Timely screening of donated blood holds the key to curb Transfusion Transmitted Syphilis

The provision of safe and efficacious blood and blood components for transfusion involves a number of processes and there is a risk of error in each process of this ‘transfusion chain’. A failure at any of the stages can have serious implications for the recipients of blood and blood components. Thus, while blood transfusion can be life-saving, there are associated risks, particularly the transmission of blood-borne infections.

The core Transfusion Transmitted Infections (TTI) tests recommended by WHO are; Hepatitis B Surface antigen, antibody to Hepatitis C, HIV 1 & 2, and serologic test for Syphilis. In India, besides these core tests, donated blood is also mandatorily tested for Malaria antigen.

Speaking particularly about Syphilis, it was once a common STD, however the prevalence was brought down from 8% of the population, to less than 1%. Infact, in 2011, the National Aids Control Organization (NACO), had announced that the country is on the verge of elimination of the infection. Ironically, for 2017-18, NACO has reported a prevalence of syphilis in blood donors as 0.18% in India. Recent studies indicate that the cases of primary syphilis have declined but there has been a parallel rise in secondary and early latent syphilis.

The causative agent of syphilis, Treponema pallidum is highly sensitive to storage for more than 72 hours at 4°C. Due to the lower prevalence rate, fragility of T. palladium, and in order to save costs of testing, screening of syphilis is often ignored, in spite of WHO recommendations. In addition to the serious damage it may cause to the different organs, which may turn out to be fatal, syphilis may also be seen as an additional indicator of other STDs such as HIV.

Despite low prevalence, the risk of transfusion-transmitted syphilis is particularly high in developing countries like India, with limited blood supplies, where blood is collected from family donors and transfused within hours. One example of high-risk situation is transfusion of platelets during dengue epidemics. Platelet concentrates are usually stored at room temperature or transfused within a few hours of collection, so they carry a higher risk of transmitting syphilis.

The serological tests for syphilis can be divided into two categories, Non-treponemal tests (NTP) and Treponemal tests (TP). NTP tests such as Venereal Diseases Research Laboratory (VDRL) and Rapid Plasma Reagin (RPR), do not detect specific anti-treponemal antibodies. These tests detect antibodies against cardiolipin-cholesterol lecithin antigens, which may be found in human tissues as well as in bacteria. RPR is currently the most commonly used test for screening of syphilis in India. NTP tests may give false negative results in early primary syphilis in 30-50% of cases. Another major problem is the possibility of biological false positives, due to cross-reactivity with other molecules in conditions such as viral infections, pregnancy, malignant neoplasm, autoimmune diseases and advanced age.

TP tests such as ELISA, use native or recombinant Treponemal antigens and therefore, allow the detection of specific anti-treponemal antibodies. Some treponemal antigens have strong immunogenicity and they appear at different stages of infection. Using the right combination of these treponemal antigens ensures that total antibodies (IgM, IgG & IgA) are captured, thereby resulting to detection of infection in any stage. Therefore, TP test is used as a confirmatory test to verify reactivity in a NTP test. These tests may also serve as diagnostic tests in late syphilis and in patients with reactive NTP tests but with signs and symptoms of late syphilis.

A recent published study compared the efficacy of ELISA and RPR, as screening tests for syphilis. ELISA was found to have better sensitivity, specificity, accuracy and less probability of biological false positives.

Syphilis can be transmitted from donors who clinically and biologically do not show any signs of the disease. There are published data indicating that the prevalence of this disease is higher in replacement donors than in voluntary blood donors. In the absence of efficient testing, donors who are reactive to syphilis may sometimes persistently continue to donate blood even after pre- and post-donation counselling. This could be attributed to difficulty in understanding the questions due to low level of education and ignorance about infections transmissible by blood transfusion. Furthermore, cultural taboos prevent donors from disclosing information in response to some kinds of questions.

It is therefore recommended that regardless of proper storage of blood components and compulsory pre-/post-counselling, all blood bags be screened for syphilis by a reliable treponemal test, along with other transfusion-transmitted infections prior to transfusion, to ensure safe blood transfusion.

The complete blood banking ELISA range from Transasia Bio-Medicals Ltd., includes ErbaLisa Syphilis ELISA, the first Indian syphilis ELISA kit to be approved by NIB. Using an ideal combination of the most immunogenic recombinant treponemal antigens - TpN15, TpN17 & TpN47, ErbaLisa Syphilis detects total antibodies (IgM, IgG & IgA) against T.pallidum, as early as two weeks post-infection.

References:

• Adegoke AO, Akanni OE. Survival of Treponema paliidum in banked blood for prevention of Syphilis transmission. North American Journal of Medical Sciences. 2011;3(7):329-332.
• Kaur G, Kaur P. Syphilis testing in blood donors: an update. Blood Transfusion. 2015;13(2):197-204.
• Sommese L, De Pascale MR, Capuano M, Napoli C. Efforts in blood safety: Integrated approach for serological diagnosis of syphilis. Asian Journal of Transfusion Science 2016;10:22-30.
• SJ Winceslaus. Screening of syphilis. The Lancet. Volume 353, Issue 9162, P1441, April 24, 1999.
• Sachdev S, Sharma AK, Sethi S, Garg S, Lamba DS, Sharma RR, et al. Comparative evaluation of enzyme-linked immunosorbent assay with rapid plasma reagin for screening of syphilis in blood donors. Asian Journal of Transfusion Science 2018;12:165-8.
• https://timesofindia.indiatimes.com/life-style/health-fitness/health-news/hiv-on-the-decline-syphilis-cases-up/articleshow/59911088.cms