HIV-positive syphilis patients harder to treat for neurological complications

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Two presentations at the Seventh International Congress on Drug Therapy in HIV Infection in Glasgow focused on syphilis, and in particular its neurological complications.

Dr Fiona Mulcahy of St James’s Hospital reviewed the 2001-2002 syphilis outbreak in Dublin. This has been covered elsewhere on aidsmap.com. Dr. Mulcahy said that the Dublin outbreak was the largest per head of population of recent ones in Europe, and was notable for the fact that 88 per cent of the 256 patients diagnosed were infected with a strain of the syphilis bacterium Treponema pallidum called Street-14, which is resistant to the antibiotic azithromycin and seems to be more common in European outbreaks.

For this presentation Dr. Mulcahy emphasised the differential course of symptoms and treatment response in the 44 HIV co-infected patients.

Glossary

syphilis

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.

central nervous system (CNS)

The brain and spinal cord. CNS side-effects refer to mood changes, anxiety, dizzyness, sleep disturbance, impact on mental health, etc.

neurological

Relating to the brain or central nervous system.

intramuscular

Injected into a muscle.

primary infection

In HIV, usually defined as the first six months of infection.

HIV positive patients were more likely to fail the standard treatment of an intramuscular injection of benzathine penicillin, when failure is defined as a fourfold reduction in a measure of antibodies called RPR (rapid plasma reagin).

Twenty-two per cent of HIV positive patients in primary infection failed according to this criterion compared with five per cent of HIV negative patients. The figures for patients with secondary syphilis were 23 per cent and ten per cent respectively.

However Dr Mulcahy warned that standard blood tests such as the RPR and TPHA assays tended to record more false positives in patients with conditions such as HIV and malaria.

Dr Mulcahy also said that HIV positive patients who manifested neurological complications of syphilis (neurosyphilis) were less likely to clear T. pallidum. In a substudy 31 per cent of patients with neurosyphilis failed to respond to benzathine penicillin.

Subclinical abnormalities in the cerebro-spinal fluid (CSF) are seen in 70-80 per cent of primary syphilis cases, and T. pallidum establishes a chronic infection of the central nervous system (CNS) in 25 per cent of cases. This can eventually cause the fatal manifestations of tertiary syphilis if left untreated, but a variety of symptoms including deafness and tinnitus, dizziness, confusion and memory loss are common in primary infection and can appear at any time during latent infection.

Dr. Angès Libois of Saint-Pierre Hospital in Belgium said diagnosis of CNS infection was difficult. The only sure diagnosis hitherto has been to perform a lumbar puncture to look for leukocytes indicating infection in the CSF. Many patients decline this invasive procedure.

This leaves doctors with a dilemma. Intramuscular benzathine penicillin is not sufficient to clear syphilis from the CNS in many cases. However the alternative treatment – intravenous procaine penicillin – would be ‘inappropriate over-treatment’ if practiced universally.

The Saint-Pierre Hospital’s own survey of 112 HIV positive patients revealed CNS infection in 23.2 per cent of patients, 11 of whom (one in 10 of the patient group) had neurological symptoms. Five of these had no skin lesions indicative of syphilis.

By comparing lumbar puncture results with RPR results, however, Libois said that an RPR of less than 1:32 (the test is expressed as the dilution needed to attain a specified titre of antibodies) generally indicates that neurosyphilis has responded to treatment, and can be used as a surrogate marker in the majority or cases.

The Brussels patients were predominantly gay men (82 per cent). But 10 were women, and five of these had CNS infection, (p=<0.05). Neurosyphilis has been observed elsewhere to occur more frequently in female patients.