Increased screening for syphilis boosts detection of early latent infections among Australian gay men

Increased syphilis testing among gay men increased detection of early latent infections and was accompanied by a fall in the proportion of cases involving secondary syphilis, investigators report in the online edition of Clinical Infectious Diseases.

“We believe this is the first study to demonstrate that increased serological screening of MSM [men who have sex with men] for syphilis is associated with greater detection of early syphilis with a measurable impact on secondary syphilis on a country level, providing evidence that screening is likely to have interrupted the progression of syphilis,” comment the authors. “This may have potentially reduced the infectiousness of syphilis, as it is believed that secondary stage of syphilis infection is particularly infectious, and prevented sequelae such as ocular and neurosyphilis.”

In his accompanying editorial, Dr Jeffrey Klausner of the University of California states that the research provides “very compelling evidence of the benefits of increased targeted screening for syphilis.”

Since the late 1990s, rates of syphilis have been increasing among gay and other MSM in major cities around the world. Many of these infections involve MSM living with HIV.

There are several stages of syphilis infection: primary syphilis; secondary syphilis; early latent syphilis and tertiary syphilis. Early syphilis can be cured with a single dose of penicillin. Prompt detection of the infection is especially important as its latter stages can lead to organ damage. Even secondary syphilis can affect the brain and eyes.

The Australian National Syphilis in Gay Men Action Plan released in 2009 recommends frequent syphilis testing for HIV-negative MSM and opt-out syphilis screening as part of the routine care provided to HIV-positive MSM. The guidelines recommend that all MSM be tested for syphilis at least once a year with more frequent testing for those at high risk of the infection.

A team of investigators examined rates of syphilis testing and diagnoses among HIV-negative and HIV-positive MSM. They especially wanted to see if increased testing was accompanied by an increase in the proportion of syphilis infections detected in the early latent stage.  

Data from 46 sexual health clinics across Australia were analysed. There were approximately 359,000 clinic visits during the study period. A third of these visits involved men with HIV.

The proportion of HIV-negative men tested for syphilis increased from 48% in 2007 to 91% in 2014 (p < 0.001). The mean number of annual tests per HIV-negative patient increased from 1.3 to 1.6 (p < 0.001).

Increased testing was accompanied by a significant increase in the proportion of cases of syphilis diagnosed in the early latent stage of infection (27 to 44%), p < 0.001), while the proportion of cases involving secondary infection decreased from 24 to 19% (p = 0.03). There was also a fall in the number of cases of primary syphilis detected (49 to 38%, p = 0.017).

An increase was also observed in the proportion of HIV-positive MSM tested for syphilis as part of their routine care, from 42 to 77% (p < 0.001). The mean number of tests per patient per year increased from 1.6 to 2.3 tests (p < 0.001). Although encouraged by these increases, the authors nevertheless comment, “as HIV-positive MSM account for a disproportionate number of syphilis infections and repeat infections in many countries, further efforts and strategies to boost syphilis screening of HIV-positive MSM in health services where testing is suboptimal are warranted.”

The proportion of early syphilis cases among HIV-positive men that were early latent infections increased from 23 to 45% (p < 0.001). At the same time, the proportion of secondary infections decreased from 45 to 26% (p = 0.0003). The proportion of cases involving primary infection remained stable.

Among men with HIV, there was a correlation between the decreasing proportion of cases of secondary syphilis and increased testing coverage (p = 0.005) and increased frequency of testing (p = 0.001).

Early latent infection can precede primary infection, occur between the primary and secondary stages, or follow secondary syphilis. One of the largest clinics involved in the research gathered data on titres. These generally increase at the beginning of the infection and fall over time, even without therapy. Median titre for early latent syphilis was 1:32, between that for primary (1:4) and secondary (1.12) syphilis. The authors believe this observation supports their hypothesis that a substantial proportion of the early latent cases they detected were likely to have been latent infections that preceded secondary syphilis.

“This study has shown that substantial increases in screening for syphilis were achieved among both HIV-positive and HIV-negative MSM across Australia and these were associated with an increase in the detection of early latent syphilis together with a relative decrease in secondary syphilis,” write the authors. “With reported rates of syphilis at historical highs in many countries other potential measures aimed at syphilis control such as vaccine development, chemoprophylaxis and community-based screening require further investigation.”

In his editorial Jeffrey Klausner notes the current political indifference to the communities most affected by syphilis. He therefore calls for infectious disease specialists and public health advocates to lobby for more public health resources to be devoted to the prevention of the infection. “A renewed syphilis response has to start somewhere,” he writes. “It has to start with us.”