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Laboratory-Reflex Cryptococcal Antigen Screening Is Associated With a Survival Benefit in Tanzania

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Date 2018 Nov 14
PMID 30422904
Citations 13
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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.

Citing Articles

Baseline C-reactive Protein as a Risk Factor for Cryptococcal Meningitis and Death in HIV-associated Cryptococcal Antigenemia With CrAg Titer as an Effect Modifier.

Skipper C, Kirumira P, Dai B, Wele A, Naluyima R, Namuli T Open Forum Infect Dis. 2024; 11(8):ofae392.

PMID: 39086467 PMC: 11288378. DOI: 10.1093/ofid/ofae392.


Adjunctive Single-Dose Liposomal Amphotericin to Prevent Cryptococcal Meningitis in People With HIV-Associated Cryptococcal Antigenemia and Low Plasma Cryptococcal Antigen Titers.

Meya D, Nalintya E, Skipper C, Kirumira P, Ayebare P, Naluyima R Clin Infect Dis. 2024; 80(1):129-136.

PMID: 39044381 PMC: 11797045. DOI: 10.1093/cid/ciae266.


Diagnosis and management of cryptococcal meningitis in HIV-infected adults.

McHale T, Boulware D, Kasibante J, Ssebambulidde K, Skipper C, Abassi M Clin Microbiol Rev. 2023; 36(4):e0015622.

PMID: 38014977 PMC: 10870732. DOI: 10.1128/cmr.00156-22.


Cryptococcal meningitis.

Tugume L, Ssebambulidde K, Kasibante J, Ellis J, Wake R, Gakuru J Nat Rev Dis Primers. 2023; 9(1):62.

PMID: 37945681 DOI: 10.1038/s41572-023-00472-z.


Disseminated Cryptococcosis Is a Common Finding among Human Immunodeficiency Virus-Infected Patients with Suspected Sepsis and Is Associated with Higher Mortality Rates.

Tufa T, Orth H, Wienemann T, Jensen B, MacKenzie C, Boulware D J Fungi (Basel). 2023; 9(8).

PMID: 37623607 PMC: 10456031. DOI: 10.3390/jof9080836.


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