Author: 'Damian' 'Walker'
Position: Honorary Lecturer
Institution: London School of Hygiene and Tropical Medicine
E-mail: damian.walker@lshtm.ac.uk
Additional Authors: Godfrey Walker
Submitted Date: February 14, 2006
Published Date: February 22, 2006
This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.

Hotez et al. provide a persuasive case for incorporating a rapid-impact package for 'Neglected Tropical Diseases' with programs for HIV/AIDS, tuberculosis (TB) and malaria as part of a pro-poor strategy for improving health in the developing world. However, we consider there is a disease which has a high claim to be included in partnerships and initiatives devoted to what they term the 'Big Three' and yet has been largely ignored.

On the basis of the criteria identified by Hotez et al. the case for giving explicit priority to programs to control syphilis and particularly congenital syphilis is high [1]. In 2002 there were 157,000 deaths contributing to more than 4 million DALYs [2]. These estimates exclude the burden attributable to maternal syphilis, which includes 460,000 abortions or stillbirths, 270,000 low birth weight babies and 270,000 cases of congenital syphilis each year [3]. This burden is concentrated in Africa and exhibits considerable geographic overlap with HIV infection. Syphilis accounts for 20% of genital ulcer diseases and is not only a co-factor in transmission of HIV but both infections appear to progress more rapidly when occurring together [4].

Infection with syphilis is curable and control is possible with existing drugs (specifically penicillin). However, little attention has been given to this in context of the 'Big Three'. Azithromycin is included in the chemotherapy package proposed by Hotez et al. for the control of trachoma and there are clear synergies with syphilis control. A recent trial in Tanzania demonstrated that a single-dose of oral azithromycin is as effective as injectable penicillin G benzathine in treating early and latent syphilis [5]. However, some caution is needed concerning the widespread use of azithromycin for syphilis in view of the recent emergence of azithromycin-resistant Treponema pallidum [6].

There are other possible synergies in having a strategy including syphilis control, e.g. during routine antenatal care, chemotherapy for soil-transmitted helminths could be provided at the same time as offering VCT for HIV infection and screening for maternal syphilis. The control of syphilis has been shown to be highly cost-effective. If the control of syphilis was integrated into programmes dealing with the four priority disease groups advocated by Hotez et al. then the cost-effectiveness of tackling not only syphilis, but the other four major public health priorities, would improve. Furthermore, it would lessen the chance of avoiding death from one disease but dying from another[7].

While it might be hoped that the case for giving priority to syphilis would have been accepted and explicit emphasis given to programs to control this disease, this has not happened. Unfortunately, limited attention is given to syphilis control as part of the several partnerships devoted to the 'Big Three'. Maybe this is because syphilis has historically had stigma to a greater extent than HIV/AIDS and has therefore been neglected. Now is the time to change this as part of a pro-poor strategy to meet the MDGs. We suggest it is explicitly included in the rapid-impact package for neglected tropical diseases.

References
[1]Walker DG, Walker GJA. Forgotten but not gone: the continuing scourge of congenital syphilis. Lancet Infect Dis 2002; 2:432-436
[2]WHO. The World Health Report 2004. Geneva: WHO, 2004; Annex, Tables 2 and 3
[3]Finelli L, Berman SM, Koumans EH, Levine WC. Congenital syphilis. Bull World Health Organ 1998; 76:Suppl 2:126-128
[4]Karumudi UR, Augenbraun M. Syphilis and HIV: a dangerous duo. Expert Rev Anti Infect Ther 2005; 3:825-831
[5]Riedner G, Rusizoka M, Todd J, et al. Single-dose azithromycin versus penicillin G benzathine for the treatment of early syphilis. NEJM 2005; 353:1236-1244
[6]Holmes KK. Azithromycin versus penicillin G benzathine for early syphilis. NEJM 2005; 353:1291-1293
[7]Peeling RW, Mabey D, Fitzgerald DW, Watson-Jones D. Avoiding HIV and dying of syphilis. Lancet 2004; 364:1561-1563