Coccidioidomycosis ( Coccidioides Species)

Etiology

Coccidioidomycosis (valley fever, San Joaquin fever, desert rheumatism, coccidioidal granuloma) is caused by Coccidioides spp., a soil-dwelling dimorphic fungus. Coccidioides spp. grow in the environment as spore-bearing (arthroconidia-bearing) mycelial forms. In their parasitic form, they appear as unique, endosporulating spherules in infected tissue. The 2 recognized species, C. immitis and C. posadasii, cause similar illnesses.

Epidemiology

Coccidioides spp. inhabit soil in arid regions. C. immitis is primarily found in California's San Joaquin Valley. C. posadasii is endemic to southern regions of Arizona, Utah, Nevada, New Mexico, western Texas, and regions of Mexico and Central and South America.

Population migrations into endemic areas and increasing numbers of immunosuppressed persons have caused coccidioidomycosis to become an important health problem. From 2000 to 2012, there were 3,453 incidents of pediatric coccidioidomycosis cases reported in California, about 9.6% of the total coccidioidomycosis cases. During the same time period, there were 1,301 hospitalizations and 11 deaths associated with coccidioidomycosis in the California pediatric population. Case and hospitalization rates per 100,000 population increased from 0.7 to 3.9 and from 0.2 to 1.2, respectively. These case and hospitalization rates were highest in males, those in the 12-17 age group, and residents of the California endemic region.

Infection results from inhalation of aerosolized spores. Incidence increases during windy, dry periods that follow rainy seasons. Seismic events, archaeologic excavations, and other activities that disturb contaminated sites have caused outbreaks. Person-to-person transmission does not occur. Rarely, infections result from spores that contaminate fomites or grow beneath casts or wound dressings of infected patients. Infection has also resulted from transplantation of organs from infected donors and from mother to fetus or newborn. Visitors to endemic areas can acquire infections, and diagnosis may be delayed when they are evaluated in nonendemic areas. Spores are highly virulent, and Coccidioides spp. are potential agents of bioterrorism (see Chapter 741 ).

Pathogenesis

Inhaled spores reach terminal bronchioles, where they transform into septated spherules that resist phagocytosis and within which many endospores develop. Released endospores transform into new spherules, and the process results in an acute focus of infection. Endospores can also disseminate lymphohematogenously. Eventually, a granulomatous reaction predominates. Both recovery and protection upon reexposure depend on effective cellular immunity.

Children with congenital primary immunodeficiency disorders may be at increased risk for infection; these disorders include interleukin-12Rβ1 deficiency, interferon-γR1 deficiency, and STAT1 gain-of-function mutations.

Clinical Manifestations

The clinical spectrum ( Fig. 267.1 ) encompasses pulmonary and extrapulmonary disease. Pulmonary infection occurs in 95% of cases and can be divided into primary, complicated, and residual infections. Approximately 60% of infections are asymptomatic. Symptoms in children are often milder than those in adults. The incidence of extrapulmonary dissemination in children approaches that of adults.

Primary Coccidioidomycosis

The incubation period is 1-4 wk, with an average of 10-16 days. Early symptoms include malaise, chills, fever, and night sweats. Chest discomfort occurs in 50–70% of patients and varies from mild tightness to severe pain. Headache and/or backache are sometimes reported. An evanescent, generalized, fine macular erythematous or urticarial eruption may be seen within the first few days of infection. Erythema nodosum can occur (more often in women) and is sometimes accompanied by an erythema multiforme rash, usually 3-21 days after the onset of symptoms. The clinical constellation of erythema nodosum, fever, chest pain, and arthralgias (especially knees and ankles) has been termed desert rheumatism and valley fever. The chest examination is often normal even if radiographic findings are present. Dullness to percussion, friction rub, or fine rales may be present. Pleural effusions can occur and can become large enough to compromise respiratory status. Hilar and mediastinal lymphadenopathy are common ( Fig. 267.2 ).