title: Cost effectiveness of cryptococcal antigen screening as a strategy to prevent HIV-associated cryptococcal meningitis in South Africa.
abstract: OBJECTIVE
  Cryptococcal 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.
  
  
  METHODS
  Cost-effectiveness analysis.
  
  
  METHODS
  Using 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.
  
  
  RESULTS
  The 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$51 per 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).
  
  
  CONCLUSIONS
  CRAG 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.
authors.affiliation: Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. joejarvis@doctors.net.uk
authors.forename: Joseph N
authors.initials: JN
authors.lastname: Jarvis
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Harrison
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Lawn
authors.forename: Graeme
authors.initials: G
authors.lastname: Meintjes
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.forename: Susan
authors.initials: S
authors.lastname: Cleary
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000175:diagnosis / Q000191:economics*; D000946:Antigens, Fungal / Q000276:immunology; D003362:Cost-Benefit Analysis; D003455:Cryptococcus neoformans / Q000276:immunology; D017048:Health Care Costs; D006801:Humans; D008390:Markov Chains; D008403:Mass Screening / Q000191:economics*; D016919:Meningitis, Cryptococcal / Q000175:diagnosis / Q000191:economics*; D015233:Models, Statistical; D063868:Patient Outcome Assessment; D013019:South Africa
chemical_list: D000946:Antigens, Fungal
references.citation: Med Decis Making. 1993 Oct-Dec;13(4):322-38
references.pmid: 8246705
references.citation: AIDS. 1989 Feb;3(2):77-8
references.pmid: 2496722
references.citation: BMC Health Serv Res. 2007 Jun 07;7:80
references.pmid: 17555564
references.citation: Clin Infect Dis. 2002 Jan 15;34(2):277-84
references.pmid: 11740718
references.citation: AIDS. 2008 Oct 1;22(15):1897-908
references.pmid: 18784453
references.citation: BMC Infect Dis. 2010 Mar 15;10:67
references.pmid: 20230635
references.citation: Lancet Infect Dis. 2011 Dec;11(12):933-41
references.pmid: 21982529
references.citation: Clin Infect Dis. 1996 Jul;23(1):82-90
references.pmid: 8816134
references.citation: AIDS. 2002 May 3;16(7):1031-8
references.pmid: 11953469
references.citation: N Engl J Med. 2007 Dec 13;357(24):2441-50
references.pmid: 18077809
references.citation: J Acquir Immune Defic Syndr. 2006 Aug 1;42(4):464-9
references.pmid: 16810113
references.citation: JAMA. 1998 Jan 14;279(2):130-6
references.pmid: 9440663
references.citation: Clin Infect Dis. 2010 Dec 15;51(12):1463-5
references.pmid: 21082878
references.citation: Clin Infect Dis. 2009 Apr 1;48(7):856-62
references.pmid: 19222372
references.citation: AIDS. 2012 Jun 1;26(9):1105-13
references.pmid: 22421244
references.citation: Int J Infect Dis. 2006 Sep;10(5):387-95
references.pmid: 16473538
references.citation: Trop Med Int Health. 2007 Aug;12(8):929-35
references.pmid: 17697087
references.citation: N Engl J Med. 1998 Mar 26;338(13):853-60
references.pmid: 9516219
references.citation: Clin Infect Dis. 1996 Oct;23(4):827-30
references.pmid: 8909854
references.citation: Clin Infect Dis. 2003 Mar 15;36(6):789-94
references.pmid: 12627365
references.citation: J Infect. 2010 Jun;60(6):496-8
references.pmid: 20307571
references.citation: Clin Infect Dis. 2010 Aug 15;51(4):448-55
references.pmid: 20597693
references.citation: Cochrane Database Syst Rev. 2005 Jul 20;(3):CD004773
references.pmid: 16034947
references.citation: PLoS One. 2010 Jan 07;5(1):e8630
references.pmid: 20062814
references.citation: S Afr Med J. 2009 May;99(5):320-5
references.pmid: 19588792
references.citation: PLoS One. 2010 Nov 09;5(11):e13856
references.pmid: 21085478
references.citation: AIDS. 2010 May 15;24(8):1233-5
references.pmid: 20421745
references.citation: Clin Infect Dis. 2007 Jul 1;45(1):76-80
references.pmid: 17554704
references.citation: N Engl J Med. 1995 Mar 16;332(11):700-5
references.pmid: 7854376
references.citation: Trop Med Int Health. 2013 Apr;18(4):495-503
references.pmid: 23368667
references.citation: HIV Med. 2004 May;5(3):140-3
references.pmid: 15139978
references.citation: Clin Infect Dis. 2003 Jan 1;36(1):86-96
references.pmid: 12491207
references.citation: Clin Infect Dis. 2008 Jun 1;46(11):1694-701
references.pmid: 18433339
references.citation: S Afr Med J. 2011 Apr;101(4):251-2
references.pmid: 21786729
references.citation: HIV Med. 2001 Apr;2(2):78-83
references.pmid: 11737382
references.citation: Health Econ. 1994 Mar-Apr;3(2):95-104
references.pmid: 8044216
references.citation: Clin Infect Dis. 1998 Jan;26(1):186-7
references.pmid: 9455533
references.citation: J Med Assoc Thai. 2006 Jun;89(6):795-802
references.pmid: 16850679
references.citation: HIV Med. 2004 May;5(3):131-2
references.pmid: 15139976
references.citation: Med Decis Making. 1997 Oct-Dec;17(4):373-81
references.pmid: 9343795
references.citation: Antimicrob Agents Chemother. 2000 Jun;44(6):1585-7
references.pmid: 10817713
references.citation: Clin Infect Dis. 1999 May;28(5):1049-56
references.pmid: 10452633
references.citation: Clin Infect Dis. 2008 Jul 1;47(1):123-30
references.pmid: 18505387
references.citation: J Infect Dis. 1999 Feb;179(2):449-54
references.pmid: 9878030
references.citation: J Acquir Immune Defic Syndr. 2007 Aug 15;45(5):555-9
references.pmid: 17577124
references.citation: Clin Infect Dis. 2011 Nov;53(10):1019-23
references.pmid: 21940419
references.citation: J Acquir Immune Defic Syndr. 2008 Apr 15;47(5):644-5
references.pmid: 18362695
references.citation: Cost Eff Resour Alloc. 2006 Dec 06;4:20
references.pmid: 17147833
references.citation: J Acquir Immune Defic Syndr. 2003 Jul 1;33(3):411-2
references.pmid: 12843756
references.citation: J Infect. 2010 Jun;60(6):474-7
references.pmid: 20347868
references.citation: Pharmacoeconomics. 1998 Apr;13(4):397-409
references.pmid: 10178664
references.citation: AIDS. 2009 Feb 20;23(4):525-30
references.pmid: 19182676