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Jornal de Pneumologia

Print version ISSN 0102-3586On-line version ISSN 1678-4642

J. Pneumologia vol.29 no.1 São Paulo Jan./Feb. 2003 



Coccidioidomycosis: an unusual cause of acute respiratory distress syndrome1



Kelson Nobre VerasI; Bruno C. de Souza FigueirêdoII; Liline Maria Soares MartinsIII; Jayro T. Paiva VasconcelosIV; Bodo WankeV

IMD, Infectologist. MSc in Tropical Medicine, Physician of the Intensive Care Service of the São Marcos Hospital, Teresina, Piauí
IIMD, Pneumologist. Physician of the Intensive Care Service of the São Marcos Hospital. Professor at "Faculdade Estadual de Medicina", Teresina, Piauí
IIIProfessor at "Faculdade Estadual de Medicina". Microbiologist at the Nathan Portela Institute for Tropical Diseases, Teresina, Piauí
IVCoordinator of the Intensive Care Service of the São Marcos Hospital, Teresina, Piauí
VFull Researcher (Pesquisador Titular) of the Evandro Chagas Institute for Clinical Research, Fundação Oswaldo Cruz-Fiocruz (Oswaldo Cruz Foundation), Rio de Janeiro, RJ





A male farmer, 20 years old, from the countryside of the State of Piauí, developed acute respiratory infection. Despite adequate antimicrobial therapy, his conditions worsened, requiring mechanical ventilation. His X-rays showed diffuse pulmonary infiltrates. His PaO2/FiO2 ratio was 58. Direct microscopy and culture of tracheal aspirates showed the presence of Coccidioides immitis. Autochthonous cases of coccidioidomycosis have only recently been described in Brazil, most of them from the State of Piauí. C. immitis has been isolated from humans, dogs and armadillos (Dasypus novemcinctus), and also from soil samples of armadillo's burrows. Failure to respond to antimicrobial therapy and a patient's origin from recognized endemic areas should alert to the possibility of acute pulmonary coccidioidomycosis.

Key words: Coccidioides immitis. Coccidioidomycosis. Respiratory distress syndrome.



Abbreviations used in this work:

AARB – Alcohol-acid resistant bacilli

HIV – Human immunodeficiency virus

PaO2/FiO2 – Ratio of partial arterial oxygen pressure and the inhaled fraction of oxygen

PEEP – Positive end expiratory pressure

ARDS – Acute respiratory distress syndrome

ICU – Intensive Care Unit



Acute respiratory distress syndrome (ARDS) is a respiratory process of acute onset, showing on X-rays as bilateral pulmonary infiltrates and severe respiratory failure, characterized by a partial arterial oxygen pressure/ inhaled oxygen fraction (PaO2/FiO2) ratio below or equal to 200(1-3).

Disorders associated with ARDS include direct lesions of the pulmonary parenchyma and lesions indirectly affecting the lung (4). Among the most frequent causes are sepsis, severe pneumonia, peritonitis, and multiple trauma (5). Coccidioidomycosis is an unusual cause of acute respiratory distress syndrome (6,7), and no Brazilian case has been described so far. However, this systemic mycosis has been increasingly diagnosed in Brazil (8,17), requiring a broader diffusion of information about this disease and its possible clinical presentations.



A male patient, 20 years old, farmer, living in the municipality of Bertolínia, countryside of the State of Piauí, was admitted to a local hospital, presenting a clinical picture of acute respiratory infection that had been developing for about seven days. During hospitalization, he received a combination of oxacillin and amycacine for six days, but his condition worsened. He was then referred to a hospital in Teresina (capital of the State of Piauí), where the oxacillin dose was increased to 12g/day, with amycacine being kept at 500mg every 12 hours.

On the third day after hospital admission, the patient's condition worsened. Needing mechanical ventilation, he was transferred to the ICU with a clinical picture of severe respiratory failure. A chest X-ray revealed lungs with bilateral diffuse condensations, and this picture worsened rapidly (Figures 1 and 2), the PaO2/FiO2 ratio being initially 71, further on dropping to 58 (FiO2 = 1.0). HIV-1 and 2 testing (ELISA method) was negative in two samples, as was the test for antigen p24.




Upon admission to the ICU, the patient was placed under mechanical ventilation with pressure control. The antibiotics were replaced by vancomycin and cyprophloxacine. The next morning, after evaluation by the Infectology Service, amphotericin B was added. However, the patient died about 48 hours after his admission to the ICU.

Bacterioscopic examination of his tracheal aspirate presented less than 10 epithelial cells and more than 25 leukocytes per field, with rare gram-positive cocci. The search for AARB in the tracheal aspirate was negative; however, direct search for fungi revealed spherical elements with a thick wall, several of them filled with endospores, characterizing mature Coccidioides immitis spherules. The tracheal aspirate culture was negative for bacteria, but the fungus cultures produced suspicious filamentous colonies which, after intraperitoneal inoculation in mice, revealed spherules which are characteristic for C. immitis, confirming this dimorphic fungus as being responsible for the etiology of the patient's clinical picture (Figure 3).




C. immitis is a dimorphic fungus found in nature as a saprophytic filament (mould) that produces propagules (arthroconidia) which spread easily in the air and are highly infectious to susceptible humans and many animals who inhale them, usually mixed with dust from the soil. As they reach the pulmonary alveoli, they are phagocyted and take, inside the alveolar macrophages, the characteristic parasite shape of spherical elements which, when they are mature and filled with endospores, constitute the spherules (18). In the human organism, before the immune response is established, dissemination to any organ or tissue can occur, establishing secondary mycosis foci.

It is estimated that, in endemic areas, approximately 60% of the infected individuals have asymptomatic or oligosymptomatic infections, followed by spontaneous regression. After this spontaneous cure, the fungus can remain viable and latent at residual foci, which may, after long latency periods, eventually become reactivated and cause clinical manifestation.

When it is symptomatic, this mycosis usually manifests as an acute feverish respiratory disease, the symptoms starting, on the average, 7 to 28 days after exposure to the fungus, being characterized mainly by fever, malaise, cough, and chest pain of the pleuritic type. The golden standard for diagnosis is the demonstration of the characteristic spherules in clinical specimens, achieved by direct microscopic examination of preparations with a 10% KOH solution, although, in some cases, specimen cultures are needed for identification. The diagnosis can also be made by immunological tests, the most commonly used being double immunodiffusion in agar gel, or by DNA hybridization (18).

Classically, coccidioidomycosis is known as an endemic systemic mycosis of semi-arid areas of the American continent, affecting the Southeast of the United States, North Mexico, and semi-arid land strips of Central and South America (19). The first autochthonous cases in Brazil were reported in 1978 and 1979 (8,9), the first case being from the State of Bahia and the second one from Piauí, where he had lived his whole life. About 15 years later, the first micro-outbreak of this mycosis in Brazil was also reported in the State of Piauí (20). Since then, the number of published cases has increased considerably (11-16), the association between this infection and the digging of armadillo (Dasypus novemcinctus) burrows was widely described (12,20), the fungus has already been isolated from tissues of this animal (17), of dogs, and from soil samples collected in armadillo burrows (16). Currently, this systemic mycosis is considered endemic in the Northeast Brazilian States of Bahia, Ceará, Piauí, and Maranhão (16). In Piauí only, 24 cases were already diagnosed, almost always related to the hunting and unearthing of armadillos.

The present report describes a patient from a municipality where another case has already been published (15). His relatives reported that he was currently busy digging the soil to build a wooden fence, besides taking often part in armadillo hunts, a proven risk activity for coccidioidomycosis in Brazil.

Upon admission to the ICU, the patient met the most recent classification criteria for acute respiratory distress syndrome (3). Gattinoni et al. (5) remarked that, when the triggering disease is a direct pulmonary lesion, such as pneumonia, the prevailing pathology is one of pulmonary consolidation, whereas extrapulmonary causes determine predominantly interstitial edema and alveolar collapse. These authors consider that, in the first case, the pulmonary volume recruitment by a positive end expiratory pressure (PEEP) of up to 15cmH2O is only marginal, whereas, in the acute respiratory distress syndrome caused by extrapulmonary disease, PEEP recruitment is marked.

The association of coccidioidomycosis with ARDS is unusual and was previously recorded only in the United States (6,7). To our knowledge, there is no Brazilian publication on this association.

Arsura et al. (6) reported that coccidioidomycosis was only considered in five out of eight immunocompetent patients with coccidioidomycotic septic shock, and that, in spite of amphotericin B therapy, they all died, similarly to the case reported here. Arsura and Kilgore (7) point out that the miliary pattern on the chest X-rays indicates a lymphatic or hematogenic dissemination of C. immitis, thus signaling the severity of the mycosis.

In conclusion, pulmonary coccidioidomycosis remains little known in the medical world, even in endemic regions. The case reported here shows how late its diagnosis is usually considered. A broader diffusion of information about the spreading of coccidioidomycosis in Brazil and the severe medical repercussions it can bring about would draw the doctors' attention to this etiology, allowing them to make a correct diagnosis and provide effective treatment.



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Correspondence to
Dr. Kelson Nobre Veras
Rua Teófilo dos Santos, 1.382, bloco 8, apto. 304
64056-450 – Teresina, PI, Brazil
Phone.: 55 (86) 981-8526, 55 (86) 232-0014

Received for publication on 07/29/02
Approved, after revision, on 12/02/02



1 Work performed at the Intensive Care Service of the São Marcos Hospital, Teresina, Piauí.

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