Abstract
ObjectivesCryptococcal meningitis (CM)-related mortality may be prevented by screening patients for sub-clinical cryptococcal antigenaemia (CRAG) at antiretroviral-therapy (ART) initiation and pre-emptively treating those testing positive. Prior to programmatic implementation in South Africa we performed a cost-effectiveness analysis of alternative preventive strategies for CM.DesignCost-effectiveness analysis.MethodsUsing South African data we modelled the cost-effectiveness of four strategies for patients with CD4 cell-counts <100 cells/µl starting ART 1) no screening or prophylaxis (standard of care), 2) universal primary fluconazole prophylaxis, 3) CRAG screening with fluconazole treatment if antigen-positive, 4) CRAG screening with lumbar puncture if antigen-positive and either amphotericin-B for those with CNS disease or fluconazole for those without. Analysis was limited to the first year of ART.ResultsThe least costly strategy was CRAG screening followed by high-dose fluconazole treatment of all CRAG-positive individuals. This strategy dominated the standard of care at CRAG prevalence ≥0.6%. Although CRAG screening followed by lumbar puncture in all antigen-positive individuals was the most effective strategy clinically, the incremental benefit of LPs and amphotericin therapy for those with CNS disease was small and additional costs were large (US$158 versus US$51per person year; incremental cost effectiveness ratio(ICER) US$889,267 per life year gained). Both CRAG screening strategies are less costly and more clinically effective than current practice. Primary prophylaxis is more effective than current practice, but relatively cost-ineffective (ICER US$20,495).ConclusionsCRAG screening would be a cost-effective strategy to prevent CM-related mortality among patients initiating ART in South Africa. These findings provide further justification for programmatic implementation of CRAG screening.
Highlights
Cryptococcal meningitis (CM) is one of the leading causes of death in HIV-infected patients in Africa
Incidence in antiretroviral therapy (ART) programmes, CM-related mortality and health service costs we modeled the cost-effectiveness of four strategies in patients with CD4 cell-counts,100 cells/ml: 1) no screening or prophylaxis, 2) universal primary prophylaxis with fluconazole 200 mg daily, 3) cryptococcal antigenaemia (CRAG) screening with high-dose fluconazole treatment for all patients testing positive (800 mg fluconazole daily for two weeks, followed by 400 mg daily for eight weeks, 200 mg daily maintenance) and 4) CRAG screening with lumbar puncture for all patients testing positive, amphotericin-B 1 mg/kg/day for two weeks for those with central nervous system (CNS) disease and fluconazole 800 mg daily for two weeks for those without, in both cases followed by fluconazole 400 mg daily for eight weeks, 200 mg daily maintenance as above
This study suggests that CRAG screening of blood from patients entering ART programmes and targeted treatment of those testing positive would be a cost-effective intervention in South Africa, saving both money and lives when compared to the current standard of care
Summary
Cryptococcal meningitis (CM) is one of the leading causes of death in HIV-infected patients in Africa. CM accounts for between 33% and 63% of all adult meningitis in southern Africa [1,2,3], and acute mortality ranges from 24% to 50% [4,5,6,7,8,9]. As a result CM is estimated to cause in excess of 500,000 deaths annually in sub-Saharan Africa [10]. Prevention strategies are of great public health importance. Recent data from South Africa suggest that the vast majority of patients who develop CM are already in care with an established HIV diagnosis [11].
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