Special Feature
Synopsis: An excellent review was published in Clinical Infectious Diseases on the fungal infections acquired during recent travel abroad. It informs and updates practitioners about the epidemiology, clinical manifestations, diagnosis, prevention, and treatment of the most common mycoses among travelers, including histoplasmosis, coccidioidomycosis, and penicilliosis.
Source: Panackal AA, et al. Fungal infections among returning travelers. Clin Infect Dis. 2002;35:1088-1095.
By Maria D. Mileno, MD
Endemic mycoses such as histoplasmosis, coccidioidomycosis, and penicilliosis have restricted geographic distributions and infections most often remains confined to areas of the world where these agents actually exist in nature. However, both outbreaks and sporadic cases of several fungal diseases have included travelers in recent years. With ever-increasing numbers of international travelers undertaking a wide range of leisure and work activities, fungal diseases, which ordinarily have specific unique exposure risks required for human infections, are now affecting the health of travelers to endemic regions of the world. Highlighted cases of systemic mycoses detected via Geosentinel network of clinics are reviewed to provide this update on fungal diseases for travel medicine experts.
Geosentinel (GS) is a communications and data collection network consisting of 25 tropical and travel medicine clinics throughout the world. Between April 1998 and March 2002, 32 cases of systemic mycoses were reported to the GS network. Two distinct types of travel may lead to the acquisition of fungal disease. In some instances, infection is acquired during short trips ("travel-related infections") while for others infection can be acquired during a longer period of residence in an area where infection is endemic. They subsequently migrate to a region where infection is not endemic ("migration-related infection"). The second group is distinctly important for practitioners to be aware of and to identify, since disease symptoms may remain silent for months or years. It is important to realize that the GS network does not capture such cases. This article focused on those fungal infections acquired during recent travel abroad.
In the United States, histoplasmosis has recently emerged as an important opportunistic infection among HIV-infected persons living in areas where it is endemic, namely the mid-western and central United States. Histoplasmosis is also endemic throughout Central and South America. Reports of either a single or several cases with no clear source of exposure have come from some parts of southern and eastern Europe, parts of Africa, eastern Asia, and Australia, yet no outbreaks have been reported outside of the Americas. The infecting agent Histoplasma capsulatum is a dimorphic fungus, which usually grows in soil enriched containing accumulations of bat or bird droppings. Human infection commonly occurs after inhalation of dust generated with disturbance of such collections in the soil. Exposures occur during activities such as construction, renovation, demolition, soil excavation, spelunking, and cleaning sites harboring the fungus. Risk of infection depends on the activities performed and both the duration and degree of exposure, with longer and more intense exposures usually resulting in more severe acute pulmonary disease. Acute histoplasmosis in returning travelers most often presents as a flu-like illness characterized by high fever, chills, headache, nonproductive cough, pleuritic chest pain, and fatigue. Chest radiographs may show diffuse reticulonodular infiltrates and mediastinal lymphadenopathy. Symptoms of infection most often present 1-3 weeks after the exposure, and most individuals recover spontaneously within 3 weeks. Persons with a severe immunodeficiency can have infections complicated by dissemination. Of note, individuals can be reinfected with H capsulatum, and in this situation the incubation period can be shorter than for primary infections.
It is well appreciated that outbreaks of histoplasmosis have occurred in North America among travelers to bat-infested caves. In 1997 and 1999 outbreaks were reported also among traveling US residents after spelunking trips to caves in both Central and South America. However, outbreaks in the setting of other forms of adventure tourism have occurred. In May 2001, 12 of 15 students who went on a field trip to visit silver mines which contained bat guano in Nicaragua developed symptoms consistent with acute histoplasmosis. Infections were later confirmed serologically and 6 patients required hospitalization. A less obvious exposure occurred in March 2001, when a large group of US college students developed acute respiratory febrile illness within 1-2 weeks after they returned from Acapulco, Mexico, after their spring break. More than 250 students developed symptoms of acute histoplasmosis, 25 were hospitalized, and over 150 persons tested had the diagnosis serologically confirmed.
Once histoplasmosis is suspected, serological diagnosis by complement fixation (CF) testing should be attempted, as it is the most sensitive serological method available, although less specific than an immunodiffusion assay. The CF test becomes positive between 2 and 6 weeks after infection. A titer of greater than or equal to 1:32 or a 4-fold increase in titer between paired acute and convalescent serum samples are considered fairly strong presumptive evidence of recent disease. Low titers of CF antibodies can persist for years. Antigen detection in urine is useful for the diagnosis of acute pulmonary histoplasmosis if the samples are obtained within 2 weeks of exposure and infection. The histoplasmin skin test can detect previous exposure to the fungus and becomes positive 2-4 weeks after a person has been infected; however, this reagent is not available in the United States.
Treatment guidelines were developed by the IDSA and should be consulted for management.1 Most healthy nonimmunocompromised persons do not require antifungal treatment, however those with severe symptoms, who do not improve after 1 month of observation, can be treated with itraconazole. Persons with underlying immunodeficiency or chronic disease should be given itraconazole for longer periods, ie, greater than 12 weeks. All persons with very severe disease, including diffuse pulmonary and disseminated histoplasmosis, should be treated with either amphotericin B or itraconazole.
Prevention of histoplasmosis is quite difficult and requires travelers to avoid situations in which contaminated material can become aerosolized. Masks and special protective equipment are advised if exposure cannot be avoided. Hosing off boots and placing clothing into airtight plastic bags after such activities as cave exploration can reduce transportation of soil, bat guano and other potential fomites. Ideally, known high-risk locations would carry warning signs from public health authorities.
Coccidioidomycosis has long been recognized as a travel-related disease associated with visits to the semiarid desert regions of the southwestern United States, including Arizona, central and southern California, New Mexico, western Texas, and parts of Utah, where the dimorphic fungus Coccidioides immitis is found. Besides US travelers, visitors from other countries have developed "Valley Fever" after trips there. Most infections have occurred among travelers returning to European countries, Japan, and Australia. The disease is also endemic in parts of Central and South America. Due to changing migration patterns, several cases have occurred recently among Indian citizens who had previously resided and worked in Arizona. An international outbreak occurred in October 2001 when more than 300 persons from 30 countries participated in the World Championship of Model Airplane Flying in Lost Hills, California, an area where coccidioidomycosis is highly endemic. One week after returning home a participant from the United Kingdom developed flu-like symptoms but was not diagnosed with coccidioidomycosis until culture of bronchoalveolar lavage specimens was performed. Other cases among participants have since been confirmed in Finland, Australia, and New Zealand.
Human infection occurs through inhalation and has been associated with ground disturbing activities such as building construction, landscaping, farming, archaeological excavation, and numerous recreational pursuits. The generation of dust clouds, including those from natural events such as earthquakes and windstorms, have resulted in large outbreaks. Approximately 40% of infected persons develop illness 1-3 weeks after exposure. Infection is characterized by fever, headaches, rash, muscle aches, nonproductive cough, weight loss and malaise. Cavitary pneumonia and severe lung disease may occur rarely, and less than 1% of infected persons develop dissemination to the meninges, joints, bones, or skin. Persons with increased risk for disseminated disease include African-Americans, Filipinos, person with various immunodeficiency states, including those with AIDS as well as those receiving immunosuppressive medications, pregnant women in the third trimester, and individuals with diabetes mellitus.
Diagnosis can be made by direct microscopic examination of lower respiratory tract specimens for C immitis spherules or by culture of such specimens. Serologic testing with the immunodiffusion tube precitin (IDTP) test is the most useful one for diagnosing recent infections. It uses heated coccidioidin as antigen and detects IgM antibodies to C immitis. These antibodies can be found within 1-3 weeks after the onset of symptoms but they disappear within a few months among persons with pulmonary disease. The CF test measures IgG titers but IgG antibodies do not appear until 4 to 12 weeks after infection and may persist for long periods in patients with chronic pulmonary or disseminated disease. High CF titres, either greater than 1:32 or increasing, suggest spread beyond the respiratory tract.
In contrast to histoplasmosis, once individuals are infected with C immitis they are usually immune to reinfection. The IDSA has developed guidelines for the management of coccidioidomycosis.2 Most patients with acute symptoms do not require antifungal therapy. Treatment may be indicated for persons with increased risk of dissemination. The drug of choice is oral fluconazole 400 mg daily for 3-6 months. Patients with bilateral reticulonodular infiltrates or miliary disease and women who are pregnant should be treated with amphotericin B.
Prevention is accomplished by limiting exposure to outdoor dust in areas where C immitis is endemic. Those groups which undertake construction projects or other dust generating activities can attempt dust control measures such as wetting the soil before disturbing the earth. Travelers should also be advised to avoid transporting such soils.
The first human case of penicilliosis was that of a splenic abscess in a 61-year-old man with Hodgkin’s disease who had traveled from the United States to Southeast Asia. A decade later a second case was reported, yet between 1988 and 1994, 14 cases of the disease were reported among HIV-infected individuals returning to their native countries after visits to Southeast Asia. The greatest effect of penicilliosis has been felt by the populations residing in Southeast Asia, particularly persons living with AIDS in northern Thailand, however the disease continues to be diagnosed among returning travelers. Fever, weight loss, nonproductive cough, lymphadenopathy, hepatosplenomegaly and anemia are hallmarks of the clinical presentations for Penicillium marneffi infection. Many patients demonstrate multiple papular skin lesions, some of which show a central necrotic umbilication, resembling molluscum contagiosum. They are often present on the face, neck, trunk, and upper limbs. Diagnosis can be made by direct microscopic examination or culture of specimens from the bone marrow, lymph nodes, skin, and other infected sites. Culture of P marneffi is the only available diagnostic as there are no widely available serologies for this disease, and accurate diagnosis is important because other fungal infection may have similar clinical manifestations especially in immunocompromised persons.
References
1. Wheat J, et al. Practice guidelines for the management of patients with histoplasmosis. Clin Infec Dis. 2000; 30:688-695.
2. Galgiani JN, et al. Practice guidelines for the treatment of coccidioidomycosis. Clin Infec Dis. 2000;30:658-661.
An excellent review was published in Clinical Infectious Diseases on the fungal infections acquired during recent travel abroad. It informs and updates practitioners about the epidemiology, clinical manifestations, diagnosis, prevention, and treatment of the most common mycoses among travelers, including histoplasmosis, coccidioidomycosis, and penicilliosis.
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