Cryptococcal meningitis treatment strategies in resource-limited settings: a cost-effectiveness analysis.
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.


RESULTS
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.
Infectious Disease Institute, Makerere University, Kampala, Uganda.
Radha
R
Rajasingham
Melissa A
MA
Rolfes
Kate E
KE
Birkenkamp
David B
DB
Meya
David R
DR
Boulware
D000349:Africa; D000666:Amphotericin B / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D000935:Antifungal Agents / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D003362:Cost-Benefit Analysis / Q000379:methods*; D015725:Fluconazole / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D005437:Flucytosine / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D006801:Humans; D016919:Meningitis, Cryptococcal / Q000188:drug therapy* / Q000191:economics*
D000935:Antifungal Agents; D000666:Amphotericin B; D015725:Fluconazole; D005437:Flucytosine