Paracoccidioidomycosis
Also known as: South American Blastomycosis, Paracoccidioides Infection
Paracoccidioidomycosis is a systemic granulomatous mycosis caused by thermally dimorphic fungi of the genus Paracoccidioides, and it is the most important systemic endemic mycosis of Latin America. It occurs mainly in rural men who work with soil, as chronic pulmonary disease and mucocutaneous lesions, and less often as an acute or subacute juvenile form with lymphoreticular involvement. It is a neglected disease, with long delays in diagnosis, with fibrotic sequelae in many survivors.
| Feature | Description |
|---|---|
| Species | Paracoccidioides brasiliensis (species complex with phylogenetic groups S1, PS2, PS3, and PS4; Paracoccidioides americana, Paracoccidioides restrepiensis, Paracoccidioides venezuelensis in some proposals) and Paracoccidioides lutzii (Central West and Amazon Brazil, and Bolivia and Ecuador) |
| Mould phase | At 25 to 30 degrees Celsius, slow growing (3 to 4 weeks), white to tan colonies with hyaline septate hyphae and microconidia and chlamydospores; non specific |
| Yeast phase | At 37 degrees Celsius and in tissue, round to oval thick walled yeasts 5 to 60 micrometres with multiple narrow necked buds arranged around a central mother cell ("ship's wheel", "pilot wheel", or "Mickey Mouse ears" forms) |
| Culture | Slow; enriched media (blood agar, brain heart infusion) at 37 degrees Celsius; mould culture is hazardous |
| Identification | Microscopy is typical; sequencing, and mass spectrometry confirm; the genus is detected in soil |
| Aspect | Details |
|---|---|
| Geography | Latin America from Mexico to Argentina, with about 80 percent of cases in Brazil (south, southeast, and Central West), and then Colombia, Venezuela, Argentina, Ecuador, and Peru; not reported in the Caribbean |
| Reservoir | Moist, acidic, forest soil with coffee, tobacco, and sugar cane farming; the armadillo (Dasypus novemcinctus) is a carrier |
| Population | Rural male workers aged 30 to 60 years, in a ratio of about 10 to 15 men per woman (oestrogen inhibits the conversion of mould to yeast); children and the young for the juvenile form |
| Risk factors | Tobacco and alcohol use, malnutrition, agricultural work, and soil disturbance; HIV (the disease is an opportunistic but uncommon infection), and transplant |
| Latency | Infection occurs early in life and disease appears after many years of latency, so it may be diagnosed in migrants who left endemic regions years before |
| Transmission | Inhalation; not person to person |
Inhaled conidia convert to yeasts in the lung and are phagocytosed. Dissemination occurs through lymphatics and blood. A T helper 1 response with interferon gamma and tumour necrosis factor alpha forms compact granulomas and controls disease; a T helper 2 and T helper 17 response with poor granuloma organisation, eosinophilia, high IgE, and high antibodies marks the severe juvenile form. The glycoprotein gp43 is the main adhesin and the main antigen. Fibrosis after healing causes sequelae, such as pulmonary fibrosis and laryngeal stenosis.
| Form | Features |
|---|---|
| Acute or subacute (juvenile) form | About 3 to 5 percent, in children and adults below 30 years (equal in both sexes); a reticuloendothelial syndrome of fever, weight loss, generalised lymphadenopathy (with suppuration and fistulae), hepatosplenomegaly, bone marrow involvement, skin lesions, abdominal masses, and obstructive jaundice, with eosinophilia; pulmonary disease is uncommon |
| Chronic (adult) form | Over 90 percent, in men aged 30 to 60 years |
| Unifocal chronic | Only one organ involved, usually the lung |
| Multifocal chronic | Lungs, mucosa, skin, lymph nodes, and adrenals |
| Pulmonary | Chronic cough, dyspnoea, weight loss, and fever; bilateral perihilar infiltrates (a "bat wing" pattern), reticulonodular infiltrates, and cavities, with emphysema and fibrosis in later disease; the lung disease mimics tuberculosis and is present in over 80 percent |
| Mucocutaneous | Painful oral and pharyngeal ulcers with a granular "mulberry like" (moriform) surface and haemorrhagic dots (Aguiar Pupo stomatitis), on the gums, palate, and tongue; with tooth loosening, dysphagia, and hoarseness; laryngeal disease with stenosis; skin ulcers, verrucous plaques, and nodules, especially on the face |
| Lymph nodes | Cervical and supraclavicular adenopathy, with suppuration |
| Adrenal | Bilateral enlargement and destruction, with Addison disease (hypotension, hyperpigmentation, hyponatraemia, and hyperkalaemia) in 5 to 15 percent |
| Central nervous system | Neuroparacoccidioidomycosis in 10 to 27 percent: pseudotumoural granulomas with seizures, headache, focal deficits, and rarely meningitis; spinal cord disease |
| Other | Bone, joint, intestinal, genital, ocular, and hepatic disease |
| Sequelae | Pulmonary fibrosis and chronic respiratory failure with cor pulmonale, laryngeal and tracheal stenosis, microstomia, adrenal insufficiency, and hydrocephalus |
| HIV coinfection | A more severe, disseminated, juvenile like pattern, with high mortality |
| Condition | Points that separate it |
|---|---|
| Tuberculosis | Acid fast bacilli; coexists in 10 percent |
| Histoplasmosis and other endemic mycoses | Yeast morphology and culture |
| Leishmaniasis (mucocutaneous) | Amastigotes, polymerase chain reaction, and Montenegro skin test |
| Squamous cell carcinoma (oral and laryngeal) | Biopsy |
| Lymphoma and Hodgkin disease | Lymph node biopsy |
| Sarcoidosis and granulomatosis with polyangiitis | Histology and autoantibodies |
| Syphilis, sporotrichosis, and chromoblastomycosis | Serology and culture |
| Test | Details |
|---|---|
| Direct microscopy | Potassium hydroxide 10 percent or calcofluor white on sputum, pus, scrapings, and bronchoalveolar lavage shows yeasts with multiple budding (pilot wheel forms); positive in 60 to 90 percent, and the fastest test |
| Histology | Granulomas with yeasts on methenamine silver or periodic acid Schiff stains; haematoxylin and eosin shows poorly formed or compact granulomas |
| Culture | 2 to 4 weeks (up to 8), positive in under 50 percent |
| Serology | Double immunodiffusion with the gp43 antigen (sensitivity 80 to 90 percent; specificity high); Paracoccidioides lutzii requires its own antigen because the common gp43 test may be negative; enzyme immunoassay and immunoblot; titres fall with treatment and are used to follow response |
| Molecular tests | Polymerase chain reaction on tissue and respiratory specimens |
| Imaging | Chest radiograph and computed tomography; brain magnetic resonance imaging; abdominal imaging for nodes and adrenals |
| Other | Cortisol and corticotrophin stimulation, laryngoscopy, and HIV test |
| Situation | Regimen |
|---|---|
| Mild to moderate disease | Itraconazole 200 mg once daily for 9 to 18 months (for 12 to 24 months in some regimens); taken with food |
| Severe disease | Liposomal amphotericin B 3 to 5 mg per kg once daily (deoxycholate 0.7 to 1 mg per kg daily) for 2 to 4 weeks until improvement, then itraconazole 200 mg daily or trimethoprim sulfamethoxazole to complete 2 years |
| Alternative to itraconazole | Trimethoprim sulfamethoxazole (trimethoprim 160 to 240 mg with sulfamethoxazole 800 to 1200 mg) every 12 hours orally for 12 to 24 months (in severe disease, 18 to 24 months), with a lower relapse in the short course and a higher adverse event rate |
| Voriconazole | 400 mg twice daily on day 1, then 200 mg twice daily, for at least 6 to 12 months; similar efficacy to itraconazole in a trial, with more visual and liver effects |
| Fluconazole | 200 to 400 mg daily is less effective and more likely to relapse, and is used for central nervous system disease or when other drugs are not tolerated |
| Sulfadiazine | 100 mg per kg per day in four doses (maximum 6 g), an alternative where available, with renal care |
| Central nervous system | Trimethoprim sulfamethoxazole (high doses, with a total of 2 years or more) or voriconazole 200 mg twice daily after loading; amphotericin B in severe disease; corticosteroids for oedema |
| Adrenal insufficiency | Hydrocortisone 15 to 25 mg daily in divided doses and fludrocortisone 0.05 to 0.1 mg daily; adrenal function can remain impaired despite cure |
| Respiratory failure and laryngeal oedema | Prednisone 0.5 to 1 mg per kg daily for a short period in severe cases (with antifungal cover), and tracheostomy for stenosis |
| HIV | Amphotericin B induction, then itraconazole or trimethoprim sulfamethoxazole, with antiretroviral therapy and secondary prophylaxis (trimethoprim sulfamethoxazole) until CD4 above 200 |
| Cure criteria | Clinical, radiological, and serological response, with stable negative or low titres (1 in 2 or below) for at least 2 years |
| Follow up | Serology every 3 months, with imaging, for at least 2 years after therapy; relapse in 5 to 20 percent, so long term follow up |
Most patients respond to treatment, with mortality of about 3 to 5 percent in treated adults, and higher in the juvenile form, in HIV, and in people with severe respiratory disease or malnutrition. Fibrotic sequelae, which are irreversible, develop in 50 percent of those with pulmonary disease. Delays in diagnosis worsen the outcome.
No vaccine is available. Avoid soil disturbance and use masks in rural work in endemic areas, stop smoking, and diagnose and treat early. Migrants from endemic regions with compatible signs are considered for the disease years after leaving.
