Reprinted from S e x u a l l y T r a n s m it t e d D i s e a s e s , April-June 1991 Vol. 18, No. 2 © J. B. Lippincott Co. Printed in U.S.A. A Population-Based Serosurveillance of Syphilis in Costa Rica SANDRA A. LARSEN, PhD, MARK W. OBERLE, MD, MPH, JUANA M. SANCHEZ'-BRAVERMAN, MD, MPH, LUIS ROSERO-BIXBY, MPH, AND KATHLEEN M. VETTER, MPH As part of a case-control study to investigate the high incidence From the Division of Sexually Transmitted Diseases of cervical cancer in Costa Rican women, the seroprevalence of Laboratory Research and the Center for Chronic Disease the treponematoses, in particular, syphilis was determined. In Prevention and Health Promotion CDC, Atlanta, Georgia, each age group, women with a history of two or more sex Emory University School of Medicine, Atlanta, Georgia, and partners were two to four times more likely to be seroreactive in the University of Costa Rica, San José, Costa Rica. tests for syphilis than women with zero or one sex partner. The highest percentage of reactive results in the microhemaggluti­ nation assay for antibodies to Treponema pallidum (MHA- TP) was seen in samples from women aged 50-59 who had had women. Details of these studies have been published else­ two or more lifetime partners (23.8%). Three observations from where.1-5 Because cervical cancer appears to be asso­ our study support reactivity due to syphilis rather than yaws or ciated with sexually transmitted diseases, these studies pinta: (/) a similar percent of reactive rapid plasma reagin also investigated the seroprevalence of antibodies to (RPR) card test results among MHA-TP reactors in the two age groups of women who were surveyed (42 vs. 49%) was ob­ syphilis,1 genital herpes,1,6 chlamydia7 and human immu­ served; (2) women who were seroreactive in the MHA-TP had nodeficiency virus.8 In the report by Irwin et al.,1 of the multiple risk factors for STD (low socioeconomic status (9.4%), 415 patients with carcinoma in situ, 9.1 % were reactive urban residence (22.8%), first intercourse under 16 years of age in serologic tests for syphilis, whereas 17.1% of the 149 (14.1%), and multiple sex partners (26.3%)|, and (j) only sex­ patients with invasive cancer were reactive in these ually experienced women had reactive results in the MHA-TP test. tests.1 The results that are reported herein are based on the serologic responses of the population-based controls IN 1984-1985, the Costa Rican Demographic Associa­ that were selected for the case-control study1 and de-: tion in collaboration with the Centers for Disease Con­ scribe the total number of both new and old cases in the trol (CDC), the Costa Rican Social Security Administra­ population (seroprevalence) rather than the total num­ tion, and Family Health International conducted a case- ber of new cases in a population at risk over a specific control study of the high incidence of cervical cancer and period of time (incidence). Although Shadid-Chaina et the low incidence of breast cancer in Costa Rican al.9 reported on the seroprevalence of syphilis among ap­ plicants for a health card, this study is the first popula­ tion-based study of seroprevalence of antibodies that are This study was supported in part by Family Health International, detected in the serologic tests for syphilis. In addition, Research Triangle Park, N.C. with funds from the US Agency for Inter­ national Development. Opinions expressed do not necessarily repre­ our study relates reactivity in serologic tests for syphilis sent those of USAID. with demographic characteristics and the medical and The authors thank the staff of the Treponemal Pathogenesis and sexual history of Costa Rican women. Immunobiology Branch, CDC, for performing the serologic test for syphilis: Principal investigators: Luis Rosero-Bixby; Mark W. Oberle, MD; project coordinators: Carmen Grimaldo, Lie; Martin Fallas; Materials and Methods Daisy Fernández, MD; data managers: Anne S. Whatley, MS; Heman Caamano; Elizabeth Rovira, MStat; A. Rampey, Jr, MS; Steve Kin- Population Studied chen; project associates: Oscar Fallas, MD; Nancy Lee, MD; Kathleen Irwin, MD; Judith Fortney, PhD; Gary S. Grubb, MD; Michele Bon- The sample of women consisted of a nationally repre­ homme, MSPH; project consultants: Raimundo Riggioni, MD; Miguel Gómez, MS; Phyllis Wingo, MS; George L. Rubin, MBBS; Howard sentative cross-section of women aged 25-59 years, se­ Ory, MD; Peter Layde, MD; Jacquelyn Arthur, Emilia León, MD; lected on the basis of the June 1984 census.1 To match Costa Rican National Tumor Registry: Georgina Muñoz de Brenes; the age distribution of the cancer patients in the original laboratory consultants: Mary Guinan MD, PhD; Jorge Ramirez; Andre Nahmais, MD; Julius Schachter, PhD; pathology consultants: case-control study,1 the sampling fraction for this popu­ Saeed Mekbel, MD; Jorge Salas Cordero, MD; and León Trópper, MD. lation-based control group varied by age group; thus, Reprint requests: S. A. Larsen, PhD, D-13, Centers for Disease Con­ women in certain age groups were oversampled. Of the trol, 1600 Clifton Rd NE, Atlanta, GA 30333. Received for publication August 14, 1989, revised November 5, 870 women who participated as controls in the case- 1990, and accepted November 5, 1990. control study, 767 consented to a venipuncture.1 The 124 Vol. 18* No. 2 SYPHILIS IN COSTA RICA 125 social and demographic characteristics of these women TABLE 2. Percentage of Women with Reactive MHA-TP Results by did not differ from those of the 103 women who did not Number of Lifetime Sexual Partners give informed consent for venipuncture.10 Age Group Total 25--39 40--59 Interviews Number of Interviews were conducted using a modified version of Sexual Partners* % N %N%N the questionnaire from the CDC Cancer and Steroid None 0.0 (36)t 0.0 (22) 0.0 (14) Hormone Study." Questions focused on reproductive, 1 4.1 (501) 3.3 (251) 5.4 (250) medical, and sexual history, and included age at first 2 9.1 (133) 3.6 (65) 17.3 (68) 3+ 17.2 (95) 15.4 (54) 20.6 (41) intercourse, number of sexual partners, history of sex­ Total 6.4 (767) 4.8 (393) 9.0 (374) ually transmitted diseases (STD), marital status, and * Two women with unknown number of sexual partners excluded, number of pregnancies. Demographic information in­ t In this and subsequent tables, numbers in parenthesis refer to the cluded socioeconomic level,12 education, age, and region unweighted number of cases in each cell. of residence. Serum Samples Tabulations For each blood sample, serum was separated from The analysis was descriptive using data from cross- other cellular constituents and shipped to the CDC. At tabulations for demographic and medical/sexual history the CDC, antibodies to Treponema pallidum subspecies variables. To calculate seroprevalence by demographic pallidum and pertenue, and T. carateum, the causative characteristics in the general population, the results, ex­ agents of syphilis, yaws, and pinta, were detected us­ cept where noted, were age-weighted to compensate for ing the microhemagglutination assay (MHA-TP).13 the oversampling of certain age groups (table l). Since Currently, all serologic tests for syphilis, including the the population survey was based on a complex, multi­ MHA-TP, cross react with antibodies that are produced stage, cluster-sample methodology, the unweighted num­ in response to these pathogenic treponemes. However, ber of cases in each cell is shown in tables 2-4 as an because reactivity in the RPR 18 mm circle card test14 indication of sample sizes rather than standard errors for the detection of antilipoidal antibodies disappears that were based on assumptions of simple random sam­ with time, the RPR card test was used to indicate possi­ pling. ble current infection with T. Pallidum subspecies palli­ dum. 15 In addition, to indicate possible current primary Results infection, we used an investigational test that was based on an enzyme-linked immunosorbent assay (ELISA), In the interviews of the 767 women from whom blood using antibodies to immunoglobulin M (IgM) to capture was collected, 17.7% reported a history of STD or pelvic IgM (Ortho Syphilis-M, Ortho Diagnostic Systems Inc., inflammatory disease (PID). Only 8 women (1.9%) re­ Carpinteria, CA). ported a history of syphilis. However, 54 of the women A portion of each serum was sent to the Division of (6.4%) had reactive serology by the MHA-TP, indicating Pediatric Infectious Diseases, Emory University, At­ either a past or present infection with pathogenic trepo­ lanta, Georgia for determination of the presence of anti­ nemes other than oral treponemes that are associated bodies to Herpes simplex virus type 2 (HSV-2).16 Sera with peridontal disease. Of these 54 women, 25 (46.3%) were also analyzed by microimmunofluorescence for an­ also had reactive RPR card test results, suggesting a re­ tibody to Chlamydia trachomatis17 in the chlamydia lab­ cent infection.14 Among MHA-TP reactors, the percent oratory of the San Francisco General Hospital, San Fran­ of serum samples that were reactive in the RPR card test cisco, California. was similar in the two age groups; 42% for ages 25-39 compared with 49% for ages 40-59. The distribution of end-point titers of the samples in the RPR card test was TABLE 1. Percent of Women with Reactive Syphilis Serology by Age also similar between the age groups. Only one serum sample from a woman aged 33 was reactive in the IgM Number Number Unweighted Weighted Age Group Reactive Tested Percent Percent capture ELISA. Only two serum samples had RPR card test titers greater than 1:8.