Document Detail

Cryptococcal meningitis treatment strategies in resource-limited settings: a cost-effectiveness analysis.
MedLine Citation:
PMID:  23055838     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Cryptococcal meningitis (CM) is the most common form of meningitis in Africa. World Health Organization guidelines recommend 14-d amphotericin-based induction therapy; however, this is impractical for many resource-limited settings due to cost and intensive monitoring needs. A cost-effectiveness analysis was performed to guide stakeholders with respect to optimal CM treatment within resource limitations.
METHODS AND FINDINGS: We conducted a decision analysis to estimate the incremental cost-effectiveness ratio (ICER) of six CM induction regimens: fluconazole (800-1,200 mg/d) monotherapy, fluconazole + flucytosine (5FC), short-course amphotericin (7-d) + fluconazole, 14-d of amphotericin alone, amphotericin + fluconazole, and amphotericin + 5FC. We computed actual 2012 healthcare costs in Uganda for medications, supplies, and personnel, and average laboratory costs for three African countries. A systematic review of cryptococcal treatment trials in resource-limited areas summarized 10-wk survival outcomes. We modeled one-year survival based on South African, Ugandan, and Thai CM outcome data, and survival beyond one-year on Ugandan and Thai data. Quality-adjusted life years (QALYs) were determined and used to calculate the cost-effectiveness ratio and ICER. The cost of hospital care ranged from $154 for fluconazole monotherapy to $467 for 14 d of amphotericin + 5FC. Based on 18 studies investigating outcomes for HIV-infected individuals with CM in resource-limited settings, the estimated mean one-year survival was lowest for fluconazole monotherapy, at 40%. The cost-effectiveness ratio ranged from $20 to $44 per QALY. Overall, amphotericin-based regimens had higher costs but better survival. Short-course amphotericin (1 mg/kg/d for 7 d) with fluconazole (1,200 mg/d for14 d) had the best one-year survival (66%) and the most favorable cost-effectiveness ratio, at $20.24/QALY, with an ICER of $15.11 per additional QALY over fluconazole monotherapy. The main limitation of this study is the pooled nature of a systematic review, with a paucity of outcome data with direct comparisons between regimens.
CONCLUSIONS: Short-course (7-d) amphotericin induction therapy coupled with high-dose (1,200 mg/d) fluconazole is "very cost effective" per World Health Organization criteria and may be a worthy investment for policy-makers seeking cost-effective clinical outcomes. More head-to-head clinical trials are needed on treatments for this neglected tropical disease. Please see later in the article for the Editors' Summary.
Radha Rajasingham; Melissa A Rolfes; Kate E Birkenkamp; David B Meya; David R Boulware
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-09-25
Journal Detail:
Title:  PLoS medicine     Volume:  9     ISSN:  1549-1676     ISO Abbreviation:  PLoS Med.     Publication Date:  2012  
Date Detail:
Created Date:  2012-10-11     Completed Date:  2013-02-04     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101231360     Medline TA:  PLoS Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1001316     Citation Subset:  IM    
Infectious Disease Institute, Makerere University, Kampala, Uganda.
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MeSH Terms
Amphotericin B / administration & dosage,  economics,  therapeutic use
Antifungal Agents / administration & dosage,  economics,  therapeutic use
Cost-Benefit Analysis / methods*
Fluconazole / administration & dosage,  economics,  therapeutic use
Flucytosine / administration & dosage,  economics,  therapeutic use
Meningitis, Cryptococcal / drug therapy*,  economics*
Grant Support
Reg. No./Substance:
0/Antifungal Agents; 1397-89-3/Amphotericin B; 2022-85-7/Flucytosine; 86386-73-4/Fluconazole
Comment In:
PLoS Med. 2012;9(9):e1001318   [PMID:  23049487 ]

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