NUMEROUS MONOGRAPHS DESCRIBING strategies for syphilis control have been produced during the past century.1–7 Indeed, few fields of public health have been scrutinized more carefully by outside groups or debated more thoroughly by venereal disease experts. Whether in economic, political, social, ethical, or epidemiologic arenas, syphilis control has been the prototypic sexually transmitted disease (STD) control program of the 20th century.7 Thus, the approaches taken, and the measures used, have been a model for control programs directed toward other STDs. In addition, many other clinical preventive services, such as those for tuberculosis, immunization, maternal and child health, and human immunodeficiency virus (HIV), have used concepts derived from syphilis control activities in their own prevention strategies.
However, much of the epidemiologic evaluation of public health measures for syphilis control occurred before the 1950s.8 This article examines the historical and epidemiologic basis for syphilis control, using unpublished data to supplement a recent model of STD transmission. We recommend building on such traditional individual-oriented strategies as case finding, partner notification, and presumptive treatment to form community-oriented, population-based strategies including (but not limited to) selective mass treatment in high-prevalence populations.
Historical Context for Syphilis Control Programs
The initial objective of syphilis control programs in the 1940s was to prevent the late complications of the disease. Public awareness programs set the stage for mass serologic testing programs to detect infected individuals, who were then generally treated with heavy metals. Beginning in 1943, the so-called rapid treatment centers were established by the federal government.4 These inpatient facilities provided a course of 5- to 10- day arsenical therapy instead of the 70 weeks required on an outpatient basis. Soon thereafter, however, the availability of penicillin for widespread use contributed to making the syphilis control program even more successful. By the early 1950s, the reservoir of untreated or inadequately treated syphilis had been dramatically reduced. In succeeding years, the incidence of complications markedly declined. During the next two decades, deaths attributable to syphilis decreased by 85%, and admissions to hospitals for syphilitic psychoses declined by 97%.5 Congenital syphilis, for which better data are available, declined by 90% between 1941 and 1972.9
As the prevention of late complications became a reality, the interruption of syphilis transmission in its infectious stages emerged as the primary objective of control programs. The focus for public health officials shifted from lowering syphilis prevalence to reducing its incidence.5 The strategy for accomplishing this has gradually evolved since the late 1950s. Building on the concept of case finding through routine blood testing, syphilis control programs increasingly emphasized case prevention by aggressive treatment of sex partners. Patients in the infectious stages of syphilis were interviewed to identify exposed sex partners, who were then offered treatment (termed epidemiologic treatment) before they could either develop symptoms or spread the infection. Although this approach was successful in stemming outbreaks and reducing community levels of syphilis, because it was generally focused on individuals, it was costly in financial and human resources.
Epidemiologic Basis for Syphilis Control Activities
Many simultaneous activities are necessary to reduce syphilis because of the interactive behavioral and biologic dynamics of sexual spread. The forces responsible for sustaining transmission of any sexually transmitted infection, including syphilis, can be represented in a simple equation, R = β × c × D.10R represents the reproductive rate of an infection, i.e., the number of new infections produced by an infected individual. β is the average probability that an infected individual will infect a susceptible partner given exposure. c is the average number of new partners exposed by an infected individual per unit of time. D is the average duration of infectiousness of the specific infection. Public health interventions to prevent syphilis are targeted at reducing the magnitude of β, c, or D by reducing the probability of infecting a susceptible partner; limiting the number of partners who have sex with infected persons; and reducing the duration of infectiousness.
Most current emphasis of syphilis control activities is on reducing the duration of infectiousness. This approach rests on certain assumptions about the natural history of syphilis (Figure 1). For our model, we will assume that, on the average, the moment of infection is followed by an incubation period of 3 weeks, by a 5-week period of primary syphilis, and by a 6-week period of secondary syphilis, after which the syphilis infection becomes latent. The 11 weeks of primary and secondary syphilis are considered the period of infectiousness.
Using a crude meta-analytic approach (Table 1) without preventive measures, 4 of 10 sexual encounters between an infected and an uninfected person will result in the transmission of syphilis.11–15 However, these studies did not stratify by stage of infection, which probably accounts for the wide range of transmission reported among the data. Empirical data from national syphilis control programs16 indicate that an untreated person with syphilis would generate, on average, 0.17 new infections per week during the 5 weeks of primary syphilis and 0.05 new infections per week during the 6 weeks of secondary syphilis, for a reproductive rate of 1.15 (Figure 1). At this level, in the absence of effective intervention, the infection will propagate in the population. This hypothetical reproductive rate is a weighted average of rates from diverse subpopulations that lie on a spectrum from no transmission (reproductive rate <1) to intense transmission (reproductive rate ≥2). Although the reproductive rate of 1.15 is probably an underestimate, given slippage in the process of partner notification, it is of heuristic value in considering the impact of an intervention program.
With a traditional control program in which education, clinical diagnosis, and partner notification are effective, syphilis can be treated early in the course of illness, and transmission will be interrupted (Figure 2). For example, community education theoretically can motivate infected persons to recognize symptoms of syphilis and to seek medical care within 2 weeks of the onset of symptoms. Physicians in the community, if properly trained, can diagnose and treat the disease promptly. A system of partner notification assures the effective identification, referral, and treatment of persons exposed to infection. Under these circumstances, most of the partners of infectious persons would still be in the incubation period when treated, and the reproductive rate would be near zero. Such a theoretical goal is unlikely to be achieved.17 However, given our hypothetical reproductive rate of 1.15, even a 25% reduction in the number of infected partners per case per week during the primary period—from 0.17 to 0.13—would lower the reproductive rate to <1 and ultimately would interrupt transmission (Figure 2).
This model for controlling syphilis transmission is based on assumptions derived directly from the biologic characteristics of Treponema pallidum and the clinical stages of the disease it produces.18T. pallidum has long division times and, as a consequence, an extended incubation period. Thus, with syphilis, we have a relatively prolonged opportunity to cure the infection before symptoms appear and the host becomes infectious. In addition, T. pallidum remains exquisitely sensitive to long-acting benzathine penicillin. If the organism were to become resistant to this drug and require higher doses or more frequent administration of antibiotic therapy, syphilis control would be compromised. For these reasons, syphilis is a disease for which the interventions of partner notification and prophylactic therapy can have substantial impact. Other STDs with shorter incubation periods (e.g., gonorrhea) or less convenient therapies (e.g., chlamydia) should not be expected to respond as dramatically to traditional control strategies as syphilis.17
These interventions can be concentrated in populations to achieve maximal impact. Community variability in syphilis reproductive rates will dictate the different levels of public health effort required. During the past two decades, the heterogeneous distribution of all STDs, including syphilis, has led to the concept of “core populations.”19,20 Core populations are defined as those that contribute a disproportionate share to sustaining STD rates in communities. From the above model, as well as from empiric data,21 syphilis core groups will need higher rates of sex partner change than other STDs to maintain the infection within their sexual network. Thus, identifying and treating these high prevalence core populations can lead to rapid decreases in the level of infection.
Current evidence supports the existence of syphilis core populations. In Seville, Spain,22 syphilis (along with gonorrhea and chlamydia) showed a distinct spatial clustering. In upstate New York,23 the distribution of syphilis was more diverse than gonorrhea but still could be connected through two endemic foci—inner city, heterosexual, black groups and suburban, homosexual-bisexual, white and black groups. Finally, in Multnomah County, Oregon,24 a syphilis core population was identified using geographic and sociodemographic measures as proxies for sociosexual networks. The Oregon core group, like others, was characterized by spatial clustering, low socioeconomic status, and a high proportion of black persons.
Implications for Syphilis Control
Widespread testing to eliminate syphilis has enormous intuitive appeal. Nonetheless, the zeal for mass screening has been tempered by detailed comparisons of screening costs versus the potential benefits of case finding and the interruption of transmission.25 Moreover, the relatively brief interval when an infected person can actually transmit syphilis is limited (Figure 1). Thus, targeted screening is more practical.
As described previously, the concept of focusing on core populations has become more popular. Whether these groups are defined by occupation (commercial sex workers), by facility (prisons, hospital emergency rooms), by risk environment (gay bathhouses, crack houses), by geographic location (census tract), or by sociodemographic variables (poverty, ethnicity), the epidemiologic principle is the same. Screening that is targeted to high prevalence areas will interrupt core transmission and have an accelerated impact on reducing community incidence. This approach has been evaluated in Oregon using geographic and sociodemographic markers for the core.24 However, the results of this screening intervention were inconclusive; new patients were identified, but their connection to true core transmitters was unclear. Small numbers and low syphilis rates limited the study's power.
No incontrovertible guidance emerges from the literature on experience with syphilis screening. Despite the development of better quantitative tools for the evaluation of costs and benefits, considerable subjective judgment still is required. Only one published report directly addressed the question of whether targeted screening interrupts the transmission of syphilis,26 though the size and scope of that study may not have been sufficient to warrant generalization. Most studies discuss “yield” from individual patients, and even similar syphilis yields evoke markedly different value judgments regarding their public health usefulness.
Nevertheless, the diversity of screening data (and opinions) suggests several common themes. Wide variation in the prevalence of syphilis is prima facie evidence of the need for screening as a form of syphilis surveillance. Moreover, the observed variation in syphilis positivity means that screening decisions should be based on local data—whatever criterion for efficacy is invoked. If screening is to have any value as a mechanism for case finding or for disease control, it must be applied and analyzed locally.
Clinical Diagnosis as a Tool for Syphilis Control
Syphilis symptoms and signs are protean. Clinical diagnosis—though difficult—is crucial for both case finding and prevention. Moreover, clinical services are the final common pathway through which treatment is given, cure is achieved, and prevention is accelerated. Thus, these services must be easily accessible to the core populations.
Few studies have documented either the percentage of infected patients who recognize their syphilis symptoms or the percentage of those with recognized symptoms who seek medical services. In one nationwide study, 45% of persons brought to treatment as sex partners admitted that they had recognized symptoms of syphilis but did not seek medical advice.6 Even when the symptoms of genital ulcers occur and the patient seeks care, diagnosis using clinical parameters alone is notoriously difficult. In one series of 100 patients with genital ulcers, clinicians were able to identify the specific microbial cause in fewer than half without definitive laboratory findings.27
Despite these difficulties, clinical diagnosis of early syphilis has produced the majority of such cases reported to public health authorities for at least half a century. In the late 1940s, approximately two thirds of all persons diagnosed with primary or secondary syphilis sought medical care on their own initiative.7,28 Similarly, in 1990, 62% of those with early syphilis obtained clinical services based on their own suspicions of illness (Centers for Disease Control; Division of STD/HIV Prevention, unpublished data, July 1991).
In the 1990s, the public health system for delivering clinical preventive services is drastically overburdened. Sexually transmitted disease clinics, traditionally the referral point for patients with syphilis, share this burden. In 1989, STD clinics in the 15 metropolitan areas with the highest syphilis rates were reaching their maximum patient capacity earlier in the day than in previous years.29 Moreover, waiting times were longer and fewer patients were treated. Patients turned away from these public facilities represent missed opportunities for STD prevention. The effect of the increasing managed care coverage on clinical services for syphilis, as well as other STDs, remains to be seen. But the implication of limited clinical care for syphilis control is to shift public health priorities from diagnosing and treating individual patients to identifying and intervening in the communities with high prevalence.
The Role of Treatment
Providing proper treatment for both symptomatic and asymptomatic persons is the sine qua non of syphilis control. Penicillin treatment based on presumptive diagnosis of syphilis is inexpensive, simple, safe, and effective. Thus, as shown in the model above, early recognition and adequate treatment of patients with syphilis and their sex partners is an essential, albeit costly, means of preventing community spread.
In addition to treating those diagnosed with syphilis, selective prophylactic (preventive or epidemiologic) treatment also has a major role in syphilis control strategies.30 Over the years, this approach of selective preventive treatment has helped to limit multiple outbreaks of syphilis. Coupled with the process of active partner notification (see next section), prophylactic treatment of persons exposed to infectious syphilis effectively has controlled epidemics in rural31 and urban32 settings. Benzathine penicillin for syphilis is especially helpful for outbreaks. Because it produces treponemicidal concentrations of penicillin for at least 3 weeks, this agent provides an interval of “antibiotic” quarantine33 during which reinfection is hindered.
In addition, within certain circumscribed communities with a high prevalence of infection, selective mass penicillin treatment has been useful. For example, in Fresno, California in 1977, selective mass treatment of commercial sex workers interrupted an ongoing syphilis epidemic.33 The same strategy, though for different indications, has been applied by the World Health Organization for eradicating yaws.34–36 Not surprisingly, this mass treatment approach also lowered the prevalence—though temporarily—of venereal syphilis in those communities in which it was applied.
Rapid investigation of sex partners is essential for bringing persons with early syphilis to treatment before they can spread the infection within the community. In fact, syphilis is the prototypic STD upon which the prevention strategy of partner notification was based, both in theoretical concept and in practical application.
Traditionally, syphilis control programs in the developed countries have emphasized active intervention by health providers to interview individual patients, to identify sex partners, and to assure that partners are evaluated and treated.37 Through the 1960s, numerous reports attested to the success of this approach for syphilis control.13,38–42 Whether applied to isolated rural communities,43,44 selected urban neighborhoods,45 or captive prison settings,46 rapid sex partner identification, location, and treatment reduced syphilis occurrence.
The partner notification process involves a series of interrelated activities: interviewing the infected patient to obtain a complete list of exposed sex partners, finding these persons in the community, and assuring that they are treated promptly. In the United States, interviewing techniques have been developed to encourage patient cooperation in naming a maximum number of partners.5 However, during the 1960s and 1970s, the contact index—a measure of the yield of the syphilis interview—steadily declined (Figure 3). Possible interactive reasons for this trend include: a true decrease in the number of sex partners in infected persons; changing environments for sexual relations whereby a greater percentage of partners are anonymous (e.g., gay bath-houses, crack houses); a growing atmosphere of distrust of all government organizations, including those delivering public health services; deteriorating interviewing techniques; and the increasing competition of other STDs, especially HIV.
Problems with syphilis interview productivity have persisted to the present. In Oregon, similar interviewing techniques produced far fewer locatable sex partners for patients with syphilis than for those with gonorrhea.47 Presumably, this reflected the condition of anonymous sex—frequently in exchange for drugs—in environments in which syphilis was being transmitted. In Oregon, 28% of patients with syphilis exchanged sex for money or drugs, but they accounted for nearly 80% of the unlocatable sex partners. For patients with gonorrhea, 17% acknowledged sex-for-drugs/money, and these accounted for 36% of the unlocatable sex partners.
Finding sex partners may also have become more difficult in recent years. Distrust of government agencies may have worsened in the black community after revelations of the Tuskegee syphilis study48. Moreover, the association of high-risk sexual behavior with environments in which illicit drug use and violence are common has made the safety of the STD outreach worker an issue.
Thus, in the 1990s, partner notification should take on a new epidemiologic dimension—gaining information about core environments in which the greatest transmission is occurring. Using specific populations, rather than infected individuals, as the units for syphilis intervention is a means for overcoming problems with naming and locating sex partners. In the past, this community-oriented approach was a type of “cluster” interviewing. Patients with syphilis, in addition to their known sex partners, were queried about other persons in whom—and specific social settings in which—syphilis transmission may have occurred.49 Although this cluster approach produced a lower yield of infected, previously untreated patients than following up those specifically named as sex partners, it still identified a relatively high percentage of persons who might not have been reached in any other way. In fact, depending on how the socially related group was defined, as many as 1 in 5 people examined had untreated syphilis.49
In recent years, similar population-based approaches have been used to identify particular communities at high risk for syphilis. Examples of situations in which this community intervention played a role in stemming syphilis outbreaks include a Native American tribe reluctant to name any partners to outside officials,50 a Philadelphia neighborhood in which crack cocaine environments led to unsafe sexual behaviors and high levels of syphilis,51 and a Montgomery County, Alabama intensive program that identified socio-sexual networks responsible for the continued, though lower level, spread of syphilis.52
Our current community health education efforts usually encourage primary prevention (preventing acquisition of syphilis) in persons at risk. During the last decade, HIV prevention resources have stimulated increased community involvement to support safer sexual behaviors. These same primary prevention approaches could help reduce syphilis. Activities include advocating risk avoidance methods and distributing condoms. Condoms, although shown to be effective in limiting the transmission of HIV and other STDs,53 are not used regularly by many persons at high risk. Thus, we need more creative methods of condom promotion, including widespread availability at little or no cost, to enhance syphilis control. However, changes in sexual behavior are not achieved easily in populations characterized by drug use, poverty, low education, unemployment, and inadequate health care. These groups need to be specifically targeted by health education campaigns, and they must be provided improved access to health care for syphilis screening, diagnosis, and treatment.
Experience with HIV community education has shown that changing social norms are fundamental to influencing safer individual sexual behavior, and reinforcing messages, delivered regularly by trusted peers, are crucial to preventing relapse to unsafe practices. Syphilis control in the homosexual community already has benefited from these lessons learned from HIV. In socially disadvantaged communities, pilot programs using commercial sex workers as outreach workers have been successful in educating women at high risk women and in identifying pregnant women who need prenatal care, including syphilis testing.
The mass media is a powerful tool to promote syphilis knowledge. Previous mass media campaigns against syphilis were temporally associated with wartime and occupationally directed against commercial sex workers.7 Traditionally, they involved judgmental messages that proved not to be an effective method of changing behavior.7 Awareness of herpes and AIDS is widespread largely because of the attention given these conditions by the media. In the past, syphilis has been relegated to a much lower priority for public education messages. However, in areas with high syphilis rates, public advertisements are increasingly aired to acquaint persons with the symptoms of syphilis, to publicize hotline numbers for further questions, to encourage condom use in high-risk settings, and to promote prenatal testing for pregnant women. Because of the high rates of syphilis among selected populations, targeted messages directed at educating them about recognizing syphilis symptoms and the importance of obtaining early treatment are crucial.
Our historical and epidemiologic analysis shows the highest priority needs for syphilis control involve a synthesis of old and new approaches. The unique biologic characteristics of T. pallidum allow it to be attacked by a combination of clinical and community interventions, depending on the prevalence of infection. Recent mathematical models have described the natural history of syphilis and pointed out specific implications for its transmission dynamics and approaches to control.54,55
By building on information gained through individually oriented strategies, we can apply the concept of population-based interventions. For example, data obtained from the process of eliciting the location of sex partners can be used for both individual and population benefit. When epidemiologic analysis of partner patterns reveals high-prevalence communities, public health officials can move quickly to intervene clinically with wider prophylactic treatment. Among selected populations in which the prevalence of infectious syphilis is greater than an epidemic threshold, epidemiologic treatment can be considered. Alternatively, targeted community screening, with immediate presumptive treatment of all patients positive for rapid plasma reagin, can be implemented.
In actuality, “environmental” or “community-based” approaches to controlling syphilis have long been with us. In multiple situations during the past four decades, after intensive screening programs documented high levels of syphilis in particular communities, the risk marker of residing in that community became enough of an epidemiologic justification to “presumptively treat” persons for syphilis. Not surprisingly, the morbidity level in the community was drastically lowered.
Education messages also should be targeted based on epidemiologic indications. The aim should be to create population-level, prevention-based, sexual and health-seeking behaviors that are reinforced by their becoming social norms. Whether establishing condom use as the routine sexual practice or genital self-examination as a means to recognize ulcers, targeted community education will complement the impact of any core population treatment strategy.
Many states now offer examples of similar community control programs based on data indicating a high prevalence of infection. For example, Oregon used geographic markers to focus on “core transmitters”; Arizona is treating persons on the basis of zip code; California is using community-based organizations to identify and aggressively treat persons “on-the-street” who otherwise would not seek care in health facilities; Philadelphia has used “crack house” locations as indications for immediate diagnosis and, where possible, presumptive treatment of syphilis; New York State and Los Angeles have used correctional facilities as locations at which rapid syphilis treatment can be delivered; and finally, New York City has used particular drugrelated diagnoses of persons seeking care in emergency rooms as reasons to deliver penicillin therapy. These represent only a few of the current population-level approaches to case identification, presumptive treatment, and targeted education based on epidemiologic indications.
1. Parran T. Shadow on the Land. New York: Reynal and Hitchcock, 1937.
2. Baumgartner L, Curtis AC, Gray AL, Kuechle BE, Richman TL. The eradication of syphilis: A task force report to the Surgeon General Public Health Service on syphilis control in the United States. Washington, DC: US Public Health Service, 1961.
3. Youmans JB, ed. Syphilis and other venereal diseases. Med Clin North Am 1964; 48:573–651.
4. Anderson OW. Syphilis and society: Problems of control in the United States, 1912–1964. Chicago: University of Chicago Center for Health Administration Studies, 1965.
5. Brown WJ, Donohue JF, Axnick NW, Blount JH, Ewen NH, Jones OG. Syphilis and other venereal diseases. Cambridge, MA: Harvard University Press, 1970.
6. World Health Organization. Treponemal infections. Geneva, Switzerland: World Health Organization, Tech Report Series 674, 1982.
7. Brandt AM. No magic bullet: A social history of venereal disease in the United States since 1880. New York: Oxford University Press, 1985.
8. Moore JE. An evaluation of public health measures for the control of syphilis: An epidemiologic study. Am J Syph Gonor Vener Dis 1951; 35:101–134.
9. Henderson RH. Venereal disease: A national health problem. Clin Obstet Gynecol 1975; 18:223–232.
10. May R, Anderson R. Transmission dynamics of HIV infection. Nature 1987; 326:137–142.
11. Alexander LJ, Schoch AG, Mantooth WB. Abortive treatment of syphilis. Am J Syph Gonor Vener Dis 1949; 33:429–436.
12. Idsoe O, Guthe T, Christiansen S, Krag P, Cutler JC. A decade of reorientation in the treatment of venereal syphilis. Bull WHO 1954; 10:507–561.
13. Moore MB Jr, Price EV, Knox JM, Elgin LW. Epidemiologic treatment of contacts to infectious syphilis. Public Health Rep 1963; 78:966–970.
14. Schroeter AL, Turner RH, Lucas JB, Brown WJ. Therapy for incubating syphilis. JAMA 1971; 218:711–713.
15. Schober PC, Gabriel G, White P, Felton WF, Thin RN. How infectious is syphilis? Br J Vener Dis 1983; 59:217–219.
16. Blount JH. Working concepts for syphilis control. Presented at International Seminar on Venereal Disease Control. Atlanta, GA: October 17, 1971.
17. Brunham RC, Plummer FA. A general model of sexually transmitted disease epidemiology and its implications for control. Med Clin North Am 1990; 74:1339–1352.
18. Hook EW III, Marra CM. Acquired syphilis in adults. N Engl J Med 1992; 325:1060–1069.
19. Brunham RC. The concept of core and its relevance to the epidemiology and control of sexually transmitted diseases. Sex Transm Dis 1991; 18:67–68.
20. Yorke JA, Hethcote HW, Nold A. Dynamics and control of the transmission of gonorrhea. Sex Transm Dis 1978; 5:51–56.
21. Stoner BP, Whittington WL, Aral SO, Holmes KK. Variation in frequency of sex partner change within sexually transmitted disease networks (Abstract no. 119). 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, LA: October 1993.
22. Alvarez-Dardet C, Marquez S, Perea EJ. Urban clusters of sexually transmitted diseases in the city of Seville, Spain. Sex Transm Dis 1985; 12:166–168.
23. Rothenberg RB. The geography of syphilis: A demonstration of epidemiologic diversity. In: Morisset R, Kurstak L, eds. Advances in Sexually Transmitted Diseases. Utrecht, The Netherlands: VNU Science Press, 1986:125–133.
24. Oxman GL. An urban epidemic of heterosexual syphilis: Evidence for core transmission and evaluation of a screening intervention program. Seattle: University of Washington; 1990. Thesis.
25. Hart G. Screening to control infectious disease: Evaluation of control programs for gonorrhea and syphilis. Rev Infect Dis 1980; 2:701–712.
26. Wolf FC, Judson FN. Intensive screening for gonorrhea, syphilis, and hepatitis B in a gay bathhouse does not lower the prevalence of infection. Sex Transm Dis 1980; 7:49–52.
27. Chapel TA, Brown WJ, Jeffries C, et al. How reliable is the morphological diagnosis of penile ulcerations? Sex Transm Dis 1977; 4:150–155.
28. Venereal Disease Control Division. Reasons for coming to venereal disease clinics. J Vener Dis Inform 1948; 29:190–193.
29. Aral SO, Holmes KK. Sexually transmitted diseases in the AIDS era. Sci Am 1991; 264:62–69.
30. Hart G. Epidemiologic treatment for syphilis and gonorrhea. Sex Transm Dis 1980; 7:149–160.
31. Ball RW. Outbreak of infectious syphilis in South Carolina. JAMA 1965; 193:101–104.
32. Lee CB, Brunham RC, Sherman E, Harding GKM. Epidemiology of an outbreak of infectious syphilis in Manitoba. Am J Epidemiol 1987; 125:277–83.
33. Jaffe HW, Rice DT, Voigt R, Fowler J, St John RK. Selective mass treatment in a venereal disease control program. Am J Public Health 1979; 69:1181–1182.
34. Hackett CJ, Guthe T. Some important aspects of yaws eradication. Bull WHO 1956; 15:869–896.
35. Grin EI, Guthe T. Evaluation of a previous mass campaign against endemic syphilis in Bosnia and Herzegovina. Br J Vener Dis 1973; 49:1–19.
36. Hart G. Syphilis control in populations previously exposed to yaws. Int J Epidemiol 1982; 11:181–187.
37. Rothenberg RB, Potterat JJ. Strategies for management of sex partners. In: Holmes KK, Mårdh P-A, Sparling PF, et al, eds. Sexually transmitted diseases, 2nd ed. New York: McGraw-Hill, 1990:1081–1086.
38. Smith DC, Brunfield WA Jr. Tracing the transmission of syphilis. JAMA 1933; 101:1955–1957.
39. Clark EG, Kampmeier RN. Contact investigation and the early recognition of syphilis. Urol Cutan Rev 1939; 43:169–170.
40. Clark EG. Studies in the epidemiology of syphilis: Epidemiologic investigations in a series of 996 cases of acquired syphilis: II. Contact investigation in a series of 824 patients with syphilis. J Vener Dis Inform 1940; 21:349–369.
41. Fiumara JN, Segal J, Jolly J. Contact investigation: Combined military-civilian program. Public Health Rep 1953; 68:289–294.
42. Dougherty WJ. Epidemiologic treatment of syphilis contacts. J Med Soc N J 1962;59:564–7.
43. Gray AL, Iskrant AP, Hibbets RS. Contact investigation in rural county in Mississippi. J Vener Dis Inform 1949; 50:165–169.
44. Kimbrough RC, Cowgill DM, Bowerman EP. Rural syphilis—a localized outbreak. Am J Public Health 1938; 28:756–758.
45. Webster B, Shelley EI. Studies in the epidemiology of primary and secondary syphilis in New York City. Am J Public Health 1941; 31:1199–1205.
46. Smith WHY. Syphilis epidemic in a southern prison. J Med Assoc Alabama 1965; 32:392–394.
47. Andrus JK, Fleming DW, Harger DR, et al. Partner notification: Can it control epidemic syphilis? Ann Intern Med 1990; 112:539–543.
48. Jones JH. Bad blood: The Tuskegee syphilis experiment. New York: The Free Press, 1981.
49. Kaufman RE, Blount JH, Jones OG. Current trends in syphilis. Public Health Rev 1974; 3:175–196.
50. Gerber AR, King LC, Dunleavy GJ, Novick LF. An outbreak of syphilis on an Indian reservation: Descriptive epidemiology and disease-control measures. Am J Public Health 1989; 79:83–85.
51. Mellinger AK, Goldberg M, Wade A, et al. Alternative case-finding in a crack-related syphilis epidemic—Philadelphia. MMWR 1991; 40:77–80.
52. Engelgau MM, Woernle CH, Rolfs RT, Greenspan JR, O'Cain M, Gorsky RD. Control of epidemic early syphilis: The results of an intervention campaign using social networks. Sex Transm Dis 1995; 22:203–209.
53. Roper WL, Peterson HB, Curran JW. Condoms and HIV/STD prevention—clarifying the message. Am J Public Health 1993; 83:501–503.
54. Garnett GP, Hoyle DV, Anderson RM. The transmission dynamics of Treponema pallidum:
Mathematical models of the impact of treatment (Abstract no. 64). Eleventh Meeting of the International Society for STD Research. New Orleans, LA, August 30, 1995.
55. Van der Ploeg CPB, Van Vliet C, De Vlas SJ, Temmerman M, Fransen L, Habbema JDF. Natural history and effects of diagnosis and treatment of syphilis: A quantitative synthesis (Abstract no. 65). Eleventh Meeting of the International Society for STD Research. New Orleans, LA, August 30, 1995.