Ending Neglect The Elimination of Tuberculosis in the United States (2000) / Chapter Skim
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5 Developing the Tools for Tuberculosis Elimination
5 Developing the Tools for Tuberculosis Elimination
Pages 122-148
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From page 122... ...
However, because so many of the cases in the United States are not the result of recent transmission of tuberculosis but rather are the result of reactivation of latent infection, the greatest needs in the United States are new diagnostic tools for the more accurate identification of individuals who are truly infected and who are also at risk of developing tuberculosis. Together with new treatments drugs or immunological adjuvants for the prevention of disease in infected individuals, that are easily administered, the elimination of tuberculosis can be a reality.
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From page 123... ...
Recommendation 5.2 To advance the development of diagnostic tests and new drugs for both latent infection and active disease, action plans should be developed and implemented. The Centers for Disease Control and Prevention (CDC)
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From page 124... ...
CURRENT STATUS AND NEEDS Diagnostic Methods Currently, the management of tuberculosis is dependent on the ability to identify individuals with active disease, those whose disease is caused by organisms resistant to antimicrobial agents, those who are infected but not ill, and those who are most likely to progress from infection to disease. Although precise numbers are not known, the World Health Organization (WHO)
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From page 125... ...
If molecular biological methods could be developed for the identification of specific strains that are highly transmissible or that have an enhanced capacity to cause progression to active disease in the host, public health officials could more efficiently focus efforts on contact identification and treatment of latent infection. In contrast to recent advances in clinical mycobacteriology, there have been no improvements in the ability to identify persons who are latently infected with M
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From page 126... ...
Even with the regimens currently available for the treatment of latent infection, a highly specific test that detects individuals at the highest risk of developing disease in the future would have a greater impact on the elimination of tuberculosis in the United States than a vaccine that prevents infection. Such a test might also make the treatment of latent infection in many countries with medium and low average incomes a practical intervention.
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From page 127... ...
In contrast to single-drug-resistant strains, which can be effectively treated with prolonged courses of alternative drugs, the success of treatment of multidrug-resistant tuberculosis is only marginally better than outcomes of tuberculosis in the prechemotherapy era. In a report on global surveillance for antituberculosis drug resistance, the data for the United States indicated that the combined rates of primary and acquired
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From page 128... ...
However, the development of new antituberculosis drugs by pharmaceutical companies in recent decades has faltered and has fallen behind that of other antimicrobial agents, to a large extent because of the perceived relatively limited market of patients with active tuberculosis in the United States (19,851 cases in 1997~. During the 5-year period between 1992 and 1996, a total of 42 new antimicrobial drugs (exclusive of topical agents, additional indications for older drugs, and new preparations of older drugs for different routes of administration)
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From page 129... ...
In combination with increasing rates of drug-resistant tuberculosis, treatment of tuberculosis infection is particularly problematic. It has been inferred, although never rigorously documented, that resistance to isoniazid negates the efficacy of treatment of latent infection with isoniazid.
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From page 130... ...
Given the unlikelihood of identifying a perfect tuberculosis vaccine in the proximate future, it is important to define what would comprise a minimally acceptable vaccine or combination of vaccines to meet global needs. The needs for and approach to tuberculosis vaccine development were recently elucidated at a workshop convened by the U.S.
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From page 131... ...
In addition, the call for programs of treatment for latent infection among foreign-born individuals presents yet another dimension of the need to understand human behavior, as ethnic variations in knowledge, attitudes, and behavior need to be elucidated and understood. There has been a recent effort to understand the costs and economics of tuberculosis, especially through the Prevention Effectiveness Studies Section, in the Research Branch of the Division of Tuberculosis Elimination.
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From page 132... ...
Thus, operational researchers require an understanding of the realities of the situations in which tuberculosis is being diagnosed (such as the factors that influence health care providers and clients) and an ability to work effectively in partnership with these communities.
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From page 133... ...
Data on funding for tuberculosis research from the National Institute of Allergy and Infectious Diseases are presented in Figure 5-2. Although most of this work is extramural, with the $35 million award to the Tuberculosis Research Unit being the largest single extramural award, three intramural research programs focus on tuberculosis.
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From page 134... ...
Centers for Disease Control and Prevention The research programs of CDC currently encompass a broad range of activities including basic bacteriological research, surveillance, operational research, behavioral studies, technology assessment, and transfer. Although it is difficult to precisely account for funds spent on these efforts (as opposed to related activities)
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From page 136... ...
Although most CDC staff report that communications are good and improving, the perception of many researchers outside of CDC is that there is often a lack of communication and coordination. New Tuberculosis Diagnostic Developments by Industry The most systematic assessment of members of industry with an interest in the development of tuberculosis diagnostic tools has been conducted by Mark Perkins, WHO, director of the Tuberculosis Diagnostics Initiative of WHO (personal communication, 1999~.
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From page 137... ...
as well as those developed by other companies and licensed for marketing under a different name. The reticence of some companies to disclose the nature and development or production site of their products has made it difficult to determine the extent to which the number of companies identified in the survey to be involved with tuberculosis diagnostic tools is inflated by marketing of duplicate products.
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From page 138... ...
drugs were noted in the titles of 374 articles. Forty percent described antibacterial drugs, 20 percent described antiviral agents, but only 3 percent described antimycobacterial agents.
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From page 139... ...
Another company noted that it had oxazolidinone compounds undergoing preliminary laboratory investigation, but it had turned over its rights to develop the drug to the company mentioned in the previous sentence. A third company noted that it has no track record with the development of antituberculosis drugs but had found a group of compounds in an antibacterial screening process that it is sending elsewhere for in vitro testing.
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From page 140... ...
One estimate puts the global expenditure for the four main antituberculosis drugs at $800 million to $900 million per year, an amount that would definitely justify the development of new drugs in market terms. Vaccine Development by Industry To attempt to answer the question as to whether industry is actively pursuing development of candidate vaccines for tuberculosis prevention, the same 22 major pharmaceutical companies and 7 biotechnology companies that were mentioned above and that were questioned about new drug discovery were queried about any prospective vaccines.
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From page 141... ...
Two of the seven biotechnology companies contacted indicated that their major activities are focused on the prevention or treatment of tuberculosis. For one company, the approach is exclusively vaccine development.
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From page 142... ...
The recent announcement by the Bill and Melinda Gates Foundation of grants for $50 million over 5 years for tuberculosis vaccine development may signal the start of interest in tuberculosis research by philanthropic foundations. United States Agency for International Development In light of the stated humanitarian and development goals of AID and its capacity to translate research advances into practice, its activities in tuberculosis have been extremely disappointing.
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From page 143... ...
At best the federal funding for research has been about half that amount. Since the development of the action plan, a Blueprintfor Tuberculosis Vaccine Development was published 1998.
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From page 144... ...
Although existing evidence and tools justify the expansion of targeted screening and treatment of latent tuberculosis infections now, better tools for the diagnosis of infection and drugs for the treatment of infected individuals would facilitate these activities. The diagnostic test might be approached as a two-step test, with the first step very sensitive and the second step highly specific.
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From page 145... ...
The opportunity to test these diagnostic assays and drugs in cooperation with publicly funded networks of clinical trials should entice pharmaceutical and biotechnology companies to expand on the knowledge gained by publicly funded basic investigators and rapidly move new products through commercial development. Formation of a joint venture between industry and public sector agencies, would speed the attainment of this goal.
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From page 146... ...
This network must reach out to community-based health care providers and for-profit health care providers. · These clinical trials should be extended by AID to include sites in other countries with high rates of tuberculosis infection.
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From page 147... ...
2000. Blueprint of tuberculosis vaccine development.
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From page 148... ...
and Jones SL.1998. Sensitivity and specificity of a gamma interferon blood test for tuberculosis infection.
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