Identification

Syphilis is a sexually transmitted bacterial infection (STIs) due to infection with Treponema pallidum. ^[1] Popa GL, Popa MI. Microbiologie medicală curs – 2010... It is characterized by four stages: primary, secondary, latent and tertiary. ^[2] Oswal S, Lyons G. Syphilis in Pregnancy. Medscape. 2008.. ^[3]Stamm LV. Syphilis: Re-emergence of an old foe. Microb Cell. 2016; 3(9):363-370. ^[4] ***. WHO Guidelines for the Treatment of Treponema pallidum (Syphilis). 2016 .

1.      Primary syphilis is manifested by the emergence of a papule which over time become depressed leading to the development of a ulceration –tough chancre. ^[5]Popa GL, Popa MI. Microbiologie Medicală. 2008. Chancre occurs at approximately three weeks (7-90 days) from sexual contact and  heals, on average, after three to six weeks. ^[6] Oswal S and co. Syphilis in Pregnancy. Medscape. 2008.. Tough chancre has variable localizations according to sexual behavior (most commonly in the anogenital area). If it appears in the cervix, the infection may go unnoticed in the initial stages. ^[7]Oswal S et al. Syphilis in Pregnancy. Medscape. 2008.. Untreated persons develop secondary syphilis ^[8] Popa GL, Popa MI. Microbiologie medicală curs – 2010.~’`. .

2.      Secondary syphilis can occur 4-10 weeks after primary infection. It manifests itself through maculopapular lesions, localized anywhere on the body. ^[9] Oswal S, Lyons G. Syphilis in Pregnancy. Medscape. 2008.~. Pale papules may be observed at the level of mucous membranes (condiloma lata). ^[10] Oswal S, Lyons G. Syphilis in Pregnancy. Medscape. 2008.~..

Attention! There have been recorded situations in which patients with secondary syphilis have not shown signs of prior primary syphilis. Both primary and secondary lesions are highly contagious. ^[11] Popa GL, Popa MI. Microbiologie medicală curs – 2010.~`.

3.      It is estimated that one third of cases are healed, a third stays in latent syphilis stage (detectable by serological laboratory techniques), and the rest evolve towards tertiary syphilis. ^[12]Popa GL, Popa MI. Microbiologie Medicală. 2008`

4.      Tertiary syphilis may occur after 2-15 years after primary infection. It has a relatively frequent cardiovascular, neurological (granulomatous lesions) manifestation. ^[13]Popa GL, Popa MI. Microbiologie Medicală. 2008`.

Congenital syphilis is the result of mother-to-child transmission. A pregnant woman infected with Treponema pallidum, can transmit bacterium:

• to fetus through the placenta between the 10-15 weeks of gestation. The bacterium can be transmitted transplacental at all stages of the infection with syphilis.^[14] Popa GL, Popa MI. Microbiologie medicală curs – 2010.’.
• at any time of pregnancy and at any stage of the infection, being more common in primary syphilis and in secondary syphilis and resulting in various effects on the fetus. ^[15] Oswal S, Lyons G. Syphilis in Pregnancy. Medscape. 2008.`. <sup>[16]</sup>Stamm LV. Syphilis: Re-emergence of an old foe. Microb Cell. 2016; 3(9):363-370.` ^[17] ***. WHO Guidelines for the Treatment of Treponema pallidum (Syphilis). 2016` .

Effects of infection on the Fetus: ^[18] ***. Congenital Syphilis – 2015 STD Treatment Guidelines. Centers for Disease Control and Prevention. 2015..

·         Fetal Hydrops,

·         Intrauterine growth restriction,

·         Premature birth,

·         Fetus born dead,

·         Spontaneous abortion in up to 50% of pregnancies.

Children with congenital syphilis may be born: ^[19]Popa GL et al. Microbiologie Medicală. 2008

-with obvious signs of syphilis (early congenital syphilis)

–apparently healthy (tardy congenital syphilis)

Manifestations of early congenital syphilis:

-Skin Lesions

-Syphilitic Coryza

-Necrotizing Funiculitis

-Generalised Adenopathy

-Hepatosplenomegaly

-Osteochondritis and Perichondritis

-Renal impairment

Manifestations of tardy congenital syphilis:

-Sensory deafness

-Interstitial keratitis ^[20]Popa GL et al. Microbiologie Medicală. 2008.'

-Hutchinson Teeth ^[21]Popa GL et al. Microbiologie Medicală. 2008′.

-Nose in saddle ^[22]Popa GL et al. Microbiologie Medicală. 2008’`

-Periostitis ^[23]Popa GL et al. Microbiologie Medicală. 2008`'

-Cheek bone Hypoplasia

-Anomalies of the central nervous system ^[24]Popa GL et al. Microbiologie Medicală. 2008|

Tests for the screening of syphilis in the pregnant woman shall be performed on the first antenatal visit and shall be repeated at the beginning of the third trimester of pregnancy.

• Initial diagnostic tests are nontreponemic tests, which detect antibodies, for example:

-VDRL (Veneral Disease Research Laboratory),

-RPR (Rapid plasma reding). ^[25] Popa GL, Popa MI. Microbiologie medicală curs – 2010.|| ^[26]Stamm LV. Syphilis: Re-emergence of an old foe. Microb Cell. 2016; 3(9):363-370.| ^[27] ***. WHO Guidelines …. Treponema pallidum (Syphilis). 2016.

• Nontreponemic tests must be confirmed with tests using treponemic antigens to exclude false positive results, these are called Treponemic tests, which detect specific-species antibodies, for example:

-TPHA passive haemagglutination test (Treponema Pallidum Haemagglutination assay),

-FTA-Abs indirect immunofluorescence test (Fluorescent Treponemal antibody Test). ^[28] Popa GL, et al. Microbiologie medicală curs – 2010.|`.

• If the pregnant infection is old, healed before pregnancy the nontreponemic tests are negative, and the treponemic ones are positive.

The pregnant woman has the possibility of a false positive reaction related to pregnancy. In these situations, determination byEIA)-IgM imunoenzimatic test of antitreponemic IgM antibodies allows the differentiation of an old syphilis with residual antibodies of a new, progressive syphilis. The first antibodies that occur are specific antitreponemic IgM antibodies, which can be detected at the end of the second week of infection; antitreponemic IgG antibodies appear later in the fourth week. Thus, at the onset of clinical symptoms, the majority of patients present IgM and IgG antibodies. ^[29]Dupin N. Syphilis- Aspects cliniques. BEH 2001;35-36: 170-172 ^[30]Peeling RW et al. Maternal and Congenital Syphilis, In Bulletin of the World Health Organization, June 2004.| ^[31]***. Syphilis in Pregnancy – 2015 STD Treatment Guidelines. 2015.|. ^[32]***. WHO Guidelines for … Treponema pallidum (Syphilis). 2016..

Diagnosis of Newborn

All newborns with seropositive mothers are tested within the first month of birth, in parallel with the mother, by quantitatively VDRL from the serum. ^[33]***. Congenital Syphilis – 2015 STD Treatment Guidelines. Centers for Disease Control and Prevention. 2015.|. If the antibodies titer detected in the newborn is four times greater than the mother antibodies titer is considered congenital syphilis. ^[34]***. Congenital Syphilis – 2015 STD Treatment Guidelines. Centers for Disease Control and Prevention. 2015.||. The diagnosis can be confirmed by direct viewing of Treponema pallidum in microscopy with dark background from lesions (more frequently in nasal secretions). ^[35]***. Congenital Syphilis – 2015 STD Treatment Guidelines. Centers for Disease Control and Prevention. 2015.~|. In cases of confirmed serology at birth, is also mandatory mother and child testing for HIV infection. ^[36]***. Syphilis in Pregnancy – 2015 STD Treatment Guidelines. 2015.|`. ^[37]***. WHO Guidelines … Treponema pallidum (Syphilis). 2016.

For neonatal screening, serum is preferred to umbilical cord blood, which leads to more false-positive reactions.

In early phases of the infection the serological tests may be unreactive.

At birth of a newborn from a HIV positive mother, the baby has the same serological profile as the mother from which the passive transfer of IgG type antitreponemic antibodies has been made and, in the case of an uninfected child, which will disappear within the first 3-6 months.

The serological control of the uninfected child is made in order to monitor the progressive decrease of antibody titers through quantitative tests.

In the infected and treated child, antitreponemic antibodies persist for a long time and only the significant decrease of VDRL allows the treatment efficacy follow up. The dosage of IgM type antitreponemic antibodies in the newborn, differentiates between the passive passage of antibodies from the mother (IgG type) and the active synthesis of antitreponemic antibodies of IgM type by the newborn. A serological profile with antitreponemic antibodies of IgM negative type does not preclude the diagnosis of congenital syphilis if the mother was tardy infected during pregnancy. ^[38]Dupin N. Syphilis- Aspects cliniques. BEH 2001;35-36: 170-172` <sup>[39]</sup>***. Syphilis in Pregnancy – 2015 STD Treatment Guidelines. 2015.`. ^[40]***. Results Interpretation for Syphilis Serology. University Hygienic Laboratory. Communication.`. ^[41]***. WHO Guidelines for the …Treponema pallidum (Syphilis). 2016.

Nota Bene. In this document, the laboratory diagnosis in infection with Treponema pallidum s.s. pallidum has not been detailed, but only few elements related to pregnancy and newborn were pointed. For complete diagnosis of this infection, those interested will address to the Dermatovenerologist colleagues.

The infectious agent

Syphilis is due to infection with a more peculiar bacterium. It is Treponema pallidum, a spirocheta belonging to Spirochaetaceae family, the Spirochaetales order. ^[42] Popa GL, Popa MI. Microbiologie medicală curs – 2010.|~. There are three subspecies, that morphologically, can not be differentiated: Treponema pallidum S.S. Pallidum, Treponema pallidum S.S. Endemicum (endemicsyphilis or Bejel) and Treponema pallidum S.S. Pertenue (piano). ^[43] Popa GL, Popa MI. Microbiologie medicală curs – 2010.||~. ^[44]***. Treponema pallidum – Pathogen Safety Data Sheet. Public Heal Agency Canada. 2011′. ^[45]Stamm LV. Syphilis: Re-emergence of an old foe. Microb Cell. 2016; 3(9):363-370.`| <sup>[46]</sup>***. WHO Guidelines for the Treatment of Treponema pallidum (Syphilis). 2016`

Incidence and prevalence

Syphilis is more common in people aged 20 to 45 years.This pathology is spread globally, with 10.6 million new cases of syphilis reported in 2008. About 1 million children are born annually with congenital syphilis. After the appearance of penicillin, the incidence of syphilis was decreasing until 2000, but in the last years a steady increase is observed. ^[47]***. Treponema pallidum – Pathogen Safety Data Sheet. Public Heal Agency Canada. 2011”. ^[48]Fantry L, Tramont E. Treponema Pallidum (Syphilis), Infectious Disease and Antimicrobial Agents. 2016.`. <sup>[49]</sup>Stamm LV. Syphilis: Re-emergence of an old foe. Microb Cell. 2016; 3(9):363-370.’` ^[50]***. WHO Guidelines for the Treatment of Treponema pallidum (Syphilis). 2016′..

Recent studies published in 2015 by CDC (Centre of Disease Control), Disease Control Centre, Atlanta, GA, United States, confirms in a large report that after a long period of decline, in the period 2012-2014 the incidence of congenital syphilis increased at alarming odds, higher odds even than 15 years ago (copies the incidence of syphilis in the adult). The growth has been observed in all races, ethnicities and religions. ^[51]Bowen W et al. Increase in Incidence of Congenital Syphilis — United States, 2012–2014: Morbidity and MortalityWeekly Report. ...continue

Source

The source is represented exclusively by man, ^[52]***. Treponema pallidum – Pathogen Safety Data Sheet. Public Heal Agency Canada. 2011’` Treponema pallidum has not been identified in the external environment. <sup>[53]</sup> Popa GL, Popa MI. Microbiologie medicală curs – 2010.’`.
^[54] ***. WHO Guidelines … of Treponema pallidum (Syphilis). 2016

Method of transmission

Most cases of syphilis are transmitted by sexual contact, but it is also possible to transmit through direct contact with active lesions in primary or secondary syphilis or through the passage at the placenta level. The transmission from the mother to the fetus can take place at any time of pregnancy and at any stage of the pregnant woman’s infection, being more frequent at the primary and secondary stage. ^[55]Fantry L, Tramont E. Treponema Pallidum (Syphilis), Infectious Disease and Antimicrobial Agents. 2016.`~. <sup>[56]</sup>***. WHO Guidelines for the Treatment of Treponema pallidum (Syphilis). 2016`.

The higher risk of transmission is from people in the initial stages. In the initial stages of the disease, it can also be transmitted through the blood. ^[57]Fantry L, Tramont E. Treponema Pallidum (Syphilis), Infectious Disease and Antimicrobial Agents. 2016.’`. <sup>[58]</sup>***. WHO Guidelines for the Treatment of Treponema pallidum (Syphilis). 2016’`.

Risk groups

The risk of sickness is increased in people over the age of 24, in those with a low education level, those who have more sexual partners, those who do not constantly use condoms, in people with homosexual behavior and those with HIV infection. ^[59]Popa GL, Popa MI. Microbiologie medicală curs – 2010.~|. ^[60]***. Congenital Syphilis – 2015 STD Treatment Guidelines. Centers for Disease Control and Prevention. 2015.|’. ^[61]***. Syphilis in Pregnancy – 2015 STD Treatment Guidelines. 2015.`’.. ^[62]Vigna-Taglianti F et al. Trends and risk factors …Piedmont Region, Italy, 2002-2008. Ital J Public Health. 2012;8(1) ^[63]Stamm LV. Syphilis: Re-emergence of an old foe. Microb Cell. 2016; 3(9):363-370.“ ^[64]***. WHO Guidelines for the Treatment of Treponema pallidum (Syphilis). 2016.”.

Incubation period

The incubation period of primary syphilis varies between 10 and 90 days, with an average of 21 days, the manifestations of the secondary appear between 7 and 90 days after contact, and for the tertiary onset of the symptoms can be identified after 2-15 years after the infectious contact. ^[65]Popa GL, Popa MI. Microbiologie medicală curs – 2010.`~`. ^[66]***. Treponema pallidum – Pathogen Safety Data Sheet. Public Heal Agency Canada. 2011~|.

Infectiousness Period

Treponema pallidum can be transmitted through direct contact with active lesions, the healed ones are no longer contagious. ^[67]***. Treponema pallidum – Pathogen Safety Data Sheet. Public Heal Agency Canada. 2011’|' ^[68]***. WHO Guidelines for the Treatment of Treponema pallidum (Syphilis). 2016!.

Prophylaxis

Considering that the modality of transmission in most cases is by sexual contact, the preventive measures must include the use of the condom, but it should be taken into account that its action is limited. ^[69]Vigna-Taglianti F et al. Trends and risk factors … in Piedmont Region, Italy, 2002-2008. Ital J Public Health. 2012;8(1). ^[70]***. WHO Guidelines for the Treatment of Treponema pallidum (Syphilis). 2016.`|| It is important to respect the moral rules and abstinence is preferred until marriage. Before marriage both spouses will perform a series of analyses to prevent sexually transmitted infections.

Vaccination

There’s no vaccine. ^[71]***. Treponema pallidum – Pathogen Safety Data Sheet. Public Heal Agency Canada. 2011`~`

Birth to the woman infected with Treponema pallidum

There are no special recommendations.

Breastfeeding

There are no special recommendations.

Treatment

With regard to disease control, several measures should be taken, including the correct treatment of all the diagnosed cases and in the same time monitoring and treating sources of infection and their contacts. Other measures include sexual hygiene and prophylaxis at the time of exposure, both condom and penicillin.

Treatment is performed with penicillin, but in some cases ceftriaxone, tetracycline or doxycycline may be administered (in case of hypersensitivity to penicillin).

All children born from seroreactive mothers should be treated with penicillin. ^[72]Popa GL, Popa MI. Microbiologie Medicală. 2008”

Bibliography

1.      Popa GL, Palm MI. Medical Microbiology Course – 2010. Retrieved from:

Http://www.microbiologie.ro/microbiologie-medical%C4%83-vol-1-2010-curs/53-germeni-spirala%C5%A3i-genul-treponema-treponema-pallidum-mi

2.      Oswal S, Lyons G. Syphilis in Pregnancy. Medscape. 2008. Retrieved from: Http://www.medscape.com/viewarticle/583494_1

3.      Popa GL, Palm MI. Medical Microbiology. 2008

4.      ***. Congenital Syphilis-2015 STD Treatment Guidelines. Centers for Disease Control and Prevention. 2015. Retrieved from: https://www.cdc.gov/std/tg2015/congenital.htm

5.      Dupin N. Syphilis-Aspects cliniques. Untold 2001; 35-36:170-172

6.      The peeling RW et al. Maternal and congenital Syphilis, In Bulletin of the World Health Organization, June 2004.

7.      ***. Syphilis in Pregnancy-2015 STD Treatment Guidelines. 2015. Retrieved from: https://www.cdc.gov/std/tg2015/syphilis-pregnancy.htm

8.      ***. Results interpretation for Syphilis Serology. University Hygienic Laboratory. Communication. Retrieved from: www.esculape.com/fmc/syphilis.html

9.      ***. Treponema pallidum-Pathogen Safety Data Sheet. Public Heal Agency Canada. 2011

10.  Fantry L, Tramont E. Treponema Pallidum (Syphilis), Infectious Disease and Antimicrobial agents. 2016. Retrieved from: http://www.antimicrobe.org/b242.asp

11.  Bowen W, JSu H, Torrone E, et al. Increase in Incidence of congenital Syphilis — United States, 2012 – 2014: Morbidity and MortalityWeekly Report. 2015; 64 (44): 1241-1245. Retrieved from: http://www.medscape.com/viewarticle/865770?src=par_cdc_stm_mscpedt&faf=1

12.  Vigna-Taglianti F, Delmonte S, Conte ID, et al. Trends and risk factors for syphilis infection in Piedmont Region, Italy, 2002-2008. Ital J Public Health. 2012; 8 ( 1).

13.  Stamm LV. Syphilis: Re-Emergence of an old foe. Cell Microbe. 2016; 3 (9): 363-370.

14.  ***. WHO Guidelines for the Treatment of Treponema pallidum (Syphilis). 2016 (available at https://www.ncbi.nlm.nih.gov/books/NBK384904/)