Disseminated Coccidioidomycosis

1. Disseminated Coccidioidomycosis Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007. • 31-year-old, African-American US Army Soldier • Presents with fever, chills, night sweats, non-productive cough of 4 weeks • Past medical history unremarkable • Recently detected a painless right breast mass • Stationed at Fort Irwin, CA

2. Disseminated Coccidioidomycosis Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007. • Physical exam: • Unremarkable • Firm, nontender, 3-cm subcutaneous mass over right breast • Multiple small nontender lymph nodes were palpable in the axillae and groin • Lab results: • WBC = 11.9/µl, 30% eosinophils • Elevated alkaline phosphatase

3. Disseminated Coccidioidomycosis Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007. Blood cultures = negative Cryptococcus antigen = negative Histoplasma urine antigen = negative HIV antibody = negative Tuberculin test = negative CT scan of chest revealed diffuse, 1-2 mm micronodules in all lobes and right chest wall mass.

4. Disseminated Coccidioidomycosis Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007. Fine needle aspirate of the mass revealed spherules filled with endospores

5. Disseminated Coccidioidomycosis Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007. Culture grew Coccidioides immitis Serology panel for C. immitis was positive CSF = normal Bone scan revealed multiple region of increased osteoblastic activity

6. Coccidioidomycosis • Epidemiology: • Endemic in arid, temperate, desert climate • especially Southwest United States • Travel history - Central-Southern CA; south NV, AZ,NM,TX • Fungus grows in soil and matures to form arthroconidia • Infection is initiated by inhalation of infectious arthroconidia • Filipinos, African/Native Americans & Hispanics - greatest risk of dissemination • Virulence factors and pathogenesis: • Highly infectious • Not highly virulent, ~99.5% of infected individuals resolve • Defects in CMI predispose to systemic disease

7. Coccidioides spp. Lifecycle • Hyphae differentiate into arthroconidia, which break loose and may be suspended in the air • Soil disruptions and wind facilitate spread and the probability of inhalation into lungs • In the human host environment, in vivo differentiation produces cleavage planes and eventually huge spherules containing endospores • Spherules rupture releasing endospores, which can then repeat the in vivo cycle

8. Coccidioidomycosis • Clinical Manifestations: • Not contagious • Route of infection: inhalation • Incubation: 10-21 days • Respiratory infection - 60% asymptomatic, all convert to skin test + • < 1% dissemination – soon after primary infection or years later • Often produces: • Meningitis • Lesions in viscera or cutaneousgranulomatous lesions which may form draining ulcers • Incidence in HIV-infected persons has increased

9. Coccidioidomycosis - Manifestations

10. Coccidioidomycosis – Laboratory diagnosis • Coccidioides immitis: • Thermally dimorphic fungus • In tissue: Huge (20-60 μm) thick-walled, round “spherules” filled with small (2-5 μm) endospores • Spherules rupture • In 25°C culture: • SDA and SDA-CC positive, 2-4 weeks; SABHI positive, 1-2 weeks • Hyaline septate hyphae forming barrel-shaped arthroconidia • At 37°C: Thermal conversion requires animals, but is not done

11. Coccidioidomycosis – Laboratory diagnosis • Coccidioidin skin test: • Not available in US • Serologic tests: • Combination of latex agglutination and immunodiffusion tests detects >90% early in symptomatic illness • Complement fixation (CF) tests for Dx • Serial CF titers are useful for prognosis • Rising titer = poor prognosis

12. Coccidioidomycosis Lung tissue with a large thick-walled spherule containing multiple endospores. The smaller spherule to its left has ruptured releasing endospores.

13. Coccidioidomycosis

14. Coccidioidomycosis

15. SDA + & SDA-CC + Coccidioidomycosis - May take ~ 2 weeks

16. Coccidioidomycosis Arthroconidia Disjuncture

17. Definitive identification of Coccidioides immitis ExoAg --or-- NA confirmation

18. Coccidioidomycosis - Treatment • Treatment: • Most do not require anti-fungals • Azoles – pneumonia & nonmeningeal dissemination • Amphotericin B – meningeal infection and previous treatment failures

19. Coccidioidomycosis Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007. • For our patient: • In spite of Amphotericin B treatment, neck pain increased and progressive enlargement of the mass was noted • Surgical debridement • Long-term antifungal therapy • Clues to the diagnosis of disseminated coccidioidomycosis included an infectious prodrome, peripheral eosinophilia, hilarlymphadenopathy, characteristic pattern of organ involvement (lungs, bones, soft tissues), residence in an endemic area, and African-American ethnicity.

20. Other Endemic Dimorphic Mycoses Histopathology: -Yeast with multiple buds -”Mariner’s Wheel” • Paracoccidioidomycosis • Paracoccidioidesbrasiliensis • Endemic to Latin American countries • Pulmonary infection – asymptomatic, self-limiting • Dissemination to mucous membranes and skin

21. Other Endemic Dimorphic Mycoses • PenicilliosisMarneffei • Penicilliummarneffei • HIV-infected individuals in Thailand and Southern China • Only species of Penicillium that is dimorphic • Intracellular yeast, with single septum • Infection mimics tuberculosis or histoplasmosis • Patient presentation: • Fever, cough, pulmonary infiltrates, organomegaly, anemia, leukopenia, thrombocytopenia