Performance of cryptococcal antigen lateral flow assay using saliva in Ugandans with CD4 Richard Kwizera  1 , Joyce Nguna  1 , Agnes Kiragga  1 , Jesca Nakavuma  2 , Radha Rajasingham  3 , David R Boulware  4 , David B Meya  5 Affiliations Expand Affiliations 1 Infectious Diseases Institute, Makerere University, Kampala, Uganda. 2 College of Veterinary Medicine, Animal Resource and Biosecurity, Makerere University, Kampala, Uganda. 3 Infectious Diseases Institute, Makerere University, Kampala, Uganda; Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America. 4 Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America. 5 Infectious Diseases Institute, Makerere University, Kampala, Uganda; Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America; Makerere University College of Health Sciences, School of Medicine, Department of Medicine, Kampala, Uganda. PMID: 25078453 PMCID: PMC4117530 DOI: 10.1371/journal.pone.0103156 Free PMC article Item in Clipboard

Richard Kwizera, Joyce Nguna, Agnes Kiragga, Jesca Nakavuma, Radha Rajasingham, David R Boulware, David B Meya, Richard Kwizera, Joyce Nguna, Agnes Kiragga, Jesca Nakavuma, Radha Rajasingham, David R Boulware, David B Meya

Abstract

Background: Cryptococcal meningitis can best be diagnosed by cerebrospinal fluid India ink microscopy, cryptococcal antigen detection, or culture. These require invasive lumbar punctures. The utility of cryptococcal antigen detection in saliva is unknown. We evaluated the diagnostic performance of the point-of-care cryptococcal antigen lateral flow assay (CrAg LFA) in saliva.

Methods: We screened HIV-infected, antiretroviral therapy naïve persons with symptomatic meningitis (n = 130) and asymptomatic persons with CD4+<100 cells/µL entering into HIV care (n = 399) in Kampala, Uganda. The diagnostic performance of testing saliva was compared to serum/plasma cryptococcal antigen as the reference standard.

Results: The saliva lateral flow assay performance was overall more sensitive in symptomatic patients (88%) than in asymptomatic patients (27%). The specificity of saliva lateral flow assay was excellent at 97.8% in the symptomatic patients and 100% in asymptomatic patients. The degree of accuracy of saliva in diagnosing cryptococcosis and the level of agreement between the two sample types was better in symptomatic patients (C-statistic 92.9, κ-0.82) than in asymptomatic patients (C-statistic 63.5, κ-0.41). Persons with false negative salvia CrAg tests had lower levels of peripheral blood CrAg titers (P<0.001).

Conclusion: There was poor diagnostic performance in testing saliva for cryptococcal antigen, particularly among asymptomatic persons screened for preemptive treatment of cryptococcosis.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. The Study enrollment and Analysis…
Figure 1. The Study enrollment and Analysis populations.
The figure displays the distribution of the participants tested, consisting of HIV-infected persons from: 1) symptomatic meningitis cohort or 2) asymptomatic outpatient cohort with CD4

References

    1. Durski KN, Kuntz KM, Yasukawa K, Virnig BA, Meya DB, et al. (2013) Cost-effective diagnostic checklists for meningitis in resource-limited settings. J Acquir Immune Defic Syndr 63: e101–108.
    1. French N, Gray K, Watera C, Nakiyingi J, Lugada E, et al. (2002) Cryptococcal infection in a cohort of HIV-1-infected Ugandan adults. AIDS 16: 1031–1038.
    1. Liechty CA, Solberg P, Were W, Ekwaru JP, Ransom RL, et al. (2007) Asymptomatic serum cryptococcal antigenemia and early mortality during antiretroviral therapy in rural Uganda. Trop Med Int Health 12: 929–935.
    1. Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, et al. (2009) Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 23: 525–530.
    1. Rajasingham R, Rolfes MA, Birkenkamp KE, Meya DB, Boulware DR (2012) Cryptococcal meningitis treatment strategies in resource-limited settings: a cost-effectiveness analysis. PLoS Med 9: e1001316.
    1. Butler EK, Boulware DR, Bohjanen PR, Meya DB (2012) Long term 5-year survival of persons with cryptococcal meningitis or asymptomatic subclinical antigenemia in Uganda. PLoS One 7: e51291.
    1. Jarvis JN, Meintjes G, Williams A, Brown Y, Crede T, et al. (2010) Adult meningitis in a setting of high HIV and TB prevalence: findings from 4961 suspected cases. BMC Infect Dis 10: 67.
    1. Meya DB, Manabe YC, Castelnuovo B, Cook BA, Elbireer AM, et al. (2010) Cost-effectiveness of serum cryptococcal antigen screening to prevent deaths among HIV-infected persons with a CD4+ cell count < or = 100 cells/microL who start HIV therapy in resource-limited settings. Clin Infect Dis 51: 448–455.
    1. Rajasingham R, Meya DB, Boulware DR (2012) Integrating cryptococcal antigen screening and pre-emptive treatment into routine HIV care. J Acquir Immune Defic Syndr 59: e85–91.
    1. Jarvis JN, Harrison TS, Lawn SD, Meintjes G, Wood R, et al. (2013) Cost Effectiveness of Cryptococcal Antigen Screening as a Strategy to Prevent HIV-Associated Cryptococcal Meningitis in South Africa. PLoS One 8: e69288.
    1. Alemu AS, Kempker RR, Tenna A, Smitson C, Berhe N, et al. (2013) High prevalence of cryptococcal antigenemia among HIV-infected patients receiving antiretroviral therapy in Ethiopia. PLoS One 8: e58377.
    1. Boulware DR, Rolfes MA, Rajasingham R, von Hohenberg M, Qin Z, et al. (2014) Multisite validation of cryptococcal antigen lateral flow assay and quantification by laser thermal contrast. Emerg Infect Dis 20: 45–53.
    1. Jarvis JN, Percival A, Bauman S, Pelfrey J, Meintjes G, et al. (2011) 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 53: 1019–1023.
    1. Lindsley MD, Mekha N, Baggett HC, Surinthong Y, Autthateinchai R, et al. (2011) Evaluation of a newly developed lateral flow immunoassay for the diagnosis of cryptococcosis. Clin Infect Dis 53: 321–325.
    1. Boulware DR, Meya DB, Muzoora C, Rolfes MA, Huppler Hullsiek K, et al. (2014) Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. N Engl J Med 370: 2487–2498.
    1. World Health Organization (2011) Rapid advice: Diagnosis, prevention and management of cryptococcal disease in HIV-infected adults, adolescents and children. Geneva: World Health Organization. Available: . Accessed 2012 May 31.

Source: PubMed

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