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