Outbreak of Coccidioidomycosis in Washington State Residents Returning from Mexico
- lisa Cairns1,3,
- David Blythe1,2,
- Annie Kao4,
- Demosthenes Pappagianis5,
- Leo Kaufman4,
- John Kobayashi1, and
- Rana Hajjeh4
- 1Section of Communicable Disease Epidemiology, Washington State Department of Health, Seattle, Washington
- 2University of Washington School of Public Health and Community Medicine Preventive Medicine Residency, Seattle, Washington
- 3Epidemic Intelligence Service, Division of Applied Public Health Training, Epidemiology Program Office, Atlanta, Georgia
- 4Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
- 5Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, California
- Reprints or correspondence: Dr. Lisa Cairns, MS E-10, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333 (kfc4{at}cdc.gov).
Abstract
In July 1996 the Washington State Department of Health (Seattle) was notified of a cluster of a flulike, rash-associated illness in a 126-member church group, many of whom were adolescents. The group had recently returned from Tecate, Mexico, where members had assisted with construction projects at an orphanage. After 1 member was diagnosed with coccidioidomycosis, we initiated a study to identify further cases. We identified 21 serologically confirmed cases of coccidioidomycosis (minimum attack rate, 17%). Twenty cases (95%) occurred in adolescents, and 13 patients (62%) had rash. Sixteen symptomatic patients saw 19 health care providers; 1 health care provider correctly diagnosed coccidioidomycosis. Coccidioides immitis was isolated from soil samples from Tecate by use of the intraperitoneal mouse inoculation method. Trip organizers were unaware of the potential for C. immitis infection. Travelers visiting regions where C. immitis is endemic should be made aware of the risk of acquiring coccidioidomycosis, and health care providers should be familiar with coccidioidomycosis and its diagnosis.
Coccidioidomycosis is caused by inhalation of the airborne arthroconidia of Coccidioides immitis, a dimorphic fungus found in the topsoil of certain semiarid regions of the Americas [1]. Symptomatic disease occurs in ∼40% of infected persons and is characterized by flulike symptoms, such as headache, fever, cough, myalgias, and rash [2]. Coccidioidomycosis is usually a self-limited disease; however, in <1% of cases, it can disseminate and be fatal [3]. A higher rate of dissemination exists among pregnant women, immunocompromised persons, and certain racial groups [2]. Outbreaks of coccidioidomycosis have been linked to events that favor production [4] and dispersion of arthroconidia in dust, such as earthquakes [1], dust storms [5], and archaeological digs [6, 7].
In July 1996 the Washington State Department of Health (Seattle) was notified that at least 15 persons from a church group, including many adolescents, had developed an unidentified, rash-associated, flulike illness. One of these cases was eventually recognized as coccidioidomycosis. The group had recently returned from a 6-day stay at an orphanage ∼15 miles south of Tecate, Mexico, a town in the Sonoran Desert adjacent to the United States—Mexico border. To determine the extent of the outbreak and risk factors for disease, we conducted an investigation, the results of which are summarized in this article.
Methods
Epidemiological studies. We conducted a retrospective cohort study, which included the administration of a questionnaire, a skin test survey, and serological testing.
Questionnaire. The church office provided the names of group members who participated in the trip to Tecate. A standard questionnaire was administered to all available group members; information obtained included demographic data, information on previous travel to areas where C. immitis is endemic, and pertinent medical history. Information about activities while in Tecate, presence and duration of any symptoms of illness since leaving Mexico until the time of interview (∼7 weeks), and medical care received for these symptoms was also obtained.
Skin test survey. Spherulin skin tests (Berkeley Biologicals, Berkeley, CA) were administered to all available consenting church group members. Tests were performed by professional nurses experienced in skin testing. Group members received intradermal injections of 0.1 mL of intermediate-strength (1 : 100) spherulin, except for 4 people whose history was consistent with erythema nodosum. Of these 4, 3 received 0.1 mL of dilute (1 : 1000) spherulin; the fourth was skin tested through her private physician and received a reduced volume of intermediate-strength spherulin. The results were read at 48 h after intradermal injection. A skin test was considered positive if an induration at 48 h was ≥5 mm [2].
Serological studies. Serum specimens were obtained from people with any flulike symptoms since leaving Mexico or from those with a positive skin test. These samples were tested at the Centers for Disease Control and Prevention (Atlanta, GA) for the presence of antibodies to C. immitis by use of quantitative complement fixation (CF) tests for coccidioidomycosis and 2 qualitative immunodiffusion tests: immunodiffusion tube precipitin (IDTP), which gave results corresponding to those obtained with the tube precipitin test for IgM antibody to C. immitis; and immuno-diffusion complement fixation (IDCF), which gave results corresponding to those obtained with the CF test for IgG antibody to C. immitis [8]. Twenty specimens were also sent to the Coccidioidomycosis Serology Laboratory at the University of California at Davis School of Medicine (Davis, CA) for repeated IDTP with use of concentrated serum [9]. In the event of discrepancies in IDTP results, those obtained through use of concentrated serum were considered conclusive. We defined a case of acute C. immitis infection as serology positive for C. immitis by IDTP, IDCF, or CF testing.
Environmental studies. Soil specimens were collected by one of us (D.P.) from 3 sites at the orphanage in Tecate: loose soil excavated for the construction of a wading pool, the proposed site for a swimming pool, and the tent site where the church group had camped. The soil was mixed with sterile saline in a sterile graduated cylinder. The coarse soil was allowed to settle, and the supernatant, which should contain the lighter arthroconidia of C. immitis, was decanted and centrifuged to sediment arthroconidia. The supernatant was discarded, and the sediment was injected intraperitoneally into female Swiss-Webster mice that were killed at 7–10 days. The lungs, liver, and spleen were cultured on Mycobiotic medium (Difco, Detroit). Mold growth from these organs was inoculated intraperitoneally into a second set of mice.
Data analysis. Risk ratios were calculated for each exposure. Univariate risk ratios, P values, and 95% CIs were determined by the χ2 method with use of Epi-Info Version 6.0 [10].
Results
Case identification and demographic characteristics. One hundred twenty-six church group members participated in the trip to Tecate, which occurred from 8 to 13 July 1996. Of 100 members (79%) who were contacted, 59 (47% of 126) completed questionnaires, underwent skin tests, and had the results read. Forty members had serological testing done; blood samples were obtained from 95% of these 40 between 5 and 11 weeks after the day of arrival in Tecate. Of the 59 members who completed the questionnaire and skin testing, 35 (59%) were female, and 51 (86%) were aged 14–18 years (median, 16 years; range, 14–71 years). All except 1 trip participant identified themselves as white. None of the 59 members reported being immunocompromised or pregnant.
Twenty-seven (46%) of the 59 church group members had a positive skin test. Serological testing for 21 of these members was positive for C. immitis; therefore these 21 met the case definition for coccidioidomycosis. The attack rate for the 59 members who responded to the questionnaire was 36%, and the minimum attack rate for the entire 126-member group was 17%. Of the 21 members who met the case definition, 20 (95%) were adolescents aged 14–18 years (median, 16 years; range, 14–43 years), and 18 (86%) were female. Four patients (19%) had negative skin tests.
Clinical characteristics and laboratory findings. Twenty (95%) of the 21 patients were symptomatic; the date of the onset of symptoms ranged from 15 to 28 July 1996 (figure 1). Assuming that exposure occurred on 8 July 1996, the average incubation period was 12 days (range, 7–20 days). Patients started developing symptoms 1–3 weeks after arrival in Tecate; these symptoms included fever (85% of patients), headache (81%), chest pain (76%), body aches (71%), cough (66%), fatigue (66%), rash (62%), muscle pain (52%), nausea (43%), and joint pain (33%). Rash was described as initially papular; it progressed to a confluent maculopapular rash, with lesions on the trunk, at times the palms and soles, and, in some instances, the buccal mucosa. Four patients reported lesions consistent with erythema nodosum. At the time our investigation was conducted, no patients had persistent rash, and no additional clinical information about this rash was available. None of the patients developed disseminated disease, and none died.
Figure 1
Date of the onset of symptoms of coccidioidomycosis in church group members from Washington State in 1996 who returned from Tecate, Mexico, where they had assisted with construction of an orphanage (information available for 19 of 20 symptomatic patients). ↔, dates of stay in Mexico.
Of the 21 patients, 15 were positive for C. immitis by both IDTP and IDCF, 4 were positive by IDCF but negative by IDTP, and 2 were negative by IDCF but positive by IDTP. Of the 4 patients with negative skin tests, 1 had a positive IDCF with a titer of CF antibody of 1 : 16 and a negative IDTP; the other 3 had a positive IDCF, a positive IDTP, and titers of CF antibody ranging from 1 : 4 to 1 : 16.
Sixteen symptomatic patients saw a total of 19 health care providers, most of whom we believe were aware of the patient's travel history. Health care providers ranged from physician's assistants to infectious disease specialists. Only 1 health care provider, an infectious disease physician trained in California, diagnosed coccidioidomycosis after seeing a patient with erythema nodosum. Other reported diagnoses included bacterial bronchitis, contact dermatitis, and viral infection. Of 11 patients who were prescribed medication, 7 could identify the medications by name; of these patients, 6 had received antibiotics, and 1 was treated with prednisone for contact dermatitis. None of the patients received antifungal therapy.
Risk factors. While in Tecate, trip participants had excavated ground for 2 swimming pools, assisted in construction projects such as roofing, cooked for group members, played outdoors, and traveled by bus and foot on dirt roads. Most of them had slept in tents. They did not routinely follow procedures that might have protected them from infection, such as wearing dust masks or sleeping upwind from construction sites [11]. Univariate analysis revealed that digging 1 of the swimming pools was significantly associated with an increased risk of acute coccidioidomycosis (RR, 2.5; 95% CI, 1.0–6.6). No other activities were associated with an increased risk of disease.
Environmental study results. No lesions were detected in killed mice after the initial intraperitoneal inoculation with supernatant. However, the second set of inoculated mice became ill and had visible lesions. These lesions contained microscopic endosporulating spherules characteristic of C. immitis.
Late report of coccidioidomycosis. In January 1998 we were notified that a 17-year-old church member who had traveled to Tecate in July 1996 and to San Diego in July 1997 was being treated for a coccidioidal pulmonary cavitary lesion that had been identified in November 1997. This person had reported being asymptomatic after returning from Mexico, had refused skin testing, and was not serologically tested during the 1996 investigation. Clinical specimens that could be cultured for comparison with C. immitis isolated from soil were not obtained.
Discussion
Our results highlight that exposure to C. immitis carries significant risk for people who are susceptible and that physicians are not aware of coccidioidomycosis in areas where C. immitis is not known to be endemic. It also demonstrates that C. immitis is endemic in the region of Tecate. The church has been sending groups to Tecate for several years and has received anecdotal reports of flulike illnesses after these trips; however, the 1996 trip organizers and participants were not aware of the potential for C. immitis infection. Although the earliest case was detected by an infectious disease specialist in early August 1996, in most cases, the health care providers did not consider coccidioidomycosis in the differential diagnosis (despite, we believe, being aware of the patient's travel history). This may have been because they saw patients individually (i.e., without being aware that that several people had had a common exposure), but also because coccidioidomycosis mimics other diseases [12]. Other studies have also pointed out that the diagnosis of coccidioidomycosis can be missed because physicians are not familiar with the disease in areas where it is not endemic [13]. This point is of particular importance for immunocompromised patients who have a higher risk of developing severe disease [14, 15].
The high incidence of rash in our study is an interesting finding. Although erythema nodosum or erythema multiforme is estimated to occur in 20% of clinically diagnosed adults [16], the incidence of rash among children and adolescents is uncertain but suspected to be higher [17]. In a study of college students at an archaeological dig, Werner and Pappagianis [7] noted a 52% incidence of rash among persons with laboratory-proven disease, a rate approaching the incidence that we observed. Children and young adults can have a clinical presentation different than older adults when they develop acute coccidioidomycosis. Another interesting finding is the high incidence of headache, ranging from 26% [18] to 74% [7] in other reports. The incidence of headache in our study is closest to that reported by Werner and Pappagianis [7], which may reflect the higher levels of exposure to C. immitis—contaminated soil in these settings. Finally, the relatively high number of patients with coccidioidomycosis for whom skin tests were negative (although all tests were administered by experienced personnel) is an unexpected finding for which there is no obvious explanation.
These results emphasize the need to increase the awareness of coccidioidomycosis among physicians and travelers to regions where C. immitis is endemic. Awareness could be increased through publications in both primary care and specialty medical journals, presentations at national and regional professional meetings, posting information on coccidioidomycosis on the Internet, and adding coccidioidomycosis to lists of other known travel-related health risks in bulletins and books. Prevention of coccidioidomycosis in visitors to areas of endemicity may be difficult; however, early suspicion of and diagnostic testing for disease may reduce health-related costs, minimize patient anxiety, and limit progression to severe disease. People at high risk for infection may be best served by the eventual development of a vaccine [19].
Acknowledgments
We acknowledge the assistance of Karen Mottram, Jan Bigelow, Richard Tucker, Alan Tice, Philip Craven, James DeMaio, Jim Schwarz, Carey Snow, Marcia Goldoft, Daniel Jernigan, Andy Pelletier, C. R. Zimmermann, and the members of the church group studied.
- Received April 6, 1999.
- Revision received August 25, 1999.
- © 2000 by the Infectious Diseases Society of America
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