Deep Endemic Mycoses

Causative agent and transmission

Distribution

• Histoplasmosis is encountered almost worldwide, but it is most prevalent in the United States around the Mississippi-Missouri-Ohio region. It is also encountered fairly frequently in Central and South America, West Africa, Australia and Asia (India and Malaysia). The disease is rare in Europe, but it has been encountered in a small area in North Italy.
• Living in endemic regions, and even a short visit to the area, may put a person at risk of contracting the disease.

Symptoms

• Symptomatic infection is uncommon.
• Incubation period 8-18 days
• Cough, fever, headache, chest pain, lethargy
• A chest x-ray shows nodular densities; the hilar and mediastinal lymph nodes may enlarge. May also resemble bacterial pneumonia or cause a histoplasmoma that mimics a tumour.
• The presentation of disseminated histoplasmosis ranges from an acute and fatal disease to a chronic and intermittent disease. In addition to fever, the patient may also present with weight loss, nausea and abdominal complaints.
• Disseminated histoplasmosis occurs mostly in patients who are immunocompromised due to AIDS, organ transplantation, cytotoxic treatment or blood disorders, for instance.

Diagnosis

• The findings of imaging studies are characteristic to the disease.
• Diagnostic workup utilises the microscopic examination and fungal culture of a sputum sample, bronchoalveolar lavage sample or biopsy, fungal nucleic acid detection tests (PCR), as well as antibody assays.
• Antigen detection is possible but not in routine use.
• The histology of a biopsy sample (granulomatous inflammation) may lead to diagnosis.
• If histoplasmosis is suspected the laboratory receiving the specimens should be alerted beforehand since transmission to laboratory personnel has been reported and because the culture may take several weeks for diagnostic growth to occur.

Differential diagnosis

• In addition to other mycoses, the differential diagnosis of acute histoplasmosis includes mycoplasma, chlamydial and legionella pneumonias whereas the differential diagnosis of chronic histoplasmosis includes tuberculosis and sarcoidosis.

Treatment

• Most patients with acute histoplasmosis recover in 4-6 weeks and require no treatment.
• For patients with prolonged symptoms, itraconazole 200 mg once or twice daily may be prescribed for at least 6-12 weeks.
• Patients with a severe acute infection leading to hypoxia should be treated with amphotericin B followed by itraconazole.
• The antifungal treatment of progressive, disseminated histoplasmosis should be continued for up to one year.Itraconazole would seem to be more effective than voriconazole against histoplasmosis. In uncontrolled patient trials, posaconazole and isavuconazole would seem to be somewhat effective in the treatment of generalized histoplasmosis.
• Methylprednisolone (note: not concomitantly with itraconazole due to interactions) is recommended initially for 1-2 weeks for hypoxic patients.

Prevention

• Avoidance of travel to endemic regions

Causative agent and transmission

Distribution

• Coccidioidomycosis is endemic in the hot and dry areas of North America (California, Arizona and the south-western regions of the United States) and South America.
• The majority of blastomycosis infections occur in the United States. Sporadic cases have also been reported in Mexico, South America, the Middle East and India.
• Paracoccidioidomycosis is encountered in the tropical and subtropical regions of Latin America.
• These infections may affect anyone who has spent long periods in endemic regions.

Symptoms

• The incubation period of coccidioidomycosis is 1-3 weeks and that of blastomycosis up to 3 months. Symptoms of paracoccidioidomycosis may take a very long time, up to decades, to develop after transmission.
• These infections are very often asymptomatic.
• In acute coccidioidomycosis and blastomycosis, the disease spectrum ranges from a flulike illness to pneumonia. In addition to pulmonary manifestations, symptoms may involve a variety of other sites:
  • skin: maculopapular rash, erythema multiforme, erythema nodosum
  • musculoskeletal system: synovitis, bony tenderness, osteomyelitis
  • central nervous system: meningitis, hydrocephalus
  • generalised: lymphadenopathy, abdominal tenderness or masses.
• The course of paracoccidioidomycosis is usually subacute in younger persons and immunocompromised individuals. The infection is more common in adults, and it tends to run a chronic course. Pulmonary manifestations are the most common symptoms but, as with other mycoses, paracoccidioidomycosis may also affect other sites, such as the skin, mucous membranes and bones.

Diagnosis

• The diagnostic workup is the same as in histoplasmosis here.
• The laboratory receiving the fungal specimens should be alerted beforehand because transmission to laboratory personnel has been reported.