Challenges of rapid plasma reagin interpretation in syphilis screening in Uganda: Variability in nontreponemal results between different laboratories

Matthew M. Hamill, Kimeze J. Mbazira, Agnes N. Kiragga, Charlotte A. Gaydos, Mary Jett-Goheen, Rosalind Parkes-Ratanshi, Yukari C. Manabe, Edith Nakku-Joloba, Anne Rompalo

Research output: Contribution to journalArticlepeer-review


Background Syphilis is a cause of morbidity and mortality and is of particular concern in pregnancy in low-income countries because of the risks associated with maternal-fetal transmission. Ugandan national guidelines recommend a nontreponemal rapid plasma reagin (RPR) followed by treponemal testing for diagnosis of syphilis. The RPR test confirms a reactive specific treponemal test, or confirms serological "cure" with a 4-fold dilutional decrease; RPR is beset with technical and biological limitations, making accurate diagnosis and appropriate treatment problematic. The aim of this analysis was to compare performance of RPR testing in different laboratories. Methods Stored, freeze-thawed sera from 215 participants were additionally tested for RPR and dilutional titer in 2 different reference laboratories. Discrepant results were tested at a third reference laboratory which served as a tie-breaker. Equivalence in RPR titer was defined as within 2-fold or less. All patients with reactive rapid tests were treated as per Ugandan National Guidelines. Results Of 215 sera, 97 (45.1%) were RPR reactive in clinic laboratory A, 81 (37.7%) and 65 (30.2%) were RPR reactive in laboratories B and C, respectively. All reported positive in laboratory C were positive in laboratory B. Discrepant results were tested in laboratory D. χ2 Test was highly significant (P = <0.001) for difference between each dyad of laboratories (A and B, A and C, and B and C) RPR results. There were significant differences between RPR titers by paired t test and Wilcox rank test (P = <0.001); with up to a 3-fold difference between laboratories. Two one-sided test approach demonstrated nonequivalence. Agreement between laboratories B-D, and C-D: 48 (98.0%) of 49 and 34 (69.4%) of 49, respectively (P = <0.001). Laboratories B and D showed no significant difference and had equivalent RPR titers. Laboratories C and D had different titers (P = <0.001) and were not equivalent. Conclusions We found significant interlaboratory discrepant RPR results. A 3-fold difference in results is likely to be clinically significant and could result in undertreatment or overtreatment. These data demonstrate a key limitation of the RPR test and underline the urgent need for a more reproducible quantitative test than the current RPR for diagnosing and determining cure of syphilis.

Original languageEnglish (US)
Pages (from-to)829-833
Number of pages5
JournalSexually transmitted diseases
Issue number12
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Dermatology
  • Public Health, Environmental and Occupational Health
  • Microbiology (medical)
  • Infectious Diseases


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