Molecular Diagnosis of Tuberculosis and Multidrug-Resistant Tuberculosis in Hawaii

             Perhaps no bacterial disease has generated as much national interest in recent years as resurgent tuberculosis (TB).  Largely because of the success of public health strategies, the incidence of TB had declined steadily in the United States since the early 1950s, and the disease was thought to be eradicable by the end of the first decade of the 21st century.  However, since 1981, when AIDS became a newly identified infectious disease, the incidence of TB in the United States and globally has risen dramatically.  In 1990, nearly 26,000 TB cases (10 per 100,000 persons) were reported nationally, and incidence rates of TB currently exceed 300 per 100,000 among certain ethnic-minority groups in the United States.  Hawaii ranks first nationally in the incidence of TB and fourth in the incidence of multidrug-resistant TB (MDR-TB).  Nearly 16% of Mycobacterium tuberculosis (MTB) isolates from Hawaii are resistant to isoniazid (INH) or rifampin and 5% are resistant to both drugs.  Immigrant groups from southeast Asia account for much of this high incidence of TB in Hawaii, and imported TB represents a major source of morbidity in the State.  During 1994, Hawaii reported 20.9 cases per 100,000 population, the highest in the nation, compared to the national TB case rate of 9.4.  Annually, Hawaii continues to report the highest percentage of foreign-born TB cases of any state in the nation, and Honolulu reports one of the highest frequencies of foreign-born TB cases of any major metropolitan area.

              Approximately a third of the worldâs population, or 1.8 billion people, is infected with MTB, and TB is responsible for 3 million deaths per year, making it a leading cause of infectious-disease deaths worldwide.  Due to the risk of contracting TB, and the potential for the emergence of MDR-TB, the rapid diagnosis of TB and MDR-TB is extremely important.  Laboratory confirmation of a tentative diagnosis of TB is essential for appropriate antimicrobial treatment and public health intervention.  The organism must be isolated for identification and susceptibility testing is essential in newly diagnosed cases.  Laboratory diagnosis and confirmation of TB and MDR-TB are labor-intensive and time-consuming, requiring approximately 6-8 weeks.  Reducing this period would be highly beneficial for patients and physicians alike.  This proposal aims to address this important issue by developing and standardizing molecular techniques for the rapid diagnosis of TB and MDR-TB in clinical samples and isolates, thereby facilitating early definitive treatment and intervention.  The specific principle of these diagnostic procedure is based on amplification of specific target MTB genes by nested PCR and rapid detection of MDR-TB by single-strand conformation polymorphism.  Once developed and standardized, this technique could then be institutionalized within the State Department of Health laboratories. 

Nerurkar, V.R., Woodward, C.L., Toma, W., Kobayashi, G., Vogt, R., and Yanagihara, R.:  Molecular diagnosis of tuberculosis and multidrug-resistant tuberculosis in Hawaii.  Journal of Clinical Microbiology  (in preparation).

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