Tracey Q. Davidoff, MD, FCUCM
Coccidiomycosis, or Valley Fever, is an infection caused by the dimorphic fungi Coccidioides. Coccidioides grows as a mold a few inches below the soil surface and can remain suspended in air for prolonged periods. When inhaled, it can penetrate human airways and lung tissue causing infection.
Traditionally, this disease is called Valley fever because most cases are identified in the San Joaquin Valley, also called the Central Valley, in California. Cases have also been reported in south-central Arizona and other areas of California, southern Nevada, southwestern Utah, southern New Mexico and the Rio Grande Valley in Texas. Approximately 150,000 infections are documented yearly (Galgiani et. al., 2016), although since many infections are asymptomatic, this number is likely higher.
Recently there has been a substantial increase in the incidence of this disease within California and Arizona. In 1990, in Arizona, the incidence was 5.2 cases per 100,000, and in 2020, the incidence increased to 160.6 cases per 100,000. Similarly, in California the incidence in 1990 was 4.3 cases per 100,000, increasing to 18.1 cases per 100,000 in 2020. It is speculated that several causes may be responsible for this drastic increase. First, serologic testing has become more sensitive and more available. Second, older, presumably previously unaffected, non-immune and therefore susceptible persons have moved to the endemic area. Lastly, recent prolonged drought has made the soil more hospitable to this organism, allowing more growth and subsequent distribution into the environment. (CDC, 2013, Hector, et. al. 2011)
Risk of infection is seasonal; infection occurs during the dry season following a rainy season. In Arizona this is typically May to July and October to early December, whereas in California, infections typically occur in late spring to late fall. Patients most at risk for infection are those with impaired cellular immunity, such as those on immunosuppressive regimens, those with HIV with CD4 cell counts < 250 cells/microL, chemotherapy patients and those with some immunodeficiency syndromes. These patients are also at risk for reactivation of a previously acquired, clinically inapparent Coccidioides infection, which may be outside of the seasonal variation, or even outside of the endemic area, if the patient has moved.
Clinical manifestations of primary pulmonary Coccidioides infection generally follows one of three patterns:
Approximately 60% of cases are thought to be asymptomatic or minimally symptomatic and may not seek medical attention. (Smith, et. al. 1946) The most common manifestation in those who do seek care is focal pneumonia occurring 7-12 days after exposure. Patients generally have chest pain, cough and fever. Diffuse reticulonodular pneumonia is a less common presentation and is due to homogeneous seeding of the lungs. Some patients may be clinically stable despite the burden of disease whereas others may have severe dyspnea, respiratory failure and fungemia. Mortality is higher for this form of the disease.
Most patients will also develop a wide array of systemic symptoms which may include night sweats, headache, rash, weight loss, and fatigue. The cutaneous manifestations may include erythema nodosum, erythema multiforme or toxic erythema. Rheumatologic manifestations, which are less common, may include symmetric arthralgias of the ankles, knees and/or wrists, usually without redness or effusion.
Routine laboratory studies such as CBC, CMP, and procalcitonin are usually unremarkable. There may be a mild increase in eosinophils and ESR. Specific serologic testing for IgM and IgG is likely to be negative early in disease. CXR may show either type of pneumonia; focal pneumonia tends to be in the upper lobes and may be associated with ipsilateral hilar adenopathy and parapneumonic effusion. Nodules and thin-walled cavities may be seen in some cases. Bronchoalveolar lavage with cytologic exam may be required in severe cases.
Infection should be suspected in patients living in or traveling from an endemic area who present with the following:
Treatment is based on disease severity. Again, the majority of patients will have mild disease and improve spontaneously without evaluation and treatment. Patients with moderate disease should be treated with an anti-fungal such as fluconazole or itraconazole. Moderate disease is defined as involvement of more than one-half of a lung, persistent symptoms for more than three weeks, or loss of more than 10% of body weight. Patients at high risk or who have severe or complicated disease may require treatment with amphotericin B. These patients are generally immune suppressed either due to AIDS, transplantation, hematologic malignancy, or chemotherapy. Patients at increased risk for complications also include second or third trimester pregnancy, those who are postpartum, diabetics, the frail elderly, those of African or Filipino descent, and those being treated with anti-cytokine therapy for rheumatologic, gastrointestinal or dermatologic disease.
Although most patients will have resolution of all symptoms in one year, some patients may develop syndromes of prolonged fatigue, and pulmonary complications including nodules, cavities, and diffuse reticulonodular pneumonia.
So how does climate change affect this disease? Remember the life cycle of Coccidioides requires dry, arid soil, and the spread of disease is related to the spores carried on the wind and dust. Climate change has been increasing times of drought, aridity, dust storms, and wildfires in the areas where Coccidioides is most prevalent. (OEHHA, 2022) This directly and indirectly affects fungal proliferation, as well as the dissemination of the spores, resulting in an increase in human infection. Keep in mind also that other areas outside of the Central Valley area of California are also subject to this same climate change. Contiguous areas such as parts of San Bernadino, Los Angeles and others are also seeing increased coccidiomycosis cases, as well as the soil testing positive for the spores.
Researchers predict that climate changes causing increasing prolonged dryness and drought in the American Southwest will cause most of the area west of the Rocky Mountains to be coccidiomycosis endemic. (Gorris, et. al. 2019) Arizona has already seen this effect and cases there now outnumber those in California. (OEHHA, 2022) Other factors include dust storms related to the Santa Ana winds, earthquakes, and wildfires. The fires change the soil composition and ground cover making it more hospitable to Coccidioides. Creating fire lines by digging also disrupts soil and potentially spreads the spores. An uptick in disease prevalence has been seen in those firefighters. The Santa Ana winds coincide with the highest fire danger, which also coincides with the seasonality of Valley fever, making a “perfect storm” for increasing the incidence of this disease in humans in the Southwest, and beyond. With increasing incidence, the Urgent Care provider needs to be aware of this disease, especially in those patients presenting from affected areas and those near affected areas, as Valley fever is no longer confined to the Central Valley of California anymore.