Syphilis, a disease of direct transfusion

This is the authors' abstract. We don't add key points for this paper.

In 1937, in a time when the word “syphilis” could not be used on the radio or in newspapers,1 that disease was the most commonly recognized disease transmitted by transfusion.2 In that year, Thomas Parran, the Surgeon General of the US Public Health Service (PHS), published his startling book, Shadow on the Land.3 In it, he reported that there were a half-million new cases of syphilis in the United States each year. Over 680,000 syphilis patients were under treatment with arsphenamine at any one time. There were as many more untreated cases, which meant that almost 1,400,000 people, or over 1 percent of the US population of 130 million, were syphilitic. Very few of those cases were due to transfusion. Before public health attention to syphilis and before the discovery of penicillin, untreated syphilis went through three lifelong stages, which led to a final deterioration of the nervous system and cardiac failure. Because patients usually presented with a generalized rash that was typical of the second stage or secondary syphilis, treatment was given by dermatologists. Some specialists from that generation who lived to see AIDS 50 years later spoke of the similarities of the effects that the two scourges had on the social life of the country. It was Surgeon General Parran who made syphilis a public health matter, just as, a half-century later, Surgeon General C. Everett Koop did for AIDS. John Mahoney, MD, of the PHS won the Lasker Award in 1947 for proving the efficacy of penicillin in treating syphilis.1 Treatment with one dose of that drug, and Parran's campaign of public awareness, drove the shadow from the land. In 1999, only 6657 cases of primary and secondary syphilis were reported in the United States,4 as compared with the half-million noted by Parran in a 1937 population half the size. The national goal is to eliminate syphilis from the United States, achieving a rate of less than 4 cases per million population, all treatable.4 Transfusion as a vehicle for syphilis was not mentioned by Parran in his book, but, in the era in which he wrote, transfusion therapy was just being introduced into medical practice. Blood was pumped directly from the donor to the patient in a procedure performed by a surgeon (direct transfusion). It was easy to transmit syphilis from donor to recipient in that way, and it was possible even to transmit it from the patient to the donor.2 There was an abundance of syphilis to transmit. In their 1942 book on transfusion, Kilduffe and DeBakey described the situation as it existed in the pre-World War II era.2 They referenced more than 100 cases that had been published after 1915, all from direct transfusion. Between 1 and 4 months after transfusion, the infection became manifest as acute secondary syphilis with a generalized rash, which was most pronounced on the extremities. The Wassermann test was in general use for the pretransfusion testing of donors, but a review of 41 cases of transfusion transmission showed that, in 18 of them, the test would not have been helpful.2 Arsphen-amine was available for treatment in a program that called for 20 injections and 192 mercurial rubs.3 There was a disease called “arsphenamine jaundice,” which was probably hepatitis B, that was transmitted through the common practice of reusing unsterilized needles and syringes for the arsphenamine injections (Greenwalt TJ, written communication, February 18, 2001). After World War II, blood was collected regularly into an anticoagulant-preservative solution, and donor and patient were separated (indirect transfusion). That allowed for several days of refrigerated blood storage, which was lethal to the treponema. Transfusion syphilis disappeared as a clinical entity.5 Surprisingly, with the introduction of fresh platelet transfusions, which were not stored, general transmission of syphilis did not reappear. When platelets began to be stored, it was at room temperature in plastic bags that allow for the diffusion of oxygen, thus possibly causing the death of the anaerobic spirochetes.5 The first federal licensing requirements for blood for transfusion were published in 1945.6 At that time, the NIH Laboratory of Biologics Control had the regulatory authority for blood that now resides with the FDA. The text addressed syphilis as follows: The serology test does not identify the donor whose infection is of too short duration to have established a positive serological reaction. The donor's history taken on the day of bleeding also may fail to identify this type of infection. Adequate physical examination is likewise not conclusive and is always impractical and not to be recommended. Epidemiological data suggest that the random selection of donors would yield only one bleeding containing viable S. palladium in approximately 9,000 bleedings.6 Physical examination of genitalia of the male blood donor for chancres was advocated by DeGowin, Hardin, and Alsever,7 on the basis of their experience with military donors during World War II. They placed their trust in that examination, as “Wassermann-negative blood is more dangerous than that which reacts in the test.”7 In 1966, a patient was seen at the Clinical Center, the hospital of the NIH, with a diagnosis of lymphoma.8 His VDRL test was negative on admission. He received 5 units of RBCs and 25 units of fresh platelets, none of which reacted in the VDRL test. Two months later, he had a maculopapular rash. One month after that, the rash was generalized and was most pronounced on the extremities. Figure 1 is from the original publication.8 His VDRL, Kolmer complement-fixation, and fluorescent treponema antibody tests were all positive. He was treated with penicillin and the rash cleared, although his VDRL was still positive 12 months later. The rash of posttransfusion syphilis in the last case of the disease reported in the United States, 1966. Reprinted with permission from Chambers RW, Foley HT, Schmidt PJ. Transmission of syphilis by fresh blood componensts. Transfusion 1969;9:32-4 (Philadelphia: Lippincott Williams & Wilkens, copyright holder). Of his 30 donors, 27 repeatedly were serologically negative, but 2 could not be traced and 1 refused to be retested. The presumption is that 1 of those latter 3 donors, a platelet donor, was infectious for syphilis. That case 35 years ago was the last reported case of posttransfusion syphilis in the United States. Two European cases were noted at about the same time.5 In 1978, because of the accepted rarity of transfusion-transmitted syphilis, the Standards Committee of the AABB deleted its requirement for the syphilis testing of blood donors.9 The FDA promised repeatedly to do the same, and, at one time, the change in the regulations was reported to be “at the printer.” At that time, AIDS appeared, and a decision was made that any test for a venereal disease would be continued as an anti-AIDS measure. Syphilis testing was put back into the AABB standards in 1991 to achieve synchronization with the federal regulations. The matter of syphilis testing as a surrogate test for AIDS transmission was considered in detail at an NIH Consensus Development Conference in 1995. It was concluded that serologic tests for syphilis had the capacity to identify less than one donor per year in the United States who had not yet developed detectable antibodies to HIV.10 Since then, tests for HIV antigen and by NAT have been added to the HIV routine, and they further reduced any possible value of syphilis testing as surrogate testing for posttrans-fusion AIDS. Serologic testing of blood donors had become mandatory in the early part of the last century, when posttransfusion syphilis was considered to be the most frequent infectious complication of direct transfusion. Testing continues today on emotional rather than on scientific grounds. Advocates of testing argue that blood banks are performing a service to public health by doing syphilis screening, although patients are no longer routinely tested on admission to hospital. It is reasoned also that the proof for nontransmissibility of treponema after blood storage does not apply to platelet transfusions. One argument for testing is that syphilis, which had once been known as “the great impersonator,” might show an obscure clinical picture in a very sick blood recipient, and that the Great Pox might be confused with a drug rash. The international plan to end the Small Pox was the reason to end the requirements for smallpox vaccination. The beginning of the end of the Great Pox in the United States, that came with the initiation of the National Plan to Eliminate Syphilis in the United States,4 could be the reason to end the nonproductive syphilis testing of blood donors. Despite the national decline and control of syphilis; despite the availability of penicillin; despite the fact that direct donor-to-patient transfusion, which was the vehicle for the transfer of syphilis, is no longer done; despite the fact that it has been accepted for 50 years that the serologic test for syphilis becomes positive only after the spirochete is probably no longer in the blood; despite the fact that 35 years have passed since a recorded case of transfusion-transmitted syphilis; and despite the evidence that syphilis screening is not helpful in the prevention of posttransfusion AIDS, the testing of all blood components still continues. The reasons for the disappearance of transfusion syphilis are not fully known. It may be due to the rarity of spirochetemia, the storage of blood components, the screening procedures already in place,11 or the ubiquity of antibiotic therapy. The intellectual pursuit of those reasons is not a valid motive for continuing to test blood donors to prevent a nonexistent disease.