Invasive Fungal Infections: Overview, Diagnosis & Treatment Approaches Iheanyi Okpala Professor of Hematology University of Nigeria
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
The Burden of IFIInvasive fungal infections tend to be under-diagnosedThis is partly because of non-specific signs & symptomsYet, unrecognised/untreated IFI could cause deathA significant number recognised only at autopsySo, a high index of clinical suspicion is required.
Prevalence of IFI in Nigeria: An InsightIn 1 centre, 23 ‘incidental’ cases in 3 yrs, at surgical biopsy. Need for greater awareness highlighted
Risk Factors For Invasive Fungal InfectionsCongenital AcquiredDefective IL-10 synthesis Exposure to high concentration of fungal sporesMannose-binding lectin Prolonged neutropeniadeficiencyPolymorphisms of Treatment with agents thattoll-like receptor impair cellular immunity - steroids, purine analogues e.g fludarabine monoclonal antibodies to lymphocytes e.g anti-CD20
Signs and Symptoms of Invasive Fungal InfectionsFever >3 dys despite broad-spectrum antibacterial therapyMay 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’
Diagnostic Tests For Invasive Fungal Infections1. High resolution CT or MRI may show macronodules, many of which are surrounded by halo signs, particularly in neutropenic patients.
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.
Evaluation and Treatment for Invasive Fungal InfectionsA 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
Evaluation and Treatment for Invasive Fungal InfectionsB 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
Which Antifungal to Use?Only voriconazole vs amphotericin B deoxycholatetrial in aspergillosis had enough patients to allow arealistic 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 Bfor primary therapy of invasive aspergillosis. N Engl J Med 2002;347:408-15
Treatment of CandidiasisAlthough invasive aspergillosis is a serious illness........in clinical practice candidiasis is more common.In recent years, the non-albicans species of candidahave been increasingly identified in clinical isolates.
Sensitivity of Candida isolates from a Nigerian Cohort Enwuru et al.
The veteran Fluconazole vs the new Anidulafungin
How Long Should Antifungal Treatment Last?If IFI is proven /probable, continue antifungals as long aspatient remains seriously immunosuppressed.Remove or avoid avoidable risk factors to IFI identifiedin the individual patient.
AcknowledgementsMany thanks to:Participants in this forum for making out time to attendPfizer for this opportunity to share experience & ideas