Coccidioidomycosis Nothing to disclose Disclosure Greg Melcher, M.D. Professor of Clinical Medicine Division of HIV, ID and Global Medicine Zuckerman San Francisco General Hospital University of California, San Francisco Learning Objectives Understand the changing epidemiology of coccidioidomycosis Recognize the varied pulmonary presentations of cocci Be familiar with common presentations of disseminated coccidioidomycosis Be familiar with treatment and clinical monitoring for coccidioidomycosis Coccidioidomycosis Cocci Coccidioides immitis and Coccidioides posadasii Dimorphic fungus spherule mycelia endospores arthroconidia 1
The Ecology of Cocci Changing Epidemiology of Cocci Transmission of Cocci Texas Missouri 45 40 35 30 25 20 15 10 5 0 1998 2011 5.3/100K 42.6/100K 0.3 0.25 0.2 0.15 0.1 0.05 0 2004 2013 0.05/100K 0.28/100K 2
Pulmonary Cocci Primary Pulmonary Cocci 60% of infections are asymptomatic or mild respiratory illness 25% of community acquired pneumonia in endemic areas Segmental or lobar consolidation, +/ regional adenopathy Eosinophilic pleural effusion Primary Pulmonary Cocci Clinical Manifestations Cough, fever, dyspnea, scant sputum production Onset 1 3 weeks after exposure to arthroconidia Possible erythema nodosum good prognosis Pleural effusion only approximately 10% Primary Pulmonary Cocci Diagnosis Most often serology immunodiffusion tube precipitin (IgM) Immunodiffusion complement fixation antibody (IgG) EIA tests are sensitive, but not specific Sputum culture Nucleic acid testing under investigation Treatment optional Fluconazole 200 400 mg/day Itraconazole 100 200 mg BID 3
Diffuse Cocci Pneumonia Other Forms of Pulmonary Cocci High inoculum Immunosuppression Pregnancy Treatment may be prolonged Solitary Pulmonary Nodule No treatment required Chronic Progressive Cavitary Treatment indicated prolonged Disseminated Coccidioidomycosis Disseminated Coccidioidomycosis Risk Factors Filipino or African ethnicity Immunosuppression Prednisone TNF inhibitors Chemotherapy Organ transplantation HIV/AIDS Diabetes mellitus Pregnancy Cardiopulmonary disease CF titer >1:16 Stockamp N, Thompson GR. Infect Dis Clin N Am, 2015. http://dx.doi.org/10.1016 4
Diagnosis of Disseminated Cocci Serology supportive if CF titer > 1:16 Definitive diagnosis Any positive CF titer from CSF Culture Histopathology (spherules in tissue) www.mycology.adelaide.edu.au Most common form of dissemination Non healing, wart like ulceration Diagnosis confirmed by skin biopsy Histopathology with spherules Culture often positive Cutaneous Cocci Soft Tissue Cocci Bone and Joint Cocci Fluctuant, usually painless fluid collections Favor bony prominences such as hips, spinal column, sternum and ribs Diagnosis confirmed by aspiration for direct smear and culture Painful joint or long bone Similar to other causes of septic arthritis Diagnosis by arthrocentesis, synovial biopsy, or bone x ray in setting of active cocci 5
Treatment of Non Meningeal Disseminated Cocci Triazoles are the mainstay of therapy Fluconazole 400 800 mg daily Itraconazole 200 mg BID preferred for bone and joint disease Monitor serum CF titer; once low or undetectable can consider lowering dose Most clinicians consider disseminated cocci to require lifelong therapy at lowest possible dose Can monitor serum CF titer as marker of disease activity Stockamp N, Thompson GR. Infect Dis Clin N Am, 2015. http://dx.doi.org/10.1016 Cocci Meningitis LP indicated for persons with symptoms suggestive of meningitis Blurred vision, headache, photophobia, meningismus, altered mental status, focal neurologic finding (CN III VIII) CSF mononuclear cell pleocytosis, elevated protein and low glucose Diagnosis confirmed by CF titer or culture (rare) Imaging studies supportive; can mimic tuberculous meningitis Treatment of Cocci Meningitis Fluconazole 800 1200 mg daily Liposomal amphotericin B 5 10 mg/kg/day Intrathecal deoxycholate amphotericin B Voriconazole Posaconazole Isavuconazole Lifelong treatment is recommended Complications of Cocci Meningitis Hydrocephalus VP shunt CNS vasculitis Cerebral ischemia/infarction Vasospasm Hemorrhage Nguyen, C. et al. Clin Microbiol Rev 2013;26:505 525. 6
Monitoring Response to Cocci Therapy Clinical signs and symptoms Serial serum and/or CSF cocci CF titer Four fold change required to be significant 7