Soil to Lungs: The Expanding Threat of Valley Fever

Coccidioides is a fungus found in soil that causes coccidioidomycosis, commonly called valley fever. The increasing trend and potential geographical expansion due to climate change set the stage for a deeper exploration into the diagnosis, treatment, and prevention of valley fever.

These fungi reside in the soil and, under specific conditions such as disturbance by wind, agricultural activities, or construction, spores become airborne to infect humans and animals. When inhaled by humans or animals, these spores can cause infection. This lifecycle and mode of transmission underpin the disease's etiology, detailing how environmental interactions and human activities contribute to the spread of Cocci.

“About 20,000 cases are reported in the United States each year, mostly from Arizona and California,” according to the Centers for Disease Control and Prevention (CDC). “The number of cases is increasing. The fungus might also live in similar areas with hot, dry climates, and the geographic range may be expanding because of climate change. Public health officials and researchers continue to investigate to see if it is found in other areas.”¹

Symptoms include fatigue, cough, fever, shortness of breath, headache, night sweats, muscle aches or joint pain, and rash on the upper body or legs. Valley fever is often misdiagnosed as an infection caused by a bacteria or virus, leading to delays in the necessary antifungal treatment and sometimes contributing to the unnecessary use of other medicines. Those who develop severe infections or whose infections spread to other parts of their body often require hospitalization and may need to take antifungal treatment for a long time.

Challenges in Diagnosis

John Galgiani, MD, Professor of Medicine at the University of Arizona College of Medicine in Tucson, and director of The Valley Fever Center for Excellence at the University of Arizona elaborates on these complex symptoms.

“While two-thirds of infections may not cause significant illness, those affected can experience weeks to months of respiratory issues such as chest pain and cough, fever, night sweats, weight loss, and notably, profound fatigue that can severely impact daily functioning. Beyond these, the disease might manifest through immune responses, including rashes, joint pains, and muscle aches, which could be mistaken for other conditions.”

According to recent CDC reports, cocci, along with other fungal infections like histoplasmosis and blastomycosis, showed a decrease in cases in the years 2019 and 2021, attributed to misdiagnoses due to symptom similarities with COVID-19. The pandemic likely impacted healthcare-seeking behavior, public health reporting, and the clinical management of these fungal diseases. Prioritizing fungal disease consideration and diagnosis could improve patient outcomes.²

“We could do better with diagnosing across the board year after year, I think statistics show that in the state of Arizona, appropriate testing in primary care and emergency rooms data that were generated in urgent care suggests that before 2020, it was less than 10% of people who should be tested were tested,” according to Galgiani. “I still think we should be up to 60% or 70% of testing those people so the effects that were illustrated by the CDC are swamped by what we could do better, just going forward on regular practice.”

Treatment

Shaun Yang, PhD, Clinical Microbiologist at UCLA Medical Center, Director of Molecular Microbiology and Pathogen Genomics, and Associate Professor at the Department of Pathology and Laboratory Medicine offers insights into their diagnosis methods:

• Serology Testing: This method checks for antibodies against a specific fungus in the blood. A positive result suggests an active fungal infection.
• Culture Testing: This test involves taking respiratory samples, like sputum, and growing the fungus in a lab. The successful growth of the fungus, usually within 2 to 3 days, helps to identify and confirm infection.
• Histopathology: Used in severe cases, such as when cavitary lung lesions are present. A lung biopsy is examined microscopically to directly observe fungal elements in the tissue, providing a direct confirmation of fungal infection.

Other methods include:

• Antigen Detection: This test detects fungal antigens in bodily fluids. It can be useful in delayed antibody production or immunocompromised patients who may not mount a robust antibody response.
• Molecular Tests: Polymerase Chain Reaction (PCR) tests can detect fungal DNA in a sample, offering a rapid and specific diagnosis.
• Imaging Tests: Chest X-rays or CT scans can provide supportive evidence of cocci. These tests can reveal characteristic changes in the lungs or other organs.

Vaccine Research and Development

Currently, there is no human vaccine for valley fever, although research has been ongoing since the 1960s. People who recover from valley fever typically have immunity against future infections. Previous vaccine attempts, including one tested in the 1980s, did not provide protection and led to side effects like swelling at the injection site.

The most recent vaccine research, as reported in a study by the Journal of Fungi concludes that exploring a live, gene-deletion vaccine candidate against cocci shows promise, with potential for human use. Its development is based on scientific and preliminary evidence, emphasizing the need for a public-private partnership to advance the vaccine. Given cocci's public health and economic impact, combining private innovation with public funding is crucial, especially for an orphan disease. The development plan for this vaccine candidate aims to address a significant healthcare challenge and may guide future vaccine development projects.³

Regional Focus

Arizona

Surveillance conducted by the Arizona Department of Health Services (ADHS) reveals concerning trends regarding valley fever. Data shows it is one of the most prevalent infectious diseases in the state. Over the last decade, the incidence of reported valley fever in Arizona has shown a notable increase, rising from 74.9 cases per 100,000 population in 2007 to 89.3 cases per 100,000 population in 2016. These findings highlight the urgent need for continued vigilance and proactive measures to address the growing threat of valley fever in Arizona.⁴

In December 2023, Arizona Senators Mark Kelly, and Kyrsten Sinema, along with Congressman David Schweikert, introduced the Finding Orphan-disease Remedies with Antifungal Research and Development (FORWARD) Act, bipartisan legislation that supports research initiatives to combat valley fever. ⁵

California

In 2023, the California Department of Public Health noted an increase in cocci cases, higher than any year since the disease was required to be reported individually in 1995. ⁶

“Over the past 3 decades, the incidence of valley fever has increased tenfold, which is remarkable,” explains Yang. “Reflecting on my early days in microbiology practice over 15 years ago, encountering cocci in our laboratory was rare, with occurrences ranging from 1 to 2 cases a month. Now, cocci detections have become routine, with 2 to 3 cases reported weekly. This significant rise over approximately 2 decades underscores the dramatic impact of climate change on the prevalence of this fungal disease.”

In California, the Central Valley remains a hotspot for cocci, but the disease is expanding its reach to include the Northern San Joaquin Valley, Central Coast, and Southern California. Healthcare providers should make inquiries about patients' travel histories and occupational exposures, especially to areas known for high incidence rates or to environments with substantial outdoor dust and dirt.

Climate Change

The impacts of climate change and natural disasters on fungal diseases are not fully understood. Global temperatures are enabling fungi to become more heat-resistant, increasing their disease-causing potential. Climate change is leading to the emergence of fungal pathogens and allows fungi to survive in new environments, even spreading some fungal species to new regions. Climate change also increases the frequency and severity of natural disasters, which can lead to more fungal disease outbreaks and the spread of fungal pathogens. Increased awareness, research, funding, and policy initiatives are needed to address these issues.⁷

“There are some well-constructed prediction models on how the expected change in temperature across the country and precipitation across the country predicts that by the end of the 21st century, the endemic range will reach the Canadian border, much involved in a large portion of the western US,” Galgiani states. “It may be more complicated than that, even if those predictions of the of temperature and precipitation are correct because there's also the ecology of the infection in rodents and other factors, soil composition, and things we don't understand very well.”

Since this fungus is sensitive to climate extremes it does not thrive in regions of the US that get year-round rain, nor can it withstand persistent drought. Particularly in California experiencing heavy rainfall after years of being in drought, the fungi are thriving, and humans will be victims of the unforeseen consequences of this disease.

Prevention Strategies

It is difficult to avoid breathing in the fungus Coccidioides in areas where it is common in the environment. People who live in these areas can try to avoid spending time in dusty places as much as possible. People who are at risk for severe valley fever, such as people who have weakened immune systems, pregnant women, people who have diabetes, or people who are Black or Filipino, may be able to lower their chances of developing the infection by trying to avoid breathing in the fungal spores.

“The group that is most at risk of complications is immunosuppressed people. Because organ transplants and cases of HIV infection,” says Galgiani for example. “Older individuals have more of a problem managing this disease than younger individuals. diabetics have more complications than non-diabetics, women in their second and third trimester, especially during pregnancy.”

The incidence and spread of valley fever underline the need for research, public health strategies, and the development of interventions. Addressing the challenges of valley fever requires diagnosis, treatment, preventive strategies, and vaccine development. Moreover, an approach that encompasses research, education, and policy reform is vital for mitigating infection risks and safeguarding public health against this threat.

References

1. CDC. Valley Fever (Coccidiomycosis) Awareness. Published January 23, 2024. Accessed April 3, 2024. https://www.cdc.gov/fungal/features/valley-fever.html
2. CDC. Surveillance for Coccidioidomycosis, Histoplasmosis, and Blastomycosis During the COVID-19 Pandemic — United States, 2019–2021. Published March 21, 2024. Accessed April 2, 2024.Accessed April 3, 2024. https://www.cdc.gov/mmwr/volumes/73/wr/mm7311a2.htm?s_cid=mm7311a2_w
3. Galgiani J, Shubitz L, Orbach M, et. al. Vaccines to Prevent Coccidioidomycosis: A Gene-Deletion Mutant of Coccidioides Posadasii as a Viable Candidate for Human Trials. Published August 10, 2022. Accessed April 3, 2024. https://www.mdpi.com/2309-608X/8/8/838
4. Arizona Department of Health Services. Accessed April 3, 2024. https://www.azdhs.gov/preparedness/epidemiology-disease-control/valley-fever/index.php
5. To support endemic fungal disease research, incentivize fungal vaccine development, discover new antifungal therapies and diagnostics, and for other purposes. Published December 11, 2023. Accessed April 3, 2024. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.kelly.senate.gov/wp-content/uploads/2023/12/Bill-Text-FORWARD-Act-of-2023.pdf
6. Substantial Rise in Coccidioidomycosis in California: Recommendations for California Healthcare Providers. State of California—Health and Human Services Agency California Department of Public Health. Published January 18, 2024. Accessed April 3, 2024. https://www.cdph.ca.gov/Programs/OPA/Pages/CAHAN/Substantial-Rise-in-Coccidioidomycosis-in-California-Recommendations-for-California-Healthcare-Providers.aspx
7. Seidel D, Wurster S, Jenks J, Sati H, Gangneux J, et. al. Impact of climate change and natural disasters on fungal infections. The Lancet. Published March 19, 2024. Accessed April 3, 2024. https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(24)00039-9/fulltext