Pulmonary histoplasmosis is a rare disease in France, as in Europe.1 Excluding cases identified in Guyana and Caribbean islands, only 18 cases of histoplasmosis due to Histoplasma capsulatum var. capsulatum have been reported in France in 2008 by the Centre National de Référence de la Mycologie et des Antifongiques (CNRMA), Institut Pasteur, Paris, France. All of them were imported from endemic areas. Infection results from inhalation of fungal spores, present in soil contamined by bat or bird droppings.2,3 Clinical manifestations and radiological features of acute pulmonary histoplasmosis are nonspecific2,4,5 and depend on the size of the inoculum.4,5 Moreover, in this clinical presentation, serological test and culture of sputum can be negative.2,4,5 For all these reasons, diagnosis of acute pulmonary histoplasmosis remains difficult in nonendemic areas, often based on travel history and risk factor, such as caving.6
Pulmonary histoplasmosis is a rare disease in France, where all cases are imported. Diagnosis is difficult in nonendemic areas, often based on travel history and observation of epidemic in a group. We report three cases of pulmonary histoplasmosis that occurred in a group of 12 French cavers traveling to Cuba.
A group of 12 French cavers traveled to Cuba from February 17 to March 4, 2008. During their trip, they visited four bat-infested caves in the Sierra de Los Organos, west Cuba: Red Ojo del Agua, Red Rio Blanco, Cueva Manuel Noda, and Cueva Del Hoyo Del Nodar. After their return to France, three of them developed fever, cough, asthenia, dyspnea, and chest pain.
The first patient, a previously healthy 40-year-old man, was admitted in the Grenoble University Hospital, France, because of fever, dyspnea, and chest pain 3 days after he came back. Physical examination was unremarkable. Chest radiography showed a miliary, and computed tomography (CT) scan confirmed the presence of bilateral multiple pulmonary nodules, micronodules, and ground glass opacities. Laboratory findings included slightly elevated liver enzymes and moderate inflammatory reaction (C-reactive protein, 40 mg/L–normal < 3 mg/L). Bronchoalveolar lavage (BAL) did not show any bacterial, mycobacterial, or fungal agents neither by direct examination nor by cultures. Serological test was positive, but not performed in the CNRMA (by immunodiffusion: H precipitin band, one precipitin arc). The patient was treated with itraconazole 400 mg/d for 3 months. After therapy, we noted a clinical and radiological improvement.
The second patient was a 54-year-old man without previous medical problem. He suffered from cough, fever, and asthenia 6 days after his return to France and consulted his general practitioner. Chest radiograph showed bilateral basal nodular opacities. His CT scan performed in the Lyon University Hospital, France, revealed bilateral nodules and micronodules associated with mediastinal lymph nodes (Figure 1). Research of respiratory pathogen in BAL remained negative. At the same time, he learned that another member of the caving group, in Grenoble, had respiratory symptoms, attributed to acute pulmonary histoplasmosis. Serological test was positive, performed in the CNRMA (Clinisciences, IMMY, Oklahoma City, OK, USA) by immunodiffusion: M precipitin band, one precipitin arc. The patient was treated with itraconazole 300 mg/d for 3 months. Clinical improvement was observed, as a reduction in number and size of pulmonary opacities during follow-up was noted.
The third patient, a previously healthy 17-year-old boy, suffered from fever and asthenia 10 days after his return to France. Physical examination was normal but chest radiography and thoracic CT scan showed bilateral nodules and micronodules; some of them were associated with cavitation. Diagnosis of acute pulmonary histoplasmosis was suspected as this patient belonged to the caver group. BAL wasn't performed. Serological test was negative at 15 days and 3 months (performed in the CNRMA). Itraconazole therapy (300 mg/d) was administered for 3 months with success.
These three cases illustrate the fact that caving activity in Cuba is associated with risk of developing acute pulmonary histoplasmosis. A previous outbreak of histoplasmosis has been described in Cuba among a team of eight bat researchers.7 In the group described above, the attack rate was 25%. Numerous series in the litterature showed a higher attack rate: 62.5% in the group of eight bats researchers quoted above,7 72% in a group of 61 tourists in Costa Rica,8 100% in a group of tourists in Martinique,9 and 100% in the participants of a geology–biology community college class trip to Nicaragua.10 We probably underestimated the attack rate because of asymptomatic forms. Moreover, serological test was not performed on the entire group.
We highlight the lack of awareness of this disease among tourists exploring caves, who should use personal protective equipment such as tight fitting masks to help prevent infection, like workers removing bird or bat guano from buildings.8 Prevalence of imported pulmonary histoplasmosis is increasing, and the contribution of histoplasmosis to travelers' morbidity is likely underestimated.11 Even if it is usually a self-limited illness in immunocompetent individuals, European clinicians should consider it when evaluating returning travelers who have a febrile respiratory syndrome.6,10 However, making the diagnosis remains difficult for many reasons: (1) symptoms are unspecific; (2) Histoplasma var. capsulatum is rarely found in respiratory samples; and (3) serological tests lack sensitivity and specificity. Pulmonary histoplasmosis requires a high index of suspicion in travelers coming back within a few days from an endemic area, especially if a group of patients is symptomatic, if they practiced caving, and if most of them developed pulmonary nodules and micronodules.
Declaration of Interests
The authors state that they have no conflicts of interest to declare.