1921
Volume 95, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract

In a cross-sectional study among hospitalized human immunodeficiency virus (HIV)–infected patients in Ethiopia, we sought to determine the rates and predictors of cryptococcal disease and evaluate the test performance of a recently introduced point-of-care test for detection in various biological samples. We tested serum, urine, and fingerstick blood samples from each patient with a cryptococcal antigen lateral flow assay (CRAG LFA; Immuno Mycologic Inc., Norman, OK). Cerebrospinal fluid was collected at the discretion of the treating physician. Logistic regression was used to identify risk factors for a positive test result. Agreement between different sample types was also assessed. Among 198 hospitalized HIV-infected patients with a median CD4 count of 93 cells/mm, 18 patients (9.1%) had a positive serum CRAG LFA. Of these, 16 (8.1%) had confirmed cryptococcal meningitis (CM), all of whom had a positive fingerstick blood LFA result. There was a very high agreement between CRAG LFA tests in serum and fingerstick blood samples (κ = 0.97, 95% confidence interval [CI] = 0.91–1.00); this was higher than that between serum and urine samples (κ = 0.76, 95% CI = 0.58–0.93). A CD4 count < 100 cells/mm was significantly associated with a positive CRAG LFA. The absence of fever, headache, meningismus, and neck stiffness had a negative predictive value of 100% for CM. In addition to finding high rates of cryptococcal disease, our study demonstrated that the use of the LFA on fingerstick whole blood is less invasive, and an effective method for CM case finding among hospitalized patients with HIV.

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2016-10-05
2017-11-25
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References

  1. Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM, , 2009. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 23: 525530.[Crossref]
  2. Jarvis JN, Lawn SD, Wood R, Harrison TS, , 2010. Cryptococcal antigen screening for patients initiating antiretroviral therapy: time for action. Clin Infect Dis 51: 14631465.[Crossref]
  3. Chayakulkeeree M, Perfect JR, , 2006. Cryptococcosis. Infect Dis Clin North Am 20: 507544 v–vi.[Crossref]
  4. World Health Organization, 2011. Rapid Advice: Diagnosis, Prevention and Management of Cryptococcal Disease in HIV-Infected Adults, Adolescents and Children. Geneva, Switzerland: World Health Organization, 44.
  5. Huang HR, Fan LC, Rajbanshi B, Xu JF, , 2015. Evaluation of a new cryptococcal antigen lateral flow immunoassay in serum, cerebrospinal fluid and urine for the diagnosis of cryptococcosis: a meta-analysis and systematic review. PLoS One 10: e0127117.[Crossref]
  6. Jarvis JN, Percival A, Bauman S, Pelfrey J, Meintjes G, Williams GN, Longley N, Harrison TS, Kozel TR, , 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: 10191023.[Crossref]
  7. Lindsley MD, Mekha N, Baggett HC, Surinthong Y, Autthateinchai R, Sawatwong P, Harris JR, Park BJ, Chiller T, Balajee SA, Poonwan N, , 2011. Evaluation of a newly developed lateral flow immunoassay for the diagnosis of cryptococcosis. Clin Infect Dis 53: 321325.[Crossref]
  8. Williams DA, Kiiza T, Kwizera R, Kiggundu R, Velamakanni S, Meya DB, Rhein J, Boulware DR, , 2015. Evaluation of fingerstick cryptococcal antigen lateral flow assay in HIV-infected persons: a diagnostic accuracy study. Clin Infect Dis 61: 464467.[Crossref]
  9. Kwizera R, Nguna J, Kiragga A, Nakavuma J, Rajasingham R, Boulware DR, Meya DB, , 2014. Performance of cryptococcal antigen lateral flow assay using saliva in Ugandans with CD4 < 100. PLoS One 9: e103156.[Crossref]
  10. Meyer AC, Jacobson M, , 2013. Asymptomatic cryptococcemia in resource-limited settings. Curr HIV/AIDS Rep 10: 254263.[Crossref]
  11. Wajanga BM, Kalluvya S, Downs JA, Johnson WD, Fitzgerald DW, Peck RN, , 2011. Universal screening of Tanzanian HIV-infected adult inpatients with the serum cryptococcal antigen to improve diagnosis and reduce mortality: an operational study. J Int AIDS Soc 14: 48.[Crossref]
  12. Harris JR, Lindsley MD, Henchaichon S, Poonwan N, Naorat S, Prapasiri P, Chantra S, Ruamcharoen F, Chang LS, Chittaganpitch M, Mehta N, Peruski L, Maloney SA, Park BJ, Baggett HC, , 2012. High prevalence of cryptococcal infection among HIV-infected patients hospitalized with pneumonia in Thailand. Clin Infect Dis 54: e43e50.[Crossref]
  13. Immuno-Mycologics Inc., 2003. CrAg Lateral Flow Assay For the Detection of Cryptococcal Antigen. Norman, OK: Immuno-Mycologics Inc. Available at: http://www.immy.com/wp-content/uploads/2016/07/CR2003-CrAg-LFA-PI-Intl-2.pdf.
  14. Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, Harrison TS, Larsen RA, Lortholary O, Nguyen MH, Pappas PG, Powderly WG, Singh N, Sobel JD, Sorrell TC, , 2010. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 50: 291322.[Crossref]
  15. Hosmer DW, Lemeshow S, , 2000. Applied Logistic Regression. New York, NY: Wiley.[Crossref]
  16. Alemu AS, Kempker RR, Tenna A, Smitson C, Berhe N, Fekade D, Blumberg HM, Aseffa A, , 2013. High prevalence of cryptococcal antigenemia among HIV-infected patients receiving antiretroviral therapy in Ethiopia. PLoS One 8: e58377.[Crossref]
  17. Boulware DRRM, Rajasingham R, von Hohenberg M, Qin Z, Taseera K, Schutz C, Kwizera R, Butler EK, Meintjes G, Muzoora C, Bischof JC, Meya DB, , 2014. Multisite validation of cryptococcal antigen lateral flow assay and quantification by laser thermal contrast. Emerg Infect Dis 20: 4553.[Crossref]
  18. Andama AO, den Boon S, Meya D, Cattamanchi A, Worodria W, Davis JL, Walter ND, Yoo SD, Kalema N, Haller B, Huang L, International HIV-Associated Opportunistic Pneumonias Study, , 2013. Prevalence and outcomes of cryptococcal antigenemia in HIV-seropositive patients hospitalized for suspected tuberculosis in Uganda. J Acquir Immune Defic Syndr 63: 189194.[Crossref]
  19. Manabe YC, Nonyane BA, Nakiyingi L, Mbabazi O, Lubega G, Shah M, Moulton LH, Joloba M, Ellner J, Dorman SE, , 2014. Point-of-care lateral flow assays for tuberculosis and cryptococcal antigenuria predict death in HIV infected adults in Uganda. PLoS One 9: e101459.[Crossref]
  20. Getahun H, Kittikraisak W, Heilig CM, Corbett EL, Ayles H, Cain KP, Grant AD, Churchyard GJ, Kimerling M, Shah S, Lawn SD, Wood R, Maartens G, Granich R, Date AA, Varma JK, , 2011. Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies. PLoS Med 8: e1000391.[Crossref]
  21. Zaeh S, Kempker R, Stenehjem E, Blumberg HM, Temesgen O, Ofotokun I, Tenna A, , 2013. Improving tuberculosis screening and isoniazid preventive therapy in an HIV clinic in Addis Ababa, Ethiopia. Int J Tuberc Lung Dis 17: 13961401.[Crossref]
  22. Meda J, Kalluvya S, Downs JA, Chofle AA, Seni J, Kidenya B, Fitzgerald DW, Peck RN, , 2014. Cryptococcal meningitis management in Tanzania with strict schedule of serial lumbar punctures using intravenous tubing sets: an operational research study. J Acquir Immune Defic Syndr 66: e31e36.
  23. Boulware DR, Meya DB, Muzoora C, Rolfes MA, Huppler Hullsiek K, Musubire A, Taseera K, Nabeta HW, Schutz C, Williams DA, Rajasingham R, Rhein J, Thienemann F, Lo MW, Nielsen K, Bergemann TL, Kambugu A, Manabe YC, Janoff EN, Bohjanen PR, Meintjes G, for the COAT Trial Team, , 2014. Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. N Engl J Med 370: 24872498.[Crossref]
  24. Longley N, Jarvis JN, Meintjes G, Boulle A, Cross A, Kelly N, Govender NP, Bekker LG, Wood R, Harrison TS, , 2016. Cryptococcal antigen screening in patients initiating ART in South Africa: a prospective cohort study. Clin Infect Dis 62: 581587.[Crossref]
  25. Jackson A, van der Horst C, , 2012. New insights in the prevention, diagnosis, and treatment of cryptococcal meningitis. Curr HIV/AIDS Rep 9: 267277.[Crossref]
  26. McMullan BJ, Halliday C, Sorrell TC, Judd D, Sleiman S, Marriott D, Olma T, Chen SC, , 2012. Clinical utility of the cryptococcal antigen lateral flow assay in a diagnostic mycology laboratory. PLoS One 7: e49541.[Crossref]
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  • Received : 28 Nov 2015
  • Accepted : 28 Jun 2016

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