Laboratory-Reflex Cryptococcal Antigen Screening Is Associated With a Survival Benefit in Tanzania.
AIDS-Related Opportunistic Infections
/ diagnosis
Adult
Antifungal Agents
/ therapeutic use
Antigens, Fungal
/ therapeutic use
Female
Fluconazole
/ therapeutic use
HIV Infections
/ complications
Humans
Longitudinal Studies
Male
Mass Screening
Meningitis, Cryptococcal
/ diagnosis
Middle Aged
Prevalence
Prospective Studies
Survival Analysis
Tanzania
/ epidemiology
Journal
Journal of acquired immune deficiency syndromes (1999)
ISSN: 1944-7884
Titre abrégé: J Acquir Immune Defic Syndr
Pays: United States
ID NLM: 100892005
Informations de publication
Date de publication:
01 02 2019
01 02 2019
Historique:
pubmed:
14
11
2018
medline:
31
10
2019
entrez:
14
11
2018
Statut:
ppublish
Résumé
Cryptococcal antigen (CrAg) screening in persons with advanced HIV/AIDS is recommended to prevent death. Implementing CrAg screening only in outpatients may underestimate the true CrAg prevalence and decrease its potential impact. Our previous 12-month survival/retention in CrAg-positive persons not treated with fluconazole was 0%. HIV testing was offered to all antiretroviral therapy-naive outpatients and hospitalized patients in Ifakara, Tanzania, followed by laboratory-reflex CrAg screening for CD4 <150 cells/μL. CrAg-positive individuals were offered lumbar punctures, and antifungals were tailored to the presence/absence of meningitis. We assessed the impact on survival and retention-in-care using multivariate Cox-regression models. We screened 560 individuals for CrAg. The median CD4 count was 61 cells/μL (interquartile range 26-103). CrAg prevalence was 6.1% (34/560) among individuals with CD4 ≤150 and 7.5% among ≤100 cells/μL. CrAg prevalence was 2.3-fold higher among hospitalized participants than in outpatients (12% vs 5.3%, P = 0.02). We performed lumbar punctures in 94% (32/34), and 31% (10/34) had cryptococcal meningitis. Mortality did not differ significantly between treated CrAg-positive without meningitis and CrAg-negative individuals (7.3 vs 5.4 deaths per 100 person-years, respectively, P = 0.25). Independent predictors of 6-month death/lost to follow-up were low CD4, cryptococcal meningitis (adjusted hazard ratio 2.76, 95% confidence interval: 1.31 to 5.82), and no antiretroviral therapy initiation (adjusted hazard ratio 3.12, 95% confidence interval: 2.16 to 4.50). Implementing laboratory-reflex CrAg screening among outpatients and hospitalized individuals resulted in a rapid detection of cryptococcosis and a survival benefit. These results provide a model of a feasible, effective, and scalable CrAg screening and treatment strategy integrated into routine care in sub-Saharan Africa.
Sections du résumé
BACKGROUND
Cryptococcal antigen (CrAg) screening in persons with advanced HIV/AIDS is recommended to prevent death. Implementing CrAg screening only in outpatients may underestimate the true CrAg prevalence and decrease its potential impact. Our previous 12-month survival/retention in CrAg-positive persons not treated with fluconazole was 0%.
METHODS
HIV testing was offered to all antiretroviral therapy-naive outpatients and hospitalized patients in Ifakara, Tanzania, followed by laboratory-reflex CrAg screening for CD4 <150 cells/μL. CrAg-positive individuals were offered lumbar punctures, and antifungals were tailored to the presence/absence of meningitis. We assessed the impact on survival and retention-in-care using multivariate Cox-regression models.
RESULTS
We screened 560 individuals for CrAg. The median CD4 count was 61 cells/μL (interquartile range 26-103). CrAg prevalence was 6.1% (34/560) among individuals with CD4 ≤150 and 7.5% among ≤100 cells/μL. CrAg prevalence was 2.3-fold higher among hospitalized participants than in outpatients (12% vs 5.3%, P = 0.02). We performed lumbar punctures in 94% (32/34), and 31% (10/34) had cryptococcal meningitis. Mortality did not differ significantly between treated CrAg-positive without meningitis and CrAg-negative individuals (7.3 vs 5.4 deaths per 100 person-years, respectively, P = 0.25). Independent predictors of 6-month death/lost to follow-up were low CD4, cryptococcal meningitis (adjusted hazard ratio 2.76, 95% confidence interval: 1.31 to 5.82), and no antiretroviral therapy initiation (adjusted hazard ratio 3.12, 95% confidence interval: 2.16 to 4.50).
CONCLUSIONS
Implementing laboratory-reflex CrAg screening among outpatients and hospitalized individuals resulted in a rapid detection of cryptococcosis and a survival benefit. These results provide a model of a feasible, effective, and scalable CrAg screening and treatment strategy integrated into routine care in sub-Saharan Africa.
Identifiants
pubmed: 30422904
doi: 10.1097/QAI.0000000000001899
pmc: PMC6825442
mid: NIHMS1045657
doi:
Substances chimiques
Antifungal Agents
0
Antigens, Fungal
0
Fluconazole
8VZV102JFY
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
205-213Subventions
Organisme : Medical Research Council
ID : MR/S004963/1
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : R01 NS086312
Pays : United States
Organisme : Medical Research Council
ID : MR/M007413/1
Pays : United Kingdom
Références
Trop Med Int Health. 2013 Sep;18(9):1075-1079
pubmed: 23937699
N Engl J Med. 2014 Jun 26;370(26):2487-98
pubmed: 24963568
PLoS One. 2017 Feb 6;12(2):e0171675
pubmed: 28166254
Clin Infect Dis. 2016 Mar 1;62(5):581-587
pubmed: 26565007
Swiss Med Wkly. 2017 Jul 11;147:w14485
pubmed: 28695551
Clin Infect Dis. 2010 Dec 15;51(12):1463-5
pubmed: 21082878
J Acquir Immune Defic Syndr. 2013 Jul 1;63(3):e101-8
pubmed: 23466647
Open Forum Infect Dis. 2015 Apr 02;2(2):ofv046
pubmed: 26213690
Clin Infect Dis. 2009 Apr 1;48(7):856-62
pubmed: 19222372
PLoS One. 2017 Aug 22;12(8):e0182154
pubmed: 28829788
Clin Infect Dis. 2017 Sep 1;65(5):779-786
pubmed: 28505328
Clin Infect Dis. 2014 Dec 1;59(11):1607-14
pubmed: 25057102
J Int Assoc Physicians AIDS Care (Chic). 2012 Nov-Dec;11(6):374-9
pubmed: 23015379
J Trop Med. 2016;2016:6573672
pubmed: 27651801
J Acquir Immune Defic Syndr. 2013 Jun 1;63(2):189-94
pubmed: 23542636
Clin Infect Dis. 2010 Aug 15;51(4):448-55
pubmed: 20597693
Trop Med Int Health. 2016 Dec;21(12):1539-1544
pubmed: 27699970
Trop Med Int Health. 2013 Apr;18(4):495-503
pubmed: 23368667
AIDS. 2015 Nov 28;29(18):2473-8
pubmed: 26372487
Lancet Infect Dis. 2017 Aug;17(8):790-791
pubmed: 28483416
J Int AIDS Soc. 2014 Aug 08;17:19040
pubmed: 25109284
J Infect. 2015 Jul;71(1):110-6
pubmed: 25644318
PLoS One. 2017 Jul 18;12(7):e0180983
pubmed: 28719610
Lancet. 2015 May 30;385(9983):2173-82
pubmed: 25765698
J Int AIDS Soc. 2011 Oct 11;14:48
pubmed: 21988905
Lancet Infect Dis. 2017 Aug;17(8):873-881
pubmed: 28483415
Clin Infect Dis. 2012 Mar 1;54(5):e43-50
pubmed: 22198791
Clin Infect Dis. 2011 Nov;53(10):1019-23
pubmed: 21940419
J Acquir Immune Defic Syndr. 2016 Jun 1;72(2):e37-e42
pubmed: 26926942
J Acquir Immune Defic Syndr. 2012 Apr 15;59(5):e85-91
pubmed: 22410867
Clin Infect Dis. 2014 Jan;58(1):113-6
pubmed: 24065327
PLoS One. 2016 Jul 08;11(7):e0158986
pubmed: 27390864
BMC Infect Dis. 2010 Mar 15;10:67
pubmed: 20230635