3/16/16 COCCIDIOIDOMYCOSIS COCCIDIOIDOMYCOSIS COCCIDIOIDOMYCOSIS COCCIDIOIDOMYCOSIS COCCIDIOIDOMYCOSIS COCCIDIOIDOMYCOSIS. Selected References

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1 10 MARCH 2006 Updated 5 June 2008 Updated 11 February 2011 Updated 4 March 2016 Herbert Boro, M.D., F.A.C.P. Selected References 1. Fiese, Marshall J Coccidioidomycosis. Charles C. Thomas. 253 pp. 2. Galgiani, John Coccidioidomycosis. West. J. Med : SELECTED REFERENCES 3. Galgiani, John, et al. Practice Guideline for the of Coccidioidomycosis. Infectious Diseases Society of America. Clin. Infect. Dis. Apr., (4): Selected References 4. Galgiani, John. Coccidioidomycosis. December, 2015 in UpToDate.com SELECTED REFERENCES 5. Johnson, Royce H. and Hans E. Einstein. Coccidioidal Meningitis. Clin. Inf. Dis. January, : Pappagianis, Demosthenes. Serologic Studies in Coccidioidomycosis. Seminars in Respiratory Infections. Dec., (4): n Earliest descriptions n n Distribution of fungus and disease n Epidemiology n Diagnosis n 1

2 Earliest descriptions n 1891 first case was Domingo Ezcura, an Argentine soldier described by Posadas and Wernicke n 1893 first U.S. case was Azores immigrant Joas Silverra described by Rixford (Stanford) n >1000 years ago is oldest case in aboriginal Indian in Arizona n Coccidioides immitis/posadasii is dimorphic arthrospores in soil and spherules in tissue n Airborn arthrospores are inhaled from dust in endemic areas n Arthrospores germinate into spherules that release endospores after rupture LIFECYCLE (U. of Arizona, Tucson) n Local pneumonia ensues. n Granulomatous model of infection follows: endospores reach regional lymphatics à thoracic duct/left subclavian vein à hematogenous dissemination 2

3 n The majority of patients recover without medical care n 5% of patients will have disseminated infection: skin > lymph nodes > bones/ joints > occult/miliary > meninges > elsewhere n Lung infection can mimic any pattern of involvement: consolidation, effusion, interstitial, cavitary, mass, nodule, atelectasis n Lung complications include primary progressive pneumonia, cavity formation (may bleed/rupture/superinfect), fistulization n All people are susceptible to inhalation infection n Risk of pneumonia severity and dissemination increase with pigmented race (black and Filipino high), diabetes m., late pregnancy, HIV (CD4 < 250), immunosuppressive Rx (steroid and chemotherapy), cachexia, extremes of age and malignancy 3

4 Distribution of fungus and disease n Southwestern U.S., Mexico, Central America, S. America n Lower Sonoran lifezone (kangaroo rat and Joshua tree, rainfall 5-20 inches, hot summers) n Travel and exportation cause worldwide pseudoexposure Epidemiology n Cases more common summer and early fall but may be seen year-round n Cases more common men than women n Rain followed by wind causes dust with spores to blow n 1977 enormous dust storm: S.F. cases 4

5 Epidemiology n Incubation is 7-20 days n The disease is under-reported to public health n This is not contagious Diagnosis n Patients present with fever/sweats, cough, weight loss n Skin manifestations pre-dissemination are toxic eruptions, e. nodosum and e. multiforme n Dissemination symptoms relate to sites of involvement Diagnosis n Maintain an idex of suspicion for all patients with pneumonia n Obtain a CXR: anything is consistent, but watch for regional adenopathy n Seek specimens for fungal culture Diagnosis n Obtain tissue for pathology; consider special stains n Send serology to U.C., Davis precipitins are IgM complement fixation are IgG both are screened by immunodiffusion 5

6 n Majority of uncomplicated pneumonias are self-limited and require no Rx unless symptoms are severe/ persistent n Complicated pneumonia needs Rx Primary persistent/progressive: be aggressive Cavitation may need resection (bleeding or rupture) Diffuse pneumonia/ards: be aggressive Pleural effusions respond conservatively n Dissemination always needs Rx Skin/Nodes respond to triazoles Bones/joints respond to triazoles itraconazole may be best Meningitis suppresses with triazoles lifelong, while intrathecal amphotericin B has 50% chance for cure n Solid organ dissemination needs extended treatment, usually with triazoles n SURGICAL therapy is useful to drain abscesses and to debulk inflammatory debris 6

7 n Amphotericin B Deoxycholate (original formulation) Liposomal Lipid complex Cholesteryl sulfate n Triazoles Miconazole Ketoconazole Fluconazole Itraconazole Voriconazole Posaconazole limited availability Pipeline of additional azoles n Nikkomycin Z not yet in phase II. n Cocci Study Group has investigational rights now. Vaccine Trial n 1981 U.S. Naval vaccine trial failed (whole fungus preparation) n Recent vaccine development is stalled (sophisticated development ultimately without pharmaceutical support) n Coccidioidomycosis is an ancient disease, likely affecting mammals for over a million years n True n False Answer: true n is caused by a. A protozoan cyst found in the soil b. A parasite ingested when drinking water from a garden hose. c. A fungus inhaled as a spore from SJV dust. Answer: c. 7

8 n Valley Fever may present like many other illnesses and often confuses the provider n True n False Answer: true n Which patient is at greatest risk of dissemination at the time of infection? a. 70 y.o. black male, otherwise healthy b. 25 y.o. female in 3 rd trimester of pregnancy c. 19 y.o. white male abusing androgenic steroids Answer: b. n For community-acquired pneumonia (CAP), which CXR finding is most suspicious for Valley Fever? a. Adenopathy in the region of consolidation b. Pleural effusion c. Multi-lobar disease Answer: a. n For treatment of CAP, empirical antifungal therapy is indicated how often in Fresno, Ca.? a. Almost never. b. When Valley Fever cannot be excluded. c. When the pneumonia is life-threatening. Answer: b. n Which scenario is least associated with a fatal outcome from Valley Fever? a. A patient with Hodgkins lymphoma treated with chemo/radiation therapy over a year ago. b. An AIDS patient with CD4 count of 34. c. An ESRD patient on maintenance hemodialysis Answer: b. n Which renowned physician treated 36 new cases of cocci meningitis in one year: a. Royce Johnson, M.D., Bakersfield b. Hans Einstein, M.D., Bakersfield c. Marshall Fiese, M.D., Fresno/Stanford d. Neil Ampell, M.D., Tucson e. Paul Williams, M.D., Visalia/Selma Answer: a. 8

9 n The most promising new drug for Valley Fever treatment is fungicidal - a. Pozaconazole b. Liposomal amphotericin B c. Nikkomycin Z d. Voriconazole Answer: c. 9