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Treponema pallidum is capable to enhance the immune response which causes the tissues to damage (Cruz et al., 2012) and sometimes capable to slow down the immune response towards the infection (Folds & Baseman, 1978). The delay response occur due to several factors that exist in the bacteria. T. pallidum contains a capsule-like structure on the outer membrane of the cell that act as the barrier which preventing the treponemicidal antibody to attack the cell. Moreover, the bacteria contain a few biological properties that can help the bacteria to run away from the macrophage. The partial tolerance also occur due to the competition between different types of treponemal antigens. The bacteria also carry the immunosuppressive substances that cause the lymphocyte and macrophage to stop functioning in normal state (Folds & Baseman, 1978).

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Syphilis is the sexually transmitted disease (STD) (Sexually Transmitted Diseases (STDs), 2015) that occur due to a bacterial infection caused by the bacterium Treponema pallidum subspecies pallidum (Sukthankar, 2014). The disease usually affects men who have sex with men (Dupin, 2016) and it is contagious. There are also several cases occur in heterosexuals in both rural and urban areas.

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Dupin, N. (2016). Syphilis. Revue de Medecine Interne, 37(11), 735–742. https://doi.org/10.1016/j.revmed.2016.05.010

Sexually Transmitted Diseases (STDs). (2015, November 13). Retrieved from Centers for Disease Control and Prevention: https://www.cdc.gov/std/syphilis/stdfact-syphilis.htm

Sukthankar, A. (2014). Syphilis. Medicine (United Kingdom), 42(7), 394–398. https://doi.org/10.1016/j.mpmed.2014.04.002

Syphilis - causes, symptoms, diagnosis, treatment, pathology. (2018, January 17). Retrieved from Osmosis: https://www.osmosis.org/

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Syphilis can be prevented by avoiding vaginal, anal or oral sex. For someone who is sexually active, it is advisable to use protection such as a latex condoms during a sexual intercourse to avoid the transmission of syphilis that prevent from in contact with a sore (Sexually Transmitted Diseases (STDs), 2015). Besides, other prevention step would be doing a screening routine. This screening routine is essential to identify this disease for an earlier diagnose and treatment. It is also important for the patients to do a regular sexually transmitted infections (STIs) check-ups ( Syphilis Prevention, 2017) for a good primary care (Klein, McLaud, & Rogers, 2015).

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Klein, J., McLaud, M., & Rogers, D. (2015). Syphilis on the rise: Diagnosis, treatment, and prevention. Journal for Nurse Practitioners, 11(1), 49–55.
https://doi.org/10.1016/j.nurpra.2014.10.020

Syphilis Prevention. (June 17) Retrieved from health direct:
https://www.healthdirect.gov.au/syphilis-prevention

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In early centuries of infection, in 1497, the first treatment use to treat syphilis was using mercury (Sartin and Perry, 1995). They use mercury to treat syphilis because penicillin were not introduce yet. After a few centuries, new medicine were introduced by Ehrlich it was arsphenamine (Salvarsan) and became drug of choice (Sartin and Perry, 1995). Unfortunately, it needed a repeated injection for over 18 months. The real treatment for syphilis occur in 1943 by Mahoney et al. where they used penicillin to treat four patients with primary syphilis and it successfull (Mahoney et al., 1943). It became the current treatment to treat syphilis.

Nowdays, penicillin still remains the first line therapy for early syphilis (Centers for Disease Control and Prevention, 1998). The treatment failures rate only approximately 10% is reported (Schroeter et al., 1972). The early syphilis include primary, secondary and early latent. However, different stage needed different concentration of penicillin. Also it need to take repeatedly for time to time depend on different stage of syphilis infection. For patient who allergic to penicillin, several therapies exist.  Tetracycline (Schroeter et al., 1972), erythromycin (Centers for Disease Control and Prevention, 1998) and ceftriaxone (Augenbraun and Workowski, 1999) (Korting et al., 1987) have shown to treat syphilis successfully but it only conciderate as alternative treatment for syphilis. In conclusion, syphilis infection still can be cure by nowday treatment using penicillin even though the patient have allergic to penicillin

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Syphilis can be transmitted through direct contact with the ulcerated site of the infected person either via sexual or casual contact (Sukthankar, 2014). Sexual contact happens through oral, anal, and genital contact. The pregnant women who have been infected by the disease also can transmit the disease to the fetus during the ninth week of pregnancy since the bacteria can cross the placenta on the period through a vertical transmission which can cause miscarriage (Sexually Transmitted Diseases (STDs), 2015). Blood transfusion by the infected person can also lead to the transmission of the bacteria into the healthy person (Sukthankar, 2014).

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The disease has several stages which are primary, secondary, latent, and tertiary that give different signs and symptoms to the infected person. On the primary stage or early syphilis stage, usually, around three weeks after sexual contact with infected person, the patient will develop single or may be more than one painless sores at the site of infection. The common sites of infection occur in genital areas such as penile shaft, anal canal and cervix. Lips and nipple can also develop sores if that non-genital sites have been contacted with the disease. The ulcer will heal around 3-6 weeks that will leave scar on the infected sites (Sexually Transmitted Diseases (STDs), 2015).

Secondary phase occurs on 6 weeks to 6 months after infection has occurred. During this period, skins will develop rashes around the arm, back, and the front part of the body. The lymph nodes will swell accompanied by fever. The first and secondary phase of infection is categorized as mild and the symptoms might not be detected.

During latent stage, no signs and symptoms will be shown. It will last for 2 years or may be more than that on certain patients. If the patients enter the late latent stage, the disease might remain asymptomatic forever in their body.

The tertiary stage is the dangerous phase for the patients because the bacteria will infect other cells in the body which can cause neurosyphilis and cardiovascular syphilis. The third stage usually occurs around 2 to 40 years after infection and can cause fatal. In the neurosyphilis, the bacteria will go to the back of the spinal cord or posterior spinal cord which damage the spinal cord that results in the loss of vibration sense (Syphilis - causes, symptoms, diagnosis, treatment, pathology, 2018). The bacteria might also damage the front part of the spinal cord or anterior spinal cord which causes the loss of sensation and paralysis. In cardiovascular syphilis, the bacteria can cause the inflammation on the arterioles that supply blood to large arteries like aorta which resulting in the aortitis if the patients have not undergone treatment for 10-25 years after infection.

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There are several ways to detect if a person is infected by Treponema pallidum and it is divided into two types; direct diagnosis and indirect diagnosis. There are no approximate symptoms of syphilis and some infected person does not show any specific symptoms of syphilis.
However, if there lesion, that sample can be used to detect this bacteria infection under miscroscope (darkfield microscopy along with immunofluorescence ). Other direct diagnosis include histological examination of tissues and nucleic acid amplification including polymerase chain reaction.

Under indirect ways, this bacteria infection can be detected by serological test. There are two types of serological test, nontreponemal test for screening and treponemal test for confirmation. Nontreponemal test is to measure both immunoglobulin M (Ig M) and Ig G. It is a result of lipoidal material from the dead cell and also from the lipid of treponeme itself.

If there are detection of Ig M and Ig G or the result is reactive, then it will proceed to treponemal test for confirmation. This test used T. pallidum or it components as antigen. One advantage of this indirect method is that it help to detect infection on latent infection because no direct method can be used during this stage. However, this serological test cannot determine what stage the infection is and how long the infection has occured.

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Cruz, A. R., Ramirez, L. G., Zuluaga, A. V., Pillay, A., Abreu, C., Valencia, C. A., … Salazar, J. C. (2012). Immune evasion and recognition of the syphilis spirochete in blood and skin of secondary syphilis patients: Two immunologically distinct compartments. PLoS Neglected Tropical Diseases, 6(7). https://doi.org/10.1371/journal.pntd.0001717

LaFond, R. E., & Lukehart, S. A. (2006). Biological Basis for Syphilis. Clinical Microbiology, 19(1), 29–49. https://doi.org/10.1128/CMR.19.1.29

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Augenbraun, M, Workowski K. Ceftriaxone theraphy for syphilis: report from the emerging infection network. Clinical Infection Disease 199 Nov. 29(5):1337-8

Centers for Disease Control and Prevention. 1998 guidelines for treatment of sexually transmitted diseases. Morbid Mortal Weekly Rep. 1998;47:28–49.

Korting H C, Walther D, Riethmuller U, Meurer M. Ceftriaxone given repeatedly cures manifest syphilis in the rabbit. Chemotherapy. 1987;33:376–380. https://www.ncbi.nlm.nih.gov/pubmed/3665636

Mahoney J F, Arnold R C, Harris A D. Penicillin treatment of early syphilis. Am J Public Health. 1943;33:1387–1391. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1527687/

Sartin J S, Perry H O. From mercury to malaria to penicillin: the history of the treatment of syphilis at the Mayo Clinic. J Am Acad Dermatol. 1995;32:255–261. https://www.ncbi.nlm.nih.gov/pubmed/7829712

Schroeter A L, Lucas J B, Price E V, Falcone V H. Treatment for early syphilis and reactivity of serologic tests. JAMA. 1972;221:471–476.

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Advantages and Disadvantages of Non-trepenomal test and Rapid trepenomal test

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Advantages and Disadvantages of Non-trepenomal test and Rapid trepenomal test

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World Health Organization (2006). The Use of Rapid Syphilis Tests. Extracted from: whqlibdoc.who.int/hq/2006/TDR_SDI_06.1_eng.pdf

CDC (2008). NC Communicable Disease Manual/Case Definition: Syphilis. Extracted from:  epi.publichealth.nc.gov/cd/lhds/manuals/cd/casedefs/SYPHILIS_CD.pdf

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1. Syphilis, primary

Infection stage where one or more ulcers appears but varies in clinical appearances

2. Syphilis, secondary

Localized mucocutaneous lesions (lymphadenopaty) with primary ulcers

3. Syphilis, latent

T. pallidum persist in infected person but asymptomatic and subdivided into early, late and unknown depending on period of infection

4. Syphilis, early latent

Current infection after 12 months of latent syphilis infection

5. Syphilis, late latent

Current infection after more than 1 year of latent syphilis infection

6. Syphilis, latent, of unknown duration

Happens when the date of initial infection cannot be determined within previous years after taking account the patient's age and titer.

7. Neurosyphilis

Central nervous system was proved to be affected by T. pallidum

8. Syphilis, late, with clinical manifestations other than neurosyphilis (late benign syphilis and cardiovascular syphilis)

When inflammatory lesions found on cardiovascular system, skin, and bone but involvement of other structures are uncommon such as the upper and lower respiratory tracts, mouth, eye, abdominal organs, reproductive organs, lymph nodes, and skeletal muscle. This stage of syphilis infection becomes clinically manifest only after a period of 15- 30 years of untreated infection.

9. Syphilitic stillbirth

Fetal death (20 weeks after gestation) with weight of 500g caused by inadequate treatment case of syphilis from the mother.

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Treponema pallidum has the abundant of lipoprotein on their membrane structure which can activate the macrophage and dendritic cell through CD14 receptor. The inflammatory process occur when the pathogen associated molecular patterns (PAMPs) bind together with Toll-like receptor 1 (TLR1) and TLR2-dependent signaling pathway which resulting to pro-inflammatory at the inoculated site. Unfortunately, the T. pallidum outer membrane is special which the surface of outer membrane is lack of lipoproteins. Based on the freeze fracture electron microscopy result, the outer membrane of T. pallidum has little exposed proteins (Bourell et al., 1994) which are called treponemal rare outer membrane proteins (Tromps) (Centurion-Lara et al., 2000). It will prevent the PAMPs to bind to the TLR or pattern recognition receptors (PRR) in order to present it to the macrophages or dendritic cells. Therefore, the bacteria can replicate themselves without triggering the innate pathogen recognition system. But, opsonic antibodies will help the PAMPs to enter to the PRR which can activate the phagocytes (Cruz et al., 2012). Opsonization is the process when the antibodies with the help of complement protein carry the antigen to bind to the macrophage which increase the efficiency of phagocytosis process (Reynolds et al., 1975) .

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Reynolds, H. Y., Kazmierowski, J. A., & Newball, H. H. (1975). Specificity of opsonic antibodies to enhance phagocytosis of Pseudomonas aeruginosa by human alveolar macrophages. Journal of Clinical Investigation, 56(2), 376–385. https://doi.org/10.1172/JCI108102

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The infection occur when the healthy person make a contact with infected person at their infection site such as on the genital sites or mouth that contain the ulcer caused by the bacteria. The bacteria will travel across the junction between the endothelial cells in order to enter into the blood or tissue. T. pallidum will trigger the matrix metalloproteinase-1 (MMP-1) that helps to break down the collagen in the dermal cell. As the result, the bacteria are capable to enter into the tissues of the host (LaFond & Lukehart, 2006). Treponema pallidum able to attach at epithelial, fibroblast-like, and endothelial cells (LaFond & Lukehart, 2006) in human body at which the attachment occur at the several sites of the bacterium. They are able to grow and enter blood vessels and lymphatics simultaneously which can lead to the invasion of T. pallidum in organ tissues (Cruz et al., 2012). Study showed that the specific surface antigens of the bacteria contribute in attachment to the host cells. Besides, the components in the host serum, cell membranes, and extracellular matrix (ECM) bind to the bacteria and promote attachment for them to attach on the fibronectin. The attachment of the bacteria on the fibronectin are caused by the bacteria proteins that have been encoded as tp0155 and tp0483. Both gene encoded are used to attach on the fibronectin but in different condition such as tp0155 binds to the matrix fibronectin while tp0483 bind at the soluble and matrix fibronectin (LaFond & Lukehart, 2006).

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One of the virulence factor of the bacteria is the motility. Treponema pallidum moves in a corkscrew-like movement which makes them easily to swim in the gel-like environment. Usually, the flagella filament of the bacteria are made of one type of protein but the flagella filament of T. pallidum is made of three types of proteins which are FlaB1, FlaB2, and FlaB3 which contribute to the flagella core. The flagella core is covered by the sheath that consists of FlaA protein. Cellular and humoral immune response can easily be induced when the infection occurs because the antibodies can detect the endoflagella of the bacteria. Unfortunately, the immunization cannot be protected completely due to the flagella is not exposed on the organism’s surface (LaFond & Lukehart, 2006).

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Folds, J. D., & Baseman, J. B. (1978). Cell-mediated immunity during syphilis. A review. The British Journal of Venereal …, 144–150. https://doi.org/10.1136/sti.54.3.144

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Bourell, K. W., Schulz, W., Norgard, M. V., & Radolf, J. D. (1994). Treponema pallidum rare outer membrane proteins: Analysis of mobility by freeze-fracture electron microscopy. Journal of Bacteriology, 176(6), 1598–1608. https://doi.org/10.1128/jb.176.6.1598-1608.1994

Centurion-Lara, A., Godornes, C., Castro, C., Van Voorhis, W. C., & Lukehart, S. A. (2000). The tprK gene is heterogeneous among Treponema pallidum strains and has multiple alleles. Infection and Immunity, 68(2), 824–831. https://doi.org/10.1128/IAI.68.2.824-831.2000

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Zoechling, N., Schluepen, E. M., Soyer, H. P., Kerl, H., & Volkenandt, M. (1997). Molecular detection of Treponema pallidum in secondary and tertiary syphilis. British Journal of Dermatology, 136(5), 683–686. https://doi.org/10.1111/j.1365-2133.1997.tb03652.x

Grange, P. A., Gressier, L., Dion, P. L., Farhi, D., Benhaddou, N., Gerhardt, P., … Dupina, N. (2012). Evaluation of a PCR test for detection of Treponema pallidum in swabs and blood. Journal of Clinical Microbiology, 50(3), 546–552. https://doi.org/10.1128/JCM.00702-11

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A conventional technique such as dark-field microscopy, immunofluorescence or the rabbit infectivity test can be used to detect the Treponema pallidum in primary and early secondary syphilis. But, unfortunately, for late secondary and tertiary syphilis, this conventional techniques cannot be used. This is due to the spirochaetes become scarce and most likely to vanish. In tertiary syphilis, the granulomatous infiltrate are initiate as an allergic reaction to treponemal antigen even though there is spirochaetes present. Thus, in order to detect Treponema pallidum specific DNA, a polymerase chain reaction method (PCR) is used (Zoechling et al., 1997).

Several PCR techniques have been used to target various Treponema pallidum genes which include classical PCR, nested PCR (nPCR), reverse transcription-PCR (rtPCR) and quantitative PCR (qPCR). It targeted several genes, bmp, tpp47, tmpA, and polA (which involve in genome duplication) (Grange et al., 2012).