in june 2001 , five persons with a febrile respiratory illness visited a community hospital .
the patients were among 15 persons ( age range 1961 years ; median 38 years ) , residents of four states , who had participated in a geology - biology community college class trip to nicaragua . to determine the cause and describe characteristics of the outbreak , we interviewed trip participants and reviewed medical records to collect demographic information , clinical history , and activities during the trip . based on the partcipant s exposure to a cave with bats and clinical characteristics suggestive of acute histoplasmosis
a case of acute histoplasmosis was defined as illness in a person who tested positive by one of the following laboratory tests : serology , urine antigen , histopathology , or culture .
immunodiffusion and complement- fixation serologic tests were performed at the centers for disease control and prevention ( cdc ) .
the immunodiffusion test was considered positive if an h or m band or both were detected .
a complement - fixation titer to the yeast or mycelial antigens of > 1:32 or a fourfold increase in the titer between acute- and convalescent - phase serum specimens was considered evidence of acute infection .
identification of the organism as h. capsulatum was confirmed by genprobe assay ( genprobe , san diego , ca ) .
urine antigen tests , which were performed 2 weeks after exposure , are considered positive if > 1 unit is detected ( 3,4 ) .
the travelers began their trip on may 19 and returned to the united states on may 30 . during their trip
, they explored rock quarries , visited a biological research station , swam in freshwater lakes , and were exposed to parrots and insects . on may 21 ,
a total of 14 of the 15 travelers entered a small cave that had previously been used as a silver mine .
they remained in the cave for 10 minutes , during which time they saw several flying bats and bat guano on the ground .
the infection rate was 100% among the 14 travelers who entered the cave , and 12 ( 86% ) were symptomatic .
of the 14 patients , 12 ( 86% ) had urine antigen tests ( table ) .
the only traveler who did not enter the cave tested negative by serology and urine antigen . among 14 persons with histoplasmosis . 
urine antigen tests were performed for 12 persons .  among the 12 symptomatic persons . 
five persons missed 2 weeks3 months of work , and five persons missed one semester of school .
the average incubation period was 11 days ( range 1012 days ) , assuming that exposure occurred on may 21 . among the 12 symptomatic persons , 12 ( 100% ) had a fever of 38.9c to 40c , nonproductive cough , myalgias , fever , chills , night sweats , loss of appetite , and mild headache .
many had nausea and vomiting ( 83% ) , chest pain ( 58% ) , and arthralgias ( 58% ) .
six persons had mild to moderate respiratory distress , with oxygen saturation of 88% to 95% . on physical examination ,
all the travelers lung fields were clear to auscultation , a feature consistent with histoplasmosis infection .
the two asymptomatic persons had previous exposure to bats or caving . among the symptomatic persons
, we found no differences in severity of symptoms according to sex , prior exposure to spelunking , residence in a histoplamosis - endemic area , or activities while in the mine . in accordance with clinical treatment guidelines
, physicians decided to treat patients with itraconazole for 6 to 12 weeks ; some patients also received steroids ( 5 ) .
laboratory studies showed normal complete blood counts , serum chemistries , and renal function tests .
four persons had mild to moderate elevation in liver function tests ( alanine aminotransferase , range 55204 ; aspartate aminotransferase , range 48153 ; and alkaline phosphatase , range 95311 ) .
all 12 symptomatic persons had abnormal chest radiograph results with bilateral nodular infiltrates ( figure ) .
chest radiograph of patient who acquired acute pulmonary histoplasmosis after visiting a cave in nicaragua .
hematoxylin and eosin  stained sections of the lung tissue from the biopsy showed macrophages and neutrophils in the interstitium ; no granulomatous inflammation was observed .
culture of the bronchoalveolar lavage fluid from this patient grew h. capsulatum after 4 weeks of incubation .
this report highlights the importance of histoplasmosis as a potentially serious travel - related illness .
histoplasmosis is usually considered a mild , self - limited illness ; however , this outbreak of histoplasmosis among previously healthy travelers was associated with a 100% infection rate of histoplasmosis and an 86% rate of symptomatic infection in the persons who entered the cave . among the symptomatic persons ,
50% required hospitalization and 83% missed school or work ( range : 2 weeks3 months ) as a result of their illness ( table ) .
because of the high attack rate and the large percentage of patients with severe infection , these travelers were likely exposed to very high concentrations of h. capsulatum spores during their brief visit inside the cave .
h. capsulatum exists throughout the world ( 1,6 ) ; however , nonimmune travelers from areas with a low prevalence of histoplasmosis , who engage in high - risk activities in disease - endemic areas , are at greater risk of acquiring symptomatic fungal infection . the number of outbreaks of histoplasmosis , especially among u.s .
histoplasmosis has been reported in groups of travelers who entered caves with bats in costa rica ( 7 ; unpub .
data , centers for disease control and prevention cdc ) , ecuador ( 8) , and peru ( 9 ) . in 2001 ,
more than 200 college students became infected with histoplasmosis during a spring break trip to acapulco , mexico ( 10,11 ) .
clinicians should consider fungal pathogens when evaluating returning travelers who have a febrile respiratory syndrome .
the differential diagnosis of acute febrile respiratory illness in international adventure travelers is extensive and includes legionellosis , psittacosis , leptospirosis , schistosomiasis , histoplasmosis , coccidioidomycosis , influenza , parainfluenza , mycoplasma , dengue , and malaria .
the timely diagnosis of histoplasmosis in travelers may be particularly challenging for clinicians evaluating one sporadic case or a patient involved in an undetected multistate outbreak .
antibody response can take 46 weeks to develop , reducing its usefulness in the acute setting and requiring the collection of a convalescent - phase specimen for confirmation .
antibodies may also persist for 5 years , making it difficult to distinguish between prior and recent infection without obtaining a convalescent - phase specimen .
the sensitivity of immunodiffusion is 72% to 85% , while that of complement fixation is 80% to 90% ( 20,21 ) .
the antigen test can be used for urine , cerebrospinal fluid , serum , and bronchoalveolar lavage fluid , and results are available in 24 hours .
this test had been used most extensively in aids patients ; however , it is less sensitive in nonimmunocompromised persons with acute pulmonary infection .
sensitivity of the urine antigen test for detection of acute pulmonary infection ranges from 44% to 75% and increases when performed early after the onset of symptoms ( 3,4 ) . in this outbreak ,
however , most clinicians may not have thought to counsel them about histoplasmosis risk and prevention . during pretravel visits
, clinicians should review patients itineraries for possible fungal exposures and should counsel them to avoid entering caves , especially those known to be bat infested .
since travelers may not know whether their itinerary includes visits to bat - infested caves , adventure travelers and persons who are at high risk for severe histoplasmosis infection , such as immunocompromised travelers ( especially persons with aids ) , should be counseled to avoid possible exposures , either by avoiding caves or by using special protective masks .
the national institute for occupational safety and health has published guidelines for special masks that can be used to reduce occupational and other exposures ( e.g. , among spelunkers ) .
unfortunately , these special masks are bulky and may be impractical for many travelers ( 22 ) . while most nonimmunocompromised patients with acute pulmonary histoplasmosis improve without treatment , persons with hypoxemia , diffuse pulmonary histoplasmosis , or severe illness requiring hospitalization may benefit from antifungal therapy and , in some cases , corticosteroids ( 5 ) .
as adventure travel becomes increasingly accessible , especially among persons at high risk , immunocompromised persons , and the elderly , histoplasmosis and other fungal infections in travelers may become more common .
enhanced surveillance for histoplasmosis and other fungal infections by public health officials , combined with heightened awareness by clinicians who are evaluating symptomatic , post - travel patients , can lead to greater understanding of the epidemiology of fungal infections among travelers and , ultimately , to improved prevention measures .
 we investigated an outbreak of unexpectedly severe histoplasmosis among 14 healthy adventure travelers from the united states who visited a bat - infested cave in nicaragua . 
 although histoplasmosis has rarely been reported to cause serious illness among travelers , this outbreak demonstrates that cases may be severe among travelers , even young , healthy persons . 
The Study
Conclusions