Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Mar 1;62(5):581-587.
doi: 10.1093/cid/civ936. Epub 2015 Nov 12.

Cryptococcal Antigen Screening in Patients Initiating ART in South Africa: A Prospective Cohort Study

Nicky Longley  1   2   3 , Joseph Nicholas Jarvis  4   5   6 , Graeme Meintjes  3 , Andrew Boulle  7   8 , Anna Cross  1 , Nicola Kelly  1 , Nelesh P Govender  9   10 , Linda-Gail Bekker  1   3 , Robin Wood  1   3 , Thomas S Harrison  2
Affiliations

Cryptococcal Antigen Screening in Patients Initiating ART in South Africa: A Prospective Cohort Study

Nicky Longley et al. Clin Infect Dis. .

Abstract

Background: Retrospective data suggest that cryptococcal antigen (CrAg) screening in patients with late-stage human immunodeficiency virus (HIV) initiating antiretroviral therapy (ART) may reduce cryptococcal disease and deaths. Prospective data are limited.

Methods: CrAg was measured using lateral flow assays (LFA) and latex agglutination (LA) tests in 645 HIV-positive, ART-naive patients with CD4 counts ≤100 cells/µL in Cape Town, South Africa. CrAg-positive patients were offered lumbar puncture (LP) and treated with antifungals. Patients were started on ART between 2 and 4 weeks and followed up for 1 year.

Results: A total of 4.3% (28/645) of patients were CrAg positive in serum and plasma with LFA. These included 16 also positive by urine LFA (2.5% of total screened) and 7 by serum LA (1.1% of total). In 4 of 10 LFA-positive cases agreeing to LP, the cerebrospinal fluid (CSF) CrAg LFA was positive. A positive CSF CrAg was associated with higher screening plasma/serum LFA titers.Among the 28 CrAg-positive patients, mortality was 14.3% at 10 weeks and 25% at 12 months. Only 1 CrAg-positive patient, who defaulted from care, died from cryptococcal meningitis (CM). Mortality in CrAg-negative patients was 11.5% at 1 year. Only 2 possible CM cases were identified in CrAg-negative patients.

Conclusions: CrAg screening of individuals initiating ART and preemptive fluconazole treatment of CrAg-positive patients resulted in markedly fewer cases of CM compared with historic unscreened cohorts. Studies are needed to refine management of CrAg-positive patients who have high mortality that does not appear to be wholly attributable to cryptococcal disease.

Keywords: HIV; antiretroviral therapy; cryptococcal antigen; cryptococcal meningitis; screening.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Flow of patients from study inclusion through to discharge. Abbreviations: ART, antiretroviral therapy; CM, cryptococcal meningitis; CrAg, cryptococcal antigen; CSF, cerebrospinal fluid; LA, latex agglutination assay; LFA, lateral flow assay; LP, lumbar puncture; LTFU, lost to follow up.
Figure 2.
Figure 2.
Kaplan–Meyer survival curves showing survival over time in patients screening cryptococcal antigen (CrAg) positive with lateral flow assay (n = 28) compared with those screening CrAg negative (n = 617). Abbreviation: LFA, lateral flow assay.
See this image and copyright information in PMC

Comment in

References

    1. Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 2009; 23:525–30. - PubMed
    1. French N, Gray K, Watera C et al. Cryptococcal infection in a cohort of HIV-1-infected Ugandan adults. AIDS 2002; 16:1031–8. - PubMed
    1. Okongo M, Morgan D, Mayanja B, Ross A, Whitworth J. Causes of death in a rural, population-based human immunodeficiency virus type 1 (HIV-1) natural history cohort in Uganda. Int J Epidemiol 1998; 27:698–702. - PubMed
    1. Corbett EL, Churchyard GJ, Charalambos S et al. Morbidity and mortality in South African gold miners: impact of untreated disease due to human immunodeficiency virus. Clin Infect Dis 2002; 34:1251–8. - PubMed
    1. Holmes CB, Losina E, Walensky RP, Yazdanpanah Y, Freedberg KA. Review of human immunodeficiency virus type 1-related opportunistic infections in sub-Saharan Africa. Clin Infect Dis 2003; 36:652–62. - PubMed

Publication types

MeSH terms