The number of cases of syphilis in Brighton and Hove has increased by more than 600 per cent in nearly three years.
There have been 46 recorded cases in the city since June 1999, compared to an expected figure of one or two a year.
A campaign has been launched to try to reduce the number of cases before they get out of control.
Health officials are targeting the city's gay community to get the message across as most sufferers are gay men.
Staff at the Claude Nicol Clinic, based at the Royal Sussex County Hospital in Brighton, and the Terrence Higgins Trust are joining forces to carry out a two-year study aimed at cutting the number of cases.
The number of syphilis cases has stayed at a low level since the Eighties when the emergence of the HIV virus led to more people using condoms.
But in recent years the number of cases of sexually-transmitted diseases has started to increase again as people risk infection.
There were 11 recorded cases in 1999 in Brighton and Hove, 13 in 2000 and approximately 20 in 2001 with two so far this year.
Health bosses say it is difficult to pinpoint the exact reason but believe part of it may be down to successful developments in drugs used for treating HIV/Aids which have led to people being less careful about protection.
Syphilis is a highly- infectious bacterial disease which can have serious implications for sufferers.
There have been other outbreaks of the disease in parts of north London and Manchester.
Paul Martin, programme manager for sexual health at East Sussex, Brighton and Hove Health Authority, said: "We are trying to get two messages across.
"One is to use a condom and the other is to have regular screenings at a clinic.
"Syphilis is easy to treat if it is spotted in the early stages.
"The more often a person is checked the less likely the chance he will pass it on to someone else.
"We tend to find a condition like this will spread among a small community of people who are regularly sleeping with different partners.
"We are doing as much as we can to try and get the message out to people and are hopeful this two-year research project will help.
"One of the areas being considered is to hold screening sessions at other locations such as well-known gay venues, instead of just at clinics, to make them more accessible."
More information is available at a web site developed by the Terrence Higgins Trust at www.sexmot.org.uk
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