Sep 13, 1991 - OFER BEN-IZHAK,4 AND LAEL ANSON BEST3'5. Departments of .... Janssen Pharmaceutica, Beerse, Belgium. 11. Johnson, P. C., and G. A. ...
Vol. 30, No. 5
JOURNAL OF CLINICAL MICROBIOLOGY, May 1992, p. 1304-1306
0095-1137/92/051304-03$02.00/0 Copyright © 1992, American Society for Microbiology
Traveller's Coccidioidomycosis: Case Report of Pulmonary Infection Diagnosed in Israel ELI LEFLER,lt* DANIEL WEILER-RAVELL,2 DAVID MERZBACH,"3 OFER BEN-IZHAK,4 AND LAEL ANSON BEST3'5 Departments of Microbiology, 1 Pathology,4 and Thoracic Surgery,S Rambam Medical Center, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 3 and Pulmonary Medicine, Lady Davis Cannel Hospital,2 Haifa, Israel Received 13 September 1991/Accepted 31 December 1991
A 60-year-old temporary Israeli resident travelled to Arizona, developed an influenzalike infection, and returned with a space-occupying lesion in the lung. Since the patient was a heavy smoker, lung cancer was suspected and he was operated on. A granuloma was reported on frozen sections, and Coccidioides immitis was revealed on stained preparations and by microbiological investigation. Coccidioidomycosis is unusual in Israel; therefore, it is important to be aware of this mycosis in patients who have a history of recent visits to areas of endemicity in North America, Central America, and South America.
bronchoscopy was performed, and transbronchial biopsies were found nonspecific, with no evidence of granulomata. Culturing of washings and tissue was not performed. Since the lesion failed to show any resolution after 6 weeks and the patient was a heavy smoker, lung cancer could not be ruled out. A left thoracotomy and wedge resection of the lesion were done, and tissue was sent for analysis of frozen sections and a microbiological investigation. A histological examination of stained tissue preparations (hematoxylineosin, Gomori, methenamine silver, and periodic acid-Schiff stains) revealed a granuloma, endospores, and spherules (Fig. 3) in various stages of maturity. Heavy growth of
Coccidioidomycosis is mainly a self-limiting respiratory infection well known in the United States and other New World countries (4, 8-10, 15-16). In the United States, the southwest, especially Arizona and the San Joaquin Valley of California, are recognized as areas in which Coccidioides immitis is endemic, and the disease has been described in many publications (1, 2, 6, 6a, 17). Sixty percent of patients with primary coccidioidomycosis are asymptomatic. The remaining 40% may demonstrate a mild to acute pulmonary infection with nonspecific influenzalike symptoms. A low percentage (0.2 to 0.5%) of infected individuals, especially Afro-Americans, Hispanics, Filipinos, and immunosuppressed people, are more susceptible to the development of a serious disease following systemic invasion. The outcome for such patients may be fatal if the condition is left untreated (2, 8, 11, 15, 15a). According to Kuttin and Beemer (13), the only case of coccidioidomycosis recorded in Israel was diagnosed in 1948, when a 55-year-old temporary resident from the United States was hospitalized because of a suspected lung tumor, which turned out to be a granuloma caused by C. immitis. That case was virtually identical to the one described in the present report. A 60-year-old man was referred to the Rambam Medical Center for a space-occupying lesion in the left upper lobe. Three months previously, he had spent 4 weeks in Arizona. Three to 4 weeks after the visit, the patient developed influenzalike symptoms, and a general practitioner in the United States prescribed antibacterial therapy. The patient's complaints persisted, and he was hospitalized in Phoenix for fever and cough. Chest roentgenograms revealed a pneumonialike nonspecific pulmonary infiltrate in the left upper lobe. Three to four weeks after the onset of the initial symptoms, the patient returned to Israel. Serial chest X rays (Fig. 1) and computerized tomographic scans (Fig. 2) revealed a space-occupying lesion in the left upper lobe with left hilar involvement, but no cavity was seen. A * Corresponding author. t Present address: Microbiology Laboratory, Western Galilee
FIG. 1. Chest radiograph showing hilar and peripheral involvement of the left upper lobe (right).
Regional Hospital-Nahariya, Nahariya 22100, Israel.
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FIG. 2. Computerized tomographic scan demonstrating occupying lesion in the left upper lobe.
a space-
white, delicate, wooly, moldlike colonies appeared on Sabouraud's dextrose agar (with and without chloramphenicol [50 ,ug/ml] and cycloheximide [500 ,ug/ml]) and blood agar plates after 2 to 3 days of incubation of lung and lymph node tissues at 28 and 37°C. Tease mounts of older colonies and slide cultures revealed arthroconidia within the mycelia, and the fungus was identified as C. immitis. The isolate, tissue specimens, and patient's serum were sent to the Division of Mycotic Diseases, Centers for Disease Control, Atlanta, Ga., for final identification and serodiagnosis. The isolate was positive in the exoantigen test for C. immitis. The tissue sections contained immature C. immitis spherules and a hyaline septate mycelium that resembled the hyphae of Aspergillus or Fusarium species. A complement fixation test for coccidioidomycosis was positive at a titer of 1:8, and the F precipitin, specific for coccidioidomycosis, was present in the immunodiffusion test.
Antifungal therapy is necessary in severe and complicated coccidioidomycosis or in cases with suspected systemic infection, a positive immunodiffusion test for F precipitin, and a complement fixation test titer of .1:8 (4, 10, 12, 18). Amphotericin B (5, 7, 14) and ketoconazole (2, 14, 18, 19) were the drugs of choice, but at present they are no longer
FIG. 3. Endospore-containing spherule lung (periodic acid-Schiff stain, x2,000).
of
a
granuloma
in
the
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considered the optimum drugs to use in cases of coccidioidomycosis; newer azoles, such as fluconazole, itraconazole, and others (2, 7), are available. Agar diffusion susceptibility tests were performed on 9-cm Sabouraud's dextrose agar plates with disks containing antifungal agents from the Institut Pasteur (a modified Bauer-Kirby technique). The isolate was susceptible to ketoconazole but resistant to amphotericin B and 5-fluorocytosine (1 and 10 ,ug per disk). The patient was treated with 200 mg of ketoconazole per day for 4 weeks. Complete recovery was recorded after a follow-up at 30 months. Pulmonary coccidioidomycosis can mimic other diseases, including lung cancer (2, 3, 15, 15a, 17); therefore, it is important to submit material for culturing as well as cytological and histological diagnoses to obtain laboratory confirmation. These analyses should be done with care, because C. immitis is an extremely infectious fungus, and even experienced laboratory personnel can easily contract a laboratory infection (15, 15a, 20). We are grateful to L. Ajello and L. Kaufman, Centers for Disease Control, for final identification and mycoserological tests and to Ruth Rose for typing the manuscript.
REFERENCES 1. Ajello, L. (ed.). 1977. Foreword, p. xi. In L. Ajello (ed.), Coccidioidomycosis, current clinical and diagnostic status. Symposia Specialists, Miami. 2. Ampel, N. M., M. A. Wieden, and J. N. Galgiani. 1989. Coccidioidomycosis: clinical update. Rev. Infect. Dis. 11:897911. 3. Bayer, A. S. 1981. Fungal pneumonias: pulmonary coccidioidal syndromes. Part 2. Miliary nodular and cavitary pulmonary coccidioidomycosis: chemotherapy and surgical considerations. Chest 79:686-691. 4. Bronnimann, D. A., and J. N. Galgiani. 1989. Coccidioidomycosis. Eur. J. Clin. Microbiol. Infect. Dis. 8:466-473. 5. Collins, M. S., and D. Pappagianis. 1977. Uniform susceptibility of various strains of Coccidioides immitis to amphotericin B. Antimicrob. Agents Chemother. 11:1049-1055. 6. Drutz, D. J., and A. Catanzaro. 1978. Coccidioidomycosis. Part I. Am. Rev. Respir. Dis. 117:559-585. 6a.Drutz, D. J., and A. Catanzaro. 1978. Coccidioidomycosis. Part II. Am. Rev. Respir. Dis. 117:727-771. 7. Graybill, J. R. 1986. Azole antifungal drugs in treatment of coccidioidomycosis. Semin. Respir. Infect. 1:53-60. 8. Grigoriu, D., J. Delacretaz, and D. Borelli. 1987. Coccidioidomycosis, p. 311-320. In D. Grigoran, J. Delacretaz, and D. Borelli (ed.), Medical mycology, Editiones Roche, Basle, Switzerland. Hans Huber Publishers, Lewiston, N.Y. 9. Huntington, R. W. 1977. Acute fatal coccidioidal pneumonia, p. 127-137. In L. Ajello (ed.), Coccidioidomycosis, current clinical and diagnostic status. Symposia Specialists, Miami. 10. Janssen Pharmaceutica. 1987. Fungus and Co. travel agentssome exotic mycoses, got to think of it, p. 37-40. In Mycology. Janssen Pharmaceutica, Beerse, Belgium. 11. Johnson, P. C., and G. A. Sarosi. 1989. Community acquired fungal pneumonias. Semin. Respir. Infect. 4:56-63. 12. Knoper, S. R., and J. N. Galgiani. 1988. Systemic fungal infections: diagnosis and treatment. I. Coccidioidomycosis. Infect. Dis. Clin. N. Am. 4:861-875. 13. Kuttin, E. S., and A. M. Beemer. 1977. Systemic mycoses in Israel, p. 46-55. In A. M. Beemer, A. Ben-David, M. A. Klingberg, and E. S. Kuttin (ed.), Host-parasite relationships in systemic mycoses. Contributions to microbiology and immunology, vol. 4. S. Karger, Basel. 14. Levine, H. B., and J. M. Cobb. 1978. Oral therapy for experimental coccidioidomycosis with R 41400 (ketoconazole), a new imidazole. Am. Rev. Respir. Dis. 118:715-721. 15. McGinnis, M. R. 1980. Coccidioides Rixford et Gilchrist 1896, p. 201-203. In M. R. McGinnis (ed.), Laboratory handbook of
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medical mycology. Academic Press, Inc., New York. 15a.McGinnis, M. R. 1980. Coccidioidomycosis, p. 484-486. In M. R. McGinnis (ed.), Laboratory handbook of medical mycology. Academic Press, Inc., New York. 16. Rippon, J. W. 1982. The systemic mycoses, p. 335-337 and 389-427. In J. W. Rippon (ed.), Medical mycology, the pathogenic fungi and the pathogenic actinomycetes, 2nd ed. The W. B. Saunders Co., Philadelphia. 17. Stevens, D. A. 1980. Coccidioidomycosis, a text. Plenum Medical Books, New York.
J. CLIN. MICROBIOL. 18. Stevens, D. A. 1983. Coccidioidomycosis and the indication for chemotherapy. Drugs 26:334-336. 19. Sugar, A. M., S. G. Alsip, J. N. Galgiani, J. R. Graybill, W. E. Dismukes, G. A. Cloud, P. C. Iraven, and D. A. Stevens. 1987. Pharmacology and toxicity of high-dose ketoconazole. Antimicrob. Agents Chemother. 31:1874-1878. 20. Wegmann, T. (ed.). 1987. Coccidioidomycosis, p. 234-240. In Medical mycology-practical guide. F. Hoffmann-La Roche and Co., Basel.
