6th Five Year Report
Future Directions

Acute Respiratory Infections

Of importance for this U.S.-Japan Cooperative Medical Science Program (USJCMSP) was the signing of the Common Agenda for Global Cooperation in July 1993 by President Clinton and Prime Minister Miyazawa. A number of areas were identified for enhanced collaboration through bilateral programs, including AIDS and Child Health/The Children's Vaccine Initiative (CVI). The AIDS Panel has vigorously embraced the Common Agenda in developing plans for future activities. Discussions, both policy (representatives of both governments) and scientific/operational (USJCMSP Subcommittee), have led to agreement on the importance of expanding bilateral efforts on CVI-related research and development, particularly in the area of acute respiratory infections (ARI). Beginning in 1993, special symposia have been held to focus on different aspects of CVI. The Joint Committee has agreed that joint research programs are indicated.

Emerging Diseases

The area of emerging diseases has been identified as an area of interest by the USJCMSP. Emerging diseases pose major health problems with significant morbidity. These threats include new strains of cholera, Lyme Disease, and hantavirus in the United States, Ebola virus infection in Africa, and antibiotic resistant scrub typhus fever in Northern Thailand. The Joint Committee is considering various approaches, including sponsoring special symposia. A conference on emerging diseases is scheduled to be held in Kyoto, Japan, in July 27-28, 1996, for the purpose of discussing problems and highlighting opportunities for collaboration in this area.

Tuberculosis and Leprosy Panels

The Joint Committee agreed to amalgamate the leprosy and tuberculosis programs into a single Panel, starting in 1996. This proposal was made based on a review of activities and the state of the art in both fields. Because Mycobacteria tuberculosis and Mycobacteria leprae are related mycobacteria, it is anticipated that some problems, particular in immunological research, could be better solved by the close collaboration of researchers with expertise in leprosy and tuberculosis. New guidelines have been adopted.

Guidelines

Global control of tuberculosis presents new problems due to increasing prevalence and the emergence of multidrug resistant strains. Leprosy remains a major public health problem although its prevalence is decreasing remarkably due to multidrug therapy. Because of the close relationship of Mycobacterium tuberculosis and Mycobacterium leprae, cooperation of researchers committed to the study of these pathogens may be synergistic.

Research areas of special relevance to tuberculosis and leprosy are the molecular genetics of virulence and pathogenicity; drug targets and mechanisms of resistance; improved animal and human models of protective immunity; mycobacterial constituents that induce pathogenetic and protective cytokines; and the molecular epidemiology of tuberculosis and leprosy.

Development of a better vaccine is of the highest priority.

The goal of the combined panel will be to foster research in the following areas:

1. Molecular genetics of M. tuberculosis and M. leprae
• The molecular basis for virulence and pathogenicity
  
• Mechanisms of drug action and drug resistance
  
• Mapping and sequencing of the genomes.
2. Immunobiology and pathogenesis of tuberculosis and leprosy
   
   • Cells and cytokines involved in pathogenesis and protective immunity
     
   • Antigen(s) in mycobacteria that evoke protection
     
   • Mycobacterial products that induce cytokine production and possess adjuvant properties
     
   • HIV-infection and tuberculosis/leprosy
     
   • Immunological mechanisms of leprosy spectrum and reactions
     
   • Molecular basis of neurotropism of M. leprae and immunological mechanisms in leprous neuropathy
     
   • Genetically-determined resistance and susceptibility in humans.

3. Development of improved animal and cell culture models
   
• Models resembling human infection and natural history
  
• Genetic manipulation of experimental animal models for the study of immunity
  
• Improved in vitro models for studying interactions of host lymphocytes and macrophages with mycobacteria.
4. Clinical and epidemiological application of basic technology
   
   • Early diagnosis of tuberculosis and leprosy, and identification of drug resistant disease
     
   • Immunological intervention for intractable tuberculosis and TB-HIV
     
   • Molecular epidemiology of tuberculosis and leprosy
     
   • Potential targets for new drug development
     
   • Development of more specific and more sensitive skin test and serodiagnostic reagents for tuberculosis and leprosy
     
   • Application of progress in genetic and immunobiological studies for development of a potent vaccine against tuberculosis and leprosy.

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