Of 27 patients with the acquired immunodeficiency syndrome (AIDS) in Tucson, Arizona, 7 had concurrent coccidioidomycosis. Early manifestations of infection in 6 patients included diffuse nodular pulmonary infiltrates and Coccidioides immitis in many extrathoracic sites. By comparison, a retrospective review of the cases of 300 patients hospitalized with coccidioidal infection identified only 13 patients without AIDS who had the same extent of infection, and only 3 of these patients had no immunosuppressing conditions. Antibodies for coccidioidal antigens at serum dilutions as high as 1:2048 were detected in 5 of the 7 patients with AIDS. Six had temporary responses to amphotericin B treatment, taken both alone and combined with ketoconazole, but all died within 14 months of their diagnosis of coccidioidomycosis. Because annual rates of coccidioidal infection in the Tucson area are 4% or less, the rate of 27% that we calculated, based on 7 patients having the infection during 26 years of risk for AIDS, suggests frequent reactivation of the infection or enhanced susceptibility to endemic exposure in persons with AIDS.
Debate continues about what constitutes significant and meaningful change in health status of individuals and populations. More importantly, the basic biological and medical criteria that are used for clinical and environmental judgments require further discussion and clarification. What proportion of loss of cardio-pulmonary function, overt disability, or mortality is sufficient to determine an "adverse health effect"? Health-oriented individuals, including researchers and clinicians, may choose to adhere to different criteria than other professional groups (e.g., legal, social). It is proposed in this paper that criteria for defining adverse health effects should represent clinically meaningful, as distinct from only statistically significant, responses. These include pulmonary function test results that indicate obstructive or restrictive diseases, and electrocardiogram results indicating coronary artery disease. Intraindividual changes that predict a meaningful medical change would be included; these changes should meet specific requirements in terms of what constitute normal vs. abnormal ranges of variation. Further, the proportion of the population defined to be impaired should be considered. These issues are the focus of this paper.
Coccidioidomycosis is a largely self-limited fungal respiratory illness. However, the infrequent case of progressive or disseminated disease can be devastating. As international travel to and from endemic areas increases, physicians unfamiliar with the disease may be called upon to recognize and treat serious coccidioidal infections. The major risk factors for dissemination are race and immunosuppression. The most common sites of dissemination are the skin, lymph nodes, bone and meninges. Diagnosis is aided by investigation of the patient's clinical history, delayed-type hypersensitivity skin test reaction, serologic testing, and recovery of organisms from infected tissue or secretions for direct examination and culture. Fungicidal agents are not available, fortunately, fungistatic therapy allows many patients to recover. The availability of both intravenous/intrathecal and oral agents now allows more therapeutic flexibility in the treatment of this disease.
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