Laboratory-reflex cryptococcal antigen screening is associated with a survival benefit in tanzania

Diana Faini; Aneth Vedastus Kalinjuma; Andrew Katende; Gladys Mbwaji; Dorcas Mnzava; Amina Nyuri; Tracy R. Glass; Hansjakob Furrer; Christoph Hatz; David R. Boulware; Emilio Letang

doi:10.1097/QAI.0000000000001899

Laboratory-reflex cryptococcal antigen screening is associated with a survival benefit in tanzania

Diana Faini, Aneth Vedastus Kalinjuma, Andrew Katende, Gladys Mbwaji, Dorcas Mnzava, Amina Nyuri, Tracy R. Glass, Hansjakob Furrer, Christoph Hatz, David R. Boulware, Emilio Letang

Medicine - Infectious Disease and International Medicine

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	205-213
Number of pages	9
Journal	Journal of Acquired Immune Deficiency Syndromes
Volume	80
Issue number	2
DOIs	https://doi.org/10.1097/QAI.0000000000001899
State	Published - Feb 1 2019

Bibliographical note

Publisher Copyright:
© 2018 Wolters Kluwer Health, Inc. All rights reserved.

Keywords

HIV
cryptococcal antigenemia
cryptococcal meningitis
fluconazole
mortality
sub-Saharan Africa
Tanzania/epidemiology
Prevalence
Prospective Studies
Humans
Middle Aged
Antigens, Fungal/therapeutic use
Male
AIDS-Related Opportunistic Infections/diagnosis
Meningitis, Cryptococcal/diagnosis
Mass Screening
HIV Infections/complications
Fluconazole/therapeutic use
Survival Analysis
Adult
Female
Antifungal Agents/therapeutic use
Longitudinal Studies

PubMed: MeSH publication types

Research Support, Non-U.S. Gov't
Journal Article
Research Support, N.I.H., Extramural

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1097/QAI.0000000000001899

https://boris.unibe.ch/121421/1/00126334-900000000-96521.pdf

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title = "Laboratory-reflex cryptococcal antigen screening is associated with a survival benefit in tanzania",

abstract = "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.",

keywords = "HIV, cryptococcal antigenemia, cryptococcal meningitis, fluconazole, mortality, sub-Saharan Africa, Tanzania/epidemiology, Prevalence, Prospective Studies, Humans, Middle Aged, Antigens, Fungal/therapeutic use, Male, AIDS-Related Opportunistic Infections/diagnosis, Meningitis, Cryptococcal/diagnosis, Mass Screening, HIV Infections/complications, Fluconazole/therapeutic use, Survival Analysis, Adult, Female, Antifungal Agents/therapeutic use, Longitudinal Studies",

author = "Diana Faini and Kalinjuma, {Aneth Vedastus} and Andrew Katende and Gladys Mbwaji and Dorcas Mnzava and Amina Nyuri and Glass, {Tracy R.} and Hansjakob Furrer and Christoph Hatz and Boulware, {David R.} and Emilio Letang",

year = "2019",

month = feb,

day = "1",

doi = "10.1097/QAI.0000000000001899",

language = "English (US)",

volume = "80",

pages = "205--213",

journal = "Journal of Acquired Immune Deficiency Syndromes",

issn = "1525-4135",

publisher = "Wolters Kluwer Health",

number = "2",

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TY - JOUR

T1 - Laboratory-reflex cryptococcal antigen screening is associated with a survival benefit in tanzania

AU - Faini, Diana

AU - Kalinjuma, Aneth Vedastus

AU - Katende, Andrew

AU - Mbwaji, Gladys

AU - Mnzava, Dorcas

AU - Nyuri, Amina

AU - Glass, Tracy R.

AU - Furrer, Hansjakob

AU - Hatz, Christoph

AU - Boulware, David R.

AU - Letang, Emilio

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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.

AB - 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.

KW - HIV

KW - cryptococcal antigenemia

KW - cryptococcal meningitis

KW - fluconazole

KW - mortality

KW - sub-Saharan Africa

KW - Tanzania/epidemiology

KW - Prevalence

KW - Prospective Studies

KW - Humans

KW - Middle Aged

KW - Antigens, Fungal/therapeutic use

KW - Male

KW - AIDS-Related Opportunistic Infections/diagnosis

KW - Meningitis, Cryptococcal/diagnosis

KW - Mass Screening

KW - HIV Infections/complications

KW - Fluconazole/therapeutic use

KW - Survival Analysis

KW - Adult

KW - Female

KW - Antifungal Agents/therapeutic use

KW - Longitudinal Studies

UR - http://www.scopus.com/inward/record.url?scp=85059918143&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059918143&partnerID=8YFLogxK

U2 - 10.1097/QAI.0000000000001899

DO - 10.1097/QAI.0000000000001899

M3 - Article

C2 - 30422904

AN - SCOPUS:85059918143

SN - 1525-4135

VL - 80

SP - 205

EP - 213

JO - Journal of Acquired Immune Deficiency Syndromes

JF - Journal of Acquired Immune Deficiency Syndromes

IS - 2

ER -

Laboratory-reflex cryptococcal antigen screening is associated with a survival benefit in tanzania

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

Publisher link

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