Updating guidance for preventing and treating cryptococcal disease: how evidence and decisions interface

Migone, Chantal; Ford, Nathan; Garner, Paul; Eshun‐Wilson, Ingrid

doi:10.1002/14651858.ed000130

Cited by 8 publications

(3 citation statements)

References 14 publications

(14 reference statements)

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“…It has been shown that CrAg screening with pre-emptive fungal therapy failed to provide survival benefit when lumber puncture was not provided, especially among patients with high serum CrAg titers [ 31 ]. Further research is urgently needed to identify optimal management of this subgroup of patients [ 32 ]. In this study, we also found an association of delayed CrAg testing with increased mortality and hospitalization later after HIV diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Screening for Cryptococcal Antigenemia and Burden of Cryptococcosis at the Time of HIV Diagnosis: A Retrospective Multicenter Study

et al. 2021

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Introduction: Screening for cryptococcal antigen (CrAg) is recommended for people living with HIV (PLWH) who present with low CD4 lymphocyte counts. Real-world experience is important to identify gaps between the guidelines and clinical practice. We investigated the trends of CrAg testing and prevalence of cryptococcal antigenemia among PLWH at the time of HIV diagnosis and the related mortality in Taiwan from 2009 to 2018. Methods: Medical records of newly diagnosed PLWH seeking care at six medical centers around Taiwan between 2009 and 2018 were reviewed. The annual trends of PLWH who had CrAg testing and cryptococcal antigenemia were examined by Cochran-Armitage test. Among PLWH with CD4 \ 200 cells/ll, timing of CrAg testing was analyzed for association with 12-month all-cause mortality in Kaplan-Yuan-Ti Lee, Chien-Ching Hung have contributed equally to the work and should be considered joint senior authors.The members of the Taiwan HIV Study Group are mentioned in the ''Acknowledgements'' section.

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Section: Discussionmentioning

confidence: 99%

Screening for Cryptococcal Antigenemia and Burden of Cryptococcosis at the Time of HIV Diagnosis: A Retrospective Multicenter Study

et al. 2021

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“…To complete the induction therapy phase, fluconazole (FLU) at 1200 mg/day is also administered in the following week, and 800 mg/day of FLU for 8 weeks and 200 mg/day are given in the consolidation and maintenance phases, respectively ( 14 ). Though preferable, AmB has not been widely available across the SSA due to high cost, thereby making FLU monotherapy the mainstay of therapy ( 15 , 16 ). Depending on availability, drugs recommended for the induction phase included a 2 weeks FLU and 5-FC or a 2 weeks AmB and FLU ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

Prevalence of cryptococcal meningitis among people living with human immuno-deficiency virus and predictors of mortality in adults on induction therapy in Africa: A systematic review and meta-analysis

et al. 2022

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BackgroundCryptococcal meningitis (CM) is a leading cause of adult meningitis in countries with a high burden of HIV. It has remained a significant cause of morbidity and mortality in Africa despite the extensive rollout of HIV antiretroviral therapy (ART). This study aimed to systematically synthesize the evidence on the prevalence of CM among people living with HIV (PLWH) and its predictors of mortality among adults who are on induction antifungal therapy in Africa.MethodsPubMed/MEDLINE, Embase, and Google Scholar were searched for randomized clinical trials or observational studies published in Africa from 1995 to April 2021. Pooled prevalence of CM among PLWH was calculated using R-studio Version 1.4.1717 software and the data extracted from eligible studies were pooled as percentage with a 95% confidence interval (CI). Predictors of mortality among adults on induction antifungal therapy were synthesized narratively.ResultsOut of 364 studies identified, 17 eligible articles were included in the analysis. The prevalence of CM among PLWH in Africa was 5.11% (95% CI 2.71–9.43%; participants = 10,813; studies = 9; I2 = 97%). In the subgroup analysis, the prevalence was 12.9% (95% CI 4.883–30.0; participants = 533; studies = 3; I2 = 63%) in the years 1995–2010 and 3.18% (95% CI 1.54–6.45; participants = 10,280; studies = 6; I2 = 98%) in the years 2011–2021, with the prevalence significantly decreased by 51% (p = 0.02). Predictors of mortality were fluconazole monotherapy, focal neurological signs, low Glasgow coma scale, and delayed diagnosis of CM at varied timepoint.ConclusionPrevalence of CM has significantly decreased from 1996–2010 to 2011–2021 among PLWH on induction therapy in Africa. Fluconazole monotherapy, focal neurological symptoms, diastolic blood pressure < 60 mmHg, and concurrent tuberculosis coinfection were significant predictors of mortality at 2- and 10-weeks timepoints. CM remains a major concern among PLWH despite increases in ART coverage. Improved access to effective antifungal therapies is needed in Africa for timely initiation of combination induction therapy and better treatment outcomes of PLWH.Systematic review registration[https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=254113], identifier [CRD42021254113].

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“…Besides, it also shows a growing number of immunocompromised and immunocompetent patients. In the USA, the death rate in HIV-negative CM individuals was around one quarter of CM-associated hospitalizations and one-third of CM-associated mortalities (Perfect et al, 2010;Williamson et al, 2017;Migone et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Sustained intrathecal delivery of amphotericin B using an injectable and biodegradable thermogel

Lin

Wang

et al. 2021

Drug Delivery

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Cryptococcal meningitis is a fungal infectious disease with a poor prognosis and high mortality. Amphotericin B (AMB) is the first choice for the treatment of cryptococcal meninges. The blood-brain barrier (BBB) is the major barrier for the effective delivery of drugs to the brain. In this study, AMB was incorporated in a thermosensitive gel for intrathecal injection. We first synthesized AMB-loaded thermogel, investigated its in vitro cumulative release, and in vivo neurotoxicity, and therapeutic effect. The thermosensitive gel was comprised of 25 wt% poly (lactic acid-co-glycolic acid)-poly (ethylene glycol)-poly (lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock polymer aqueous solution. The AMB loaded in the thermosensitive gel (AMB in gel) had low viscosity at low temperature and resulted in the formation of a non-flowing gel at 37 C (physiological temperature). AMB loading in gel sustained its release for 36 days and the in vitro cumulative release rate was satisfactory. Compared with the AMB solution, intrathecal administration of AMB in gel could reduce the neurovirulence of AMB and get a better treatment effect. The findings of the current study show that the injectable PLGA-PEG-PLGA thermogel is a biocompatible carrier for the delivery of drugs into the intrathecal.

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Updating guidance for preventing and treating cryptococcal disease: how evidence and decisions interface

Cited by 8 publications

References 14 publications

Screening for Cryptococcal Antigenemia and Burden of Cryptococcosis at the Time of HIV Diagnosis: A Retrospective Multicenter Study

Screening for Cryptococcal Antigenemia and Burden of Cryptococcosis at the Time of HIV Diagnosis: A Retrospective Multicenter Study

Prevalence of cryptococcal meningitis among people living with human immuno-deficiency virus and predictors of mortality in adults on induction therapy in Africa: A systematic review and meta-analysis

Sustained intrathecal delivery of amphotericin B using an injectable and biodegradable thermogel

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