kenya, Benin, Senegal and Nicaragua. Twenty years later, the success of these model programs was undeniable. Official kudos were awarded by the Health Sector Priorities Review, a study centred at Harvard University and sponsored by the World Bank, that concluded that the extraordinary benefits of the tuberculosis program developed and implemented by IUATLD were among the most cost-effective of all available interventions in low-income countries, including measles vaccination and oral rehydration in children, and the most cost-effective intervention in adults.5 Another notable outcome of these model programs was the demonstration that it is possible to use rifampicin in a modified short-course chemotherapy regimen without, as had been feared, the emergence of strains of tubercle bacilli resistant to the drug. These accomplishments proved without doubt that it is possible to deal effectively and efficiently with tuberculosis in desperately poor countries, provided all elements of the IUATLD-designed program are in place and functioning well. This is why IUATLD was called ‘the hero of the piece’—the champion in the fight against the resurgence of tuberculosis.6 In addition, the success of the IUATLD's model program furnished sound scientific support for the World Health Organization's (WHO) Global Tuberculosis Programme7 and IUATLD's tested concepts form the basic core of what WHO has adopted, packaged, and widely publicized under the rubric, Directly Observed Therapy, Short-Course, better known as ‘DOTS’. Despite the IUATLD's scientific achievements and the vigorous promotion of the DOTS strategy by WHO, tuberculosis has not only survived, but has prospered, particularly in sub-Saharan Africa, where it is fuelled by the overlapping HIV epidemic, and in Eastern Europe, where failing public health services and spreading HIV have created many new cases, often with multidrug-resistant organisms. To combat these new threats, new strategies are needed and they are being organized and implemented. As usual, IUATLD occupies centre stage in these innovative efforts, which include the following new initiatives and programs. In 1998, members from IUATLD participated in discussions with representatives of WHO, the Royal Netherlands Tuberculosis Association (KNCV), the American Thoracic Society (ATS) and the American Lung Association (ALA) about how to improve coordination in the global fight against tuberculosis. These deliberations led to the development of the Stop TB Partnership, comprised of the founding organizations, plus governments of high-burden tuberculosis countries, donor agencies, foundations, non-governmental organizations and other interested parties. The Board is responsible for guiding the direction of global tuberculosis control activities in DOTS expansion, HIV/TB, treatment of multidrug-resistant tuberculosis, and development of new vaccines, diagnostic tests and drugs. The IUATLD holds one of only two positions on the Board of Directors allocated to non-governmental organizations, and is the only one with a permanent seat. The Tuberculosis Global Drug Facility was inaugurated in 2001 to provide high-quality, low-cost antituberculosis medications to low-income countries to accelerate expansion of their DOTS programs. A representative from IUATLD serves on the Technical Review committee charged with reviewing and approving country applications. In June 2001, the United Nations, with strong support from Secretary General Kofi Annan, convened a United Nations General Assembly Special Session on HIV/AIDS, the first time a single disease had been the focus of discussion. From this was born the idea of generating a global fund to fight HIV/AIDS, a concept that was later expanded, thanks in part to IUATLD, to include two other diseases closely associated with poverty: the Global Fund to Fight AIDS, Tuberculosis and Malaria. The IUATLD was one of only four non-governmental organizations, and the only one representing the tuberculosis community, invited to work with representatives from both donor and high-burden countries on the shape and substance of the fund. IUATLD served on the ad-hoc committee to choose the two board members and one ex-officio participant for the seats for non-governmental groups. Finally, from a pool of over 500 applications for a seat on the Technical Review Panel, which is charged with reviewing all applications for funding, an IUATLD staff member was chosen to be one of the 17 members, and only one of three representing tuberculosis. IUATLD is one of six organizations (the others being WHO, KNCV, ALA, ATS and Centers for Disease Control and Prevention (CDC)) in the Tuberculosis Coalition for Technical Assistance (TBCTA), a USAID-funded initiative to coordinate global tuberculosis control activities, especially the expansion of DOTS. Funds from this source have been used to expand IUATLD's activities in training, health policy and technical assistance. One promising IUATLD initiative funded by TBCTA is attempting to answer questions that have arisen concerning how policy developed at international and national levels is then translated to peripheral levels of the healthcare delivery system where the actual work occurs. Following the closure of the British Medical Research Council (BMRC) Tuberculosis Trials Unit in 1986, the global infrastructure for large-scale clinical trials was dismantled. In 1992, IUATLD, at the request of its international partners, including WHO, CDC and the BMRC itself, began a Clinical Trials Programme, with strong financial support from USAID. The first trial was an evaluation of thrice-weekly versus daily dosing of medications in the intensive phase of antituberculosis treatment, followed by a comparison of two continuation phase regimens, one using isoniazid and ethambutol for an additional 6 months, and the other using isoniazid and rifampicin for an additional 4 months. Eight sites enrolled 1300 patients, making it the largest tuberculosis clinical trial ever conducted. Preliminary results were reported at the 33rd IUATLD World Conference on Lung Health, Montreal, October 2002. Thrice-weekly administration during the intensive phase was not as effective as daily dosing. The 4-month regimen of isoniazid and rifampicin was superior (97.3%) to the 6-month regimen of isoniazid and ethambutol (87.6%) during the continuation phase. A second trial, comparing fixed dose combinations of 2 months of isoniazid, rifampicin, pyrazinamide and ethambutol, followed by 4 months of isoniazid and rifampicin, to the same drugs given separately in the intensive phase, has just commenced. The Clinical Trials Programme, in addition to providing valuable information on current treatment regimens, is also laying the groundwork and infrastructure for future trials of promising medications and vaccines. Incontrovertible data show that HIV infection drives the tuberculosis epidemic. In recognition of this inextricable link, the IUATLD has begun activities related to strengthening the links between national tuberculosis and AIDS control programmes, HIV/AIDS and TB, and is in the process of developing a model for improving the access of HIV-infected patients with tuberculosis to HIV counselling, testing and care, and developing the infrastructure needed to deliver treatment for opportunistic infections, and eventually HIV itself. IUATLD has continued to excel in areas related to support of tuberculosis programmes for which it is already well known: technical assistance to countries, training courses and conferences. From July 2001 through June 2002, IUATLD provided intensive technical assistance to 15 countries in Africa, Latin America and the Middle East. Technical assistance includes defining the magnitude of the nation's tuberculosis burden, helping in-country colleagues to organize and conduct effective national tuberculosis control programmes, assisting with the development of an investment plan shared among the government and external donors, and monitoring progress of the programme and suggesting corrective measures, when needed. In addition to its courses for country-level tuberculosis programme managers held in Benin, Nicaragua, Tanzania and Vietnam, IUATLD has courses on research methods, operational research in epidemiology, and laboratory performance. IUATLD has also initiated new courses, most importantly on tuberculosis control for private sector physicians and university and medical school faculty, as well as a course on the management of multidrug-resistant tuberculosis. To acknowledge the important contributions of nurses, both in the care of individual patients with tuberculosis and in public health control efforts, IUATLD is striving to give these professionals a stronger voice in programme development and evaluation. To further these activities, IUATLD has published several guides in 2001 and 2002, including Research Methods for the Promotion of Lung Health, a Guide to Protocol Development for Low Income Countries, the Guide d’Achat des Médicaments Antituberculeux, and Epidemiologic Basis of Tuberculosis Control. Forthcoming is a tuberculosis guide in Spanish for specialists (Guia de la Tuberculosis para los Medicos Especialistas). IUATLD's yearly World Conference on Lung Health remains the most important professional forum for issues pertaining to tuberculosis and lung health in low-income, high-burden countries. In addition, regional conferences held in collaboration with local respiratory societies focus on issues relevant to the particular part of the world. During the year 2002, successful conferences were held in the Middle Eastern, European, North American, African, and Latin American regions of IUATLD. In this brief overview, we have detailed some of the latest programmes undertaken by IUATLD as it joins forces with other organizations in the global battle against resurgent tuberculosis. The colossal expansion of the HIV pandemic projected for the future is already having a devastating effect on the severe and worsening problem of tuberculosis and threatens to overwhelm current efforts at control. In addition, using the same principles introduced and perfected by Karel Styblo in his model of country-wide tuberculosis control, IUATLD is now undertaking a highly successful programme in Malawi to combat the huge burden of acute respiratory infections in children under 5 years of age. Much remains to be done and IUATLD, as it has been for over 70 years, is in the forefront of the planning and implementation of these activities.