Invasive Fungal Infections: Overview, Diagnosis & Treatment Approaches

1. Invasive Fungal Infections: Overview, Diagnosis
& Treatment Approaches
Iheanyi Okpala
Professor of Hematology
University of Nigeria

2. Outline of Talk
• Burden of IFI – the magnitude of the problem
• Epidemiology – who, where & when
• Risk factors & risk groups
• Signs & symptoms
• Diagnosis of Aspergillosis and Candidiasis

3. The Burden of IFI
Invasive fungal infections tend to be under-diagnosed
This is partly because of non-specific signs & symptoms
Yet, unrecognised/untreated IFI could cause death
A significant number recognised only at autopsy
So, a high index of clinical suspicion is required.

4. Prevalence of IFI in Nigeria: An Insight
In 1 centre, 23 ‘incidental’ cases in 3 yrs, at surgical biopsy.
Need for greater awareness highlighted

5. Risk Factors For Invasive Fungal Infections
Congenital Acquired
Defective IL-10 synthesis Exposure to high concentration
of fungal spores
Mannose-binding lectin Prolonged neutropenia
deficiency
Polymorphisms of Treatment with agents that
toll-like receptor impair cellular immunity
- steroids, purine analogues e.g
fludarabine
monoclonal antibodies to
lymphocytes e.g anti-CD20

6. Signs and Symptoms of Invasive Fungal Infections
Fever >3 dys despite broad-spectrum antibacterial therapy
May be subtle, e.g temp rise >10C with absolute temp <380C
in a severely neutropenic patient with
little source of the endogenous pyrogen IL-1β
...or downright non-specific, e.g feels ‘unwell’
‘less well than usual’

7. Diagnostic Tests For Invasive Fungal Infections
1. High resolution CT or MRI may show macronodules,
many of which are surrounded by halo signs,
particularly in neutropenic patients.

8. 2. Detection of specific fungal antigens and certain
components of the fungal cell or DNA.
- serial levels of galactomannan in serum/plasma
(particularly with high-resolution CT)
useful for early detection of invasive aspergillosis
in hematological malignancies.
3. At times, direct detection of fungi in samples of
deep tissues.

9. Evaluation and Treatment for Invasive Fungal Infections
A Where diagnostic facilities are lacking....
.....treatment started if fever does not respond to a 3–7 day
course of adequate antibacterial therapy
....or, less often, when clinical features suggest IFI.
if persisting unexplained fever is the reason for starting
therapy, empirical treatment can stop when fever resolves

10. Evaluation and Treatment for Invasive Fungal Infections
B Where diagnostic facilities are available....
....persisting fever does not serve as a trigger to start
antifungal therapy, but may provide an impetus to
use all diagnostic tools available.
a rising level of galactomannan on serial measurements
may be considered an indication to start antifungals

11. Treatment of IFI: the earlier the better

12. Which Antifungal to Use?
Only voriconazole vs amphotericin B deoxycholate
trial in aspergillosis had enough patients to allow a
realistic comparison of two different antifungals....
....voriconazole proved more effective;
now drug of choice for invasive aspergillosis.
Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B
for primary therapy of invasive aspergillosis. N Engl J Med 2002;347:408-15

13. Treatment of Candidiasis
Although invasive aspergillosis is a serious illness...
.....in clinical practice candidiasis is more common.
In recent years, the non-albicans species of candida
have been increasingly identified in clinical isolates.

14. Sensitivity of Candida isolates from a Nigerian Cohort
Enwuru
et al.

16. The veteran Fluconazole vs the new Anidulafungin

19. How Long Should Antifungal Treatment Last?
If IFI is proven /probable, continue antifungals as long as
patient remains seriously immunosuppressed.
Remove or avoid avoidable risk factors to IFI identified
in the individual patient.

20. Acknowledgements
Many thanks to:
Participants in this forum for making out time to attend
Pfizer for this opportunity to share experience & ideas