Sexual Health Sexual Health Society
Publishing on sexual health from the widest perspective
RESEARCH ARTICLE

Case report and evaluation of the frequency of the prozone phenomenon in syphilis serology – an infrequent but important laboratory phenomenon

Jeffrey J. Post A B C E , Candice Khor A B C , Virginia Furner B , Don E. Smith B , L. Ross Whybin D and Peter W. Robertson D
+ Author Affiliations
- Author Affiliations

A Department of Infectious Diseases, Prince of Wales Hospital, Randwick, NSW 2031, Australia.

B Albion Street Centre, Prince of Wales Hospital, Surry Hills, NSW 2010, Australia.

C Prince of Wales Clinical School, University of New South Wales, Randwick, NSW, Australia.

D Department of Microbiology, Serology Laboratory, South Eastern Area Laboratory Services, Prince of Wales Hospital, Randwick, NSW, Australia.

E Corresponding author. Email: Jeffrey.Post@sesiahs.health.nsw.gov.au

Sexual Health 9(5) 488-490 https://doi.org/10.1071/SH11156
Submitted: 9 November 2011  Accepted: 1 May 2012   Published: 10 September 2012

Abstract

Background: Treponema pallidum specific serology generally remains reactive for life. Therefore, the diagnosis of syphilis reinfection relies on clinical assessment and nontreponemal (reagin) serologic testing. The prozone phenomenon can lead to a falsely nonreactive rapid plasma reagin (RPR) assay result. Methods: We report a case of secondary syphilis in a HIV infected patient with a previous history of syphilis infection, where a falsely nonreactive RPR assay was associated with a delayed diagnosis of reinfection and infectious syphilis. The prozone phenomenon was detected in several of the patient’s serum samples collected around this time. We subsequently undertook a prospective evaluation for the prozone phenomenon in 3222 consecutive sera, which were assayed using the RPR assay for clinical purposes over a 10-month period. Results: The overall rate of the prozone phenomenon was 2 out of 3222 samples (0.06%; 95% confidence interval (CI): 0.02–0.22%) and the rate per reactive sample was 2 out of 397 (0.5%; 95% CI: 0.14–1.81%). Conclusion: Clinicians should request RPR testing at dilutions of sera when syphilis is suspected clinically and the RPR assay is nonreactive.

Additional keywords: false negative reactions, HIV, serology, testing.


References

[1]  Jin F, Prestage GP, Kippax SC, Pell CM, Donovan BJ, Kaldor JM, et al Epidemic syphilis among homosexually active men in Sydney. Med J Aust 2005; 183 179–83.
| 16097913PubMed | open url image1

[2]  Botham SJ, Ressler K-A, Bourne C, Ferson MJ. Epidemic infectious syphilis in inner Sydney – strengthening enhanced surveillance. Aust N Z J Public Health 2006; 30 529–33.
Epidemic infectious syphilis in inner Sydney – strengthening enhanced surveillance.CrossRef | 17209268PubMed | open url image1

[3]  The Kirby Institute. HIV, viral hepatitis and sexually transmissible infections in Australia annual surveillance report 2011. Sydney: The Kirby Institute, University of New South Wales; 2011.

[4]  Larsen SA, Steiner BM, Rudolph AH. Laboratory diagnosis and interpretation of tests for syphilis. Clin Microbiol Rev 1995; 8 1–21.
| 1:STN:280:DyaK2M3hvFyhtg%3D%3D&md5=2b17dfe26e30990f43feb4109ff1fc95CAS | 7704889PubMed | open url image1

[5]  Jurado RL, Campbell J, Martin PD. Prozone phenomenon in secondary syphilis. Has its time arrived? Arch Intern Med 1993; 153 2496–8.
Prozone phenomenon in secondary syphilis. Has its time arrived?CrossRef | 1:STN:280:DyaK2c%2FivFenug%3D%3D&md5=34f3937c9a777f453d294a1f68881a6cCAS | 7832818PubMed | open url image1

[6]  Spangler AS, Jackson JH, Fiumara NJ, Warthin TA. Syphilis with a negative blood test reaction. JAMA 1964; 189 87–90.
Syphilis with a negative blood test reaction.CrossRef | 1:STN:280:DyaF2c7gsF2rtw%3D%3D&md5=058e7b01b93e7b0eee4be93aba6ab8f9CAS | 14148055PubMed | open url image1

[7]  el-Zaatari MM, Martens MG, Anderson GD. Incidence of the prozone phenomenon in syphilis serology. Obstet Gynecol 1994; 84 609–12.
| 1:STN:280:DyaK2cznslSrug%3D%3D&md5=17a74c41d87f530cfb57791923e0feb2CAS | 8090401PubMed | open url image1

[8]  Smith G, Holman RP. The prozone phenomenon with syphilis and HIV-1 co-infection. South Med J 2004; 97 379–82.
The prozone phenomenon with syphilis and HIV-1 co-infection.CrossRef | 15108832PubMed | open url image1

[9]  Nnoruka EN, Ezeoke ACJ. Evaluation of syphilis in patients with HIV infection in Nigeria. Trop Med Int Health 2005; 10 58–64.
Evaluation of syphilis in patients with HIV infection in Nigeria.CrossRef | 1:STN:280:DC%2BD2M%2FivVyrtg%3D%3D&md5=4a76411d9c8de1323cf7014a3a6d5629CAS | 15655014PubMed | open url image1

[10]  Hunter MG, Robertson PW, Post JJ. Significance of isolated reactive treponemal chemiluminescence immunoassay results. J Infect Dis ;
Significance of isolated reactive treponemal chemiluminescence immunoassay results.CrossRef | open url image1



Rent Article (via Deepdyve) Export Citation Cited By (5)