Syphilis

Introduction

Syphilis is a sexually transmitted disease (STD) in which humans are the only known host. Confirmed in 2005, syphilis is caused by the bacterium Treponema pallidum [1]. Infection can occur by blood transfusion through open wounds or the mucosal membrane during sexual intercourse. Syphilis can also be transmitted from mother to child via the placenta during pregnancy, leading to congenital cases of syphilis. Syphilis has four stages (primary, secondary, latent, late) with characteristic symptoms in which infectivity is greatest during the first two stages [2].

Primary syphilis is characterized by a painless ulcer, usually at the site of infection, and swollen lymph nodes [3]. Secondary syphilis is usually when infected patients seek medical help due to painful lesions as well as rash on their hands, feet and trunk [3]. Latent syphilis patients have bouts of secondary syphilis symptoms appearing and disappearing without medical intervention. This is stage is when fetal transmission can occur. Late syphilis is dominated with patients who have no further symptoms than those of previous stages. A small but significant portion experience gumma that can manifest in critical organs such as the heart and the liver. Many die at this stage from cardiovascular and neurological complications [3].

History

There are three hypotheses concerning the origin of syphilis. One theory is that syphilis was brought back to Europe by the explorer, Christopher Columbus, and his crew. A second hypothesis proposes that syphilis is a mutation from a bacterial disease already present in Europe. The last and least supported hypothesis suggests that the Old World, or Europe, had transported syphilis to the New World, or North America [4].

As syphilis victims have distinct skeletal characteristics which include periosteal reaction, tibial remodeling and bone destruction or gumma, this was used to confirm the existence of syphilis at Dominance Republic pre-Columbus as Columbus and his crew had landed in Dominican Republic. Furthermore, examination of individual cases with similar skeletal marks in Europe are not indicative of syphilis or other treponemal diseases [4]. This evidence, then, also overturns the second and third hypotheses.

Tibia with periosteal reaction [4

It is important to note that although syphilis itself did not exist in pre-Columbian Europe, other treponemal diseases are noted. For instance, the origin is speculated to be from Africa in the form of yaws which was transmitted through to Asia becoming bejel. Further migration led to the spread of bejel from Asia to North America. During this time period, bejel is thought to have mutated into the treponemal disease we now call syphilis.

First Recorded Case and Early Treatments

The first written record of syphilis was recorded in 1495 when Charles the VIII invaded Naples. His troops then spread the disease through Europe. Lesions were the main symptom among the infected. Early treatments for syphilis varied from simple heat baths to mercury treatment, which persisted until the early 1900s [5].

Development of Treatments

When Treponema pallidum was first observed in 1905 by Schaudinn and Hoffman, many more effective treatments followed this discovery. Primitive chemotherapy using arsenic was explored by John Stokes and later in 1917, malaria therapy or "fever treatment" was used to treat later stage syphilis [5]. Revolutionarily effective treatment in the form of salvarsan was developed by Ehrlich in 1909. However, it was not until 1943, was penicillin was used to treat syphilis [5]. Penicillin, administered intramuscularly, is still the primary treatment in modern medicine.

 Figure 2. Summary of important events in the history of syphilis treatment [7,9,10,11,12]

Treponema pallidum

Treponema pallidum (T. pallidum) is a gram-negative bacteria with a spiral-shaped body characteristic of the family Spirochetes. It has a thin layer of peptidoglycan characteristic of all gram-negative bacteria but does not have LPS in its outer membrane. T. pallidum varies in length from 6 to 15 micrometers with a diameter of 2 micrometers [3]. In host, it is extracellular and does not release toxins [2]. It has an atypically small genome with only 1.14 Mb. In comparison, the well-studied E. coli has a genome size of 4.6 Mb. This is likely due to the lack of important metabolic processes like an electron transport chain. However, T. pallidum compensates for this with the uptake of host macromolecules through specific transporters [3].

 Figure 3. Electron micrograph of T. pallidum [8]

Pathogenicity

T. pallidum, despite its small genome, is a competent pathogen. It has many pathways into the human body and can infect many different tissue types. It is also highly motile and attachment to host cell can occur at either end of the bacterium, possible through adhesins. The virulence of T. pallidum is also contributed to its ability to evade the host immune system with its slow-growing nature. However, antibodies against T. pallidum are made against many properties like flagellar protein. In a rabbit model, antibodies were found 6 days after infection[3].

Diagnosis

Syphilis caused by T. pallidum is best verified by dark-field microscopy [6]. However, identification of the pathogen requires experience, direct fluorescent antibody tests are also another known and popular method. Further serological tests such as various enzyme immunoassays are also utilized to detect the presence of T. pallidum [3].

Current Treatment

Penicillin, given intramuscularly, is the primary treatment option for syphilis. Lumbar punctures are an option for patients with neurosyphilis [6]. Currently, there is no vaccine available for syphilis and prevention of syphilis through safe sex practices are highly recommended.

References

1. Heymann, Warren R. "The History of Syphilis." Journal of the American Academy of Dermatology, 2006.

2. Zeltser, R., Kurban, A. "Syphilis." Clinics in Dermatology, 2004.

3. LaFond, R., Lukehart, S. "Biological Basis for Syphilis." Clinical Microbiology Reviews, 2006.

4. Rothschild, B. "History of Syphilis." Clinical Infectious Diseases, 2005.

5. Sartin, S., Perry, H. "From mercury to malaria to penicillin: The history of the treatment of syphilis at the Mayo Clinic - 1916-1955)." Journal of the American Academy of Dermatology, 1995.

6. Farhi, D., Dupin, N. "Origins of syphilis and management in the immunocompetent patient: Facts and controversies." Clinics in Dermatology, 2010.

7. "History of syphilis." Wikipedia. Wikimedia Foundation, 17 Nov. 2013. Web. 22 Nov. 2013. <http://en.wikipedia.org/wiki/History_of_syphilis>.

8. "Molecular Architecture of Treponema Pallidum, Bacterium That Causes Syphilis." ScienceDaily. ScienceDaily, 30 Nov. 2009. Web. 22 Nov. 2013. <http://www.sciencedaily.com/releases/2009/11/091130121443.htm>.

9. "Paul Ehrlich." Paul Ehrlich. N.p., n.d. Web. 22 Nov. 2013. <http://www.paul-ehrlich.de/Research/research.htm>.

10. "Science Museum. Brought to Life: Exploring the History of Medicine.."Albarello pharmacy jar for mercury ointment, Italy, 1520-1560. N.p., n.d. Web. 22 Nov. 2013. <http://www.sciencemuseum.org.uk/broughttolife/objects/display.aspx?id=4064>.

11. "Treponema pallidum." Wikipedia. Wikimedia Foundation, 21 Nov. 2013. Web. 22 Nov. 2013. <http://en.wikipedia.org/wiki/Treponema_pallidum>.

12. "The Role of Chemistry in History." The Role of Chemistry in History RSS. N.p., n.d. Web. 22 Nov. 2013. <http://itech.dickinson.edu/chemistry/?cat=65>.