Syphilis is enjoying a resurgence in parts of the United Kingdom. In 2009, there were 1179 newly diagnosed cases of primary, secondary, or early latent syphilis in London, a 24% increase on the previous year.1 For England, overall, there was a 1% increase during the same time period.1 In Scotland, 2009 saw the first decrease in reports of infectious syphilis since the data collection was started in 2002, with a total of 189 cases of infectious syphilis reported.2 However, despite this overall decrease, a localized outbreak occurred in 2009 in 1 Scottish health board.2
Although once considered a contraindication to transplantation, donor criteria in several countries have been extended and donors with serological evidence of syphilis are now accepted.3 With scarcity of donor organs clearly, the management of syphilis among transplant patients is an important issue and one, which may present itself more often in the future.
In March 2011, a 41-year-old recipient with a history of idiopathic dilated cardiomyopathy received a cardiac transplant. The donor was known to be a white male of undisclosed age with his cause of death being pneumococcal meningitis. In view of this history, the donor recipient was commenced on prophylactic piperacillin tazobactam. Screening tests results for HIV and hepatitis in the donor were negative. After the transplant had taken place, the donor was found to be enzyme immunoassay (EIA) (IgM/IgG) (Biostat syphilis) screening test positive. On subsequent confirmatory testing, Treponema pallidum particle agglutination assay (TPPA) (Mast Diagnostics) was 1:>20,000 and result of Venereal Disease Research Laboratory (VDRL) (Abbott Murex) and IgM tests were negative. Information from the transplant coordinator revealed no history of donor treatment for syphilis in the past. The transplant coordinator informed the donor's clinician who initiated contact tracing. The decision was taken to begin treatment because on the basis of the results, it was impossible to differentiate between treated syphilis and late syphilis. The piperacillin tazobactam was discontinued after 8 doses, and the recipient was treated with 3 doses of benzathine penicillin 2.4 MU intramuscularly administered weekly for 3 weeks as per the UK treatment of syphilis guidelines for management of late disease.4 Cardiac transplant patients routinely undergo cardiac biopsy at 2 weeks postprocedure. A sample of cardiac tissue was obtained for syphilis polymerase chain reaction, which was negative. Baseline syphilis testing on the recipient at 2 days post-transplant showed him to be VDRL negative, TPPA negative, and enzyme-linked immunosorbent assay IgM negative. Repeat serology at 1 and 3 months showed negative results. Follow-up with repeat syphilis serology is planned at 6, 9, and 12 months post-transplant.
Gibel et al5 estimate the prevalence of syphilis among organ donors to be around 0.15% based on the incidence of untreated syphilis in the general population. Using these assumptions, there would be 143 potentially infected donors per year in the United Kingdom.6 More recently in Scotland, Galea and Dow7 found 42 bone/tissue donors of 14,058 positive for T. pallidum during a 7-year period from 1998 to 2004. In England, Brant and Davidson8 found a prevalence of 49.58/100,000 screened deceased donors positive for T. pallidum. Shortages of donor organs for transplantation are a limiting factor in many countries. Although awaiting a transplant mortality rates can be as high as 30%,7 and in Europe, 12 patients die per day9 waiting for a suitable organ.
Screening for syphilis is mandatory in the United Kingdom for organ tissue and cell donors. Traditionally, screening in the United Kingdom involves the use of a nontreponemal anticardiolipin test, for example, VDRL or rapid plasma reagin (RPR). Positive results are then confirmed by the use of a specific treponemal test, for example, TPPA. These are also the current recommendations from the Centers for Disease Control.10 However, many laboratories in Europe and North America have implemented the more cost-effective reverse sequence testing whereby treponemal-specific tests (EIA/chemiluminescence immunoassay) are used for screening, and positive results are confirmed by nontreponemal tests (VDRL/RPR).11,12 The current Advisory Committee on the Microbiologic safety of blood and tissues for transplantation guidelines from the UK Department of Health13 suggest that either nontreponemal- or treponemal-specific tests can be used for screening. However, had the donor in our case been tested by the traditional method of screening, the syphilis positivity would have been missed because the VDRL test result was negative. Laboratories using this traditional screening algorithm should be aware that positive syphilis cases may be missed. However, reverse sequence testing is not without its problems, and discordant test results are common, with up to 17% of EIA results being false-positives in one study.14 Where reverse sequence testing is in use, it is recommended that discordant results should be tested using the TPPA test.12
Syphilis in the context of solid organ transplantation is rare. There are 3 documented cases in the literature of organ transplantation from donors testing positive on serological testing for syphilis (Caballero et al,15 Gibel et al,5 Ko et al16). Transplanted organs included kidney, heart, lung, and liver. In all 3 cases, there was no evidence of ongoing transmission in the recipients all of whom had received appropriate therapy with benzathine penicillin.
Cortes et al17 describe serological evidence of syphilis in 2 recipients who received renal transplants from a common donor. This was thought to be due to an error in the initial therapy administered to the recipients who received a single dose of benzylpenicillin rather than long-acting benzathine penicillin. Both of these patients were subsequently treated for early latent syphilis, and follow-up serology finding was negative. Steinmann et al18 report an isolated IgG seroconversion in a female patient who received a double lung transplant from a donor with serological evidence of past syphilis despite treatment. They postulate that this was due to transmission of immunocompetent B cells with the transplanted lungs and the phenomenon of microchimerism and not active syphilis infection.
Many patients with positive EIA and TPPA results are unlikely to have active syphilis and may not be infectious. However, about management of the recipients of potentially infected organs, Fischer et al19 recommend that where the donor is identified as being positive on serological testing for syphilis, the standard regimens for late latent syphilis would be appropriate for treatment of the recipient, for example, 3-weekly doses 2.4 MU of intramuscular benzathine penicillin. However, Gibel et al5 recommend a single dose of 2.4 MU of benzathine penicillin, and Caballero et al15 gave their 2 patients 18 million units of penicillin for 10 days. In our case, the effects of the prophylactic piperacillin tazobactam are unclear. The case reports by Ko et al16 and Caballero et al15 both refer to the use of prophylactic antibiotics with activity against syphilis but neither comment on the likely effects of these.
The duration of follow-up of patients exposed to T. pallidum through transplanted organs is unclear. In patients infected with late latent syphilis, the UK guidelines4 suggest serological follow-up for 3 months until serofast state is reached. However, transplant patients who have received potentially infected organs may never seroconvert, and the effect of their immunosuppressive regime is unknown. Ko et al16 monitored their organ recipients at, using VDRL and Treponema pallidum hemagglutination (TPHA), 2, 4, 6, and 12 months following transplant. Caballero et al15 describe the RPR and TPHA being repeatedly negative up to 16 months, but they do not describe the frequency. Steinmann et al18 monitored their patient up to 230 days post-transplant using TPHA titer, RPR, FTA-ABS for IgM and IgG, and an immunoblot for IgM and IgG.
The use of polymerase chain reaction to diagnose syphilis from oral or other ulcers or in other tissue and fluid samples is recommended by the UK guidelines for the management of syphilis. None of the articles discussed previously mention the use of molecular techniques to evaluate the transplanted organs. These techniques may be of particular use where the alternative diagnosis of microchimerism through transplanted B cells is being considered.
This case report and literature review highlight the issues surrounding the use of organs from donors who are seropositive for syphilis and the management of recipients. Syphilis remains prevalent within the population, and in some parts of the United Kingdom, it is on the increase. With organs always required, it is vital to be familiar with the management of a recipient in the setting of a transplant from a donor with serological evidence of syphilis. Laboratories should be aware of the limitations of traditional screening methods which utilize nontreponemal tests (e.g., VDRL); as by doing so cases of syphilis could be missed.
3. Grossi PA, Fishman JA. Donor-derived infections in solid organ transplant recipients. Am J Transplant 2009; 9(suppl 4):S19–S26.
4. Kingston M, French P, Goh B, et al.. UK National Guidelines on the management of syphilis. Int J STD AIDS 2008; 19:729–740.
5. Gibel LJ, Sterling W, Hoy W, et al.. Is serological evidence of infection with syphilis a contra-indication to kidney donation? Case report and review of the literature. J Urol 1987; 138:1226–1227.
7. Galea G, Dow BC. Comparison of prevalence rates of microbiological markers between bone/tissue donations and new blood donors in Scotland. Vox Sang 2006; 9:28–33.
8. Brant LJ, Davison KL. Infections detected in English surgical bone and deceased donors (2001–2006) and estimated risk of undetected hepatitis B and hepatitis C virus. Vox Sang 2008; 95:272–279.
10. Workowski KA, Berman S. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep 2010; 59:1–110.
11. Park IU, Chow JM, Bolan G, et al.. Screening for syphilis with the treponemal immunoassay: Analysis of discordant serology results and implications for clinical management. J Infect Dis 2011; 204:1297–1304.
12. Hoover KW, Radolf JD. Serodiagnosis of syphilis in the recombinant era: Reversal of fortune. J Infect Dis 2011; 204:1295–1296.
14. Centers for Disease Control and Prevention. Syphilis testing algorithms using treponemal tests for initial screening—four laboratories, New York City, 2005–2006. Morb Mortal Wkly Rep 2008; 57:872–875.
15. Caballero F, Domingo P, Rabella N, et al.. Successful transplantation of organs retrieved from a donor with syphilis. Transplantation 1998; 65:598–599.
16. Ko WJ, Chu SH, Lee YH, et al.. Successful prevention of syphilis transmission from a multiple organ donor with serological evidence of syphilis. Transplant Proc 1998; 30:3667–3668.
17. Cortes NJ, Afzali B, MacLean D, et al.. Transmission of syphilis by solid organ transplantation. Am J Transplant 2006; 6:2497–2499.
18. Steinmann J, Marggraf G, Buer J, et al.. Syphilis-specific immunoglobulin G seroconversion after double-lung transplantation. J Heart Lung Transplant 2009; 28:857–859.
19. Fischer SA, Avery RK. Screening of donor and recipient prior to solid organ transplantation. Am J Transplant 2009; 9 (suppl 4):S7–S18.