Coccidioidomycosis San Joaquin Valley Fever

Disseminated Coccidioidomycosis31-year-old, African-American US Army Soldier

Presents with fever, chills, night sweats, non-productive cough of 4 weeksPast medical history unremarkableRecently detected a painless right breast massStationed at Fort Irwin, CAStafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007.Disseminated CoccidioidomycosisPhysical exam:UnremarkableFirm, nontender, 3-cm subcutaneous mass over right breastMultiple small nontender lymph nodes were palpable in the axillae and groinLab results:WBC = 11.9/l, 30% eosinophilsElevated alkaline phosphataseStafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007.Disseminated CoccidioidomycosisBlood cultures = negativeCryptococcus antigen = negativeHistoplasma urine antigen = negativeHIV antibody = negativeTuberculin 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.Disseminated CoccidioidomycosisFine needle aspirate of the mass revealed spherules filled with endospores

Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007.Disseminated CoccidioidomycosisCulture 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.CoccidioidomycosisEpidemiology: Endemic in arid, temperate, desert climateespecially Southwest United StatesTravel history - Central-Southern CA; south NV, AZ,NM,TXFungus grows in soil and matures to form arthroconidiaInfection is initiated by inhalation of infectious arthroconidiaFilipinos, African/Native Americans & Hispanics - greatest risk of dissemination

Virulence factors and pathogenesis:Highly infectiousNot highly virulent, ~99.5% of infected individuals resolveDefects in CMI predispose to systemic diseaseCoccidioides 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 lungsIn the human host environment, in vivo differentiation produces cleavage planes and eventually huge spherules containing endosporesSpherules rupture releasing endospores, which can then repeat the in vivo cycleCoccidioidomycosisClinical Manifestations: Not contagiousRoute of infection: inhalationIncubation: 10-21 daysRespiratory infection - 60% asymptomatic, all convert to skin test + < 1% dissemination soon after primary infection or years laterOften produces:MeningitisLesions in viscera or cutaneous granulomatous lesions which may form draining ulcers Incidence in HIV-infected persons has increased

Coccidioidomycosis - ManifestationsCoccidioidomycosis Laboratory diagnosisCoccidioides immitis:Thermally dimorphic fungusIn tissue: Huge (20-60 m) thick-walled, round spherules filled with small (2-5 m) endosporesSpherules ruptureIn 25C culture:SDA and SDA-CC positive, 2-4 weeks; SABHI positive, 1-2 weeksHyaline septate hyphae forming barrel-shaped arthroconidiaAt 37C: Thermal conversion requires animals, but is not doneCoccidioidomycosis Laboratory diagnosisCoccidioidin skin test: Not available in US

Serologic tests:Combination of latex agglutination and immunodiffusion tests detects >90% early in symptomatic illnessComplement fixation (CF) tests for DxSerial CF titers are useful for prognosisRising 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 SDA + & SDA-CC +

- May take ~ 2 weeksCoccidioidomycosis

ArthroconidiaDisjunctureCoccidioidomycosis

ExoAg --or-- NA confirmationDefinitive identification of Coccidioides immitisCoccidioidomycosis - TreatmentTreatment:

Most do not require anti-fungals

Azoles pneumonia & nonmeningeal dissemination

Amphotericin B meningeal infection and previous treatment failuresCoccidioidomycosisFor our patient:In spite of Amphotericin B treatment, neck pain increased and progressive enlargement of the mass was notedSurgical debridementLong-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.Other Endemic Dimorphic MycosesParacoccidioidomycosisParacoccidioides brasiliensisEndemic to Latin American countriesPulmonary infection asymptomatic, self-limiting Dissemination to mucous membranes and skin

Histopathology:-Yeast with multiple buds-Mariners WheelOther Endemic Dimorphic MycosesPenicilliosis MarneffeiPenicillium marneffeiHIV-infected individuals in Thailand and Southern ChinaOnly species of Penicillium that is dimorphicIntracellular yeast, with single septumInfection mimics tuberculosis or histoplasmosisPatient presentation:Fever, cough, pulmonary infiltrates, organomegaly, anemia, leukopenia, thrombocytopenia