Coccidioidomycosis: What a long strange trip it's been

Abstract

The recorded history of coccidioidomycosis began in 1892 with the report of the illness of Domingo Escurra by Alejandro Posadas followed by a description of the first North American cases by Rixford and Gilchrist. Originally considered a protozoan, William Ophüls determined that Coccidioides was a fungus and that the lungs were the apparent initial site of infection. During the 1930s, both Gifford and Dickson determined that a self-limited illness, Valley Fever, was caused by the same fungus that caused the often fatal coccidioidal granuloma. Charles Smith, over a period of approximately 2 decades, comprehensively described the clinical and geographic epidemiology of coccidioidomycosis in California. Demosthenes Pappagianis continued this work after Smith's death. In 1957, one year before Marshall Fiese published his masterful monograph on coccidioidomycosis, the use of the first effective agent for the therapy of coccidioidomycosis, amphotericin B, was reported. This was followed by descriptions of its appropriate clinical use by William Winn and by Hans Einstein, among others. The development of the much less toxic azole antifungal agents greatly simplified therapy in many cases, but much of the management of patients with coccidioidomycosis still relies more on art than science. The search for the "Holy Grail" - a vaccine capable of preventing this disease-continues.

Figure 1.

1a. Domingo Escurra. The head of Domingo Escurra was discovered in a jar of formalin by Dr. Flavio Niño in November 1948 in the Pathology Museum of the Hospital of the University of Buenos Aires Medical School. It remains on display as Exhibit No. 1 at the Institute of Parasitology. Permission: Creative Commons. 1b. The left foot of Domingo Escurra discovered in 1947 by Dr. R. Sammartino in the museum of the Telémaco Susini Institute of Pathologic Anatomy and Physiology of the Faculty of Medical Sciences in Buenos Aires. Permission: Creative Commons. This Figure is reproduced in color in the online version of Medical Mycology.

Figure 2.

Alejandro Posadas. Posadas, whose father had emigrated from Spain, was born in Argentina in 1870. He attended the University of Buenos Aires Medical School and published the first description of coccidioidomycosis. He received his MD from the University of Buenos Aires Medical School two years later, in 1894, and subsequently died of consumption in 1902. Permission: Creative Commons.

Figure 3.

3a. Domingo Escurra as seen by Posadas. Frontal view demonstrating involvement of his face, trunk and arms. 3b, 3c. Domingo Escurra as seen by Posadas. Extensive confluent verrucous lesions of coccidioidal granuloma involving the face. 3d. Domingo Escurra as seen by Posadas. Large confluent verrucous lesion of his back. Permission: Creative Commons. This Figure is reproduced in color in the online version of Medical Mycology.

Figure 4.

Emmett Rixford, Professor of Surgery at Stanford Medical School. Rixford, with others, described the first North American cases of coccidioidomycosis. Rixford lived from 1865 to 1938. Permission: Creative Commons. This Figure is reproduced in color in the online version of Medical Mycology.

Figure 5.

Cooper Medical College circa 1892 at the corner of Sacramento and Webster in San Francisco. Cooper became the Stanford Medical School in 1912. Permission: Stanford Medical Alumni Association.

Figure 6.

Joas Furtado Silverra. The first reported case of coccidioidal granuloma in North America (and the second overall). 6a. Joas Furtado Silverra. Facial lesions. Permission: Stanford Medical History Center. 6b. Joas Furtado Silverra. Facial and neck lesions. Permission: Stanford Medical History Center. 6c. Joas Furtado Silverra. Facial and hand lesions. Permission: Stanford Medical History Center.

Figure 7.

Texeira Pereira. North American patient with coccidioidal granuloma contemporaneous with Silverra. He was admitted to St. Mary's Hospital in San Francisco at the end of August, 1894, and died on September 21, 1894. Permission: Stanford Medical History Center.

Figure 8.

Joas Furtado Silverra. The photographs demonstrate progression of his infection (although it is possible that worsening of the skin lesions may, at least in part, have been the consequence of the therapies he received). 8a. Joas Furtado Silverra. November 1893, 4 months after admission to the City and County Hospital of San Francisco. 8b. Joas Furtado Silverra. Later in his illness – June 26, 1894, 7 months before his death on January 31, 1895. Permission: Public domain.

Figure 9.

William Ophüls. William Ophüls, who became the second Dean of Stanford Medical School, determined that Coccidioides was a fungus, not a protozoan, described its life cycle and, using guinea pig inoculation, fulfilled Koch's postulates. 9a. William Ophüls as a young man in Germany. Although of low resolution, his dueling scar appears to be visible on his cheek. 9b. William Ophüls as the 2^nd Dean of the Stanford Medical School. Born in 1877, Ophüls died in 1933. Permission: Stanford Medical Alumni Association. This Figure is reproduced in color in the online version of Medical Mycology.

Figure 10.

Illustrations of the morphological forms of Coccidioides from Ophüls. Permission: Journal of Experimental Medicine.

Figure 11.

Myrnie Ada Gifford. Gifford received her MD from Stanford in 1920 and, subsequently, an MPH from Johns Hopkins, and became Chief Assistant Health Officer of Kern County, California. She was key in the determination that San Joaquin Valley fever was caused by Coccidioides, the same fungus that caused coccidioidal granuloma. The first Coccidioidomycosis Symposium was held in her honor and a library in the Kern County Public Health Department was named after her. Gifford lived from 1892 to 1966. Permission: Bakersfield Observer, courtesy of Kern County Museum.

Figure 12.

Ernest C. Dickson. Dickson received his MD from the University of Toronto in 1907. Arriving at Stanford in 1908 as an assistant to Ophüls, he became Professor of Medicine at Stanford in 1923 and Professor of Public Health and Preventive Medicine in 1926 and was Chair of that department. He was internationally known for his work on botulism. With Gifford, Dickson provided evidence that San Joaquin Valley fever was caused by Coccidioides. He died in 1939. Permission: Kern County Health Department. http://kerncountyvalleyfever.com/history-of-valley-fever/#prettyPhoto. This Figure is reproduced in color in the online version of Medical Mycology.

Figure 13.

Harold Chope. His self-limited illness consisting of pneumonia and erythema nodosum after accidental laboratory exposure to Coccidioides greatly contributed to the determination that San Joaquin Valley fever was caused by the fungus. Chope received his MD at Stanford in 1931 and went on to an MPH (1933) and PhD (1940), both from Harvard and became a Clinical Professor of Medicine at Stanford in 1955. He had a remarkable career in public health and in 1970 the name of the San Mateo County General Hospital was changed to the Harold C. Chope Community Hospital. The name subsequently reverted back to the original in 1989 (but was subsequently changed once again, this time to the San Mateo County Medical Center). Chope lived from 1904 to 1976. Permission: Open Access. NIH National Library of Medicine Digital Collections NLM Unique ID: 101411966 NLM Image ID: B04617. http://resource.nlm.nih.gov/101411966.

Figure 14.

Charles Smith. Smith, affectionately nicknamed Snuffy after the then popular cartoon “Barney Google and Snuffy Smith,” received his MD from Stanford in 1931 where he was Professor of Public Health and Preventive Medicine from 1948 to 1952, during which time he was also President of the California State Board of Health. He became Dean of the School of Public Health at the University of California at Berkeley in 1952. Smith defined the geographic and clinical epidemiology of coccidioidomycosis, among many other important contributions to our knowledge of the disease. Born in 1904, he died in 1967. Permission: Creative Commons. Permission: Open Access, U.S. Army Medical History Department Office of Medical History. http://history.amedd.army.mil/booksdocs/historiesofcomsn/section1.html.

Figure 15.

Demosthenes Pappagianis – back row, center. The photograph, taken at the last meeting of the US Army Commission on Acute Respiratory Diseases in 1972, includes (clockwise from Pappagianis) Ted Eickhoff, Maxwell Finland, Jay Sanford, and Harry Feldman. Pappagianis received an MD from Stanford and a PhD from the University of California, Berkeley. He worked with Smith and took over the coccidioidomycosis activities upon Smith's death in 1967 moving to the University of California at Davis, where, among other things, he became Chair of the Department of Microbiology and Medical Director of the Coccidioidomycosis Serology Group Laboratory. In the latter capacity, he has been invaluable to clinicians by his ready availability to them, providing insightful advice regarding test interpretation and sharing his vast knowledge about coccidioidomycosis. Permission: Open Access, US Army Medical History Department, Office of Medical History, http://history.amedd.army.mil/booksdocs/historiesofcomsn/section1.html.

Figure 16.

Hans Einstein. Einstein, a distant relative of Albert (his grandfather was a first cousin), spent most of his life as a physician in Bakersfield, California. He and another physician, William Winn, in Springville, California, were crucial in defining the clinical course of coccidioidomycosis and defining the use of amphotericin B in its treatment. His font of knowledge led to continual requests for consultative advice by physicians dealing with the disease. Born on February 3, 1923, Einstein died at age 89 on August 11, 2012. Permission: the Bakersfield Observer. This Figure is reproduced in color in the online version of Medical Mycology.

Figure 17.

William A. Winn. Winn was a personal friend of Charles Smith. He received his MD from Harvard after obtaining his undergraduate degree at Stanford. From 1935 to 1966, Winn was the Medical Director of the Springville County Hospital, which had been founded as the Tulare County and Kings County Joint Tuberculosis Sanitarium in 1918. Both Einstein and Winn realized that many patients they encountered who had received a diagnosis of tuberculosis had, instead, coccidioidomycosis. Winn delineated many of the clinical aspects of coccidioidomycosis and the appropriate use of amphotericin B, including its intrathecal administration for the treatment of coccidioidal meningitis. He was born on September 22, 1903, in Butte, Montana and died in 1967. Courtesy of William R. Winn. This Figure is reproduced in color in the online version of Medical Mycology.