The neurological manifestations of syphilis are strongly associated with one particular subtype of the Treponema pallidum organism that causes the disease, the 17th Conference on Retroviruses and Opportunistic Infections (CROI) heard today.
In a study conducted by the University of Washington, Seattle, it was found that neurosyphilis caused by other subtypes was quite rare.
Neurosyphilis in early syphilis infection needs to be distinguished from the neurological manifestations of tertiary syphilis, occurs decades after infection and is now rare in developed countries due to treatment.
Early neurosyphilis occurs in primary, secondary and early latent infection, usually within the first year of infection. It most commonly causes headache, visual disturbances and loss of concentration and more rarely difficulty walking and hearing loss. It may occasionally cause meningitis and strokes, and is associated with a significant mortality risk.
The US Centers for Disease Control found that it was diagnosed in about 2% of syphilis sufferers with HIV, but neurosyphilis symptoms can be subtle and attributed to depression or HIV brain impairment, so this may be a considerable underestimate.
In this study one-third of patients had neurosyphilis as defined by a positive VDRL test in cerebro-spinal fluid (CSF).
Another study from Ireland found that HIV-positive sufferers were more likely to fail treatment. This is because neurosyphilis is strongly associated with a high RPR titre (roughly equivalent to a high viral load in HIV) and may require more intensive treatment with injected or intravenous penicillin to be cured.
Dr Christina Marra told the conference that some researchers thought that there were particularly neuropathogenic strains of syphilis while others thought developing neurosyphilis was a random event, dependent on titre; the risk was raised at titres of more than 1:32.
To test the hypothesis that a strain was involved, her team genotyped the T pallidum organisms in 79 people infected in an outbreak of syphilis in Seattle in 1999-2008.
Seventy-six of the patients were men and 66 (83.5%) HIV-positive. The average titre was 1:128 (four times higher than the neurosyphilis threshold) and 18 (23%) had evidence of syphilis in their cerebro-spinal fluid, a sign of neurosyphilis.
Altogether her team have identified 21 strains of syphilis around the world, and six were present in the Seattle outbreak, namely strains 4, 9, 10, 12, 13 and 20.
Starting in 1999, the outbreak built to a peak in 2004, when 21 of the infections were diagnosed, and then tailed off to just one in 2008.
During this time the strain types varied. Strain 9 was the most common (57% of infections) and was present for all years except 2008 though tailed off towards the end of the epidemic with fewer infections after 2004. It is one of the most common global strains. Strain 10 first appeared in 2004 and was responsible for 24% of infections including the 2008 one. Strain 12 appeared from 2002 to 2005 and contributed 13% of infections. Other strains were only responsible for one to four infections each; strain 13 was only seen in a heterosexual couple.
Neurosyphilis was overwhelmingly associated with strain 9, with 15 cases (83%), two cases in strain 10 and one in strain 12. Over a third of strain 9 infections involved neurosyphilis and it was 8.6 times more likely to cause the condition.
Dr Marra said the changes seen in strain type might simply be due to new strains arriving in the pool, but could also be due to people acquiring immunity to other types.
Now one strain had been strongly associated with neurosyphilis, she added, more research was needed to see how strains spread through networks, why some were more pathogenic, and how host characteristics (such as having HIV) made some people more vulnerable to it.
Marra C et al. Treponema pallidum strain type is associated with neurosyphilis. Seventeenth Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 177, 2010.