Evaluation of a nanophosphor lateral-flow assay for self-testing for herpes simplex virus type 2 seropositivity

Autoři: Heather J. Goux aff001;  Balakrishnan Raja aff002;  Katerina Kourentzi aff003;  João R. C. Trabuco aff003;  Binh V. Vu aff003;  Andrew S. Paterson aff002;  Alexander Kirkpatrick aff002;  Blane Townsend aff002;  Miles Lee aff002;  Van Thi Thanh Truong aff004;  Claudia Pedroza aff004;  Richard C. Willson aff001
Působiště autorů: Department of Biology and Biochemistry, University of Houston, Houston, Texas, United States of America aff001;  Luminostics, Inc., San Jose, California, United States of America aff002;  Department of Chemical and Biomolecular Engineering, University of Houston, Houston, Texas, United States of America aff003;  Medical School Center for Clinical Research and Evidence-Based Medicine, University of Texas Health Science Center at Houston, Houston, Texas, United States of America aff004
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225365


Herpes Simplex Virus Type 2 (HSV-2) is a common human pathogen that causes life-long illness. The US prevalence of HSV-2 infection is 11.9% for individuals between 15 and 49 years of age. Individuals with HSV-2 infection are more likely to contract and spread other sexually-transmitted infections. Eighty percent of individuals with HSV-2 are unaware of their infection, in part because of the social stigma associated with in-clinic testing for sexually-transmitted infections. We conducted an initial evaluation of a prototype smartphone-based serological lateral-flow immunoassay (LFA) for HSV-2 infection that uses strontium aluminate persistent luminescent nanoparticles (nanophosphors) as reporters. When applied to a test panel of 21 human plasma/serum samples varying in anti-HSV titer, the nanophosphor HSV-2 LFA had 96.7% sensitivity and 100% specificity for detection of HSV-2 infection. The sensitivity of the nanophosphor HSV-2 LFA was higher than that of commercially-available rapid HSV-2 assays tested with the same panel. Analysis of the iPhone nanophosphor HSV-2 LFA strip images with our custom smartphone app gave greater reproducibility compared to ImageJ analysis of strip images. The smartphone-based nanophosphor LFA technology shows promise for private self-testing for sexually-transmitted infections (STI).

Klíčová slova:

Apps – Cell phones – Enzyme-linked immunoassays – Herpes simplex virus-2 – Image analysis – Nanoparticles – Strontium – Cross reactivity


1. McQuillan G, Kruszon-Moran D, Flagg EW, Paulose-Ram R. Prevalence of Herpes Simplex Virus Type 1 and Type 2 in Persons Aged 14–49: United States, 2015–2016. NCHS Data Brief. 2018; 1–8.

2. Corey L. The current trend in genital herpes. Progress in prevention. Sex Transm Dis. 1994;21: S38–44. 8042114

3. Sudenga SL, Kempf M-C, McGwin G Jr, Wilson CM, Hook EW 3rd, Shrestha S. Incidence, prevalence, and epidemiology of herpes simplex virus-2 in HIV-1-positive and HIV-1-negative adolescents. Sex Transm Dis. 2012;39: 300–305. doi: 10.1097/OLQ.0b013e318244a90f 22421698

4. Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect. 1999;75: 3–17. doi: 10.1136/sti.75.1.3 10448335

5. Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS. journals.lww.com; 2006;20: 73–83.

6. Barnabas RV, Celum C. Infectious co-factors in HIV-1 transmission herpes simplex virus type-2 and HIV-1: new insights and interventions. Curr HIV Res. 2012;10: 228–237. doi: 10.2174/157016212800618156 22384842

7. Corey L, Wald A, Celum CL, Quinn TC. The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: a review of two overlapping epidemics. J Acquir Immune Defic Syndr. 2004;35: 435–445. doi: 10.1097/00126334-200404150-00001 15021308

8. Mertz GJ, Benedetti J, Ashley R, Selke SA, Corey L. Risk factors for the sexual transmission of genital herpes. Ann Intern Med. 1992;116: 197–202. doi: 10.7326/0003-4819-116-3-197 1309413

9. Johnston C, Corey L. Current Concepts for Genital Herpes Simplex Virus Infection: Diagnostics and Pathogenesis of Genital Tract Shedding. Clin Microbiol Rev. 2016;29: 149–161. doi: 10.1128/CMR.00043-15 26561565

10. Phipps W, Saracino M, Magaret A, Selke S, Remington M, Huang M-L, et al. Persistent genital herpes simplex virus-2 shedding years following the first clinical episode. J Infect Dis. 2011;203: 180–187. doi: 10.1093/infdis/jiq035 21288817

11. Wald A, Zeh J, Selke S, Warren T, Ryncarz AJ, Ashley R, et al. Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons. N Engl J Med. 2000;342: 844–850. doi: 10.1056/NEJM200003233421203 10727588

12. Corey L, Wald A, Patel R, Sacks SL, Tyring SK, Warren T, et al. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med. 2004;350: 11–20. doi: 10.1056/NEJMoa035144 14702423

13. Corey L, Ashley R, Valaciclovir HSV Transmission Study Group. Prevention of herpes simplex virus type 2 transmission with antiviral therapy. Herpes. 2004;11 Suppl 3: 170A–174A.

14. Martin ET, Krantz E, Gottlieb SL, Magaret AS, Langenberg A, Stanberry L, et al. A pooled analysis of the effect of condoms in preventing HSV-2 acquisition. Arch Intern Med. 2009;169: 1233–1240. doi: 10.1001/archinternmed.2009.177 19597073

15. Wald A, Langenberg AG, Link K, Izu AE, Ashley R, Warren T, et al. Effect of condoms on reducing the transmission of herpes simplex virus type 2 from men to women. JAMA. 2001;285: 3100–3106. doi: 10.1001/jama.285.24.3100 11427138

16. Gottlieb SL, Douglas JM Jr, Foster M, Schmid DS, Newman DR, Baron AE, et al. Incidence of herpes simplex virus type 2 infection in 5 sexually transmitted disease (STD) clinics and the effect of HIV/STD risk-reduction counseling. J Infect Dis. 2004;190: 1059–1067. doi: 10.1086/423323 15319854

17. Wald A, Ashley-Morrow R. Serological testing for herpes simplex virus (HSV)-1 and HSV-2 infection. Clin Infect Dis. 2002;35: S173–82. doi: 10.1086/342104 12353203

18. Guerry SL, Bauer HM, Klausner JD, Branagan B, Kerndt PR, Allen BG, et al. Recommendations for the selective use of herpes simplex virus type 2 serological tests. Clin Infect Dis. 2005;40: 38–45. doi: 10.1086/426438 15614690

19. Feltner C, Grodensky C, Ebel C, Middleton JC, Harris RP, Ashok M, et al. Serologic Screening for Genital Herpes: An Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2016;316: 2531–2543. doi: 10.1001/jama.2016.17138 27997660

20. LeGoff J, Péré H, Bélec L. Diagnosis of genital herpes simplex virus infection in the clinical laboratory. Virol J. 2014;11: 83. doi: 10.1186/1743-422X-11-83 24885431

21. Giljohann DA, Mirkin CA. Drivers of biodiagnostic development. Nature. nature.com; 2009;462: 461–464.

22. Chun P. Colloidal Gold and Other Labels for Lateral Flow Immunoassays. In: Wong R, Tse H, editors. Lateral Flow Immunoassay. Totowa, NJ: Humana Press; 2009. pp. 1–19.

23. Posthuma-Trumpie GA, Korf J, van Amerongen A. Lateral flow (immuno)assay: its strengths, weaknesses, opportunities and threats. A literature survey. Anal Bioanal Chem. 2009;393: 569–582. doi: 10.1007/s00216-008-2287-2 18696055

24. Laderman EI, Whitworth E, Dumaual E, Jones M, Hudak A, Hogrefe W, et al. Rapid, sensitive, and specific lateral-flow immunochromatographic point-of-care device for detection of herpes simplex virus type 2-specific immunoglobulin G antibodies in serum and whole blood. Clin Vaccine Immunol. 2008;15: 159–163. doi: 10.1128/CVI.00218-07 18003814

25. O’Farrell B. Evolution in Lateral Flow–Based Immunoassay Systems. In: Wong R, Tse H, editors. Lateral Flow Immunoassay. Totowa, NJ: Humana Press; 2009. pp. 1–33.

26. Paterson AS, Raja B, Garvey G, Kolhatkar A, Hagström AEV, Kourentzi K, et al. Persistent luminescence strontium aluminate nanoparticles as reporters in lateral flow assays. Anal Chem. 2014;86: 9481–9488. doi: 10.1021/ac5012624 25247754

27. Finley E, Cobb A, Duke A, Paterson A, Brgoch J. Optimizing Blue Persistent Luminescence in (Sr1-δBaδ)2MgSi2O7:Eu2+,Dy3+ via Solid Solution for Use in Point-of-Care Diagnostics. ACS Appl Mater Interfaces. 2016;8: 26956–26963. doi: 10.1021/acsami.6b10303 27635436

28. Paterson AS, Raja B, Mandadi V, Townsend B, Lee M, Buell A, et al. A low-cost smartphone-based platform for highly sensitive point-of-care testing with persistent luminescent phosphors. Lab Chip. 2017;17: 1051–1059. doi: 10.1039/c6lc01167e 28154873

29. Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9: 671–675. doi: 10.1038/nmeth.2089 22930834

30. Herpes—Q & A—2015 STD Treatment Guidelines [Internet]. [cited 5 Mar 2018]. https://www.cdc.gov/std/tg2015/qa/herpes-qa.htm

31. Schmid DS, Brown DR, Nisenbaum R, Burke RL, Alexander D, Ashley R, et al. Limits in reliability of glycoprotein G-based type-specific serologic assays for herpes simplex virus types 1 and 2. J Clin Microbiol. 1999;37: 376–379. 9889222

32. Ashley RL. Performance and use of HSV type-specific serology test kits. Herpes. 2002;9: 38–45. 12106510

33. New CDC Treatment Guidelines Promote Use of HerpeSelect(R) Type- Specific Serology Tests to Help Diagnose Genital Herpes [Internet]. PR Newswire; New York. New York, United States, New York: PR Newswire Association LLC; 2002. pp. 1–1. http://search.proquest.com/docview/449052089

34. Koo TK, Li MY. A Guideline of Selecting and Reporting Intraclass Correlation Coefficients for Reliability Research. J Chiropr Med. 2016;15: 155–163. doi: 10.1016/j.jcm.2016.02.012 27330520

35. Jun W, Hu R, Hyland L, Crandall D, Ramachandran P, Pangarkar C, et al. Expression and characterization of the soluble form of recombinant mature HSV-2 glycoprotein G for use in anti-HSV-2 IgG serodiagnostic immunoassay. J Virol Methods. 2018;252: 65–69. doi: 10.1016/j.jviromet.2017.10.021 29104048

36. Bradley H, Markowitz LE, Gibson T, McQuillan GM. Seroprevalence of herpes simplex virus types 1 and 2—United States, 1999–2010. J Infect Dis. 2014;209: 325–333. doi: 10.1093/infdis/jit458 24136792

37. Mindel A. Psychological and psychosexual implications of herpes simplex virus infections. Scand J Infect Dis Suppl. 1996;100: 27–32. 9163020

Článek vyšel v časopise


2019 Číslo 12