The U.S. Role in Global Tuberculosis Control
Tuberculosis is a leading cause of death worldwide, even though it is a readily treatable and preventable disease. Although an altruistic argument for promoting the global control of tuberculosis can easily be advanced, worldwide control of this disease is also in the nation's self-interest. The proportion of foreign-born tuberculosis patients in the United States has been steadily increasing. In 1998, 41 percent of all tuberculosis patients were foreign-born. It benefits the United States to help strengthen tuberculosis control programs globally, particularly in the countries that are the source of most tuberculosis cases imported into the United States. Tuberculosis will not be eliminated in the United States until the worldwide epidemic is brought under control. This chapter outlines the contributions that the United States can make to this effort.
Recommendation 6.1 To decrease the number of foreign-born individuals with tuberculosis in the United States, to minimize the spread and impact of multidrug-resistant tuberculosis, and to improve global health, the committee recommends that
The United States expand and strengthen its role in global tuberculosis control efforts, contributing to these efforts in a substantial manner through bilateral and multilateral international efforts.
The United States contribute to global tuberculosis control efforts through targeted use of financial, technical, and human resources and research, all guided by a carefully considered strategic plan.
The United States work in close coordination with other government and international agencies. In particular, the United States should continue its active role in and support of the Stop TB Initiative.
The U.S. Agency for International Development (AID), the Centers for Disease Control and Prevention (CDC), and the National Institutes of Health (NIH) should jointly develop and publish strategic plans to guide U.S. involvement in global tuberculosis control efforts.
GLOBAL CONTEXT OF TUBERCULOSIS
Even from the perspective of a developed country, such as the United States, it is increasingly clear that tuberculosis must be viewed in a global context to have a full understanding of the epidemiology of the disease and to develop effective strategies for its control. In the United States, as well as in other countries in which the incidence of tuberculosis is low (less than 25 cases per 100,000 population per year), increasing proportions of the new cases are occurring among individuals born in countries with a high incidence of tuberculosis. Although it is frequently stated that tuberculosis has undergone a resurgence in industrialized countries, at least in part it would be more accurate to view the increases that occurred in the late 1980s and early 1990s as a consequence of shifting global patterns of the disease. No longer are populations and the diseases prevalent within them forced by circumstances to remain in the countries or areas where they originate. Diseases such as tuberculosis are not constrained by national boundaries any more than people are constrained by national boundaries. Thus, in addition to the factors that influence rates of disease in a given country, the global distribution of tuberculosis is also influenced by the factors that determine the movements of populations in general. This is true for at least two reasons. First, in many areas of the world the majority of adults, not just a small subgroup, have latent tuberculosis infection. Second, tuberculosis infection causes no symptoms and results in no alteration in activities; consequently, movement is not limited.
A number of the factors that have been identified as predispositions to the emergence of “new” pathogens have also influenced the spread of tuberculosis (Stephens et al., 1998). Population movements within and between countries both shift persons from high- to low-incidence coun
tries and cause increased crowding in urban areas, thereby facilitating tuberculosis transmission. Increasing economic gradients increase the allure of wealthier countries for poor people in the developing world. In many parts of the world, wars, worsening economic circumstances, reordering of priorities, and lack of political commitment have all led to deterioration in the public health infrastructure while, at the same time, the need for disease control programs and surveillance is increasing. Consequently, overall, there are probably more cases of tuberculosis in the world today than there have ever been. It would be easy to blame human immunodeficiency virus (HIV) infection for the world's worsening tuberculosis situation, and, clearly, it is an important factor. However, one could contend that HIV merely illuminated the existing weaknesses of existing tuberculosis control programs.
In view of the current state of global tuberculosis control efforts, it is not surprising that in low-incidence countries, increasing proportions of new cases are arising from among individuals born in high-incidence areas. In general, low-incidence, industrialized countries have in place screening processes by which applicants for immigrant visas are examined for tuberculosis and individuals with infectious tuberculosis are denied visas. However, the systems are imperfect and, depending on the circumstances, may break down entirely. For example, because of the need for rapid resettlement of a large number of Southeast Asian refugees in the United States in the late 1970s, screening for tuberculosis was not performed. As a consequence, persons with active tuberculosis entered the country, resulting in a reduction of the previous years' rate of decline and an actual slight increase in the number of cases of tuberculosis in 1980. San Francisco was the destination for many of the refugees, and the number of cases rose from approximately 300 in 1978 to 400 in 1979 to 500 in 1980. A similar impact on case numbers was seen in Hawaii with the unannounced arrival of a large number of Filipino World War II veterans who much earlier had been promised citizenship in return for serving in the U.S. armed forces.
The combination of the natural history of tuberculosis, with its often long period of latency and the high prevalence of both latent infection and disease in many parts of the world, together with the many factors that cause individuals and groups of people to move from country to country ideally suits global distribution of the disease. The phenomenon of the globalization of tuberculosis is clearly seen in most industrialized countries. In the United States foreign-born persons made up 41 percent of the new cases reported in 1998 (see Chapter 2). During the 1990s, this proportion has progressively increased, in part because the intensified control measures applied early in the 1990s were directed more toward U.S.-born individuals. As noted in Chapter 2 , the proportion of cases among U.S.-
born persons decreased by 44 percent between 1992 and 1998, whereas there was a 4 percent increase in the proportion among the foreign-born population (Centers for Disease Control and Prevention, 1999). A similar impact has been described in other industrialized countries (Raviglione, 1993).
The conclusion is inescapable that globalization is inevitable, and unless the United States is going to close its borders, the control and ultimate elimination of tuberculosis in the United States will require vast improvements in global tuberculosis control efforts. At this point the outlook is not good for any substantial improvements in tuberculosis control in high-incidence countries unless there is considerable new external assistance.
GLOBAL TUBERCULOSIS CONTROL EFFORTS
To meet the challenge of tuberculosis there must be developed within the world community a sense of shared responsibility and mutual confidence to mount a global tuberculosis control program. A commitment to basic, translational (from research laboratory to clinical practice), and operational research is essential. In addition to research there must be a commitment to training. A trained cadre of clinicians and scientists is essential for implementation of control measures, evaluation of their effectiveness, and development of new knowledge (see Chapter 3).
The global epidemic of tuberculosis presents a dynamic and evolving situation. It must be met with a new level of international commitment and collaboration, with assiduous application of existing tools and with new knowledge and approaches. Tuberculosis is not like smallpox, which was eradicated by a massive but short-term campaign. Tuberculosis control requires patience, persistence, and continued emphasis on the provision of more permanent systems of care. This can be accomplished only by a coordinated global approach with effective partnership between developing and industrialized countries (see the box Pedro's and Juan's Stories).
Given this context and overall framework, what is the role of the United States in global tuberculosis control? In general terms the United States should have concerns founded in self-interest and humanitarianism. These concerns, however, are not the polar opposites that they might seem. The unity of self-interest and humanitarianism is perhaps best conveyed by a quote from an earlier Institute of Medicine (IOM) report, The Future of Public Health, (Institute of Medicine, 1988) “The direct interests of the American people are best served when the U.S. acts decisively to promote health around the world.” Furthermore, it is stated in the same publication, “The failure to engage in the fight to anticipate, prevent, and
advocate global health problems would diminish America's stature in the realm of health, and jeopardize our own health, economy and national security.”
Despite the very strong arguments that can be mounted for the justification of foreign assistance, the United States contributes a smaller percentage (0.1 percent) of its gross national product to overseas aid than any of the other countries in the Organization for Economic Cooperation and Development. Moreover, of the total of $9.9 billion for foreign assistance provided by the United States in 1994, only $1 billion was for health-related activities.
The IOM report cited above presents a compelling, eloquent, and well-documented case for the involvement of the United States in global health as a general concern. Such involvement, the report argues, serves to protect the U.S. population, enhance the U.S. economy, and advance the international interests of the United States. Virtually all of the generic arguments could also be made specifically for tuberculosis but will not be repeated here. However, it has only been in the past few years that governmental agencies, as well as nongovernmental organizations (NGOs), in the United States have taken any interest in tuberculosis beyond our borders. Currently, and for the past several years, funds that are specifically targeted for international tuberculosis activities have been appropriated to AID and CDC, although the amounts are quite small.
It is possible to argue that, on grounds of narrow self-interest, the United States and other industrialized nations should be concerned with tuberculosis abroad because it is not possible to erect a protective cordon sanitaire. This is especially the case with tuberculosis at the border, as is the case with the United States and Mexico. To so frame the issue, however, is to unduly restrict the moral vision of the United States. Eight million cases of tuberculosis annually and 2 million to 3 million deaths a year demand U.S. attention, regardless of their ultimate impact on the well-being of Americans. The United States shares with other industrialized nations the obligation to shoulder the task of fostering the development of new drugs and therapies for the treatment of tuberculosis, new tools for the diagnosis of tuberculosis, and an antituberculosis vaccine. Only the industrialized nations have the scientific, technological, and financial resources necessary to make possible the long-term effort that vaccine development will require. It is that capacity that imposes on the United States the moral duty to act to save the lives of millions who would otherwise die. That the national epidemiological interests are also well served by intelligent efforts to contain tuberculosis adds to the compelling case for U.S. involvement.
NIH has also recently begun to support tuberculosis research projects that are based in developing countries and that target research questions
relevant to areas with a high incidence of tuberculosis. The greatest strength of the U.S. vis-à-vis other countries is its scientific and technological capacity. The United States should take a lead role in basic investigation of tuberculosis. NIH should be the lead agency in this undertaking but should work in close collaboration with the Research and Development Unit of the World Health Organization (WHO) in defining a coordinated global research strategy. The focus of this basic research effort should be on the development of new tools that can be used against tuberculosis. These include new diagnostic tests, new drugs, and an effective vaccine. Development efforts in these areas, in addition to requiring strong efforts in the basic sciences, will also entail participation by private industry. To foster these specific research endeavors a coordinating council that would include NIH, CDC, WHO, industry, and NGOs should be developed. This group should develop a specific tuberculosis research agenda and a strategic plan for achieving it, including advocacy efforts to generate funding.
Pedro's and Juan's Stories
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One of the most important roles of the CURE-TB Binational Referral System is educating tuberculosis patients about their disease and the importance of finishing the prescribed treatment. Pedro's and Lupe's stories are examples of how CURE-TB helps patients finish their treatment.
Pedro was diagnosed with tuberculosis in April 1998 in a northern California county. He was started on medications and left for Jalisco, Mexico, a week later. The California doctor sent a referral to CURE-TB, and CURE-TB staff contacted Pedro in Jalisco via telephone. At the same time, CURE-TB notified the Mexican National Tuberculosis Program of Pedro's arrival in Jalisco.
Pedro informed CURE-TB staff that upon his arrival he had visited a local clinic, where he was evaluated by available diagnostic procedures (sputum smear tests and a clinical evaluation) and was told that he did not appear to have tuberculosis. CURE-TB staff asked Pedro for the local clinic's number to provide his Mexican physician with Pedro's past medical history. CURE-TB counselors immediately called Pedro's physician to provide information on Pedro's previous diagnostic studies, which included culture results positive for Mycobacterium tuberculosis, and his treatment course while he was in the United States. Pedro's physician appreciated this information and decided to continue Pedro's treatment. CURE-TB staff communicated with Pedro again to let him know that he needed to visit his physician as soon as possible.
A month later, CURE-TB staff received the final results on Pedro's tuberculosis drug resistance tests from the California clinic. Pedro's infecting M. tuberculosis strain was resistant to one drug, isoniazid. This was immediately communicated to Pedro's physician, who added ethambutol to his original three-drug regimen. Pedro finished his treatment in November 1998 and is one of the success stories of the CURE-TB referral system. The county in California where Pedro currently resides after returning from Jalisco was also informed of his successful completion of the treatment.
In May 1999, the Los Angeles County tuberculosis Program informed the CURE-TB system about a symptomatic contact of one of their patients, Lupe. The contact, Lupe's brother, Juan, was living in Michoacan, Mexico. Lupe reported that she had lived with Juan months earlier, before she traveled to the United States, and that he had been sick and coughing at that time.
CURE-TB notified national and state health officials in Mexico about Juan's suspect status. CURE-TB also contacted Juan directly by phone and he informed them that he was indeed ill but that he was moving to the United States within the week. Juan was provided with information about the available tuberculosis services at his intended U.S. destination and was urged to seek care immediately upon his arrival. Within days of his arrival Juan did indeed visit a health center and was found to have infectious tuberculosis. He was started on treatment and directly observed treatment regimen.
In this case CURE-TB was able to facilitate rapid access to appropriate care for a symptomatic individual. Not only was the patient able to get the care he needed, but a potential source of prolonged transmission in the community was averted. In addition, Mexican health authorities were able to conduct a contact investigation in Michoacan. Both countries and families on both sides of the United States-Mexico border were able to benefit from the interventions of the CURE-TB system.
Cases such as Juan's and Pedro's are common to the CURE-TB system. The exchange of information between providers, as well as patient education and guidance, are essential factors for the successful completion of treatment for tuberculosis patients moving between the United States and Mexico. CURE-TB staff are committed and eager to continue providing these services.
The research agenda should include not only basic research but also the capacity to undertake applied investigations including clinical trials. In this area of investigation the U.S.-based organization should coordinate both with WHO and with NGOs that are in a position to facilitate and participate in such studies. A major component of applied research should be research training and building of research capacity in developing countries.
In addition to providing leadership in the science of tuberculosis, the United States should do several other things. First, it should take the lead in developing incentives for research and development within private
industry and for developing pricing schemes that would allow innovations to be affordable in high-incidence countries. Such incentives should build upon those already in the Orphan Drug Act and could take the form of, for example, an extension of patent rights on any new products or the implementation of mechanisms to ensure the protection of intellectual property rights. With regard to affordability, tiered pricing schemes could be developed and supported internationally. Additional mechanisms that should be explored include the development of a large central purchase pool fund for drugs and diagnostic tools with a guaranteed volume of sales.
Training and education is a second area of major importance in which the United States should be involved. As with research, the United States should work in close coordination with WHO and NGOs involved in tuberculosis training in developing countries, especially the International Union Against Tuberculosis and Lung Disease and the Royal Netherlands Antituberculosis Association. With regard to education and training, U.S.-based education must overcome a significant barrier. In many quarters it is believed that the United States has little to offer to people from high-incidence countries because different approaches to education are used in the United States. Only by progressive involvement in training efforts will this attitude be overcome. The particular area of strength of U.S.-based or U.S.-conducted training is in the area of research. Currently, Fogarty International Center of NIH, with funding from AID, is supporting the training of investigators. Such training should be maintained, if not expanded, and should target persons from high-incidence countries.
A planning process should define the roles and responsibilities of various organizations involved in the training of individuals involved in tuberculosis control. This process would include the organizations mentioned above as well as people from high-incidence countries. These international training plans should take into account of and should be incorporated into the strategic training plans (for providers, patients, and the public) mentioned in Chapter 3 .
A third area in which the United States should play a prominent role in global tuberculosis control is leadership. As noted above the United States is not perceived as having much to offer other than financial resources and basic research. This, however, is clearly not the case. United States-based agencies and organizations are viewed as world leaders in many areas. From this position these same agencies and organizations can operate to mobilize similar agencies and organizations globally in support of tuberculosis control activities. To gain the trust of the tuberculosis control community, however, it is essential that United States-based agencies and organizations operate within a coordinated overall frame
work. Such a framework is in the process of being developed. The Stop TB Initiative is a partnership hosted by WHO that seeks to accelerate global tuberculosis control via a coordinated multisectoral effort. Funding provided by AID served to catalyze the development of the initiative.
The willingness of the United States to support the use of both patient-centered therapy and fixed-dose medications is vital to their adoption by countries experiencing high rates of tuberculosis, thereby strengthening efforts to eliminate tuberculosis within the borders of the United States. Immigrants, refugees, tourists, and students bring with them both their country's rates of tuberculosis and rates of drug resistance.
Ideally, all tuberculosis patients would be enrolled in well-organized and adequately funded programs. However, there will be occasions and circumstances in which directly observed therapy is not a viable option. The establishment of fixed-dose combination medications as the only acceptable standard of care when directly observed therapy is not available could benefit tuberculosis control both in the United States and throughout the world. Encouraging the removal of rifampin and other single-drug antituberculosis medications from the open markets of countries with a high incidence of tuberculosis and from direct access of physicians who are not trained as tuberculosis specialists could further enhance this tuberculosis control effort.
The United States can also assert leadership by the strategic use of technical and financial assistance. AID is critical in this regard. Only recently has AID begun to exploit its presence in high-incidence countries to address tuberculosis. Ongoing efforts are limited to India, El Salvador, Mexico, Kazakhstan, Russia, and South Africa. The largest effort to date has been the development of a center in Tamil Nadu, India, that is focused on the implementation and evaluation of a model DOTS program. A New Infectious Disease Initiative has identified tuberculosis as one of its four components. However, a rational plan for prioritizing and implementing these activites remains to be elucidated, and at this point, there is little central coordination of funding of tuberculosis control projects by AID, thus precluding a strategic approach. The agency should develop more effective mechanisms for internal coordination and develop its own strategic plan that will enable its assistance to be used most effectively.
United States-based foundations could also be used in a strategic manner to fund tuberculosis control programs or elements of programs in high-incidence countries. Given the wealth and power of some foundations, their involvement could have substantial impacts. The Stop TB Initiative that would target foundations with specific requests upon which there is a strong global consensus should develop a funding plan.
To again quote the IOM report on The Future of Public Health, “Our nation's vital interests are clearly best served by sustained and strength
ened U.S. engagement in global health” (Institute of Medicine, 1998). There is no better example of a situation to which the statement applies than global tuberculosis control.
Centers for Disease Control and Prevention . 1999 . Reported Tuberculosis. Atlanta: Centers for Disease Control and Prevention .
Institute of Medicine . 1988 . The Future of Public Health . Washington, DC : National Academy Press .
Raviglione MC , Sudre P , Rieder HL , Spinaci S , and Kochi A. 1993 . Secular trends of tuberculosis in western Europe . Bull WHO 71(3–4) : 297–306 .
Stephens DS , Moxon ER , Adams J , et al. 1998 . Emerging and reemerging infectious diseases: A multidisciplinary perspective . Am J Med Sci 315(2) : 64–75 .