 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 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 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. Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007.

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

 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

-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

 Clinical Manifestations: Not contagious Route of infection: inhalation Incubation: 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 cutaneous granulomatous lesions which may form draining ulcers Incidence in HIV-infected persons has increased

Coccidioidomycosis - Manifestations

 Coccidioides immitis: Thermally dimorphic fungus In tissue: Huge (20-60 μ m) thick-walled, round “spherules” filled with small (2-5 μ m) 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

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

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

Coccidioidomycosis

Coccidioidomycosis

- May take ~ 2 weeks Coccidioidomycosis

Arthroconidia Disjuncture Coccidioidomycosis

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

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

 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, hilar lymphadenopathy, characteristic pattern of organ involvement (lungs, bones, soft tissues), residence in an endemic area, and African- American ethnicity. Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007.

 Paracoccidioidomycosis Paracoccidioides brasiliensis Endemic to Latin American countries Pulmonary infection – asymptomatic, self- limiting Dissemination to mucous membranes and skin Histopathology: -Yeast with multiple buds -”Mariner’s Wheel”

 Penicilliosis Marneffei Penicillium marneffei 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