Histoplasmosis L. Joseph Wheat - PowerPoint PPT Presentation

1 / 39
About This Presentation
Title:

Histoplasmosis L. Joseph Wheat

Description:

Newman Sem Res Infec 2001. Yeast Pathogenic. MoldYeast 24 hr ... Rosenberg Arth Rheum 1983. Rheumatologic Syndrome Mistaken as Sarcoidosis. Wheat Medicine 1983 ... – PowerPoint PPT presentation

Number of Views:496
Avg rating:3.0/5.0
Slides: 40
Provided by: blair7
Category:

less

Transcript and Presenter's Notes

Title: Histoplasmosis L. Joseph Wheat


1
Histoplasmosis L. Joseph Wheat
  • Request CD
  • Notes in normal view

2
Endemic in US
3
Endemic Impact for 2002
4
Microconidia Infectious
5
Yeast Pathogenic
  • Mold?Yeast lt24 hr
  • Disseminates in pre-immune phase
  • Splenic granuloma
  • Bone marrow abnormalities
  • Hepatic enzymes
  • Cellular defense prevents progression

6
Heavy Inoculum?Acute Diffuse
  • Moderate-severe
  • Retic-nod or miliary
  • Dissemination 37
  • Prolonged recovery

7
Light Inoculum?Subacute Focal
  • Asympt or mild illness
  • Focal or patchy infiltrates
  • Hilar or mediastinal adenopathy
  • Spontaneous recovery in 1 month

8
Rheumatologic Syndrome Mistaken as Sarcoidosis
9
Histoplasma Pericarditis
10
COPD?Chronic Pulmonary
  • Underlying COPD
  • Cavitary infiltrates
  • Resembles TB
  • Slowly progressive

11
Histo on Etanercept
12
Reactivation Latent Histo Rare
  • Group /total Incidence
  • BMT 0/147 0
  • SOT 0/449 0
  • --Sero 0/48 0
  • --CXR 0/23 0
  • Literature
  • AIDS 1
  • Infliximab lt0.1
  • Etanercept lt0.01

13
Smoldering or New Exposure
  • Rationale
  • lt0.1 too low for reactivation
  • Why not 50-80?
  • Rate endemic rate
  • lt 60 d after start infliximab
  • Too early to reactivate
  • Implications
  • RO active infection at initiation
  • CXR and/or CT
  • Antigen antibody?
  • Workup new illness
  • Pulmonary symptoms
  • Fever weight loss
  • Screen during high risk?
  • Infliximab first 6 mo
  • Etanercept first year

14
Mucocutaneous Dissemination
15
Gastrointestinal Dissemination
16
Adrenal Dissemination
  • lt10 of cases
  • Adrenal mass
  • Adrenal insufficiency if extensive necrosis
  • Think histo
  • Think Addisons

17
CNS Dissemination
18
Clinical Manifestations
19
Rapid Diagnosis
20
Histopathology
21
3rd Gen Histo Antigen Assay
22
Reproducibility 3rd Gen Histo Antigen Assay
23
Interpretation Guideline
24
Antigen Detection in BAL
25
Antigenemia Clears First
26
Summary Diagnosis
  • Battery of test recommended
  • Antigen, cytology/histopath, culture, serology
  • Only culture 100 specific, but insensitive
  • Antigen not perfect
  • Sensitivity not 100 negative not exclude
  • Specificity not 100 positive not prove
  • Should validated antigen!
  • Repeat positive antigen
  • Do other tests
  • Seek advice if uncertain
  • 317-856-2681 ext 452
  • jwheat_at_miravistalabs.com

27
Indications for Treatment
  • Indicated and effective
  • Progressive disseminated
  • Chronic pulmonary
  • Acute diffuse pulmonary
  • Indication and effectiveness uncertain
  • Subacute localized pulmonary
  • Mediastinal granuloma

28
Response of PDH in AIDS to Ampho B
Severe Non-Severe
29
L-AmB vs. D-AmB Study Design
  • AIDS with moderate or severe PDH
  • Randomized, double blind
  • 21 randomization AmB for 7-14 d
  • Liposomal AmB 3 mg/kg/d
  • Deoxycholate-AmB .7 mg/kg/d
  • Itra 200 mg bid for 10 weeks

30
L-AmB vs D-AmB Outcome
31
Response to Itraconazole or Fluconazole in PDH in
AIDS
32
Causes Itraconazole Failure
  • Inadequate drug exposure
  • Adherence/tolerance
  • Drug-interactions
  • Absorption
  • Resistance
  • Not reported or observed
  • Measure random drug levels, gt2 µg/ml

33
Cause for Fluconazole Failure
34
Activity Newer Triazoles
35
Emergence of Resistance
36
CYP51 Tyr?Phenylalanine at Y136F
37
Voriconazole MIC vs Blood Concentration
38
IDSA Histo Guideline 2007
  • Liposomal Ampho B 3 mg/kg/d
  • Moderate to severe
  • Initial therapy
  • Itraconazole 200 mg bid
  • Milder cases
  • Continued therapy
  • Monitor levels
  • Posaconazolegtgtfluconazole voriconazole?
  • Alternative to itraconazole
  • Monitor levels voriconazole posaconazole
  • Seek advise if uncertain!

39
New in 2007
  • Quantitative 3rd generation antigen assay
  • Cross reaction in coccidioidomycosis
  • Monitor clearance antigenemia then antigenuria
  • BAL 92 sensitive
  • Posaconazole preferred alternative to itra
  • Therapeutic drug monitoring
Write a Comment
User Comments (0)
About PowerShow.com