The Topic of This Month Vol.23 No.3(No.265)

Imported Mycoses in Japan

(IASR 2002; 23: 55-56)

Imported mycoses imply to acquiring the infection overseas with a fungus, basically not existing in Japan, and the symptoms develop in Japan. In Japan, general mycoses; particularly deep mycoses involving internal organs, tend to be regarded as opportunistic infections affecting immunocompromised hosts. In contrast, imported mycoses differ from general mycoses by affecting even healthy persons. Among the imported mycoses, coccidioidomycosis is regarded as the most dangerous one. The impact of imported mycoses is not fully understood because of limited knowledge and a lack of interest in these relatively infrequent infections. Coccidioidomycosis was obliged to notify after enactment of the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections in April 1999. The following discussion deals with the reported incidence of four kinds of imported mycoses; coccidioidomycosis, histoplasmosis, paracoccidioidomycosis, and penicilliosis marneffei, all of which are likely to occur in Japan. The data include those collected by the Research Center for Pathogenic Fungi and Microbial Toxicosis, Chiba University, by a questionnaire survey by a study group of the Ministry of Health, Labour and Welfare (MHLW), and the results of retrieval information (Kamei et al., 2000, A Report on the Survey of Current Diagnoses, Therapy and Epidemiology of Imported Mycoses in Japan).

In Japan, 27 cases of coccidioidomycosis, 30 of histoplasmosis, 17 of paracoccidioidomycosis and one penicilliosis marneffei have been reported.

Coccidioidomycosis is a disease endemic to semidry areas such as California, Arizona, and New Mexico in southwestern United States, western Mexico and Argentina (Canada CDR Vol.18, No.19, 1992, CDC MMWR Vol.49, No.49, 2000 and Vol.50, No.45, 2001, and Eurosurveillance Weekly, No.50, 2001). The etiological agent is a fungus, Coccidioides immitis , having the highest virulence among all known fungi. Healthy persons may be infected with it and the disease is sometimes fatal. The hypha of the fungi in the soil will change into arthroconidia, which are light and easily dispersed in the air by natural processes, such as storms or by environmental disruption, such as building constructions. Arthroconidia is inhaled and swell in the lung and develop into tissue spherules that are filled by numerous endospores. After maturation, a part of the spherule wall ruptures, and endospores are released into the surrounding tissue, where they enlarge to form new spherules. The fungus proliferates in the body by repeating the same cycle. The incubation period is between 7 days and one month. The symptoms often resemble those of common cold and pneumonia. When lung infection is in its chronic phase, bloody phlegm and hemoptysis may develop. According to the studies in USA, 30-40% of those infected will become ill, about 9% of patients will deteriorate into serious conditions and about 3% will be fatal.

In Japan, two cases were reported before 1980, six between 1981 and 1990, followed by rapid increase in incidence, with 19 after 1991 (Fig. 1). Since it was first found, there has been one fatal case in Japan. Of the patients, 85% acquired the infection in USA (principally Arizona and California). There were two domestic cases with no history of overseas travel. However, both patients were dealers of imported cotton and may have acquired the infection from fungi attached to the imported cotton (Table 1). All cases were without any serious underlying disease. According to the National Epidemiological Surveillance of Infectious Diseases (NESID), three cases were reported during April 1999 through February 2002.

Histoplasmosis occurs often in Ohio and south portions of the Mississippi River Valley. In addition, it occurs sporadically in many districts of Central and South Americas, Southeast Asia, and Europe. Airborne infection occurs by inhalation of macro- and microconidia of Histoplasma capsulatum . Internal organs such as the lung, liver, and spleen are involved. This fungus usually grows in the form of mycelia in soil. In human body, it multiplies by budding as yeast-form cells within macrophages. In such cases with decreased cellular immunity as AIDS patients, the disease tends to worsen giving a high fatality rate. As with coccidioidomycosis, healthy persons are infected. The symptoms of respiratory infection often resemble those of common cold and pneumonia, without any characteristic features.

In Japan, there were six cases before 1980, five cases between 1981 and 1990, and cases increased to 19 after 1991 (Fig. 1). Fatal cases numbered seven (23%) among the 30. Some patients involved opportunistic infection with histoplasmosis over an underlying disease like AIDS. Infection was primarily acquired in Central and South Americas, accounting for 67% of the cases. There was an outbreak among explorers who inhaled organisms proliferating in the feces of bats in caves (Suzaki, A., et al.: Kansenshogaku Zasshi, 69, 444-449, 1995). Similar outbreak has been reported in USA (CDC, MMWR, Vol. 50, No. 18, 2001). Cases with no history of overseas travel and regarded as domestic infection accounted for 20%. It is obvious that histoplasmosis can not be ruled out because of no history of overseas travel as with coccidioidomycosis.

Paracoccidioidomycosis is a mycosis that often occurs in Brazil, particularly in Sao Paulo and its vicinities. The etiological agent is Paracoccidioides brasiliensis . The infection is principally airborne and the etiological agent proliferates by multiple budding as yeast-like cells in the body. Lesions develop in the lung and spread throughout the whole body via mucous membrane and lymph nodes. Sometimes, the presence of ulcerative lesions of the oral mucous membrane and a marked swelling of cervical lymphnodes are helpful for diagnosis. Paracoccidioidomycosis causes fibroid lung, which sometimes leads to severe respiratory failure.

In Japan, this disease, similar to other imported mycoses, has increased conspicuously during the past 10 years; four cases were reported before 1980, two cases between 1981 and 1990, and 11 cases after 1991 (Fig. 1). No fatal case was reported. Almost all infections were acquired in Brazil (all the patients but one were Brazilians staying in Japan). Like coccidioidomycosis, no case was associated with severe underlying disease.

Penicilliosis marneffei is an infection caused by Penicillium marneffei . In Japan, only a single case was recognized in 1995. Since this disease is likely to occur in AIDS patients and AIDS is on the increase in Japan, we should take precaution to avoid this disease for those traveling Thailand and Vietnam, endemic areas of this disease. Because the clinical symptoms and pathological findings of this disease resemble histoplasmosis that is endemic in comparable areas of Asia, the disease may be misdiagnosed as histoplasmosis.

Diagnosis and laboratory examinations depend on histopathological tests, the isolation of the etiological agent, and serological tests. In histopathological examination, in accordance with the form of the disease, the lung, mucous membrane, lymphnodes, and skin may be subjected to special staining to detect the organisms. Specimens used for the isolation of the fungus in respiratory infection are sputum and bronchial wash. For histoplasmosis, the antigen may be immunologically detected in the serum, urine, and cerebrospinal fluid. Antibody tests for coccidioidomycosis and histoplasmosis are being undertaken by the Research Center for Pathogenic Fungi and Microbial Toxicosis, Chiba University. Detection by PCR is currently under development.

Most of the etiological agents of imported mycoses are highly virulent pathogens, which can infect even healthy individuals. In fact, person to person infection occurs very rarely. Nevertheless technical experts may be infected during isolation and identification of C. immitis and other fungal species. There have been several reports of such accidental infection. It is very dangerous to handle the pathogens in ordinary laboratory settings. C. immitis becomes increasingly virulent as the growth in culture medium proceeds. For this reason, if C. immitis is likely to be involved, the personal physician should provide sufficient information to the laboratory.

It is anticipated that the more often people travel abroad, the more cases of imported mycoses may occur in future. The knowledge and concern of medical staffs about these diseases are not sufficient at present (see p. 57 of this issue), it is therefore necessary to educate and provide accurate information to medical staffs. It is also important to organize a national reference system for further diagnosis and laboratory examinations (see p. 59 of this issue).

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