Eye on IDPublication Exclusive

Syphilis: An old, easily diagnosed and treated disease … on the rise

Syphilis is currently epidemic among men who have sex with men in the United States and in many other parts of the world. Since 2000, rates of syphilis have been increasing in the U.S., as well as Canada, the United Kingdom, Australia and Europe, primarily among MSM. This is occurring despite more than 70 years of remarkable progress in control of this disease.

We have excellent diagnostics, effective therapy and a pathogen that remains penicillin-susceptible. Syphilis, although highly infectious, is easily curable in its early (primary and secondary, or P&S), most contagious stages of disease. If untreated, syphilis can lead to serious long-term complications that include neurological and cardiovascular damage. Congenital syphilis, if acquired during the 4 years before pregnancy, can lead to infection of the fetus in 80% of cases and can cause stillbirth and neonatal death in up to 40% of cases and physical deformity and neurological complications in children who survive. In addition, syphilis, like many other sexually transmitted infections (STIs), can increase transmission of HIV at least two- to fivefold.

In the mid-1940s, the incidence rate of P&S syphilis peaked at about 70 per 100,000 and then fell dramatically in the late 1940s, only to rise again in the late 1980s.

From 1986 through 1990, an epidemic of syphilis occurred throughout the U.S. In 1990, more than 50,000 cases of P&S syphilis — 20.3 cases per 100,000 population — were reported, the highest number of cases since 1948. This spike, which has been attributed to an epidemic of crack cocaine use and exchange of sex for drugs among heterosexual men and women, occurred despite a fall in the incidence of syphilis in men attributed to changes in sexual behavior due to AIDS. In 1991, syphilis rates began to decline again in the U.S., eventually reaching 2.1 per 100,000 in 2000, the lowest incidence of P&S syphilis since annual reporting began in 1941. However, over the next decade, the incidence rate gradually rose. By 2013, the incidence of P&S syphilis more than doubled, reaching 5.5 cases per 100,000.

Matthew E. Levison

Donald Kaye

From 2000 to 2013, the rate of P&S syphilis among men rose almost fourfold from 2.6 per 100,000 in 2000 to 10.3 per 100,000 in 2013. Because many states do not routinely report information on sexual practices or the sex of sex partners, the CDC had not collected data by sex of sex partners until 2005. Instead, male-to-female (M:F) ratios were used as a surrogate measure to monitor occurrence of syphilis among MSM. M:F ratios in excess of 1:1 suggest male-to-male transmission. While the rates were nearly equal in 1997, since that time men have contributed an increasing proportion of cases. The M:F rate ratio (10.3:0.9) increased steadily to 11.4 in 2013. The increased rate of P&S syphilis occurred among men of all ages and all racial and ethnic groups. In addition, the CDC estimated that MSM comprised 5% of P&S syphilis cases in 1999; by 2013, men accounted for 91.3% of all cases. Although rates remain highest among black men, the recent increases were greatest among Hispanic and white men.

In the 49 states and the District of Columbia that provided information about sex of sex partners of patients with syphilis, MSM accounted for 75% of all P&S cases in 2013. In areas where information for both sex of sex partner and HIV status was relatively complete (70% or greater for all cases), 52% of MSM with P&S syphilis also were coinfected with HIV; coinfection in men who have sex with women (MSW) and women was 9.9% and 5.2%, respectively.

Although the majority of U.S. syphilis cases have occurred among MSM, transmission among MSW and women continues to occur in certain localities. For example, in New York City in 2007, the syphilis outbreak that had been largely limited to MSM began to involve women and newborns after years of nearly no female cases. Health officials hypothesized that bisexual activity among homosexual men may have spurred the increase in female cases.

Cities with large, well-established populations of MSM have been the most affected by this change in the epidemiology. For example, in 2003 and 2004, San Francisco had the highest P&S M:F rate ratio (107.5 and 181.4, respectively) of any U.S. city. However, many other U.S. cities had P&S syphilis M:F rate ratios greater than 10 in 2003 or 2004, including Boston; Denver; Indianapolis; Jersey City, New Jersey; Los Angeles; New York; St. Petersburg, Florida; San Diego; Seattle; and Tampa, Florida.

Some of the increasing incidence of P&S syphilis in MSM may come from the fact that clinicians are encouraged to conduct more routine syphilis testing in this population (ie, better case finding), but it is likely that the recent shift in epidemiology can be attributed in large part to additional factors described below. However, increases in high-risk sexual behavior among MSM have been documented since the mid-1990s, before many of these factors were commonly prevalent.

Some of these factors include:

  • a decrease in safer sex practices secondary to HIV prevention fatigue, which involves limiting use of condoms and is often combined with overly optimistic thinking that HIV is no longer the serious problem that it once was as a consequence of ART;
  • use of pre-exposure HIV chemoprophylaxis;
  • an increase in recreational drug use that facilitates high-risk sexual behavior; and
  • serosorting, which is selective unprotected sex with partners of the same HIV-serostatus. 

Use of “club” drugs, such as methamphetamines, gamma hydroxybutyrate, or GHB, ecstasy and ketamine, can lead to unsafe sex with multiple partners. Serosorting among HIV-positive persons may partially explain the divergence between HIV and syphilis rates among MSM that is taking place in some municipalities. Having unprotected sex, while using pre-exposure HIV chemoprophylaxis, also could cause a divergence between syphilis and HIV incidence rates. However, HIV-positive men who select other HIV-positive men for sexual activity to avoid use of condoms risk coinfection with other HIV strains that may be drug resistant. They also risk coinfection with other types of STIs such as syphilis, which can ultimately increase their susceptibility to HIV infection and potentially accelerate HIV disease progression. The extent to which STIs affect HIV disease progression differs for specific pathogens. Serosorting among supposedly HIV-negative men is also risky, because many MSM are actually unaware of their HIV status, may have acute HIV infection and be transiently seronegative, or may just lie about their true HIV status. In any case, men who serosort to avoid condom use place themselves at risk for STIs.

Unprotected oral sex, which may decrease the risk for HIV transmission, will not decrease the risk for acquiring other STIs, including syphilis, gonorrhea, chlamydia, HPV and herpes. Younger people, especially, are using oral sex more than intercourse because they mistakenly think this will minimize their risk for HIV.

The Internet is increasingly being used to meet anonymous sex partners who subsequently cannot be reached for partner tracing. An outbreak of syphilis among MSM who met their sex partners on the Internet in 1999 presaged a rapidly expanding syphilis epidemic in San Francisco. Of the 759 MSM who had early syphilis during 2001-2003, 23% reported using the Internet to meet sex partners. Now there are multiple websites and smartphone apps such as Tinder and Grindr, which are used to find sex partners. Tinder and Grindr are examples of smartphone apps that use global-positioning technology to find anonymous sex partners within close proximity who are also on the app. Grindr is popular among gay men, with 5 million monthly active users worldwide. A discussion of the risk for acquisition of STIs associated with use of the Internet, mobile phones and social networking sites can be found at www.cdc.gov/std/life-stages-populations/Adolescents-white-paper.pdf.

In the absence of a vaccine, syphilis control is largely dependent upon avoidance of risky sexual behavior, identification of infected individuals and treatment of these individuals and their contacts with antibiotics. To change the trend of increasing syphilis in MSM, prevention measures must be directed specifically to MSM of all races/ethnicities throughout the U.S. With the growing popularity of dating apps such as Tinder and Grindr, these Internet sites can be used for public service announcements alerting users to the dangers of unprotected sexual activity and to encourage safer sexual practices (eg, reducing the number of sex partners, using latex condoms for all forms of sexual activity and having a long-term, mutually monogamous relationship with a partner who has negative test results for STIs). Syphilis awareness and screening, as well as appropriate screening for gonorrhea, chlamydia and HIV infection should be promoted, and sex partners need to be notified and treated promptly. In addition, efforts to prevent and treat P&S syphilis among bisexual men and women should continue in order to prevent spread into the wider community.

References:

CDC. Adolescents, Technology and Reducing Risk for HIV, STDs and Pregnancy. Accessed April 17, 2015 at: http://www.cdc.gov/std/life-stages-populations/Adolescents-white-paper.pdf.
CDC. MMWR. 1999;48:45-48.
CDC. MMWR. 2004;53;129-131.
CDC. Primary and Secondary Syphilis – United States, 2000-2001. Table 1. MMWR. 2002;51:971-973. Accessed April 17, 2015 at: www.cdc.gov/mmwr/preview/mmwrhtml/mm5143a4.htm#tab1.
CDC. Primary and Secondary Syphilis – United States, 2005-2013. MMWR. 2014:63;402-406. Accessed April 17, 2015 at: www.cdc.gov/mmwr/preview/mmwrhtml/mm6318a4.htm.
CDC. Sexually Transmitted Disease Surveillance 2004 Supplement. Accessed April 17, 2015 at: www.cdc.gov/std/syphilis2004/syphsurvsupp2004.pdf.
CDC. Sexually Transmitted Disease Surveillance 2013. Accessed April 17, 2015 at: www.cdc.gov/std/stats13/surv2013-print.pdf.
CDC. 2004 Sexually Transmitted Diseases Surveillance. Trends in Reportable Sexually Transmitted Diseases in the United States, 2004. Accessed April 17, 2015 at: www.cdc.gov/std/stats04/trends2004.htm.
CDC. 2011 Sexually Transmitted Diseases Surveillance. Accessed April 17, 2015 at: www.cdc.gov/std/stats11/syphilis.htm.
CDC. 2013 Sexually Transmitted Diseases Surveillance. Table 1. Sexually Transmitted Diseases – Reported Cases and Rates of Reported Cases per 100,000 Population, United States, 1941-2013. Accessed April 17, 2015 at: www.cdc.gov/std/stats13/tables/1.htm.
CDC. 2013 Sexually Transmitted Diseases Surveillance. Table 29. Primary and Secondary Syphilis among Men – Reported Cases and Rates of Reported Cases by State/Area and Region in Alphabetical Order, United States and Outlying Areas, 2009-2013. Accessed April 17, 2015 at: www.cdc.gov/std/stats13/tables/29.htm.
Ekstrand ML, et al. AIDS. 1999;13:1525-1533.
Klausner JD, et al. JAMA. 2000;284:447-449.
McFarlane M, et al. Sex Transm Dis. 2005;32:S60-S64.
Nakashima AK, et al. Sex Transm Dis. 1996;23:16–23.
Webster LA, et al. MMWR. 1993;42(SS-3);13-19.

For more information:

Matthew E. Levison, MD, is a ProMED-mail bacterial disease moderator, professor of public health, Drexel University School of Public Health, and adjunct professor of medicine and former chief of the division of infectious diseases, Drexel University College of Medicine.
Donald Kaye, MD, is a professor of medicine at Drexel University College of Medicine, associate editor of ProMED-mail, section editor of news for Clinical Infectious Diseases and an Infectious Disease News Editorial Board member.

Disclosure: Kaye and Levison report no relevant financial disclosures.

Syphilis is currently epidemic among men who have sex with men in the United States and in many other parts of the world. Since 2000, rates of syphilis have been increasing in the U.S., as well as Canada, the United Kingdom, Australia and Europe, primarily among MSM. This is occurring despite more than 70 years of remarkable progress in control of this disease.

We have excellent diagnostics, effective therapy and a pathogen that remains penicillin-susceptible. Syphilis, although highly infectious, is easily curable in its early (primary and secondary, or P&S), most contagious stages of disease. If untreated, syphilis can lead to serious long-term complications that include neurological and cardiovascular damage. Congenital syphilis, if acquired during the 4 years before pregnancy, can lead to infection of the fetus in 80% of cases and can cause stillbirth and neonatal death in up to 40% of cases and physical deformity and neurological complications in children who survive. In addition, syphilis, like many other sexually transmitted infections (STIs), can increase transmission of HIV at least two- to fivefold.

In the mid-1940s, the incidence rate of P&S syphilis peaked at about 70 per 100,000 and then fell dramatically in the late 1940s, only to rise again in the late 1980s.

From 1986 through 1990, an epidemic of syphilis occurred throughout the U.S. In 1990, more than 50,000 cases of P&S syphilis — 20.3 cases per 100,000 population — were reported, the highest number of cases since 1948. This spike, which has been attributed to an epidemic of crack cocaine use and exchange of sex for drugs among heterosexual men and women, occurred despite a fall in the incidence of syphilis in men attributed to changes in sexual behavior due to AIDS. In 1991, syphilis rates began to decline again in the U.S., eventually reaching 2.1 per 100,000 in 2000, the lowest incidence of P&S syphilis since annual reporting began in 1941. However, over the next decade, the incidence rate gradually rose. By 2013, the incidence of P&S syphilis more than doubled, reaching 5.5 cases per 100,000.

Matthew E. Levison

Donald Kaye

From 2000 to 2013, the rate of P&S syphilis among men rose almost fourfold from 2.6 per 100,000 in 2000 to 10.3 per 100,000 in 2013. Because many states do not routinely report information on sexual practices or the sex of sex partners, the CDC had not collected data by sex of sex partners until 2005. Instead, male-to-female (M:F) ratios were used as a surrogate measure to monitor occurrence of syphilis among MSM. M:F ratios in excess of 1:1 suggest male-to-male transmission. While the rates were nearly equal in 1997, since that time men have contributed an increasing proportion of cases. The M:F rate ratio (10.3:0.9) increased steadily to 11.4 in 2013. The increased rate of P&S syphilis occurred among men of all ages and all racial and ethnic groups. In addition, the CDC estimated that MSM comprised 5% of P&S syphilis cases in 1999; by 2013, men accounted for 91.3% of all cases. Although rates remain highest among black men, the recent increases were greatest among Hispanic and white men.

In the 49 states and the District of Columbia that provided information about sex of sex partners of patients with syphilis, MSM accounted for 75% of all P&S cases in 2013. In areas where information for both sex of sex partner and HIV status was relatively complete (70% or greater for all cases), 52% of MSM with P&S syphilis also were coinfected with HIV; coinfection in men who have sex with women (MSW) and women was 9.9% and 5.2%, respectively.

Although the majority of U.S. syphilis cases have occurred among MSM, transmission among MSW and women continues to occur in certain localities. For example, in New York City in 2007, the syphilis outbreak that had been largely limited to MSM began to involve women and newborns after years of nearly no female cases. Health officials hypothesized that bisexual activity among homosexual men may have spurred the increase in female cases.

Cities with large, well-established populations of MSM have been the most affected by this change in the epidemiology. For example, in 2003 and 2004, San Francisco had the highest P&S M:F rate ratio (107.5 and 181.4, respectively) of any U.S. city. However, many other U.S. cities had P&S syphilis M:F rate ratios greater than 10 in 2003 or 2004, including Boston; Denver; Indianapolis; Jersey City, New Jersey; Los Angeles; New York; St. Petersburg, Florida; San Diego; Seattle; and Tampa, Florida.

Some of the increasing incidence of P&S syphilis in MSM may come from the fact that clinicians are encouraged to conduct more routine syphilis testing in this population (ie, better case finding), but it is likely that the recent shift in epidemiology can be attributed in large part to additional factors described below. However, increases in high-risk sexual behavior among MSM have been documented since the mid-1990s, before many of these factors were commonly prevalent.

Some of these factors include:

  • a decrease in safer sex practices secondary to HIV prevention fatigue, which involves limiting use of condoms and is often combined with overly optimistic thinking that HIV is no longer the serious problem that it once was as a consequence of ART;
  • use of pre-exposure HIV chemoprophylaxis;
  • an increase in recreational drug use that facilitates high-risk sexual behavior; and
  • serosorting, which is selective unprotected sex with partners of the same HIV-serostatus. 

Use of “club” drugs, such as methamphetamines, gamma hydroxybutyrate, or GHB, ecstasy and ketamine, can lead to unsafe sex with multiple partners. Serosorting among HIV-positive persons may partially explain the divergence between HIV and syphilis rates among MSM that is taking place in some municipalities. Having unprotected sex, while using pre-exposure HIV chemoprophylaxis, also could cause a divergence between syphilis and HIV incidence rates. However, HIV-positive men who select other HIV-positive men for sexual activity to avoid use of condoms risk coinfection with other HIV strains that may be drug resistant. They also risk coinfection with other types of STIs such as syphilis, which can ultimately increase their susceptibility to HIV infection and potentially accelerate HIV disease progression. The extent to which STIs affect HIV disease progression differs for specific pathogens. Serosorting among supposedly HIV-negative men is also risky, because many MSM are actually unaware of their HIV status, may have acute HIV infection and be transiently seronegative, or may just lie about their true HIV status. In any case, men who serosort to avoid condom use place themselves at risk for STIs.

Unprotected oral sex, which may decrease the risk for HIV transmission, will not decrease the risk for acquiring other STIs, including syphilis, gonorrhea, chlamydia, HPV and herpes. Younger people, especially, are using oral sex more than intercourse because they mistakenly think this will minimize their risk for HIV.

The Internet is increasingly being used to meet anonymous sex partners who subsequently cannot be reached for partner tracing. An outbreak of syphilis among MSM who met their sex partners on the Internet in 1999 presaged a rapidly expanding syphilis epidemic in San Francisco. Of the 759 MSM who had early syphilis during 2001-2003, 23% reported using the Internet to meet sex partners. Now there are multiple websites and smartphone apps such as Tinder and Grindr, which are used to find sex partners. Tinder and Grindr are examples of smartphone apps that use global-positioning technology to find anonymous sex partners within close proximity who are also on the app. Grindr is popular among gay men, with 5 million monthly active users worldwide. A discussion of the risk for acquisition of STIs associated with use of the Internet, mobile phones and social networking sites can be found at www.cdc.gov/std/life-stages-populations/Adolescents-white-paper.pdf.

In the absence of a vaccine, syphilis control is largely dependent upon avoidance of risky sexual behavior, identification of infected individuals and treatment of these individuals and their contacts with antibiotics. To change the trend of increasing syphilis in MSM, prevention measures must be directed specifically to MSM of all races/ethnicities throughout the U.S. With the growing popularity of dating apps such as Tinder and Grindr, these Internet sites can be used for public service announcements alerting users to the dangers of unprotected sexual activity and to encourage safer sexual practices (eg, reducing the number of sex partners, using latex condoms for all forms of sexual activity and having a long-term, mutually monogamous relationship with a partner who has negative test results for STIs). Syphilis awareness and screening, as well as appropriate screening for gonorrhea, chlamydia and HIV infection should be promoted, and sex partners need to be notified and treated promptly. In addition, efforts to prevent and treat P&S syphilis among bisexual men and women should continue in order to prevent spread into the wider community.

References:

CDC. Adolescents, Technology and Reducing Risk for HIV, STDs and Pregnancy. Accessed April 17, 2015 at: http://www.cdc.gov/std/life-stages-populations/Adolescents-white-paper.pdf.
CDC. MMWR. 1999;48:45-48.
CDC. MMWR. 2004;53;129-131.
CDC. Primary and Secondary Syphilis – United States, 2000-2001. Table 1. MMWR. 2002;51:971-973. Accessed April 17, 2015 at: www.cdc.gov/mmwr/preview/mmwrhtml/mm5143a4.htm#tab1.
CDC. Primary and Secondary Syphilis – United States, 2005-2013. MMWR. 2014:63;402-406. Accessed April 17, 2015 at: www.cdc.gov/mmwr/preview/mmwrhtml/mm6318a4.htm.
CDC. Sexually Transmitted Disease Surveillance 2004 Supplement. Accessed April 17, 2015 at: www.cdc.gov/std/syphilis2004/syphsurvsupp2004.pdf.
CDC. Sexually Transmitted Disease Surveillance 2013. Accessed April 17, 2015 at: www.cdc.gov/std/stats13/surv2013-print.pdf.
CDC. 2004 Sexually Transmitted Diseases Surveillance. Trends in Reportable Sexually Transmitted Diseases in the United States, 2004. Accessed April 17, 2015 at: www.cdc.gov/std/stats04/trends2004.htm.
CDC. 2011 Sexually Transmitted Diseases Surveillance. Accessed April 17, 2015 at: www.cdc.gov/std/stats11/syphilis.htm.
CDC. 2013 Sexually Transmitted Diseases Surveillance. Table 1. Sexually Transmitted Diseases – Reported Cases and Rates of Reported Cases per 100,000 Population, United States, 1941-2013. Accessed April 17, 2015 at: www.cdc.gov/std/stats13/tables/1.htm.
CDC. 2013 Sexually Transmitted Diseases Surveillance. Table 29. Primary and Secondary Syphilis among Men – Reported Cases and Rates of Reported Cases by State/Area and Region in Alphabetical Order, United States and Outlying Areas, 2009-2013. Accessed April 17, 2015 at: www.cdc.gov/std/stats13/tables/29.htm.
Ekstrand ML, et al. AIDS. 1999;13:1525-1533.
Klausner JD, et al. JAMA. 2000;284:447-449.
McFarlane M, et al. Sex Transm Dis. 2005;32:S60-S64.
Nakashima AK, et al. Sex Transm Dis. 1996;23:16–23.
Webster LA, et al. MMWR. 1993;42(SS-3);13-19.

For more information:

Matthew E. Levison, MD, is a ProMED-mail bacterial disease moderator, professor of public health, Drexel University School of Public Health, and adjunct professor of medicine and former chief of the division of infectious diseases, Drexel University College of Medicine.
Donald Kaye, MD, is a professor of medicine at Drexel University College of Medicine, associate editor of ProMED-mail, section editor of news for Clinical Infectious Diseases and an Infectious Disease News Editorial Board member.

Disclosure: Kaye and Levison report no relevant financial disclosures.