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

The development of an online risk calculator for the prediction of future syphilis among a high-risk cohort of men who have sex with men and transgender women in Lima, Peru

Lao-Tzu Allan-Blitz A F , Kelika A. Konda A B , Silver K. Vargas B C , Xiaoyan Wang D , Eddy R. Segura A , Boris M. Fazio B , Gino M. Calvo B C , Carlos F. Caceres B C and Jeffrey D. Klausner A E
+ Author Affiliations
- Author Affiliations

A Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Ave, Los Angeles CA, 90095, USA.

B Centre for Interdisciplinary Studies in Sexuality, AIDS and Society, Cayetano Heredia University, Av. Honorio Delgado 430, San Martín de Porres, 15102, Peru.

C Laboratory of Sexual Health, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martín de Porres, 15102, Peru.

D Department of General Internal Medicine and Health Services Research, University of California Los Angeles, 911 Broxton Avenue, Los Angeles, CA, 90095, USA.

E Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles, 650 Charles E Young Drive South, Los Angeles CA, 90095, USA.

F Corresponding author. Email: lallanblitz@mednet.ucla.edu

Sexual Health 15(3) 261-268 https://doi.org/10.1071/SH17118
Submitted: 5 July 2017  Accepted: 24 October 2017   Published: 23 January 2018

Abstract

Background: Syphilis incidence worldwide has rebounded since 2000, particularly among men who have sex with men (MSM). A predictive model for syphilis infection may inform prevention counselling and use of chemoprophylaxis. Methods: Data from a longitudinal cohort study of MSM and transgender women meeting high-risk criteria for syphilis who were followed quarterly for 2 years were analysed. Incidence was defined as a four-fold increase in rapid plasma reagin (RPR) titres or new RPR reactivity if two prior titres were non-reactive. Generalised estimating equations were used to calculate rate ratios (RR) and develop a predictive model for 70% of the dataset, which was then validated in the remaining 30%. An online risk calculator for the prediction of future syphilis was also developed. Results: Among 361 participants, 22.0% were transgender women and 34.6% were HIV-infected at baseline. Syphilis incidence was 19.9 cases per 100-person years (95% confidence interval (CI) 16.3–24.3). HIV infection (RR 2.22; 95% CI 1.54–3.21) and history of syphilis infection (RR 2.23; 95% 1.62–3.64) were significantly associated with incident infection. The final predictive model for syphilis incidence in the next 3 months included HIV infection, history of syphilis, number of male sex partners and sex role for anal sex in the past 3 months, and had an area under the curve of 69%. The online syphilis risk calculator based on those results is available at: www.syphrisk.net. Conclusions: Using data from a longitudinal cohort study among a population at high risk for syphilis infection in Peru, we developed a predictive model and online risk calculator for future syphilis infection. The predictive model for future syphilis developed in this study has a moderate predictive accuracy and may serve as the foundation for future studies.


References

[1]  Centers for Disease Control and Prevention. Sexually transmitted disease surveillance 2015. Atlanta: U.S. Department of Health and Human Services; 2016. Available at: https://wwwcdcgov/std/stats15/std-surveillance-2015-printpdf [verified 21 January 2017].

[2]  Clark EG, Danbolt N. The Oslo study of the natural history of untreated syphilis; an epidemiologic investigation based on a restudy of the Boeck-Bruusgaard material; a review and appraisal. J Chronic Dis 1955; 2 311–44.
The Oslo study of the natural history of untreated syphilis; an epidemiologic investigation based on a restudy of the Boeck-Bruusgaard material; a review and appraisal.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaG28%2Fgtl2jsQ%3D%3D&md5=f3cf850b9420bb908cb8bce0027188d3CAS | 1:STN:280:DyaG28%2Fgtl2jsQ%3D%3D&md5=f3cf850b9420bb908cb8bce0027188d3CAS |

[3]  Solomon MM, Mayer KH, Glidden DV, Liu AY, McMahan VM, Guanira JV, Chariyalertsak S, Fernadez T, Grant RM, iPrEx Study Team Syphilis predicts HIV incidence among men and transgender women who have sex with men in a preexposure prophylaxis trial. Clin Infect Dis 2014; 59 1020–6.
Syphilis predicts HIV incidence among men and transgender women who have sex with men in a preexposure prophylaxis trial.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XhvFWlsL7M&md5=c89d589a7075d71193eb4991e873482dCAS | 1:CAS:528:DC%2BC28XhvFWlsL7M&md5=c89d589a7075d71193eb4991e873482dCAS |

[4]  Lama JR, Lucchetti A, Suarez L, Laguna-Torres VA, Guanira JV, Pun M, Montano SM, Celum CL, Carr JK, Sanchez J, Bautista CT, Sanchez JL, Peruvian HIV Sentinel Surveillance Working Group Association of herpes simplex virus type 2 infection and syphilis with human immunodeficiency virus infection among men who have sex with men in Peru. J Infect Dis 2006; 194 1459–66.
Association of herpes simplex virus type 2 infection and syphilis with human immunodeficiency virus infection among men who have sex with men in Peru.Crossref | GoogleScholarGoogle Scholar |

[5]  Sanchez J, Lama JR, Peinado J, Paredes A, Lucchetti A, Russell K, Kochel T, Sebastian JL. High HIV and ulcerative sexually transmitted infection incidence estimates among men who have sex with men in Peru: awaiting for an effective preventive intervention. J Acquir Immune Defic Syndr 2009; 51 S47–51.
High HIV and ulcerative sexually transmitted infection incidence estimates among men who have sex with men in Peru: awaiting for an effective preventive intervention.Crossref | GoogleScholarGoogle Scholar |

[6]  Perez-Brumer AG, Konda KA, Salvatierra HJ, Segura ER, Hall ER, Montano SM, Coates TJ, Klausner JD, Caceres CF, Clark JL. Prevalence of HIV, STIs, and risk behaviors in a cross-sectional community- and clinic-based sample of men who have sex with men (MSM) in Lima, Peru. PLoS One 2013; 8 e59072
Prevalence of HIV, STIs, and risk behaviors in a cross-sectional community- and clinic-based sample of men who have sex with men (MSM) in Lima, Peru.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXntFaqsr8%3D&md5=b6cf61adf90f5430ff18009bb2718283CAS | 1:CAS:528:DC%2BC3sXntFaqsr8%3D&md5=b6cf61adf90f5430ff18009bb2718283CAS |

[7]  Snowden JM, Konda KA, Leon SR, Giron JM, Escobar G, Coates TJ, Caceres CF, Klausner JD, NIMH Collaborative HIV/STD Prevention Trial Group Recent syphilis infection prevalence and risk factors among male low-income populations in coastal Peruvian cities. Sex Transm Dis 2010; 37 75–80.
Recent syphilis infection prevalence and risk factors among male low-income populations in coastal Peruvian cities.Crossref | GoogleScholarGoogle Scholar |

[8]  NIMH Collaborative HIV/STD Prevention Trial Group Sexually transmitted disease and HIV prevalence and risk factors in concentrated and generalized HIV epidemic settings. AIDS 2007; 21 S81–90.
Sexually transmitted disease and HIV prevalence and risk factors in concentrated and generalized HIV epidemic settings.Crossref | GoogleScholarGoogle Scholar |

[9]  Cárcamo CP, Campos PE, Garcia PJ, Hughes JP, Garnett GP, Holmes KK, Peru PREVEN Study Team Prevalences of sexually transmitted infections in young adults and female sex workers in Peru: a national population-based survey. Lancet Infect Dis 2012; 12 765–73.
Prevalences of sexually transmitted infections in young adults and female sex workers in Peru: a national population-based survey.Crossref | GoogleScholarGoogle Scholar |

[10]  Park H, Konda KA, Roberts CP, Maguina JL, Leon SR, Clark JL, Coates TJ, Caceres CF, Klausner JD. Risk factors associated with incident syphilis in a cohort of high-risk men in Peru. PLoS One 2016; 11 e0162156
Risk factors associated with incident syphilis in a cohort of high-risk men in Peru.Crossref | GoogleScholarGoogle Scholar |

[11]  Phipps W, Kent CK, Kohn R, Klausner JD. Risk factors for repeat syphilis in men who have sex with men, San Francisco. Sex Transm Dis 2009; 36 331–5.
Risk factors for repeat syphilis in men who have sex with men, San Francisco.Crossref | GoogleScholarGoogle Scholar |

[12]  Cohen SE, Chew Ng RA, Katz KA, Bernstein KT, Samuel MC, Kerndt PR, Bolan G. Repeat syphilis among men who have sex with men in California, 2002–2006: implications for syphilis elimination efforts. Am J Public Health 2012; 102 e1–8.
Repeat syphilis among men who have sex with men in California, 2002–2006: implications for syphilis elimination efforts.Crossref | GoogleScholarGoogle Scholar |

[13]  Sakala J, Chizuni N, Nzala S. A study on usefulness of a set of known risk factors in predicting maternal syphilis infections in three districts of Western Province, Zambia. Pan Afr Med J 2016; 24 75
A study on usefulness of a set of known risk factors in predicting maternal syphilis infections in three districts of Western Province, Zambia.Crossref | GoogleScholarGoogle Scholar |

[14]  Falasinnu T, Gustafson P, Hottes TS, Gilbert M, Ogilvie G, Shoveller J. A critical appraisal of risk models for predicting sexually transmitted infections. Sex Transm Dis 2014; 41 321–30.
A critical appraisal of risk models for predicting sexually transmitted infections.Crossref | GoogleScholarGoogle Scholar |

[15]  Tuite AR, Fisman DN, Mishra S. Screen more or screen more often? Using mathematical models to inform syphilis control strategies. BMC Public Health 2013; 13 606
Screen more or screen more often? Using mathematical models to inform syphilis control strategies.Crossref | GoogleScholarGoogle Scholar |

[16]  Bolan RK, Beymer MR, Weiss RE, Flynn RP, Leibowitz AA, Klausner JD. Doxycycline prophylaxis to reduce incident syphilis among HIV-infected men who have sex with men who continue to engage in high-risk sex: a randomized, controlled pilot study. Sex Transm Dis 2015; 42 98–103.
Doxycycline prophylaxis to reduce incident syphilis among HIV-infected men who have sex with men who continue to engage in high-risk sex: a randomized, controlled pilot study.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXhtlGkt7s%3D&md5=4146d56aeaf5501b7b44aaee94e0da36CAS | 1:CAS:528:DC%2BC2MXhtlGkt7s%3D&md5=4146d56aeaf5501b7b44aaee94e0da36CAS |

[17]  Deiss RG, Leon SR, Konda KA, Brown B, Segura ER, Galea JT, Caceres CF, Klausner JD. Characterizing the syphilis epidemic among men who have sex with men in Lima, Peru to identify new treatment and control strategies. BMC Infect Dis 2013; 13 426
Characterizing the syphilis epidemic among men who have sex with men in Lima, Peru to identify new treatment and control strategies.Crossref | GoogleScholarGoogle Scholar |

[18]  Kojima N, Park H, Konda KA, Joseph Davey DL, Bristow CC, Brown B, Leon SR, Vargas SK, Calvo GM, Caceres CF, Klausner JD. The PICASSO cohort: baseline characteristics of a cohort of men who have sex with men and male-to-female transgender women at high risk for syphilis infection in Lima, Peru. BMC Infect Dis 2017; 17 255
The PICASSO cohort: baseline characteristics of a cohort of men who have sex with men and male-to-female transgender women at high risk for syphilis infection in Lima, Peru.Crossref | GoogleScholarGoogle Scholar |

[19]  Pop-Eleches C, Thirumurthy H, Habyarimana JP, Zivin JG, Goldstein MP, de Walque D, MacKeen L, Harber J, Kimaiyo S, Sidle J, Ngare D, Bangsberg DR. Mobile phone technologies improve adherence to antiretroviral treatment in a resource-limited setting: a randomized controlled trial of text message reminders. AIDS 2011; 25 825–34.
Mobile phone technologies improve adherence to antiretroviral treatment in a resource-limited setting: a randomized controlled trial of text message reminders.Crossref | GoogleScholarGoogle Scholar |

[20]  Barbor TF, Higgins-Biddle JC, Saunders JB, Monteiro MG. AUDIT: the alcohol use disorders identification test: guidelines for use in primary health care. Geneva: World Health Organization Department of Mental Health and Substance Dependence; 2001.

[21]  Ministry of Health. Peru: Health Technical Standard for the Management of Sexually Transmitted Infections In Peru. Lima. 2009. Available at: ftp://ftp2.minsa.gob.pe/docconsulta/documentos/dgsp/vihsida/GuiaNacionalITS_Dic2006.pdf [verified 10 May 2017]

[22]  Long CM, Klausner JD, Leon S, Jones FR, Giron M, Cuadros J, Pajuelo J, Caceres C, Coates TJ, NIMH Collaborative HIV/STD Prevention Trial Group Syphilis treatment and HIV infection in a population-based study of persons at high risk for sexually transmitted disease/HIV infection in Lima, Peru. Sex Transm Dis 2006; 33 151–5.
Syphilis treatment and HIV infection in a population-based study of persons at high risk for sexually transmitted disease/HIV infection in Lima, Peru.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhvFCks78%3D&md5=de747d4eb671c001383c9135c7201c4cCAS |

[23]  Justice AC, Covinsky KE, Berlin JA. Assessing the generalizability of prognostic information. Ann Intern Med 1999; 130 515–24.
Assessing the generalizability of prognostic information.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1M7msFCjsg%3D%3D&md5=6c5155233a6dbe2d71997147da0c6001CAS |

[24]  Hajian-Tilaki K. Receiver operating characteristic (roc) curve analysis for medical diagnostic test evaluation. Caspian J Intern Med 2013; 4 627–35.

[25]  Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 1982; 143 29–36.
The meaning and use of the area under a receiver operating characteristic (ROC) curve.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL387ltFyksQ%3D%3D&md5=56e8cd3cb4304922bce8c1dd9d3d3159CAS |

[26]  Sun JJ, Wang ZY, Shen JY, Shen YZ, Liu L, Wang JR, Zhang RF, Lu HZ. Serum TRSUT titer >/=1: 6 is a predictor for neurosyphilis among hiv-infected patients with concurrent syphilis and no neurological symptoms. Medicine (Baltimore) 2015; 94 e2023
Serum TRSUT titer >/=1: 6 is a predictor for neurosyphilis among hiv-infected patients with concurrent syphilis and no neurological symptoms.Crossref | GoogleScholarGoogle Scholar |

[27]  Zhu L, Gu X, Peng RR, Wang C, Gao Z, Zhou P, Gao Y, Shi M, Guan Z, Sena AC. Comparison of the cerebrospinal fluid (CSF) toluidine red unheated serum test and the CSF rapid plasma reagin test with the CSF venereal disease research laboratory test for diagnosis of neurosyphilis among HIV-negative syphilis patients in China. J Clin Microbiol 2014; 52 736–40.
Comparison of the cerebrospinal fluid (CSF) toluidine red unheated serum test and the CSF rapid plasma reagin test with the CSF venereal disease research laboratory test for diagnosis of neurosyphilis among HIV-negative syphilis patients in China.Crossref | GoogleScholarGoogle Scholar |

[28]  Dumaresq J, Langevin S, Gagnon S, Serhir B, Deligne B, Tremblay C, Tsang RS, Fortin C, Coutlee F, Roger M. Clinical prediction and diagnosis of neurosyphilis in HIV-infected patients with early Syphilis. J Clin Microbiol 2013; 51 4060–6.
Clinical prediction and diagnosis of neurosyphilis in HIV-infected patients with early Syphilis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXjtlWrtro%3D&md5=d211c6e120d3f1e820edd1a5d1724a19CAS |

[29]  Rekart ML, Ndifon W, Brunham RC, Dushoff J, Park SW, Rawat S, Cameron CE. A double-edged sword: does highly active antiretroviral therapy contribute to syphilis incidence by impairing immunity to Treponema pallidum? Sex Transm Infect 2017; 93 374–378.
A double-edged sword: does highly active antiretroviral therapy contribute to syphilis incidence by impairing immunity to Treponema pallidum?Crossref | GoogleScholarGoogle Scholar |

[30]  Azzam R, Lal L, Goh S-L, Kedzierska K, Jaworowski A, Naim E, Cherry CL, Wesselingh SL, Mills J, Crowe SM. Adverse effects of antiretroviral drugs on HIV-1-infected and -uninfected human monocyte-derived macrophages. J Acquir Immune Defic Syndr 2006; 42 19–28.
| 1:CAS:528:DC%2BD28XlsFGqtrs%3D&md5=4480d3d72186302c63462e5d4a66c42cCAS |

[31]  Antonelli A, Brandi G, Casabianca A, Magnani M. 2ʹ,3ʹ-dideoxycytidine cytotoxicity in human macrophages. Biochim biophys Acta 1997; 1358 39–45.
2ʹ,3ʹ-dideoxycytidine cytotoxicity in human macrophages.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXlt1Gnu7s%3D&md5=45650bdbce3d10ea30c9cf4b194adcbcCAS |

[32]  de Simone C, Maffione AB, Calvello R, Nacci C, Sciannameo G, Greco B, Caradonna L, Pece S, Antonaci S, Jirillo E. In vitro effects of 3ʹ-azido-3ʹ-deoxythymidine (AZT) on normal human polymorphonuclear cell and monocyte-macrophage functional capacities. Immunopharmacol Immunotoxicol 1996; 18 161–78.
In vitro effects of 3ʹ-azido-3ʹ-deoxythymidine (AZT) on normal human polymorphonuclear cell and monocyte-macrophage functional capacities.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XjvV2hurY%3D&md5=6dfc5f3b47a73f5e643fad69eedea9dbCAS |

[33]  Workowski KA, Bolan GA. Centers for Disease, Control and Prevention: sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015; 64 1–137. [verified May 2017]. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htm

[34]  Gray RT, Hoare A, Prestage GP, Donovan B, Kaldor JM, Wilson DP. Frequent testing of highly sexually active gay men is required to control syphilis. Sex Transm Dis 2010; 37 298–305.

[35]  Hoenigl M, Green N, Mehta SR, Little SJ. Risk factors for acute and early HIV Infection Among Men Who Have Sex With Men (MSM) in San Diego, 2008 to 2014: a cohort study. Medicine (Baltimore) 2015; 94 e1242
Risk factors for acute and early HIV Infection Among Men Who Have Sex With Men (MSM) in San Diego, 2008 to 2014: a cohort study.Crossref | GoogleScholarGoogle Scholar |

[36]  Zetola NM, Bernstein KT, Wong E, Louie B, Klausner JD. Exploring the relationship between sexually transmitted diseases and HIV acquisition by using different study designs. J Acquir Immune Defic Syndr 2009; 50 546–51.
Exploring the relationship between sexually transmitted diseases and HIV acquisition by using different study designs.Crossref | GoogleScholarGoogle Scholar |

[37]  Beymer MR, Weiss RE, Sugar CA, Bourque LB, Gee GC, Morisky DE, Shu SB, Javanbakht M, Bolan RK. Are Centers for Disease Control and Prevention guidelines for preexposure prophylaxis specific enough? Formulation of a personalized HIV risk score for pre-exposure prophylaxis initiation. Sex Transm Dis 2017; 44 49–57.
Are Centers for Disease Control and Prevention guidelines for preexposure prophylaxis specific enough? Formulation of a personalized HIV risk score for pre-exposure prophylaxis initiation.Crossref | GoogleScholarGoogle Scholar |

[38]  Wand H, Guy R, Donovan B, McNulty A. Developing and validating a risk scoring tool for chlamydia infection among sexual health clinic attendees in Australia: a simple algorithm to identify those at high risk of chlamydia infection. BMJ Open 2011; 1 e000005
Developing and validating a risk scoring tool for chlamydia infection among sexual health clinic attendees in Australia: a simple algorithm to identify those at high risk of chlamydia infection.Crossref | GoogleScholarGoogle Scholar |

[39]  Gaydos CA, Jett-Goheen M, Barnes M, Dize L, Barnes P, Hsieh YH. Use of a risk quiz to predict infection for sexually transmitted infections: a retrospective analysis of acceptability and positivity. Sex Transm Infect 2016; 92 44–8.
Use of a risk quiz to predict infection for sexually transmitted infections: a retrospective analysis of acceptability and positivity.Crossref | GoogleScholarGoogle Scholar |

[40]  Wantland DJ, Portillo CJ, Holzemer WL, Slaughter R, McGhee EM. The effectiveness of web-based vs. non-web-based interventions: a meta-analysis of behavioral change outcomes. J Med Internet Res 2004; 6 e40
The effectiveness of web-based vs. non-web-based interventions: a meta-analysis of behavioral change outcomes.Crossref | GoogleScholarGoogle Scholar |

[41]  Reisner SL, Poteat T, Keatley J, Cabral M, Mothopeng T, Dunham E, Holland CE, Max R, Baral SD. Global health burden and needs of transgender populations: a review. Lancet 2016; 388 412–36.
Global health burden and needs of transgender populations: a review.Crossref | GoogleScholarGoogle Scholar |