The Origin of Syphilis

Introduction

There are four treponemal diseases of humans, Syphilis, Yaws, Bejel and Pinta. The organisms are so similar as to be almost indistinguishable. The first three are now classified as subspecies of the same species, Treponema pallidum, whereas Pinta is given its own species.

At present this classification is not based on DNA sequence data. Syphilis has been sequenced but the others have not. Nevertheless a single difference in DNA sequence is known that separates syphilis from the other treponemal infections and this has been used to identify syphilis in 200 year old bones. It is the involvement of bone in syphilis, yaws and bejel that allows treponemal infection to be identified in the archaeological record.

One consequence of the similarity of the organisms is cross immunity, in other words if you have one of these illnesses you have a degree of immunity to the others. This is a feature of untreated infection.

In general treponemal infections are characterised by three stages. Primary disease at the site of inoculation. Secondary disease as the organisms spread throughout the body and which is followed by a period of latency and finally late or tertiary disease.

Potted clinical descriptions (in other words gross oversimplifications).

Syphilis starts with a primary lesion, the chancre which is usually on the genitalia but can be wherever the infection entered the body. After this the organisms spread throughout the body and a few weeks later secondary syphilis develops. The individual feels unwell and has a variety of symptoms including skin rashes. After the individual gets over secondary syphilis, they enter a latent period that may last many years. A proportion of individuals will then go on to develop late syphilis including neurological syphilis and cardiovascular syphilis. Another late complication of syphilis is bone involvement which can be very painful especially at night.

Syphilis is transmitted primarily by the sexual route and seems to favour civilised urban populations. Although sexual transmission is the norm, it can also be transmitted by any close physical contact. Syphilis is normally acquired in adulthood however it can be transmitted from mother to foetus resulting in congenital infection.

Yaws starts with a primary lesion called the mother yaw at the site of inoculation, which is most commonly on the legs. The infection then becomes generalised producing a variety of skin lesions that can persist for several months. In many cases there is bone pain caused by early bone involvement which sometimes leads to a deformity called sabre tibia. Symptoms may grumble on for months of several years before the disease becomes latent. The skin lesions of yaws are more obvious and longer lasting than those of syphilis. Late or tertiary disease can involve skin and bone but unlike syphilis, it does not affect the heart or nervous system.

Yaws is essentially a disease acquired in childhood and in hyper-endemic areas can involve 90% of the population. It is thought to enter the body through minor abrasions and is transmitted by close physical contact. It is seen in rural populations with poor hygiene in humid tropical areas.

Bejel is found in arid tropical and subtropical areas, the main focus being the Middle East. It affects mainly children and appears to be spread by sharing eating and drinking utensils. The primary lesion is rarely seen as it it small and in the mouth. Secondary lesions affect the oro-pharynx and the corners of the mouth. There may be bone involvement but it is not as prominent at this stage as they are in late disease. Cardiac and neurological disease is rare.

Pinta occurs only in remote rural areas of southern Mexico, central America and Columbia. It is acquired in childhood and is transmitted by direct contact. Its effects are largely confined to the skin and in particular there is no bone involvement which means that bones cannot be used to follow its history.

Yaws Bejel and Pinta are sometimes known collectively as nonvenereal or endemic treponematoses.

Returning now to the concept of cross-immunity between the different treponemal infections. The non-venereal treponematoses are acquired in childhood before sexual maturity. This means that syphilis does not thrive in populations where they are widespread.

For example in countries where both Bejel and syphilis occur, syphilis tends to occur in the towns and Bejel in the rural communities. In populations where yaws eradication has taken place by mass use of penicillin, syphilis has become a problem whereas it was not before yaws eradication.

Historical sources

I have taken much of this section from A History of Syphilis by Charles Clayton Dennie published in the 1960s. Unfortunately Dennie is an ardent adherent of the Columbian theory and this leads him to simply dismiss contrary evidence out of hand. Particularly he mentions some references to the Great Pox before Columbus but he simply dismisses them as obvious errors without elucidating. Nevertheless it is a useful source of information about the early authors. For Fracastoro I have consulted Latin English editions of the poem "Syphilis" and "De Conagione"

The first record of a new disease that later became known as syphilis was in Barcelona in 1493. The disease then appears in Naples and an epidemic was raging there when in December 1494, King Charles VIII crossed the Alps to besiege Naples. The city quickly fell and the soldiers mingled with the local population. Many soldiers became infected and were sent home spreading the infection far and wide. Within five years observers from all over Europe were writing of a new disease.

Here are a few highly selective snippets from early sources.

Fransisco Lopez de Villalobos 1498: Lopez writes one of the first great accounts of syphilis although it is mentioned briefly in 10 earlier accounts. Lopez describes a new disease first appearing in Spain. The first stage is the appearance of a small button like hard painless ulcer on the genitalia, clearly recognisable as the chancre. After a certain time general symptoms appear accompanied by a variety of florid skin lesions. He also describes pains in the joints and bones that are particularly severe at night. This sounds very like treponemal bone involvement. Lopez searches all the medical sources available to him and concludes that this is a new disease. Importantly this early author make no mention of a new world source.

Juan de Vigo 1514:This author also describes the primary chancre on the genitalia followed by a latent period and the secondary disease with skin manifestations. He also describes severe pains especially at night in the head, arms, tibia, breast and hips. Again de Vigo regards this as a new disease and does not associate it with the new world.

Fracastoro – Syphilis 1530: Fracastoro gave syphilis its name in this famous poem. "The first man to display disfiguring sores over his body was Syphilus, who by the shedding of blood instituted divine rights in the king’s honour and altars in the mountains sacred to him; he was the first to experience sleepless nights and tortured limbs, and from this first victim the disease derived its name and from him the farmers called the sickness syphilis." The clinical description of the disease is less clear cut but broadly similar to the previous authors. Again we hear of pain in the limbs at night.

Ruy Diaz de Isla 1539: This author writing in old age, claimed to have treated sailors of the Columbian expedition for this new disease. Here is a quote on the origin: "This appeared [the serpentine Disease] and was seen in Spain in the year of our lord, 1493, in the city of Barcelona, which city was infected and consequently all Europe and the Universe in all known communicable parts, which disease had its origin and birth in the Island which today is named Espanola, as has been found by long and well proved experience, and this island was discovered and found by the Admiral Don Crisobal Colon, at present holding intercourse and communication wth the Indes."

The clinical descriptions are consistent with the previous authors although he adds features which suggests that he did not differentiate clearly between different sexually transmitted diseases. One feature of syphilis that he notes for the first time is alopecia, he also recommends mercurial treatment.

Fracastoro – De Conagione 1546: This great book covers many diseases besides syphilis. Again we get a description of severe skin lesions and pains in the limbs, "These pains were persistent, tormented the suffered chiefly at night, and were the most cruel of all the symptoms."

An interesting point is that Fracastoro notes that syphilis was becoming less severe and he believed it might disappear completely. He seems ambivalent about the New World origin of syphilis – "Moreover, it would have been impossible that this contagion, which per se is slow to act and is not easily received, should have traversed so much of the world after having been first conveyed to the Spanish by a single fleet of ships. For it is well known that at the same time, it was observed in Spain, France, Italy, Germany, and almost all Scythia."

A description from the Breviary of Helthe 1547 quoted in an infectious diseases textbook.

..In englyshe Morbus Gallicus is named the french pockes, whan I was yonge they were named the spanyshe pockes the whyche be of many kyndes of pockes, some be moyst, some be waterashe, some be drye, and some be skorvie, some be lyke scabbes, some be lyke ring wormes, some be fistuled, some be festered, some be cankarus, some be lyke wenne, some be lyke biles, some be lyke knobbles or burres, and some be ulcerous havynge a lytle drye scabbe in the middle of the ulcerous skabbe, some hath ache in the jointes and no singe of the pockes yet it may be the pockes … The cause of these impediments or infyrmytes doth come many wayes, it maye come by lyenge in the shetes or bedde there where a pocky person hath the night before lyenin, it may come with lyenge with a pocky person, it maye come by syttenge on a draught or sege where as a pocky person did lately syt, it may come by drynkynge oft with a pocky person, but specially it is taken when a pocky person doth synne in letchery the one with another.

Taking these descriptions together, we get a picture of a sexually transmitted disease that is recognisably syphilis-like but more severe. There is one particular feature that I would like to draw attention to and that is the severe pains especially at night, which is a feature of treponemal bone involvement. Syphilitic bone disease is a well recognised but late feature of the disease and is not normally seen until the tertiary stage. Early bone involvement is a feature of yaws and having planted that seed I will move on.

The archaeological record

Treponemal bone disease produces changes in bone that can be recognised after death. Although there are a number of conditions that can be confused in single bones, if a reasonable number of bones are available for examination, it is possible to reasonably confident of correctly identifying treponmal infection.

The big question is, is it possible to reliably identify the individual treponematoeses and in particular, syphilis. This is a controversial and difficult subject and it is advisable to be very suspicious of anyone who claims to be able to do it. Syphilis, yaws and bejel produce similar bone changes but differences in frequency, age and distribution can be identified. Involvement of the skull is more common in syphilis and a particular worm eaten appearance called "caries sicca" is suggestive of syphilis.

Bruce and Christine Rothschild of the Arthitis Centre, Ohio have done a lot of work on skeletal discriminators for yaws, bejel and syphilis. The have produced a set of criteria based on the examination of large populations of bones from the Negev desert (bejel), Gognga Gum Beach (yaws) and the Todd Collection (modern syphilis).

They take a statistical approach to the pattern of bone involvement and have come up with a set of criteria called SPIRAL.

The authors are the first to admit that these criteria depend on one huge assumption, namely that the distribution remains constant across time and place. They have done some validation with yaws and bejel but I am particularly concerned about syphilis. The collection is modern and we know that syphilis was undergoing rapid change in the early stages of the epidemic. How can we possibly extrapolate findings in modern syphilis back beyond the time of Columbus?

So it is possible to identify treponemal infection in bones, but discrimination between yaws, bejel and syphilis is hard.

There is very good evidence that treponemal infections existed in the New World before Columbus but I will only mention one piece. The Rothschilds have examined a collection of bones from Haiti that have been reliably dated to before Columbus. Using their criteria they believe the bones show clear evidence of Syphilis at one of the sites visited by Columbus on his first voyage. I am not qualified to judge their finding but I have consulted a British expert in osteoarchaeology and their view is that the Rothschild’s criteria are not strict enough.

Until recently there was a distinct lack of archaeological evidence for treponemal infection in the Old World. This gave great comfort to those who believe in the Columbian origin of syphilis however the situation has now completely changed.

In the British Isles alone, the following sites have been identified:

Evidence for pre-Columbian treponemal infection has also been found at Hull Magistrate’s Court but the finding haven’t been published yet because the carbon dating is having to be redone because it was found that population had a high fish diet which apparently affects the calibration of the carbon dating.

There are also reports from other parts of Europe including an ancient Greek Colony of Metaponto, Southern Italy dated 580-250 BCE.

If treponemal infections were present in the Old and New World before Columbus, then treponemal infection of humans must predate the migrations into the Americas. It is widely assumed that treponemal infections of humans first evolved in Africa but at present there is a lack of archaeological evidence. This may be because people haven’t looked or perhaps because the prototype treponemal infection did not affect bone as is the case with pinta today.

Putting it all together

We have seen that in untreated populations, treponemal infection confers considerable protection against re-infection not only with the original organism, but any of the treponema.

In populations where yaws is hyper-endemic, 90% or more of the population acquire infection in childhood. This means that by the time sexual maturity is reached, most of the population are resistant to infection.

The non-venereal treponemal infections are seen in primitive rural populations in tropical and subtropical regions, whereas syphilis favours urban conditions.

It is difficult to see how syphilis could possibly evolve in populations where non-venereal treponematoses are endemic. There is simply nothing to drive evolution in the direction of sexual transmission. Children acquire their infection through close contact in poor hygienic conditions and children do not indulge in sex.

It is only in conditions that do not favour transmission in childhood that syphilis could have evolved. This suggests cooler more civilised conditions where children wear clothes, in fact the civilised urban conditions that syphilis favours today.

Looking at the Rothschilds report of pre-Columbian syphilis in Haiti, we only have to look at the conditions there to realise that this is extremely unlikely. Haiti would have had the primitive humid tropical conditions that favour transmission of treponemal infection in childhood.

We now know that treponemal infections were in Europe before Columbus so how do we explain the great epidemic around the time of Columbus? All the contemporary commentators believed that the Great Pox or Morbus Gallicus was an entirely new disease. It seems most probable that syphilis was not introduced into Europe, it evolved there from non-venereal treponemal infection.

This begs the question, where did the non-venereal infection come from and I see two possibilities:

A: It was introduced perhaps from returning Crusaders, African explorers or least likely because of the timing, the New World. On the subject of Crusaders I have read references to accounts of Crusaders getting "leprosy" that was successfully treated with mercury ointment. This suggests the possibility of treponemal infection although I have not yet pinned down the references. There would certainly be opportunities for Crusaders to acquire treponemal infections in the Middle East. Presumably bejel was endemic there and the African slave trade would also have provided opportunities.

Once infected adults arrived back in Europe, the best opportunity for transmission to others would be through sexual intercourse because of the closeness of the contact and the indigenous population would be susceptible. The opportunity for transmission between children would be low because of clothes wearing and thus natural selection would favour organisms that became more efficient at sexual transmission. Infections tend to be more pathogenic when they arrive in virgin populations as was seen when European diseases were introduced into the New World. It is also possible that the process of evolving towards sexual transmission resulted in an increase in pathogenicity.

Over the course of a generation or so the host and parasite adapted to each other and the disease we know today as syphilis emerged.

B: The other possibility is that non-venereal treponemal infection was endemic in Europe, perhaps mainly the warmer south. Then conditions changed so that opportunities for transmission amongst children were reduced. This could occur in a number of ways but cooling of the climate with increased clothes wearing or thinning of the population in the black death are possibilities.

At this point we need to make a small digression into epidemiological theory. If we consider a disease where average age at which infection is acquired is 5 years old. If the transmissibilty of the infection is reduced, that is to say the probability of an individual acquiring infection goes down, then the average age at which infection is acquired is increased. This can be proved mathematically (not by me) but most people can see this intuitively if they think about it.

If we take our infection with an average age of acquisition of 5 years and just about every one getting it before puberty. Now if we reduce the opportunity for transmission so the average age of acquisition goes up to say 10 or more, then quite a few individuals will reach sexual maturity either uninfected or still infectious. This will provide opportunities for natural selection to act and organisms more efficient at sexual transmission will have an advantage. We would also have to propose that this evolutionary change also produced an increase in pathogenicity. It is perhaps worth noting that syphilis first emerged in the warmer south of Europe but of course this is also closer to possible sources of importation of treponemal infection as well.

So there we have it, my interpretation of the evidence for the origin of Syphilis. It was not introduced from elsewhere but was born here in Europe.

Simon Pugh

November 2001