An 8-year-old, previously healthy Caucasian boy was brought to his family physician with a 2-month history of neck pain and stiffness. The pain was not sufficient to wake the child at night, but it prevented participation in athletics. No history of trauma, fever, weakness, paresthesias, weight loss, or change in bowel or bladder function was noted. The initial diagnosis was muscular strain, and rest and antiinflammatory medication was recommended. When his symptoms did not improve, a cervical spine radiograph showed a lytic lesion of the fifth cervical vertebra.

On hospital admission, physical examination was unremarkable, with the exception of pain on palpation over the posterior cervical spine. Laboratory results at admission showed normal leukocyte count (8.0 × 10⁹/L), differential (polymorphs 4.48 × 10⁹/L, eosinophils 0.08 × 10⁹/L, lymphocytes 2.80 × 10⁹/L, monocytes 0.56 × 10⁹/L), electrolytes, and renal function. Erythrocyte sedimentation rate was mildly elevated at 38 mm/h. Computed tomographic scan of the region showed a well-defined lytic lesion with a "bubbly" appearance involving the posterior elements of the C5 vertebral body. An incidental note was made of a small, nonspecific lesion within the posterior upper lobe of the right lung. Bone scintillography showed positive uptake at C5. Magnetic resonance imaging (MRI) of the cervical spine demonstrated an enhancing mass that involved the posterior aspects of C5 plus an abnormal signal within the adjacent spinous processes.

The patient underwent a C5 laminectomy and a C4 partial hemilaminectomy. During dissection, a small amount of purulent liquid was extruded from the tissue above C5. Gram stain of the pus aspirate showed no organisms. A calcofluor stain was positive for large, broad-based budding yeast forms. Pathologic examination showed a destructive lesion involving bone and soft tissues with both granulomatous and necrotizing suppurative components. The numerous epithelioid granulomas contained Langhans cells and foreign body giant cells, while the necrotizing lesions contained neutrophilic and eosinophilic infiltrates. Fungal elements highlighted with periodic acid–Schiff and Gomori methenamine silver stains showed double-contoured cell walls surrounding a cytoplasmic mass and proliferation in the form of broad-based buds. On the basis of these features, a presumptive diagnosis of blastomycosis was made. Subsequent fungal cultures grew a filamentous dimorphic fungus identified as B. dermatitidis and confirmed by DNA probe (Accuprobe, Gen-Probe Inc., San Diego, CA, USA).

The lung lesion in the right upper lobe could have also been a focus of blastomycotic infection; however, bronchoalveolar lavage or biopsies were not performed. Intravenous amphotericin B, 30 mg every 24 h (1.0 mg/kg/d) was initiated. After 10 days, the dose was reduced by 50% because of renal toxicity. On day 17 of treatment, itraconazole (200 mg orally once per day) was initiated and given concurrently with amphotericin B for 5 days, at which point amphotericin B was discontinued because of laboratory evidence of renal failure. At the time of discontinuation, 480 mg (16 mg/kg) had been given. The patient's clinical status improved, with resolution of pain and a return of full cervical range of motion by time of discharge.

Three weeks after completing a 6-month course of itraconazole, fever associated with vomiting and a sore throat developed in the patient. Chest radiograph showed a consolidation in the upper lobe of the right lung. MRI of the lung fields and cervical spine did not provide evidence of recurrence of blastomycosis. Clarithromycin was initiated and continued for 3 days with no improvement, at which time itraconazole (200 mg orally once per day) was resumed because blastomycosis could not be conclusively ruled out. Antifungal therapy was continued for 6 months, after which the patient was clinically healthy, and radiographs of the cervical spine and chest were normal.

The patient had visited a cottage on the lakeshore of an island in the north health region of Ontario 5 months before his hospitalization. Shortly after the owner purchased the property, his dog and an adult male companion both developed laboratory-confirmed, nonfatal blastomycosis. Six months later, another adult male visitor developed a pneumonialike condition and was diagnosed with laboratory-confirmed blastomycosis. A provincial epidemiologic team also determined that a dog belonging to a previous owner of the property died of blastomycosis ≈2 years earlier.

A year and a half after the initial human infection, the cottage owner contacted the mycology laboratory at the Ontario Ministry of Health and requested an environmental investigation. A total of 50 environmental samples were taken from the property, including from a beaver lodge (similar to those previously associated with blastomycosis [8]) located underneath a boathouse. The samples were taken ≈3 months after our patient's presumed exposure. Material from the samples was prepared in sterile physiologic saline and injected into 4 mice per sample, as outlined by Ajello and Weeks (9) for environmental isolation of Histoplasma capsulatum. This technique had previously been used successfully to isolate B. dermatitidis (10). No mice died of blastomycosis within 6 weeks (autopsy of 2 mice that died showed bacterial infection), and examination of the remaining 198 mice, euthanized after 6 weeks, showed that livers, spleens, and lungs were clear of B. dermatitidis by histopathology and by culture on Sabouraud glucose agar with cycloheximide, chloramphenicol, and gentamicin (CCG) and blood agar with CCG and 2.3% egg albumin (11,12).

Figure 1

Figure 1. Incidence of blastomycosis by Ontario health region.

A total of 309 culture-positive cases of blastomycosis were identified in Ontario during the study period. Each of Ontario's 7 health regions had cases identified (Figure 1); 61% (n = 188) of the cases were diagnosed in the north region, and 21% (n = 66) were diagnosed in the Toronto region. Of the north region cases, 89% (n = 167) were from the Northwestern Health Unit's district, which includes Kenora.

Figure 2

Figure 2. Blastomycosis diagnosed by year, Ontario, 1994–2003.

Figure 3

Figure 3. Blastomycosis diagnosed by season, Ontario, 1994–2003.

Figure 4

Figure 4. Number of blastomycosis cases and incidence rates by age, Ontario, 1994–2003.

The mean number of cases diagnosed per year was 33.7; the fewest number of cases was in 1995 (n = 10), and the greatest number was in 2002 (n = 71) (Figure 2). The number of cases has increased in recent years; 57% (n = 175) were reported in the 3-year period from 2001 to 2003. While cases were diagnosed year-round, 59% (n = 181) occurred in the fall and winter months, from October to March (Figure 3). The age of patients with positive isolates was recorded for 92% (n = 283) of cases; ≈60% were 30–59 years of age (range 6 months to 83 years) (Figure 4). The sex of the affected person was available in 97% (n = 301); 65% (n = 196) were male, and 35% (n = 105) were female. The incidence ranged from a low in the south-central Ontario region of 0.02 cases per year per 100,000 population to a high in the north Ontario region of 2.44 cases per year per 100,000 population (Figure 1). Age-specific incidence rates are shown in Figure 4.

The understanding of the natural distribution of blastomycosis and other mycoses endemic in Ontario (such as histoplasmosis) is minimal. This study is the first to describe the Ontario-wide incidence of blastomycosis and to provide incidence rates in each of the 7 provincial health regions. Clinicians practicing throughout the province and country may encounter persons infected with this organism and need to be familiar with its varied clinical signs and symptoms and be aware of regions where disease is endemic or hyperendemic. Our data suggest that the number of diagnoses of blastomycosis has increased over several years. However, the disease likely remains underrecognized. As delay to diagnosis can contribute to illness and death, clinicians should consider blastomycosis in their differential diagnoses of lung, skin, and bone diseases, particularly if the patient does not respond to conventional antimicrobial drug therapy. The lack of rapid and effective diagnostic tools contributes to the underrecognition of blastomycosis. Advances in molecular diagnosis of B. dermatitidis (39), particularly in regions identified as higher risk, hold the potential for improving case detection and decreasing delay to diagnosis.

Infection by B. dermatitidis is more common than was thought before its removal from the list of reportable diseases in Ontario in 1989. Our group advocates strongly for returning blastomycosis to the reportable diseases list in this province. Travel history must be included in the reporting of blastomycosis. While identifying the point of infection in well-traveled individuals may be impossible, a specific or negative travel history would make a valuable contribution to understanding where blastomycosis is contracted in Ontario. Such reporting would facilitate tracking cases and clinical education regarding this potentially fatal invasive fungal infection.