FunDgnCaseStudies2005

Case Studies in Fungal Diagnostics 2005: 

Case Studies in Fungal Diagnostics 2005 L. Joseph Wheat 4444 Decatur Blvd. Suite 300 Indianapolis, IN 46241 317 856 2681 www.miravistalabs.com

Which Most Sensitive in PDH: 

Which Most Sensitive in PDH

Histopathology : 

Histopathology

Antigen Detection: 

Antigen Detection

Sensitivity in PDH: 

Sensitivity in PDH

Hc PCR in Haguric Specimens: 

Hc PCR in Haguric Specimens

Serum + Urine - Hag After SOT: 

Serum + Urine - Hag After SOT 1st patient Recent liver transplant Prednisone, tacrolimus, mycophenylate, thymoglobulin Pneumonia 3 weeks post transplant Improving or antibiotics Hag serum 41.8, urine 0.6 2nd patient 2 months later- same story

What is HARA?: 

What is HARA?

False-positive Hag Antigenemia: 

False-positive Hag Antigenemia

New 2nd Gen Assay: 

New 2nd Gen Assay

Heavy vs. Light Inoculum : 

Heavy vs. Light Inoculum

Acute v Subacute v Chronic: 

Acute v Subacute v Chronic

Slide13: 

Urine Disseminated Pulmonary AIDS Others NIS Acute Sub-acute Chronic Sensitivity (%) 0 10 20 30 40 50 60 70 80 90 100 95% (75/79) 82% (14/17) 80% (8/10) 81% (26/32) 34% (22/65) 14% (2/14)

How To ↑Sensitivity: 

How To ↑Sensitivity 24 yo construction Demolished old house Fever, cough, SOB Urine Hag 0.9

BAL Improved Sensitivity Pulmonary Syndromes: 

BAL Improved Sensitivity Pulmonary Syndromes

What’s Likely Diagnosis? : 

What’s Likely Diagnosis? 9 yo from Illinois 7 wk productive cough, SOB, 7 kg wt loss Azithro for CAP 6 weeks later: resp failure, diffuse pneumonia, papular rash Ceftriaxone + azithro Day 3 empyema→ decortication Day 4 yeast sputum & pleural fld→ampho B Day 6: Died

Rapid Diagnosis Blastomycosis: 

Rapid Diagnosis Blastomycosis Test Sensitivity KOH 29-83% Cytology 50-93% Antigen 93%

Blasto Antigen Detection : 

Blasto Antigen Detection

Meaning of Persistent Hag? : 

Meaning of Persistent Hag? Renal transplant with PDH on itra Haguria persists ↓ing renal function Infected allograft removed

Hag Clearance=Cure?: 

Hag Clearance=Cure? PDH in normal host Hag clearance serum 1 y urine 2 y When to stop Rx? Viable yeast→relapse Dead yeast→delayed Hag clearance

Antigen During Relapse : 

Antigen During Relapse Blasto 2 years earlier→60d itra Relapse→itra 2 mo before To 2nd relapse 4 mo later, ↑Ag=16.1 → 3rd course itra

What Tests Are Indicated: 

What Tests Are Indicated Findings 26 yo Afr-Amer man from Ohio, healthy Non-productive cough ACE 120 Differential Infection: Hc, TB Sarcoid Lymphoma

Histo vs. Sarcoid: 

Histo vs. Sarcoid

Methods for Early Diagnosis: 

Methods for Early Diagnosis

Antibody Response Slow: 

Antibody Response Slow

Slide26: 

Symptoms % Seropositive Patients 0 10 20 30 40 50 60 70 80 90 100 Severe Moderate None Mild Larrabee Am J Trop Med Hyg 1978

CF Titer vs Symptoms (N=437): 

CF Titer vs Symptoms (N=437) p <0.0001 *High titer: >1:128 † † Chi-square for trend 37% 48% 55% 77%

Heavy vs. Light Inoculum : 

Heavy vs. Light Inoculum Acute pulmonary Few weeks High fungal burden Sensitivity Hag antigen 80% Antibody <25% Subacute pulmonary Months Low fungal burden Sensitivity Hag <25% Antibody 90%

R/O Histo Before Rx Sarcoidosis : 

R/O Histo Before Rx Sarcoidosis Antibodies: ID & CF Antigen: Urine & BAL Bronchoscopy: BAL: cytology, antigen & culture TBBx: fungal stain & culture

Differential & Work-Up?: 

Differential & Work-Up? Clinical 32 yo non-smoker Military, OH Chest pain CT → Differential Granuloma Malignancy Work-up?

HcAg Negative=Role Serology: 

HcAg Negative=Role Serology Urine Hag 0.5 Antibody M-band, CFY 1:16 Histopathology → Culture Not done!

Histo After Anti-TNF: 

Histo After Anti-TNF Findings 50 wm from Indiana RA MTX and steroids Infliximab 10 weeks Fever and hypoxia Hag urine 10.3 BAL yeast

% Reactivation if >50% ST+: 

% Reactivation if >50% ST+ Group #/total Incidence % BMT 0/147 0 SOT 0/449 0 --Sero+ 0/48 0 --CXR+ 0/23 0 Literature AIDS ~1 Infliximab <0.1 Etanercept <0.01

Smoldering or New Exposure: 

Smoldering or New Exposure Rationale <0.1% too low for reactivation Why not 50-80%? Rate ~ endemic rate < 60 d after start infliximab Too early to reactivate Implications Screen pre anti-TNF Hag & antibody Screen during high risk: Infliximab: first 6 mo Etanercept: first year Workup illness Pulmonary symptoms Fever &weight loss