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

12 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

Funding Information:
Supported by the Meningitis Research Foundation (MRF 1505) and the National Institute of Neurologic Diseases and Stroke (R01NS086312) and United Kingdom Medical Research Council (MR/M007413/1). The Chronic Diseases of Ifakara receives funding from the Government of Tanzania, the Government of the Canton of Basel, the Swiss Tropical and Public Health Institute, and the Ifakara Health Institute.

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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@article{6c3ac32708b140a4b99a2c34d29726f5,

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",

note = "Funding Information: Supported by the Meningitis Research Foundation (MRF 1505) and the National Institute of Neurologic Diseases and Stroke (R01NS086312) and United Kingdom Medical Research Council (MR/M007413/1). The Chronic Diseases of Ifakara receives funding from the Government of Tanzania, the Government of the Canton of Basel, the Swiss Tropical and Public Health Institute, and the Ifakara Health Institute. Publisher Copyright: {\textcopyright} 2018 Wolters Kluwer Health, Inc. All rights reserved.",

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 and Human Retrovirology",

issn = "1525-4135",

publisher = "Lippincott Williams and Wilkins",

number = "2",

}

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

N1 - Funding Information: Supported by the Meningitis Research Foundation (MRF 1505) and the National Institute of Neurologic Diseases and Stroke (R01NS086312) and United Kingdom Medical Research Council (MR/M007413/1). The Chronic Diseases of Ifakara receives funding from the Government of Tanzania, the Government of the Canton of Basel, the Swiss Tropical and Public Health Institute, and the Ifakara Health Institute. Publisher Copyright: © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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

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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 and Human Retrovirology

JF - Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology

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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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