Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 20, Number 1—January 2014
Research

Multisite Validation of Cryptococcal Antigen Lateral Flow Assay and Quantification by Laser Thermal Contrast

David R. BoulwareComments to Author , Melissa A. Rolfes, Radha Rajasingham, Maximilian von Hohenberg, Zhenpeng Qin, Kabanda Taseera, Charlotte Schutz, Richard Kwizera, Elissa K. Butler, Graeme Meintjes, Conrad Muzoora, John C. Bischof, and David B. Meya
Author affiliations: University of Minnesota, Minneapolis, Minnesota, USA (D.R. Boulware, M.A. Rolfes, R. Rajasingham, M. von Hohenberg, Z. Qin, E.K. Butler, J.C. Bischof, D.B. Meya); Makerere University, Kampala, Uganda (R. Rajasingham, R.K. Kwizera, D.B. Meya); Mbarara University of Science and Technology, Mbarara, Uganda (K. Taseera, C. Muzoora); G.F. Jooste Hospital, Cape Town, South Africa (C. Schutz, G. Meintjes); University of Cape Town, Cape Town (C. Schutz, G. Meintjes)

Main Article

Figure 3

A) Prediction of cryptococcal antigen titer based on laser thermal contrast measurement and concept of lateral flow immunochromatographic assay (LFA) thermal contrast measurement in which a laser irradiates the test line in the LFA (19). The test line is formed by gold–monoclonal antibody–antigen sandwich complex with a monoclonal antibody affixed at the test line. When irradiated by a green laser (532 nm), any gold present absorbs light from the laser and generates heat in direct proportion to

Figure 3. . A) Prediction of cryptococcal antigen titer based on laser thermal contrast measurement and concept of lateral flow immunochromatographic assay (LFA) thermal contrast measurement in which a laser irradiates the test line in the LFA (19). The test line is formed by gold–monoclonal antibody–antigen sandwich complex with a monoclonal antibody affixed at the test line. When irradiated by a green laser (532 nm), any gold present absorbs light from the laser and generates heat in direct proportion to the amount of gold (and thereby antigen) present at the test line. This temperature change can be measured by using an infrared camera. B) Association of measured semiquantitative LFA cryptococcal antigen (CRAG) titer starting at a 1:250 dilution by the predicted CRAG titer based on thermal contrast measurement. Measurements on the negative portion of the x-axis are beyond the visual range when specimens were diluted 1:250, yet still detectable by thermal contrast. The Pearson correlation coefficient was r = 0.91 (p<0.001, R2 = 0.84) among 115 positive specimens quantified. A total of 58 LFA CRAG–negative specimens established background levels of heat radiation.

Main Article

References
  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 .DOIPubMed
  2. Hakim  JG, Gangaidzo  IT, Heyderman  RS, Mielke  J, Mushangi  E, Taziwa  A, Impact of HIV infection on meningitis in Harare, Zimbabwe: a prospective study of 406 predominantly adult patients. AIDS. 2000;14:1401–7 .DOIPubMed
  3. Cohen  DB, Zijlstra  EE, Mukaka  M, Reiss  M, Kamphambale  S, Scholing  M, Diagnosis of cryptococcal and tuberculous meningitis in a resource-limited African setting. Trop Med Int Health. 2010;15:910–7 .DOIPubMed
  4. 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 .DOIPubMed
  5. 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 .DOIPubMed
  6. French  N, Gray  K, Watera  C, Nakiyingi  J, Lugada  E, Moore  M, Cryptococcal infection in a cohort of HIV-1-infected Ugandan adults. AIDS. 2002;16:1031–8 .DOIPubMed
  7. Liechty  CA, Solberg  P, Were  W, Ekwaru  JP, Ransom  RL, Weidle  PJ, Asymptomatic serum cryptococcal antigenemia and early mortality during antiretroviral therapy in rural Uganda. Trop Med Int Health. 2007;12:929–35 .DOIPubMed
  8. World Health Organization. Rapid advice: diagnosis, prevention and management of cryptococcal disease in HIV-infected adults, adolescents and children, 2011 [cited 2012 May 31]. http:// www.who.int/hiv/pub/cryptococcal_disease2011
  9. Jarvis  JN, Govender  N, Chiller  T, Park  BJ, Longley  N, Meintjes  G, Cryptococcal antigen screening and preemptive therapy in patients initiating antiretroviral therapy in resource-limited settings: a proposed algorithm for clinical implementation. J Int Assoc Physicians AIDS Care (Chic). 2012;11:374–9 .DOIPubMed
  10. Rajasingham  R, Meya  DB, Boulware  DR. Integrating cryptococcal antigen screening and pre-emptive treatment into routine HIV care. J Acquir Immune Defic Syndr. 2012;59:e85–91 .DOIPubMed
  11. Bicanic  T, Harrison  TS. Cryptococcal meningitis. Br Med Bull. 2004;72:99–118 .DOIPubMed
  12. Kambugu  A, Meya  DB, Rhein  J, O’Brien  M, Janoff  EN, Ronald  AR, Outcomes of cryptococcal meningitis in Uganda before and after the availability of highly active antiretroviral therapy. Clin Infect Dis. 2008;46:1694–701 .DOIPubMed
  13. Kisenge  PR, Hawkins  AT, Maro  VP, McHele  JP, Swai  NS, Mueller  A, Low CD4 count plus coma predicts cryptococcal meningitis in Tanzania. BMC Infect Dis. 2007;7:39 .DOIPubMed
  14. Trachtenberg  JD, Kambugu  AD, McKellar  M, Semitala  F, Mayanja-Kizza  H, Samore  MH, 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 .DOIPubMed
  15. Brouwer  AE, Teparrukkul  P, Pinpraphaporn  S, Larsen  RA, Chierakul  W, Peacock  S, Baseline correlation and comparative kinetics of cerebrospinal fluid colony-forming unit counts and antigen titers in cryptococcal meningitis. J Infect Dis. 2005;192:681–4 .DOIPubMed
  16. Taseera  K, Siedner  MJ, Klausner  JD, Muzoora  C, Boulware  DR. Point-of-care diagnosis and prognostication of cryptococcal meningitis with the cryptococcal antigen lateral flow assay on cerebrospinal fluid. [Epub ahead of print]. Clin Infect Dis. 2013.
  17. Diamond  RD, Bennett  JE. Prognostic factors in cryptococcal meningitis. A study in 111 cases. Ann Intern Med. 1974;80:176–81 .DOIPubMed
  18. Boulware  DR, Meya  DB, Bergemann  TL, Wiesner  DL, Rhein  J, Musubire  A, Clinical features and serum biomarkers in HIV immune reconstitution inflammatory syndrome after cryptococcal meningitis: a prospective cohort study. PLoS Med. 2010;7:e1000384 .DOIPubMed
  19. Qin  Z, Chan  WC, Boulware  DR, Akkin  T, Butler  EK, Bischof  JC. Significantly improved analytical sensitivity of lateral flow immunoassays by using thermal contrast. Angew Chem Int Ed Engl. 2012;51:4358–61 .DOIPubMed
  20. Boulware  DR, Bonham  SC, Meya  DB, Wiesner  DL, Park  GS, Kambugu  A, Paucity of initial cerebrospinal fluid inflammation in cryptococcal meningitis is associated with subsequent immune reconstitution inflammatory syndrome. J Infect Dis. 2010;202:962–70 .DOIPubMed
  21. Brouwer  AE, Rajanuwong  A, Chierakul  W, Griffin  GE, Larsen  RA, White  NJ, Combination antifungal therapies for HIV-associated cryptococcal meningitis: a randomised trial. Lancet. 2004;363:1764–7 .DOIPubMed
  22. Bicanic  T, Meintjes  G, Wood  R, Hayes  M, Rebe  K, Bekker  LG, 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 .DOIPubMed
  23. Wiesner  DL, Moskalenko  O, Corcoran  JM, McDonald  T, Rolfes  MA, Meya  DB, Cryptococcal genotype influences immunologic response and human clinical outcome after meningitis. MBio. 2012;3:e00196–12 .DOIPubMed
  24. Jarvis  JN, Percival  A, Bauman  S, Pelfrey  J, Meintjes  G, Williams  GN, 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 .DOIPubMed
  25. Gates-Hollingsworth  MA, Kozel  TR. Serotype sensitivity of a lateral flow immunoassay for cryptococcal antigen. Clin Vaccine Immunol. 2013;20:634–5 .DOIPubMed
  26. Rutjes  AW, Reitsma  JB, Coomarasamy  A, Khan  KS, Bossuyt  PM. Evaluation of diagnostic tests when there is no gold standard. A review of methods. Health Technol Assess. 2007;11:iii: ix–51.
  27. Meya  DB, Manabe  YC, Castelnuovo  B, Cook  BA, Elbireer  AM, Kambugu  A, Cost-effectiveness of serum cryptococcal antigen screening to prevent deaths among HIV-infected persons with a CD4+ cell count ≤100 cells/microL who start HIV therapy in resource-limited settings. Clin Infect Dis. 2010;51:448–55 .DOIPubMed
  28. Jarvis  JN, Lawn  SD, Vogt  M, Bangani  N, Wood  R, Harrison  TS. Screening for cryptococcal antigenemia in patients accessing an antiretroviral treatment program in South Africa. Clin Infect Dis. 2009;48:856–62 .DOIPubMed
  29. Joint Medical Store. Product catalogue. 2013 June 5, [cited 2013 Sep 1]. http://www.jms.co.ug/resources
  30. Lindsley  MD, Mekha  N, Baggett  HC, Surinthong  Y, Autthateinchai  R, Sawatwong  P, Evaluation of a newly developed lateral flow immunoassay for the diagnosis of cryptococcosis. Clin Infect Dis. 2011;53:321–5 .DOIPubMed
  31. Binnicker  MJ, Jespersen  DJ, Bestrom  JE, Rollins  LO. Comparison of four assays for the detection of cryptococcal antigen. Clin Vaccine Immunol. 2012;19:1988–90 .DOIPubMed
  32. Hansen  J, Slechta  ES, Gates-Hollingsworth  MA, Neary  B, Barker  AP, Bauman  S, Large-scale evaluation of the immuno-mycologics lateral flow and enzyme-linked immunoassays for detection of cryptococcal antigen in serum and cerebrospinal fluid. Clin Vaccine Immunol. 2013;20:52–5 .DOIPubMed
  33. McMullan  BJ, Halliday  C, Sorrell  TC, Judd  D, Sleiman  S, Marriott  D, Clinical utility of the cryptococcal antigen lateral flow assay in a diagnostic mycology laboratory. PLoS ONE. 2012;7:e49541 .DOIPubMed
  34. Kaplan  JE, Benson  C, Holmes  KH, Brooks  JT, Pau  A, Masur  H. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009;58:1–207 .PubMed
  35. Govender  NP, Meintjes  G, Bicanic  T, Dawood  H, Harrison  TS, Jarvis  JN, Guideline for the prevention, diagnosis and management of cryptococcal meningitis among HIV-infected persons: 2013 update. South African Journal of HIV Medicine. 2013;14:76–86 .DOI
  36. Perfect  JR, Dismukes  WE, Dromer  F, Goldman  DL, Graybill  JR, Hamill  RJ, 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 .DOIPubMed
  37. Lortholary  O, Poizat  G, Zeller  V, Neuville  S, Boibieux  A, Alvarez  M, Long-term outcome of AIDS-associated cryptococcosis in the era of combination antiretroviral therapy. AIDS. 2006;20:2183–91 .DOIPubMed
  38. Sungkanuparph  S, Filler  SG, Chetchotisakd  P, Pappas  PG, Nolen  TL, Manosuthi  W, Cryptococcal immune reconstitution inflammatory syndrome after antiretroviral therapy in AIDS patients with cryptococcal meningitis: a prospective multicenter study. Clin Infect Dis. 2009;49:931–4 .DOIPubMed

Main Article

Page created: January 03, 2014
Page updated: January 03, 2014
Page reviewed: January 03, 2014
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external