The National Heart, Lung, and Blood Institute (NHLBI) has a strong commitment to reduce the disproportionate burden of disease among minority populations and to disseminate information regarding treatment and prevention of cardiovascular, pulmonary, and hematologic diseases, sleep disorder, and AIDS and as it relates to these disease areas. To gather information about the etiology and pathology of these diseases in minority population, the National Institutes of Health (NIH) implemented a policy requiring the inclusion of minorities and women in all research involving human subjects. Thus minorities are represented in all AIDS clinical research studies.
In addition, minority supplements have been added to six tuberculosis grants to enable minority individuals to pursue research and to gain experience and recognition in the area. At present, minority investigators are involved in projects examining sufactants effect in tuberculosis in the lung, regulation of granuloma in tuberculosis, promotion of adherence to TB regimens in Latino adolescents, and for control of TB. Details regards two of the projects are presented below.
The study characterizes the granulomatous response of tuberculosis. Although generally viewed as a critical element in host defense against M. tuberculosis, little is known about the tuberculosis granuloma at the cellular, molecular, and biochemical levels. The unusually high incidence of disseminated tuberculosis and the markedly deficient granulomatous response seen in AIDS patients suggest a significant role for T-cells in the regulation of granuloma formation. The investigators have developed a murine experimental tuberculosis model of protein calorie malnutrition (PCM) in which mice receiving a protein-deficient diet experienced fulminant and rapidly fatal infection associated with markedly increased bacterial burden and poorly formed granuloma. In contrast, control animals fed a regular diet developed a vigorous granulomatous response and remained clinically well for months. Thus, the PCM model provides a system that allows comparative studies of the granulomatous reaction during the course of tuberculous infection. The investigators believe the results of the study will provide insight into the host defense mechanisms against the tubercle bacillus, and ultimately, to enable appropriate manipulation of the granulomatous response in various disease states.
Minority infants and children constitute one of the most rapidly growing groups of infected people in this country. P. carinii pneumonia and lymphoid interstitial pneumonia are major problems affecting infants and children with HIV. Yet these disorders have not been well investigated and a large number of questions remain unanswered. Although frequent cardiac abnormalities have also been demonstrated in infected adults, the incidence and etiology of these abnormalities have not been delineated for the very young, who have been infected in utero and perinatally. An NHLBI study (P2C2) that started in 1989 is supporting investigation of the pathogenesis of these disorders along with their natural history. These investigators are attempting to determine the types, incidence, course, outcome and origin of cardiac and pulmonary disorders in the pediatric patient group exposed to or infected with HIV. The study population of 800 predominantly black and Hispanic children includes two groups: (1) infants and children with vertically transmitted HIV infection, including AIDS, and (2) infants born to HIV-infected mothers. The mothers are recruited prior to delivery and receive prenatal care, including fetal echocardiography and viral studies; their infants are enrolled at birth.
The use of HIVIG in HIV-infected pregnant women taking AZT is currently being studied to determine the efficacy of HIVIG in preventing HIV infection in the fetus. The study population consists of black and Hispanic women primarily, since AIDS disproportionately affects these groups. The pharmacokinetic portion of the study has been completed and the full trial of HIVIG is now under way. Approximately 80 percent of those enrolled in the trial are black or Hispanic women. A similar study using HIVIG in African women not taking AZT is also being jointly sponsored by the NIAID and the NHLBI. It will provide additional information on the efficacy of HIVIG in the absence of anti-viral therapy.
In addition to its research support, the NHLBI has taken a number of steps to ensure increased minority participation in its research training and career development programs. Minority individuals may compete for any of the mechanisms of support available through the NHLBI, but the NHLBI has also implemented a number of minority-specific programs designed to encourage the recruitment and development of minority scientists. These programs include the Minority Institutional Research Training Program (T32M), the NHLBI MARC Summer Research Training Program, the Minority Institution Mentored Research Scientist Development Award (K01), the Research Supplement for Under represented Minorities (Minority Supplements Program), the Short-Term Training for Minority Students Program (T35), the Mentored Research Scientist Development Award for Minority Faculty (K01) award. It is anticipated that the minority investigators currently supported on AIDS and AIDS-related grants will compete successfully for Minority Institution Mentored Research Scientist Development Awards and the Mentored Research Scientist Development Award for Minority Faculty. (Requests for information about any of these programs should be directed to Dr. Norbert Weber, (301) 496-4950, E-mail: webern@nhlbi.nih.gov .)
The goal of this initiative is to foster collaborative clinical research that focuses on new and improved approaches for diagnosis, management and prevention of cardiovascular, lung and blood diseases in minorities. Pathogenesis and management of TB are the focus of the grants in this program. A special feature of this study was the concurrent submission of research grant applications by investigators who wished to collaborate on a common theme. The studies address the pathogenesis of TB in the setting of HIV infection. One group of investigators is studying the roles of cytokines and adhesion molecules in immune lung function. These studies include a project that will explore lung defense mechanisms against mycobacterial infection in a gamma interferon knockout mouse. Other researchers, have complementary projects that look at the molecular mechanisms of drug resistance in Mycobacterium tuberculosis. An epidemiologic project on HIV-TB co-infection in a multi-ethnic inner city population provides a clinical framework for the more basic studies.
The project tests a public health model of screening, preventive INH treatment, and adherence counseling plus medical education of primary care clinicians to enhance their skills and attention to TB control. The investigators are testing a behavioral adherence intervention for Latino adolescents with latent disease and a medical education program designed to enhance primary care (community clinic) practitioners' treatment of active and latent TB infection.
To extend the proposed model to most community clinic setting, the investigators plan to demonstrate outcome effectiveness as well as cost effectiveness in relation to the costs of failing to control latent TB in Latino adolescents. Public school adolescents will be screened and 300 PPD positive male and female Latino youth, age 13-18, will be assigned at random to either usual treatment plus non-directed (attention control) counseling, or medical care plus behavioral adherence counseling. Concurrently, participating clinic personnel will receive training in TB control. The primary aims of the study are to determine whether behavioral counseling increases clinic attendance and adherence to prescribed INH medication relative to controls, and to determine if training increases professionals' knowledge and practice of TB screening and control treatment.