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865 CONCISE COMMUNICATION Coccidioidomycosis Outbreak among United States Navy SEALs Training in a Coccidioides immitis–Endemic Area—Coalinga, California Nancy Crum,1 Carla Lamb,2 Gregory Utz,1 Dennis Amundson,2 and Mark Wallace1 1 Infectious Diseases Division and 2Pulmonary Division, Department of Internal Medicine, Naval Medical Center San Diego, San Diego, California An outbreak of coccidioidomycosis among 22 Navy SEALs occurred during training exercises in Coalinga, California. Ten (45%) of the 22 men had serologic evidence of acute coccidioidomycosis, the highest attack rate ever reported for a military unit. All case patients were symptomatic, and 50% had abnormal chest radiographs. There were no cases of dissemination and no deaths to date. Coccidioidomycosis continues to be a threat to military members and civilians who reside or train in areas where Coccidioides immitis, the causative agent, is endemic. Coccidioidomycosis is an endemic mycosis of the southwestern United States. Acquisition is through inhalation of arthroconidia that reside in the soil in semiarid regions, particularly the south-central valley of California (hence the name “valley fever”) and the southern Arizona deserts. Activities that disturb the soil, such as archeological digs, construction, and military training exercises are risk factors for the development of coccidioidomycosis [1–3]. Natural events, such as earthquakes and dust storms, may also cause arthroconidia to separate from the parent mycelium and become airborne [4, 5]. Coccidioidomycosis is considered to be a reemerging disease due to the dramatic increase in cases over the past decade. The increase in Coccidioides immitis infections may be related to increasing numbers of people residing in and visiting areas where the fungus is endemic. Because many military bases are located in C. immitis–endemic areas, the potential risk to military personnel is substantial. Coccidioidomycosis outbreaks have been described among military members training or stationed within C. immitis–endemic areas, and infections have resulted in substantial disability and forced military medical retirements [2, 3, 5, 6]. From 10 September to 27 October 2001, a group of 23 Navy SEALs from San Diego and Honolulu participated in a military training exercise near Coalinga, California, which is located 60 miles southwest of Fresno, in a C. immitis–endemic area within the San Joaquin Valley. During the 6-week training period, the Received 24 April 2002; revised 13 May 2002; electronically published 16 August 2002. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the US Government. Reprints or correspondence: Dr. Nancy Crum, Clinical Investigation Dept. (KCA), Naval Medical Center San Diego, 34800 Bob Wilson Dr., San Diego, CA 92134-1005 ([email protected]). The Journal of Infectious Diseases 2002; 186:865–8 This article is in the public domain, and no copyright is claimed. 0022-1899/2002/18606-0022$15.00 men camped in tents on sandy soil, drove in open military vehicles, ran on poorly vegetated land, and occasionally dug holes to conceal themselves. During these activities, all men reported extensive dust exposure and none used protective measures, such as facemasks. Of the 23 Navy SEALs, 6 were seen in the first week of October at a local medical clinic for treatment of cough, fever, chills, night sweats, and malaise. Two of the men asked if this illness could be “valley fever.” Tests for C. immitis were not done for any of the men, and they were diagnosed with a “viral illness.” Because of continued symptoms, 1 Navy Seal was evaluated in San Diego in mid-November 2001. A qualitative coccidioidomycosis EIA was positive, and the complement fixation (CF) titer was 1:8. Following the identification of 5 additional men with positive serologic tests for C. immitis, an outbreak investigation was initiated to determine the extent of coccidioidomycosis infection among this Navy Seal unit. Subjects and Methods Personal interviews and physical examinations were conducted at the time the outbreak was recognized during the second week of December 2001. Using a standard questionnaire, each Navy Seal provided demographic information, medical history, recent medications, details of any illness in the past 12 weeks, types of activities during training, and a military and personal travel history. Medical records were reviewed, chest x-rays were taken, and serum specimens were obtained for hemograms, liver function tests, and a human immunodeficiency virus (HIV) EIA. Each unit member was tested for C. immitis by detection of antibodies, using an EIA (Meridian Diagnostics), and CF titer at the Veteran’s Medical Center in La Jolla, California. Cases of coccidioidal infection were defined by either a positive IgM antibody test or CF titer of ⭓1: 2 [7]. Case subjects and noncase subjects were compared by use of Fisher’s exact test for dichotomous variables and the Mann-Whitney U test for continuous variables (EpiInfo, version 6.02) [8]. 866 Crum et al. Results Twenty-two (96%) of the 23 Navy SEALs who participated in the training exercise were evaluated. All were male, and their ages were 20–40 years (median, 29 years). Twenty-one (95%) were white, and 1 was Hispanic (5%). Nineteen were stationed in San Diego, and 3 were stationed in Honolulu. None of the men had a remarkable medical history, and all were HIV negative. Ten (45%) of 22 men had serologic evidence of a recent C. immitis infection. CF titers in case subjects ranged from !1:2 to 1:16. The sole Hispanic man in this training group developed coccidioidomycosis with a CF titer of 1:16. Of the 10 men with serologic evidence of recent infection, all reported symptoms consistent with a C. immitis infection. Symptoms reported by case subjects and noncase subjects are shown in table 1. No one reported joint swelling, bone pain, or a rash consistent with erythema nodosum or erythema multiforme. The onset of symptoms in 8 of the 10 case subjects occurred during the last week of September or the first week of October, ∼2–3 weeks after their arrival at the Coalinga training site. Two case subjects reported symptoms beginning during the first 2 weeks of November. Symptoms persisted for 2–63 days (median, 19 days), and 3 patients reported missing 1–3 work days. All case subjects had normal findings on physical examination at the time of the outbreak investigation, and basic laboratory values were unrevealing. Five of the 10 case subjects had abnormalities on chest radiographs, including parenchymal consolidation, nodules, cavitary lesions, hilar/mediastinal adenopathy, and/or pleural inflammation (table 2). All chest radiographs were normal in noncase subjects except for one that showed a single 0.7-mm pulmonary nodule. Two men underwent lumbar punctures because of complaints of headaches. Both men had normal examination results, including negative cerebrospinal fluid CF test results for C. immitis. Three men with high initial titers (1:16) had bone scans that were negative for C. immitis bony involvement. There have been no cases of disseminated disease to date. Five men who had persistent symptoms and/or elevated CF titers of 1:16 at the time of the investigation were treated with oral fluconazole (400 mg daily) for 3–6 months. All men have returned to full military duty except 1 who is restricted from diving because of a pulmonary cavity. During the 6-week training period, all men performed the same activities and reported similar exposure to dust and soil. A review of the environmental conditions showed no atypical rainfall or wind patterns in this area. Seismographic activity (magnitude 3.7) was reported on 2 September, but this occurred before trainees arrived in Coalinga [9]. Discussion This outbreak of coccidioidomycosis in US Navy SEALs represents the highest attack rate (45%) ever reported for a military unit during temporary field exercises. It is possible that even more JID 2002;186 (15 September) Table 1. Demographic and clinical characteristics for 22 Navy SEALs with and without coccidioidomycosis—Coalinga, California, 2001. a Characteristic Median age (range), years Ethnicity White Hispanic Fever Night sweats Chills Cough Dyspnea on exertion Chest pain Anorexia Nausea/vomiting Myalgias Arthralgias Headache Weight loss Median duration of sympb toms (range) , days a b a Case subjects (n p 10) Noncase subjects (n p 12) 26 (20–36) 29 (20–40) 9 1 9 7 6 8 4 1 5 3 5 4 5 6 (90) (10) (90) (70) (60) (80) (40) (10) (50) (30) (50) (40) (50) (60) 19 (1–63) 12 0 2 1 1 5 2 1 1 2 1 0 1 2 P .68 .45 (100) (0) (17) (8) (8) (42) (17) (8) (8) (17) (8) (0) (8) (17) .003 .005 .02 .08 .23 .74 .04 .41 .04 .03 .04 .05 9 (2–21) .02 Data are no. (%) of subjects, except for age and duration of symptoms. Duration of symptoms was total duration of illness. of the 22 men may have developed coccidioidomycosis, because 6 of the 12 noncase subjects had similar symptoms and because current serologic testing may be give false-negative results. This outbreak demonstrates the risks that military personnel face when training in the southwestern United States. Although the classic literature states that 60% of infections are asymptomatic, all of our patients with coccidioidomycosis described prominent symptoms, which may be related to the high intensity of exposure [2]. High rates of infection and symptomatic disease have also occurred during high-inoculum exposures associated with archeological digs [1]. The lack of complicated disease in the current group is consistent with reports that only 1% of cases develop dissemination and that is likely related to the fact that all men were previously healthy and 95% were white [2]. The sole Hispanic man in our group developed coccidioidomycosis and had the most remarkable radiographic findings, consisting of extensive mediastinal adenopathy and an upper lobe cavity. An increased risk of severe disease is well described among African Americans, Filipinos, Hispanics, Asians, and Native Americans. Six (27%) of the 22 patients had abnormal chest radiographs despite the fact that x-rays were taken ∼2 months after symptom onset. Pulmonary disease is the most common form of the infection and can include lobar or multilobar parenchymal consolidation, solitary or multiple pulmonary nodules, thin- or thickwalled cavities, hilar or mediastinal adenopathy, and pleural effusion [10]. Although the adenopathy can persist for months or years, it may be associated with disseminated disease. This report emphasizes the importance of coccidioidomycosis in military personnel. More than 350,000 military personnel are currently stationed in C. immitis–endemic regions in the United States [6]. C. immitis–endemic areas in the United States include California, Arizona, New Mexico, Nevada, western Texas, and, JID 2002;186 (15 September) Coccidioidomycosis Outbreak among Navy SEALs 867 Table 2. Clinical syndromes, serologic test results, and radiographic findings in 10 Navy SEALs with Coccidioides immitis infection—Coalinga, California, 2001. Patient 1 2 3 4 5 6 7 8 9 10 a Clinical manifestations (duration) IgM/IgG CF titer Radiologic findings Fever (2 days) Fever, sweats, chills, cough, dyspnea, myalgias, headache, weight loss (63 days) Fever, sweats, chills, cough, dyspnea, headache, weight loss (63 days) Fever, cough, myalgias (2 days) Fever, sweats, cough, myalgias, headache (14 days) Fever, sweats, chills, headache, weight loss (2 days) Fever, sweats, chills, cough, dyspnea, myalgias, weight loss (21 days) b Fever, sweats, chills, cough, dyspnea, myalgias, weight loss (7 days) Fever, sweats, chills, cough, headache, weight loss (7 days) Cough (14 days) ⫹/⫹ ⫹/⫹ ⫹/⫹ ⫹/⫹ ⫹/⫹ ⫹/⫹ ⫹/⫹ ⫹/⫹ ⫹/⫹ ⫺/⫹ 1:16 1:16 1:16 !1:2 1:8 !1:2 1:8 1:16 !1:2 1:2 Normal Normal Right hilar adenopathy Normal Left hilar adenopathy Normal Left lower lobe consolidation Right upper lobe cavity/mediastinal adenopathy Right middle lobe nodule Normal NOTE. CF, complement fixation. a IgM/IgG, coccidioidomycosis titers by EIA. b Patient 8 is Hispanic and had the most remarkable radiographic findings. most recently, Utah [1]. Semiarid conditions in these areas are optimal for many military training operations. Several reports have demonstrated that coccidioidomycosis is an occupational hazard for military personnel stationed or training in C. immitis–endemic areas [2, 3, 5, 6]. The first recognized case of coccidioidomycosis was reported in a soldier from Argentina in 1892 [11]. During World War II, members of the armed forces who resided in C. immitis–endemic areas were infected at a rate of 8%–25% per year [2]. Furthermore, many infected soldiers were unable to work for weeks, disrupting military readiness. Despite dust-control measures instituted after World War II, coccidioidomycosis has remained an occupational risk for the military in C. immitis–endemic areas. In 1977, an outbreak of 18 cases occurred near Naval Air Station Lemoore (California) after a natural dust storm [5]. Lemoore is located ∼25 miles northeast of Coalinga and has similar terrain. In this outbreak, 4 nonwhite persons developed disseminated diseases. The most recently reported outbreak in military members involved 8 (30%) of 27 military men from Tennessee who presented after a 3-week training exercise in California [3]. Similar to our group, these men had substantial exposure to the dust and soil. This outbreak among Navy SEALs emphasizes that coccidioidal infection should be considered in symptomatic patients who recently traveled to the southwestern United States. Recognition of the Coalinga outbreak led to the diagnosis of coccidioidomycosis in all 3 men stationed in Honolulu, a region far removed from C. immitis–endemic areas. One of these patients had severe pulmonary disease requiring restriction of his military duties. Without notification to the medical community in Hawaii, these case subjects would likely have been missed. Given increasing rates of travel, clinicians outside C. immitis–endemic areas should consider the diagnosis of coccidioidomycosis in patients presenting with a respiratory illness 2–3 weeks after exposure. This is highlighted by the recent outbreak at a model airplane flying championship in Kern County, California, involving persons worldwide [12]. Missed diagnoses are usually due to unfamiliarity with the disease or failure to obtain a travel history. The diagnosis may be easily missed since coccidioidomycosis often mimics common respiratory illnesses. It is important to make an early diagnosis to relieve patient anxiety, reduce unnecessary use of antibiotics, and detect complications, such as osteomyelitis, skin rashes, or meningitis. Diagnosis of coccidioidomycosis is by fungal culture, histopathologic testing, or serologic testing, such as EIA, CF, or immunodiffusion. Results from serologic tests are rapid and can detect cases with few or no apparent symptoms. However, serologic tests may give false-negative results, especially early in the disease course [13]. IgM antibodies appear during the first 3 weeks of infection and then fall to undetectable levels. In our patients, symptoms typically began in the first week of October, and IgM antibodies were still present in 9 of 10 case subjects in December. There may be a window of opportunity during which IgM antibodies have fallen and IgG has not appeared, leading to false-negative test results. Thus, at least 2 samples should be obtained for IgM and IgG testing during a 2-month period [7]. CF testing is useful because titers of ⭓1:2 reflect a recent or current infection, and a rising titer may reflect progressive or disseminated disease. Skin testing, which is currently unavailable, does not distinguish current from past infection. It is debatable whether mild, early cases should be treated since it is unknown if therapy hastens resolution or prevents complications. Five of the 10 Navy SEALs with coccidioidomycosis were treated with fluconazole (400 mg daily) because of persistent symptoms lasting ⭓60 days and/or a CF titer of 1:16. Indications for early therapy include loss of 110% of body weight, night sweats for ⭓3 weeks, infiltrates involving portions of both lungs or more than one-half of 1 lung, persistent hilar adenopathy, and inability to work. In such cases, fluconazole (400 mg once daily) or itraconazole (200 mg twice daily) for 3–6 months is recommended [14]. Newer agents for C. immitis infections are becoming available, but there is no clear evidence that these are more effective than traditional therapies. The most effective method for preventing C. immitis infections would be a coccidioidal vaccine; however, this is not currently available. A guideline for geologic fieldwork is available and may be useful for persons with dust exposures in C. immitis–endemic locations [15]. Preventative strategies include wearing a face mask, avoiding working outdoors during windy 868 Crum et al. conditions, using vehicles with enclosed cabs, wetting the soil before digging, avoiding rodent burrow sites, camping upwind of dusty areas, and setting campsites on vegetated areas. However the feasibility of these methods may be limited for residents and for military personnel performing military maneuvers in areas where C. immitis is endemic, making vaccine development a most important strategy to reduce coccidioidal infections. 6. 7. 8. Acknowledgments 9. We thank Brad Hale and Helen Chun (Naval Medical Center, San Diego) and Kim Moran (Tripler Army Medical Center, Honolulu) for their assistance in evaluating cases. 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