HIV-positive gay men with early syphilis risk once-rare neurosyphilis

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A four city review from the United States has estimated that the risk of an HIV-positive gay man experiencing early neurosyphilis following recent infection with syphilis is greater than one in 60. The review’s findings, published in the June 29th issue of the Centres for Disease Control (CDC) and Prevention’s MMRW Weekly emphasise the importance of prompt syphilis diagnosis and adequate treatment in HIV-positive individuals.

As in the United Kingdom, there has been a resurgence of syphilis in the United States in the 21st century. In both countries gay men have been disproportionately affected and around half of these men were also HIV-positive.

Symptomatic early neurosyphilis is a rare manifestation of syphilis that usually occurs within the first twelve months of infection. Symptoms of early neurosyphilis include meningitis, cranial nerve function abnormalities, and stroke. It is often difficult to treat, particularly in HIV-positive individuals, and can result in permanent neurological problems.



A sexually transmitted infection caused by the bacterium Treponema pallidum. Transmission can occur by direct contact with a syphilis sore during vaginal, anal, or oral sex. Sores may be found around the penis, vagina, or anus, or in the rectum, on the lips, or in the mouth, but syphilis is often asymptomatic. It can spread from an infected mother to her unborn baby.


Having symptoms.



Inflammation of the outer lining of the brain. Potential causes include bacterial or viral infections.



Injected into a vein.


Relating to the brain or central nervous system.

In order to describe the clinical course of symptomatic early neurosyphilis and to better characterise the risk for this illness among HIV-positive gay men, the CDC conducted a review of possible neurosyphilis cases in four cities (Los Angeles, San Diego, Chicago, and New York) over a 30 month period, from January 2002 to June 2004.

A total of 49 HIV-positive gay men with symptomatic early neurosyphilis were identified. Their average age was 38.4 years; 63% were non-Hispanic white, 18% were non-Hispanic black, 14% were Hispanic, and 5% were of other or unknown ethnicity.

For the majority (53%) neurosyphilis signs and symptoms were the only indication of syphilis infection. The most commonly reported symptoms were visual disturbances (51%); headache (32%); difficulty walking (4%); and hearing loss (4%).

At the time of neurosyphilis diagnosis, 47% had secondary syphilis, 10% had signs of secondary syphilis within a week of neurosyphilis diagnosis, 24% had "early latent" syphilis, and 18% had “late latent” syphilis.

One in four had had a previous history of syphilis, although nine (of twelve) had “adequate” previous penicillin treatment documented, and six had clinical notes suggesting they had an appropriate response to treatment.

Of these 49 men, twelve were diagnosed with HIV at the same time, or within 45 days, or their neurosyphilis diagnosis. Among the 28 men with HIV diagnosed more than a year before the onset of neurosyphilis symptoms, 11 (45%) were receiving highly active antiretroviral therapy (HAART) at the time of neurosyphilis diagnosis.

Nearly all the men (86%) were hospitalised and all but two received intravenous penicillin treatment, which lasted for ten days or longer in most. The median time from the onset of neurosyphilis symptoms to the start of treatment was 25 days (range: 2-256 days).

Although most of the men were treated according to the most recent CDC guidelines, symptoms often persisted for months following treatment. Three experienced a neurosyphilis relapse and were retreated. Of the remaining 46, 37 (80%) had six-month follow-up information available; of these, 11 (30%) experienced persistent symptoms.

The investigators found that there was no statistically significant association between persistence of symptoms at six months and time from neurosyphilis symptom onset to treatment, receipt of HAART, initial CD4 count, or initial HIV viral load.

Of these 49 HIV-positive men with symptomatic early neurosyphilis, 40 were reported as having early syphilis between January 1, 2002 and June 30, 2004. During the same period, in these four cities, an estimated 2,380 cases of early syphilis were diagnosed in HIV-positive gay men.

The investigators therefore estimate the risk of an HIV-positive gay man with early syphilis having symptomatic early neurosyphilis was 1.7% (40 of 2,380), or one in 59.

In addition, they estimate the risk for having neurosyphilis with persistent symptoms six months after treatment was 0.5%, or one in 200.

However, the editors of MMRW note that the findings in this report are subject to several limitations. The 49 cases and other estimates of early syphilis and early neurosyphilis used to calculate risk are likely to be an underestimation due to “undiagnosed or unreported” syphilis or neurosyphilis. They also note that the cases from New York and Chicago “were selected as part of a convenience subsample and might reflect bias toward patients with more severe illness.”

They conclude by recommending that “health-care providers should be alert to signs and symptoms of neurosyphilis among [gay men and other men who have sex with men]” and suggest that “counseling [gay men] about neurosyphilis and its consequences might promote safer sexual behaviors and decrease transmission of syphilis and other sexually transmitted infections.”