Evaluation of fingerstick cryptococcal antigen lateral flow assay in HIV-infected persons: a diagnostic accuracy study

Darlisha A Williams, Tadeo Kiiza, Richard Kwizera, Reuben Kiggundu, Sruti Velamakanni, David B Meya, Joshua Rhein, David R Boulware, Darlisha A Williams, Tadeo Kiiza, Richard Kwizera, Reuben Kiggundu, Sruti Velamakanni, David B Meya, Joshua Rhein, David R Boulware

Abstract

Background: Cryptococcus neoformans is the most common cause of adult meningitis in sub-Saharan Africa. The cryptococcal antigen (CRAG) lateral flow assay (LFA) has simplified diagnosis as a point-of-care test approved for serum or cerebrospinal fluid (CSF). We evaluated the accuracy of the CRAG LFA using fingerstick whole blood compared with serum/plasma and CSF for diagnosing meningitis.

Methods: From August 2013 to August 2014, CRAG LFA (IMMY, Norman, Oklahoma) tests were performed on fingerstick whole blood, plasma/serum, and CSF in 207 HIV-infected adults with suspected meningitis in Kampala, Uganda. Venous blood was also collected and centrifuged to obtain serum and/or plasma. CSF was tested after lumbar puncture.

Results: Of 207 participants, 149 (72%) had fingerstick CRAG-positive results. There was 100% agreement between fingerstick whole blood and serum/plasma. Of the 149 fingerstick CRAG-positive participants, 138 (93%) had evidence of cryptococcal meningitis with a positive CSF CRAG. Eleven participants (5%) had isolated cryptococcal antigenemia with a negative CSF CRAG and culture, of whom 8 had CSF abnormalities (n = 3 lymphocytic pleocytosis, n = 5 elevated protein, n = 4 increased opening pressure). No persons with cryptococcal meningitis had negative fingersticks.

Conclusions: The 100% agreement between whole blood, serum, and plasma CRAG LFA results demonstrates that fingerstick CRAG is a reliable bedside diagnostic test. Using point-of-care CRAG testing simplifies screening large numbers of patients and enables physicians to prioritize on whom to measure CSF opening pressure using manometers.

Keywords: HIV; cryptococcal meningitis; cryptococcus; lateral flow assay; point-of-care systems.

© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Distribution of cryptococcal diagnostics in blood and cerebrospinal fluid (CSF). The concordance of fingerstick cryptococcal antigen (CRAG) testing was κ = 1.0 for blood (P = .99) and κ = 0.947 for CSF representing 5% of participants (n = 11) having isolated cryptococcal antigenemia in peripheral blood with early disseminated cryptococcal infection but without microbiologically proven meningeal involvement. Of these 11 blood CRAG-positive and CSF CRAG-negative participants, 8 participants had abnormal CSF profiles with CSF inflammation or increased opening pressure. Fifty-eight participants were negative for all cryptococcal testing in blood and CSF. No person had CSF cryptococcal involvement by CRAG or culture who was CRAG-negative by fingerstick or in peripheral blood.

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.
    1. Group for Enteric, Respiratory and Meningeal disease Surveillance in South Africa. GERMS-SA annual report 2012. Available at: . Accessed 7 April 2015.
    1. Durski KN, Kuntz KM, Yasukawa K, Virnig BA, Meya DB, Boulware DR. Cost-effective diagnostic checklists for meningitis in resource-limited settings. J Acquir Immune Defic Syndr 2013; 63:e101–8.
    1. Jarvis JN, Meintjes G, Williams A, Brown Y, Crede T, Harrison TS. Adult meningitis in a setting of high HIV and TB prevalence: findings from 4961 suspected cases. BMC Infect Dis 2010; 10:67.
    1. Cohen DB, Zijlstra EE, Mukaka M, et al. Diagnosis of cryptococcal and tuberculous meningitis in a resource-limited African setting. Trop Med Int Health 2010; 15:910–7.
    1. Hakim JG, Gangaidzo IT, Heyderman RS, et al. Impact of HIV infection on meningitis in Harare, Zimbabwe: a prospective study of 406 predominantly adult patients. AIDS 2000; 14:1401–7.
    1. Siddiqi OK, Ghebremichael M, Dang X, et al. Molecular diagnosis of central nervous system opportunistic infections in HIV-infected Zambian adults. Clin Infect Dis 2014; 58:1771–7.
    1. Boulware DR, Rolfes MA, Rajasingham R, et al. Multisite validation of cryptococcal antigen lateral flow assay and quantification by laser thermal contrast. Emerg Infect Dis 2014; 20:45–53.
    1. Jarvis JN, Percival A, Bauman S, et al. Evaluation of a novel point-of-care cryptococcal antigen test on serum, plasma, and urine from patients with HIV-associated cryptococcal meningitis. Clin Infect Dis 2011; 53:1019–23.
    1. Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 2010; 50:291–322.
    1. Rolfes MA, Hullsiek KH, Rhein J, et al. The effect of therapeutic lumbar punctures on acute mortality from cryptococcal meningitis. Clin Infect Dis 2014; 59:1607–14.
    1. Bicanic T, Brouwer AE, Meintjes G, et al. Relationship of cerebrospinal fluid pressure, fungal burden and outcome in patients with cryptococcal meningitis undergoing serial lumbar punctures. AIDS 2009; 23:701–6.
    1. Meda J, Kalluvya S, Downs JA, et al. Cryptococcal meningitis management in Tanzania with strict schedule of serial lumber punctures using intravenous tubing sets: an operational research study. J Acquir Immune Defic Syndr 2014; 66:e31–6.
    1. Bicanic T, Meintjes G, Wood R, et al. Fungal burden, early fungicidal activity, and outcome in cryptococcal meningitis in antiretroviral-naive or antiretroviral-experienced patients treated with amphotericin B or fluconazole. Clin Infect Dis 2007; 45:76–80.
    1. Kwizera R, Nguna J, Kiragga A, et al. Performance of cryptococcal antigen lateral flow assay using saliva in Ugandans with CD4 <100. PLoS One 2014; 9:e103156.
    1. World Health Organization. Rapid advice: diagnosis, prevention and management of cryptococcal disease in HIV-infected adults, adolescents and children. Geneva, Switzerland: WHO, 2011.
    1. Boulware DR, Meya DB, Muzoora C, et al. Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. N Engl J Med 2014; 370:2487–98.
    1. Trachtenberg JD, Kambugu AD, McKellar M, et al. The medical management of central nervous system infections in Uganda and the potential impact of an algorithm-based approach to improve outcomes. Int J Infect Dis 2007; 11:524–30.

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