Coccidioidomycosis [kok-sid-ee-oi-doh-mahy-koh-sis]

1. Coccidioidomycosis[kok-sid-ee-oi-doh-mahy-koh-sis] Also known as: “Cocci,” Valley Fever, & San Joaquin Fever

2. Coccidioides immitis: Lifecycle phases

3. History • 1892: First reported as disease • 1920-1930 • Soil recognized as reservoir for agent • 1987 • CDC adds coccidioidomycosis to annual survey of HIV-associated diseases

4. History • 1991-1995 • Incidence increases tenfold in San Joaquin Valley, CA The number of new cases of coccidioidomycosis identified by serologic testing at the Kern County Public Health Laboratory (source of data: Dr. Ron Talbot). The asterisk indicates a projected number. Emerging Infectious Diseases. Coccidioidomycosis: A reemerging disease. Vol 2 (3). July-Sept. 1996.

5. Economic Impact • Infection is costly • Time lost from work • Direct medical costs • 1990: Kern County, CA • Cost more than $66 million • Infection can be widespread

6. Morbidity/Mortality • Two forms in humans • 60% asymptomatic • Only identified with positive skin test • 40% mild to severe disease • Can be fatal • Immuno-compromised persons highly susceptible to serious infection • Difficult to assess morbidity in animals

7. Human Transmission • Direct inhalation of C. immitis spores • Present in contaminated soil and dust • Only established mode of transmission • Not person-to-person • Not animal-to-person • Increased incidence after disturbance

8. Human Transmission • Natural disturbances • Dust storms • Earthquakes • Human disturbances • Construction sites • Archaeological digs http://vfce.arl.arizona.edu http://griefnet.org

9. Clinical Signs: Primary Form • Incubation period: 1-4 weeks • Usually subclinical • Fever, chills, cough, sore throat • Chest pain • Nodular lesions • Nonspecific respiratory symptoms • Complications less common • Pneumonia, pleural effusion

10. Clinical Signs: Disseminated Form • Severe form of disease • Weeks to months to years after primary infection • Symptoms include • Low-grade fever, anorexia, weight loss • Muscle aches and stiffness, weakness • Excessive sweating • Widespread focal lesions • In HIV-infected persons • Mucopurulent or bloody sputum

11. Diagnosis • Differentials • Tuberculosis • Clinical • Coccidioidomycosis should be considered • In endemic areas • Following a dust/soil disturbance • With characteristic clinical signs

12. “Cocci” Endemic Areas The geographic distribution of coccidioidomycosis. Cross-hatching indicates the heavily disease-endemic area, single hatching, the moderately disease-endemic area. Emerging Infectious Diseases. Coccidioidomycosis: A reemerging Infectious Disease. Vol. 2 (3). July-September 1996

13. Diagnosis • C. immitis spherules visualized in • Sputum, pleural fluid, cerebrospinal fluid or exudates from draining lesions • Complement fixation • IgG anticoccidioidal antibodies • Titer 1:4 = current or recent infection • Titer 1:32 = increased risk of extrapulmonary dissemination • Skin test of epidemiological value

14. Treatment • Primary coccidioidomycosis • Treatment generally unnecessary • Severe/chronic coccidioidomycosis • Antifungal agents effective • Prognosis generally good • Disseminate coccidioidomycosis • May require invasive or long-term therapy • Prognosis poor to guarded

15. Vaccination • No effective immunization available • Efforts being made to develop vaccine • Precautionary measures should be taken to avoid infection • Reduce exposure to soil and dust • Man and animal • Of particular importance in endemic areas

16. Acknowledgments Author: Co-author: Reviewer: Jean Marie Gladon, BS James Roth, DVM, PhD Bindy Comito Sornsin, BA

17. Valley Fever Vaccine Project:where they’re headed next... Valley Fever Vaccine Project (VFVP)

18. Goals of Vaccine Project • Identify safe and effective acellular vaccine for prevention of coccidioidomycosis • Evaluate the vaccine in humans • Find a commercial partner Valley Fever Vaccine Project

19. The good news is... The vaccine is in hand! Ag2/PRA106 + CSA chimeric fusion protein Valley Fever Vaccine Project

20. Development Budget 100,000 50,000 1,200,000 100,000 75,000 55,000 180,000 440,000 20,000 400,000 $2,620,000 Project Activity 05-06 • Pilot Manufacturing • Formulation • GMP Manufacturing • Fill/Finish • Stability/analytical • Toxicology • Primate trials • UCSF • Regulatory expenses • Phase 1 trial Valley Fever Vaccine Project

21. Supporting Organizations • CHCF • State of California (Ashburn) • CDC (via Congressman Thomas) • VFVPA & Rotary & VFVF • Kern County • NIAID (genome project) Valley Fever Vaccine Project

22. Overall Status • The VFVP has met its research goals • We have a good, immunogenic vaccine • We have a plan that takes us to human trials • We have expectations of success but... • We need time, effort & continued financial support to reach Phase 1 Valley Fever Vaccine Project

23. Valley Fever Cost Effectiveness - 2001 • Children: save 1.9 quality adjusted life day(QALD), save $33/person • Adults: save 0.5 QALD at cost of $62k per QA Life year • Comparable to other vaccines • Assumes $180/series of 3 vac. • Dissemination rate 0.038% • <200k cases/yr =“orphan disease”

24. COCCIDIOIDOMYCOSIS Reported cases, United States* and U.S. Territories, 2002 *In the United States, coccidiodomycosis is endemic in the southwestern region. However, Cases have been reported in other states, usually among travelers returning from areas of endemic disease.

25. COCCIDIOIDOMYCOSIS Number of reported cases, United States* and U.S. Territories, 2003 *In the United States, coccidiodomycosis is endemic in the southwestern states. However, cases have been reported in other states, usually among travelers returning from areas in which the disease is endemic.

32. (As of 3/22/2007)