Drama and Discovery: The Story of Histoplasmosis (review)

Samuel Taylor Darling, a pathologist working in the Panama Canal Zone, reported the first case of histoplasmosis to the Journal of the American Medical Association in 1906. He thought he had encountered a new protozoan similar to the agent of malaria, and named it Histoplasma capsulatum because of its surrounding capsule. Later case reports appeared in tropical medicine journals, so the disease was little recognized by American physicians until the late 1930s. Thomas Daniel and Gerald Baum, pulmonary physicians who spent their careers doing research on the mycobacterial and fungal diseases, participated in much of this history. They provide an interesting and lucid account of the complex story behind the transformation in the medical understanding of histoplasmosis.

At first, histoplasmosis was encountered in patients with fulminating cases of the disease and usually fatal consequences. It caused granulomas in the tissues like those caused by tuberculosis, for which it often was mistaken. Careful study of individual cases revealed that it was not an animal parasite at all, but the yeast phase of a biphasic fungus that was in the tissues. Researchers later learned to grow and identify it, but until well into the 1940s histoplasmosis was thought to be a rare cause of granulomas, most of which were due to tuberculosis.

The puzzle over why some patients with TB-like lung calcifications had negative tuberculin tests led Amos Christie to develop the histoplasmin skin test in 1945. A complement-fixation blood test, developed in 1947 by Samuel B. Salvin, gave researchers a second important tool for unraveling the story of histoplasmosis. Skin-testing data collected from thousands of nursing students and naval recruits defined the endemic areas in the United States, and information gleaned from sporadic epidemics revealed the mild and asymptomatic course of most H. capsulatum infections and its association with guano-enriched soils. The disease manifests itself most frequently in adults who move into an endemic area, not having been exposed in childhood (when infections often go unnoticed), and are then exposed to heavy concentrations of the organism. It has the most serious consequences for people with weakened immune systems. Over the course of the past fifty years, our understanding of histoplasmosis has changed from that of a rare and uniformly fatal disease to that of a widespread but mild fungal infection with occasionally serious cases.

Histoplasmosis is a particularly interesting example of the interplay of new diagnostic procedures and the understanding of the etiology of a disease. Daniel and Baum show how the use of these tests for analyzing epidemic outbreaks of histoplasmosis was critical for realizing both the ubiquity of the fungus and the fact that infection was rarely fatal. In the 1960s Leo Kaufman and his staff at the Fungus Immunology Branch of the Centers for Disease Control standardized the complement-fixation and immunodiffusion tests for histoplasmosis, developed fluorescent antibody reagents to fungal pathogens, and made the tests widely available. Their laboratory at the CDC has become the world's most comprehensive serodiagnostic service for the mycoses.

Daniel and Baum tell the story of histoplasmosis well. As they recount the research, they clearly explain the biology of the fungus, the details of the science, and the complexity of clinical diagnosis. Biographical sketches of the major players throughout the text, and helpful appendices including a chronology of events and a glossary of terms, make this book the recommended place to begin when looking into the history of mycoses.