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Diagnosis and Management of Cryptococcal Relapse
Abdu K Musubire1, David R Boulware2, David B Meya3
1Infectious Disease Institute, Makerere University, Kampala, Uganda.
Abstract:
Despite improvements in the antifungal regimens and the roll out of antiretroviral therapy (ART) in sub-Saharan Africa, mortality due to cryptococcal meningitis remains high. Relapse of an initially successfully treated infection contributes to this mortality and is often a clinical dilemma in differentiating between paradoxical immune reconstitution inflammatory syndrome (IRIS) and culture-positive relapse or treatment failure. Herein, we present a clinical case scenario and review the case definitions, differential diagnosis, and management of relapse with an emphasis on the current diagnostic and management strategies. We also highlight the challenges of resistance testing and management of refractory relapse cases. The risk of relapse is influenced by: 1) the choice of induction therapy, with higher mortality risk with fluconazole monotherapy which can select for resistance; 2) non-adherence to or lack of secondary prophylaxis; 3) failure of linkage-to-care or retention-in-care of HIV ART programs.
Insights
Cryptococcal meningitis relapse remains a high mortality risk in sub-Saharan Africa. Strategies to prevent relapse include appropriate antifungal therapy, adherence to prophylaxis, and effective HIV care linkage.
Area of Science:
- Infectious Diseases
- Immunology
- Public Health
Background:
- Cryptococcal meningitis mortality remains high in sub-Saharan Africa despite advances in antifungal therapy and antiretroviral therapy (ART).
- Relapse of cryptococcal meningitis is a significant contributor to mortality and presents a diagnostic challenge, often confused with immune reconstitution inflammatory syndrome (IRIS).
Purpose of the Study:
- To review diagnostic and management strategies for cryptococcal meningitis relapse.
- To highlight challenges in resistance testing and managing refractory cases.
- To identify factors influencing relapse risk.
Main Methods:
- Clinical case scenario presentation.
- Review of case definitions and differential diagnoses for relapse.
- Emphasis on current diagnostic and management strategies.
- Discussion of challenges in resistance testing and refractory case management.
Main Results:
- Relapse risk is influenced by induction therapy choice (fluconazole monotherapy increases risk and selects for resistance).
- Non-adherence to or lack of secondary prophylaxis is a key risk factor.
- Poor linkage-to-care or retention-in-care within HIV ART programs contributes to relapse.
Conclusions:
- Effective management of cryptococcal meningitis relapse requires careful consideration of induction therapy, secondary prophylaxis, and robust HIV care programs.
- Addressing challenges in resistance testing and managing refractory cases is crucial for improving outcomes.
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