Table of Contents
Epidemiology of Coccidiomycosis
Coccidiomycosis is endemic in areas where the hot summer or mild winter prevails with an annual rainfall of 10 – 50 cm. The causative organism is found in alkaline soil, about 10 – 30cm below the surface. It remains dormant during dry spells and develops into a mold with long filaments during the rainy season.
These filaments break off into tiny pieces leading to spore formation. The spores are swept away during construction, farming and natural disasters, such as earthquakes and windstorms.
Coccidiomycosis is endemic in Southwestern United States, northern Mexico, parts of Central and South America.
The population working in an agriculture setup or at construction sites is at higher risk of developing the disease. Pregnant females, especially those in their last trimester, are more prone to get the disseminated infection. Similarly, tourists traveling to the endemic areas may also contract the disease.
Immunocompromised patients, such as those on immunosuppressants, steroids or have HIV, are always at risk of getting the infection. Diabetics and individuals who underwent thymectomy are also included in the high-risk group.
Life Cycle of Coccidioides
The life cycle of the Coccidioides begins with dormant barrel shaped cells known as arthroconidia measuring 8 – 30μm. These are the degenerative form of hyphae during prolonged dry spells. These arthroconidia form spores which are lightweight structures, swept away during farming, construction or during natural calamities.
These spores are inhaled, thus land in the alveoli. Inside the alveoli, they develop into spherules, which are doubled walled structures measuring 20 – 200μm. Within the next 48 – 72 hours, these spherules result in the formation of septa and endospores.
When these spherules rupture, the endospores are released, which infect other body tissues causing dissemination of the disease. The endospores again mature into spherules and the parasitic life cycle is completed.
In certain cases, nodules are formed around the spherules which, when burst into alveoli, cause characteristic chest pain, cough and hemoptysis. Immuno-compromised people are more prone to get blood spread infection.
Pathogenesis of Coccidiomycosis
The innate immune cells are particularly involved in the defense against the organism. This activates the T lymphocytes. The inflammatory cytokines, specifically the gamma interferon, are released causing the destruction of the organism.
Any impairment in the cell-mediated immunity results in incomplete evacuation of the organism from the body. The phagocytized arthroconidia, if drained into lymph vessels, may cause lymphangitis.
In addition to the activation of cell-mediated immunity, these organisms also activate the complement pathway, which promotes the chemotaxis of the eosinophils and the neutrophils. The pathogenicity of the organism is particularly related to its ability to bypass phagocytosis.
The non-respiratory transmission involves direct invasion into the skin causing local lymph nodes infection. This is, however, a self-limiting condition, which resolves spontaneously.
Signs and Symptoms of Coccidiomycosis
The incubation period of Coccidioides is 10 – 16 days. While more than half of the infected people remain asymptomatic, others develop signs and symptoms. The primary infection most of the time starts with respiratory symptoms of a cough and breathlessness. The organism causes bronchitis and pneumonia which resolves in a few weeks.
In endemic areas, however, Coccidioides result in community-acquired pneumonia in 20% of the individuals. Other notable symptoms include lethargy, muscle and joint ache, fever, rash and headaches. The classic triad of the disease comprise of fever, erythema nodosum and joint pain, also termed as ‘desert rheumatism.’
The acute infection is also known as Valley fever. Around 5% of the infected individuals do not recover from the acute infection and go into a chronic state. The morbidity and mortality rate increases in the chronic state.
Typical features of chronic disease include a cough, fever, night sweats, weight loss, osteomyelitis and meningitis. The disseminated form of the disease is more severe resulting in multiple skin lesions, inflammation of the vital organs, leading to death. The figure shows the skin lesion in disseminated infection.
Management of Coccidiomycosis
Coccidiomycosis is diagnosed with the help of clinical history and investigations. It is important to differentiate coccidiomycosis from bacterial infections such as bacterial pneumonia or bacterial meningitis.
The initial investigations which can be performed include culture and staining of body fluids and exudates with Papanicolaou or Grocott’s methenamine silver stains which demonstrate the presence of spherules.
Tube precipitin (TP) assay, complement fixation assays and enzyme-linked immunosorbent assay (ELISA) are also used. TP assay is very specific for coccidiomycosis, while ELISA is more sensitive and is therefore used as a screening tool.
CSF findings help in the diagnosis of meningitis. Similarly, a chest x-ray may point towards the underlying lung disease. The gold standard is DNA detection of coccidioides through polymerase chain reaction (PCR).
The treatment plan of coccidiomycosis involves azoles as a first line of therapy. However, due to its teratogenicity, it is not recommended in pregnancy or to lactating females. Amphotericin B is reserved for severe worsening cases which involve the vital organs.
Follow-up visits on a regular basis are required. These are to monitor the adverse effects of antifungal treatment and the response to therapy after every 1 – 3 months, to be continued for a period of 1 – 2 years, or until the resolution of the disease.