The recommended treatment for early syphilis is a single injection of penicillin G benzathine. Although easy for patients to adhere to, disadvantages include pain, possible penicillin allergy and the risk of HIV transmission from re-used needles. The lack of injection equipment and appropriately trained staff may also be a problem in settings with limited resources.

Previous studies in the United States have suggested that a drug called azithromycin, taken orally, could be an effective alternative to penicillin G benzathine for treating and preventing early syphilis. However, there was evidence that some high-risk groups became resistant to the drug over time. A research team led by the London School of Hygiene and Tropical Medicine carried out a trial to evaluate the efficacy of both treatments.

The trial, which took place in Mbeya, Tanzania, involved 328 participants with either primary or latent (undeveloped) syphilis, recruited through screening high-risk groups such as female bar workers. More than 50 percent of the participants were HIV-positive. Chosen at random, half received 2 grams of azithromycin orally, and the other half 2.4 million units (MU) of injected penicillin G benzathine.

The researchers assessed all the participants every three months over a period of nine months. They found that initial cure rates were the same for both groups and remained similar during the follow-up period. After this period, they tested 65 bar workers again. Results showed that:

• Side effects of azithromycin were mild to moderate, involving minor stomach cramps, and were no worse with the 2 grams dose than with the lower dose used in previous studies.
• After three months, cure rates were approximately 59.5 percent for both groups.
• After six months, they were 85.5 percent for the azithromycin group and 81.5 percent for the penicillin G benzathine group.
• Overall treatment efficacy was 97.7 percent for azithromycin and 95 percent for penicillin G benzathine.
• Up to nine months, there was little difference in cure rate between HIV-positive participants and those without the virus.
• After this period, eight of the 65 bar workers tested had relapsed; all were HIV-positive and at high risk of being re-infected with syphilis.

The study argues from these findings that a single 2 grams dose of azithromycin is as effective as a 2.4 MU injection of penicillin G benzathine, the standard treatment for early syphilis. Since it is taken orally, azithromycin is particularly useful in settings with limited resources where there is a lack of equipment and trained staff. The authors conclude that:

• azithromycin can be regarded as an alternative to penicillin G benzathine and should be used more widely in syphilis control programmes, particularly in developing countries
• there should be long-term follow-up of lower risk groups where re-infection is less likely, in order to measure relapse rates more accurately
• continued monitoring of azithromycin resistance among high-risk and lower risk groups is of paramount importance.

Source(s):
'Single-Dose Azithromycin versus Penicillin G  Benzathine for the Treatment of Early Syphilis', New England Journal of Medicine 353: 1236-1244, by Gabriele Riedner, Jim Todd, David Mabey, Richard Hayes, Mary Rusizoka, Donan Mmbando, Leonard Maboko, Michael Hoelscher, Eleuter Samky, Eligius Lyamuya and Heiner Grosskurth, 2005 

Funded by: Wellcome Trust Research Training Fellowship, European Commission

id21 Research Highlight: 15 May 2007

Further Information:
Gabriele Riedner
WHO Eastern Mediterranean Regional Office
Adul Razzak Al-Sanhouri St.
P.O. Box 7068
Nasr City
Cairo 11371
Egypt

Contact the contributor: riednerg@emro.who.int

London School of Hygiene and Tropical Medicine (LSHTM), UK

Other related links:
'Implementing and sustaining antenatal syphilis control programmes'

'Is antenatal syphilis screening still cost effective in sub-Saharan Africa?'

'Screen test: detecting and treating syphilis in pregnant women in Tanzania'

'One step at a time - estimating STI cure rates'

'Altogether now? HIV prevention by mass treatment of sexually-transmitted infections'

Wiikipedia: Syphilis

WHO TDR Disease Watch: Syphilis