Sandbox:Reddy 2
Overview
Historical Perspective
- In the 19th century congenital syphilis was believed to be transmitted during conception by the father’s sperm, during delivery in the birth canal, or from infected milk or breasts.[1]
- In 1905, Schaudinn and Hoffmann identified Spirochaeta pallida.
- Transplacental transmission from an asymptomatic infected mother was first described in 1906.[2]
- In 1943, Lentz and Ingraham reported penicillin as treatment for congenital syphilis.
- In 2006, the WHO launched a global effort to eliminate congenital syphilis.
Classification
Congenital Syphilis is classified based on the timing of appearance of signs and symptoms into:[3]
- Early congenital Syphilis:If the signs and symptoms are identified in children aged less than 2 years. It is usally diagnosed in new born or in the first few weeks after birth.[4]
- Late congenital Syphilis: If the signs and symptoms of the disease are identified in children aged more than 2 years. The signs are usually non-specific and more than half the children are asymptomatic. They can present with interstitial keratitis, eighth nerve deafness or clutton's joints.
- Stigmata: These are the scars resulting from early or late congenital syphilis. The features of stigmata in early congenital syphilis include saddle nose deformity, Hutchinson's teeth, rhagades, choriod scarring and onychia. Stigmata secondary to late congenital syphilis include perforation of the palate, corneal opacities, optic atrophy and periosteal changes of tibia.
Pathophysiology
Pathogenesis
- Transmission to the fetus is transplacental, it can also occur during delivery in the presence of maternal genital lesions.[5][6][7]
- The risk of transmission to the fetus is dependent on the stage of the maternal disease(dependent on the spirochete concentration in the blood stream) and the duration of exposure to the fetus in utero.[8]
- The risk of vertical transmission of syphilis from an infected untreated mother decreases as maternal disease duration progresses: transmission risk of 70–100% for primary syphilis and 40% for early latent syphilis to 10% for late latent disease. The variation in the percentages with the duration of infection is because the concentration of spirochetes in the blood stream decrease with the duration of maternal syphilis infection.[9]
- Kassowitz's law describes the an inverse relationship of interval between the disease and pregnancy. Longer the interval between infection and pregnancy more benign is the outcome.[3]
- Transmission of infection typically takes place between the 16th and 28th week of pregnancy, however the transmission can be as early as the first trimester of pregnancy.[10][11][12][13][14][15]
- Inadequate antenatal care
- Multiple sexual partners
- Prostitution
- Illicit drug use
- Unprotected sex
- Residence in highly prevalent areas
- HIV infection
- Presence of other STIs
- Previous history of STIs
- Intravenous drug use
- Health care professionals who are predisposed to occupational risk
- Low socioeconomic status
Screening
Effective prevention and detection of congenital syphilis depends on the identification of syphilis in pregnant women and screening is a key component to decrease the incidence of congenital syphilis. The recommendations for screening are as follows:
Screening Recommendations | |
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Timing of Screening | Test all pregnant women at the first prenatal visit. |
Screening Tests |
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High Risk Population |
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Epidemiology, Demographics
Incidence
- It is estimated that every year 2 million pregnant women are infected with syphilis every year.
- In 2005, WHO reported that 460,000 abortions or still birth and 270,000 cases of congenital syphilis every year can be attributed to maternal syphilis.
- The incidence of congenital syphilis in United States in the year 2014 is 11.6 cases per 100,000 live births. The incidence of congenital syphilis has increased when compared to the numbers from 2008 to 2012 and the change is attributed to the increase in the number of women with primary and secondary syphilis.[16]
Race
- Congenital syphilis is ten times and three times more prevalent in black population compared to whites and Hispanics respectively.
Natural History, Complications and Prognosis
Natural History
- Syphilis is a sexually transmitted disease and is prevalent in high risk population. Women with syphilis infection can transmit the infection to the fetus in utero resulting in a wide spectrum of outcomes. The risk of transmission is higher in pregnant women who do not undergo regular antenatal screening or in women who are untreated or adequately treated during the period of gestation. The risk of transmission to the fetus is dependent on the stage of syphilis infection in the mother (primary, secondary, tertiary or latent), duration of maternal infection and the exposure to fetus in utero. The transmission of infection typically occurs during the second trimester but early transmission also occurs. Syphilis can complicate the outcome of pregnancy and is dependent on the severity of infection in the fetus, severe infection has adverse outcomes in the new born.[17]
Complications
- Severe infection in the fetus can result in spontaneous abortion, stillbirth, non-immune hydrops, intrauterine growth restriction, and perinatal death, and serious sequelae in liveborn infected children.[18]
Prognosis
- Adequate treatment of infected mother during the period of gestation can prevent the transmission of disease significantly and treatment of the mother with one dose of pencillin is proven to improve outcomes in the fetus.[19]
- In newborns and infants with congenital syphilis treatment with penicillin has a good prognosis with normal development.[20]
Diagosis
History and Symptoms
Early syphilis: It is diagnosed at birth or in the first few weeks of life. A combination of maternal risk factors and symptoms in the baby are essential to suspect congenital syphilis. The most common symptoms in the new born include:
- Skin rash occurs in 70% of affected cases
- Yellowish discoloration of the skin
- Abdominal distension
- Generalized edema
- Irritability
- Low birth weight
- Failure to thrive
- Fever
- Difficulty breathing
Late Syphilis: It is diagnosed in children aged greater than 2 years. The symptoms are non specific.
Physical Examination
The physical examination findings suggestive of congenital syphilis include:[21]
- Vesiculobullous or maculopapular rash occurring on the palms and soles is present in 70% of the children with congenital syphilis. Other patterns of rash such as vesiculobullous lesions, condylomata lata lesions, annular lesions, and erythema multiforme-like targetoid lesions are present in affected infants.[22]
- Low birth weight with signs of prematurity
- Nonimmune hydrops : It is characteristic of congenital syphilis and the features of non-immune hydrops include ascites, pericardial effusion, pleural effusion and skin edema, however Rh incompatability should be ruled out as a cause of hydrops.[23]
- Jaundice
- Hepatosplenomegaly
- Rhinitis
- Pseudoparalysis of an extremities
Laboratory Findings
Prenatal Diagnosis
- Detection of IgM antibodies aganist T.pallidum in the blood collected by chordocentesis.[24]
- PCR of the amniotic fluid to detect the T. pallidum DNA.[25]
- Antenatal ultrasound is commonly done and the findings suggestive of congenital syphilis include: hydrops fetalis characterised by scalp oedema, placental thickening, serous cavity effusion, and polyhydramnios. Other additional findings inlcude hepatosplenomegaly, placentomegaly, non-continuous gastrointestinal obstruction and dilatation of the small bowel.[26][27][28]
Postnatal Diagnosis
- Examination of the placenta or umbilical cord using a silver stain demonstrates spirochetes or a T. pallidum PCR test can be done.
- Darkfield microscopic examination or PCR testing of suspicious lesions or body fluids (e.g., bullous rash and nasal discharge) helps confirm the diagnosis.
- The use of serological tests to identify the infection in infants less than 15months of age born to infected mothers is not performed as passive transfer of IgG antibodies to the fetus occurs during the pregnancy.
- Other laboratory findings in the new born include:[29]
- Elevated liver enzymes
- Leucocytosis
- Coombs negative haemolytic anaemia
- Thrombocytopenia
- Hypoalbuminemia
- Hyperbilirubinemia
Imaging Studies
X-Ray
- Skeletal survey is done in a still born, typical osseous lesions are demonstrated in congenital syphilis.
Ultrasound
Antenatal sonographic features include:[30][31]
- Fetal hepatosplenomegaly
- Placentomegaly
- Fetal ascites
In severe cases findings include:
- Fetal hydrops
- Bent fetal long bones
Doppler Studies
Doppler ultrasound of the uterine and umbilical arteries show increases in the mean systolic to diastolic ratios in mothers infected with syphilis indicating an increased resistance to perfusion of the placenta secondary to vasculitis, placental villitis and obliterative arteritis caused by syphilis.[32]
Treatment
Medical Therapy
Management during the period of gestation
CDC Recommendations for management of pregnant woman with Syphilis infection | |
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Approach during the Prenatal Period |
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Recommended Regimen for Treatment |
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Additional Considerations |
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In patients with Penicillin Allergy |
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Pregnant Woman with HIV Infection |
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Follow Up |
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Management of a Neonate or an Infant with Congenital Syphilis
The diagnosis of congenital syphilis can be difficult, as maternal nontreponemal and treponemal IgG antibodies can be transferred through the placenta to the fetus, complicating the interpretation of reactive serologic tests for syphilis in neonates. Therefore, treatment decisions frequently must be made on the basis of:
- Identification of syphilis in the mother
- Adequacy of maternal treatment
- Presence of clinical, laboratory, or radiographic evidence of syphilis in the neonate
- Comparison of maternal (at delivery) and neonatal nontreponemal serologic titers using the same test, preferably conducted by the same laboratory.
Evaluation and Approach
- All neonates born to mothers who have reactive nontreponemal and treponemal test results should be evaluated with a quantitative nontreponemal serologic test (RPR or VDRL) performed on the neonate's serum, because umbilical cord blood can become contaminated with maternal blood and yield a false-positive result, and Wharton's jelly within the umbilical cord can yield a false-negative result.
- Conducting a treponemal test (i.e., TP-PA, FTA-ABS, EIA, or CIA) on neonatal serum is not recommended because it is difficult to interpret.
- Any neonate at risk for congenital syphilis should receive a full evaluation and testing for HIV infection.
- The following scenarios describe the congenital syphilis evaluation and treatment of neonates born to women who have reactive serologic tests for syphilis during pregnancy. Maternal history of infection with T. pallidum and treatment for syphilis must be considered when evaluating and treating the neonate for congenital syphilis in most scenarios, except when congenital syphilis is proven or highly probable.
CDC Recommendations for management of neonates with Congenital Syphilis | |
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Clinical senario 1 |
Recommended Evaluation
Preferred regimen 1: Aqueous crystalline penicillin G 100,000-150,000 U/kg/day, administered as 50,000 U/kg/dose IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days |
Clinical senario 2 |
Recommended Evaluation
Preferred regimen 1: Aqueous crystalline penicillin G 100,000-150,000 U/kg/day, administered as 50,000 U/kg/dose IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days |
Clinical senario 3 |
Recommended Evaluation'
Preferred regimen: Benzathine penicillin G 50,000 U/kg/dose IM single dose |
Clinical senario 4 |
Recommended evaluation
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Follow up |
Note: Treponemal tests should not be used to evaluate treatment response because the results are qualitative and passive transfer of maternal IgG treponemal antibody might persist for at least 15 months |
Penicillin Allergy |
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CDC Recommendations for management of Infants and Children with Congenital Syphilis | |
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Congenital Syphilis in infants and children |
Recommended Evaluation
Preferred regimen: Aqueous crystalline penicillin G 50,000 U/kg q4–6h for 10 days
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Follow Up |
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Penicillin Allergy |
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Prevention
Primary Prevention
Primary prevention of syphilis in women of reproductive age and men who have sex with women and prevention of mother to infant transmission in infected individuals plays a important role in decreasing incidence of congenital syphilis.Effective measures for the primary prevention of congenital syphilis include reducing the risk of mother having syphilis infection and also screening during the antenatal period:[41][42][43][44]
- Routine screening in pregnant females, individuals with high risk behaviours, and those residing in highly prevalent areas.
- Abstinence from intimate physical contact with an infected person.
- Consistent use of latex condoms.
- Limiting no of sexual partners.
- Avoid sharing sex toys.
- Practising safe sex.
Secondary Prevention
- Regular follow up of infants with congenital syphilis to examine for the re-appearance of signs and symptoms of syphilis after recommended treatment has shown to improve outcomes.[45][46][47]
References
- ↑ Obladen, Michael (2013). "Curse on Two Generations: A History of Congenital Syphilis". Neonatology. 103 (4): 274–280. doi:10.1159/000347107. ISSN 1661-7819.
- ↑ "Guidelines for the Prevention and Control of Congenital Syphilis".
- ↑ 3.0 3.1 Balaji G, Kalaivani S (2013). "Observance of Kassowitz law-late congenital syphilis: Palatal perforation and saddle nose deformity as presenting features". Indian J Sex Transm Dis. 34 (1): 35–7. doi:10.4103/0253-7184.112869. PMC 3730472. PMID 23919053.
- ↑ Cavagnaro S M F, Pereira R T, Pérez P C, Vargas Del V F, Sandoval C C (2014). "[Early congenital syphilis: a case report]". Rev Chil Pediatr. 85 (1): 86–93. doi:10.4067/S0370-41062014000100012. PMID 25079189.
- ↑ Wicher V, Wicher K (2001). "Pathogenesis of maternal-fetal syphilis revisited". Clin Infect Dis. 33 (3): 354–63. doi:10.1086/321904. PMID 11438902.
- ↑ Domingues RM, Leal Mdo C (2016). "[Incidence of congenital syphilis and factors associated with vertical transmission: data from the Birth in Brazil study]". Cad Saude Publica. 32 (6). doi:10.1590/0102-311X00082415. PMID 27333146.
- ↑ Peeling RW, Hook EW (2006). "The pathogenesis of syphilis: the Great Mimicker, revisited". J Pathol. 208 (2): 224–32. doi:10.1002/path.1903. PMID 16362988.
- ↑ Berman SM (2004). "Maternal syphilis: pathophysiology and treatment". Bull World Health Organ. 82 (6): 433–8. PMC 2622860. PMID 15356936.
- ↑ Genç M, Ledger WJ (2000). "Syphilis in pregnancy". Sex Transm Infect. 76 (2): 73–9. PMC 1758294. PMID 10858706.
- ↑ Zhou H, Chen XS, Hong FC, Pan P, Yang F, Cai YM; et al. (2007). "Risk factors for syphilis infection among pregnant women: results of a case-control study in Shenzhen, China". Sex Transm Infect. 83 (6): 476–80. doi:10.1136/sti.2007.026187. PMC 2598725. PMID 17675391.
- ↑ Hook EW, Peeling RW (2004). "Syphilis control--a continuing challenge". N Engl J Med. 351 (2): 122–4. doi:10.1056/NEJMp048126. PMID 15247352.
- ↑ Buchacz K, Greenberg A, Onorato I, Janssen R (2005). "Syphilis epidemics and human immunodeficiency virus (HIV) incidence among men who have sex with men in the United States: implications for HIV prevention". Sex Transm Dis. 32 (10 Suppl): S73–9. PMID 16205297.
- ↑ Solomon MM, Mayer KH (2015). "Evolution of the syphilis epidemic among men who have sex with men". Sex Health. 12 (2): 96–102. doi:10.1071/SH14173. PMC 4470884. PMID 25514173.
- ↑ Hakre S, Arteaga GB, Núñez AE, Arambu N, Aumakhan B, Liu M; et al. (2014). "Prevalence of HIV, syphilis, and other sexually transmitted infections among MSM from three cities in Panama". J Urban Health. 91 (4): 793–808. doi:10.1007/s11524-014-9885-4. PMC 4134449. PMID 24927712.
- ↑ Newell, J., et al. "A population-based study of syphilis and sexually transmitted disease syndromes in north-western Tanzania. 2. Risk factors and health seeking behaviour." Genitourinary medicine 69.6 (1993): 421-426.
- ↑ Peterman TA, Su J, Bernstein KT, Weinstock H (2015). "Syphilis in the United States: on the rise?". Expert Rev Anti Infect Ther. 13 (2): 161–8. doi:10.1586/14787210.2015.990384. PMID 25487961.
- ↑ Charles D (1983). "Syphilis". Clin Obstet Gynecol. 26 (1): 125–37. PMID 6340889.
- ↑ Cohen SE, Klausner JD, Engelman J, Philip S (2013). "Syphilis in the modern era: an update for physicians". Infect Dis Clin North Am. 27 (4): 705–22. doi:10.1016/j.idc.2013.08.005. PMID 24275265.
- ↑ Watson-Jones D, Gumodoka B, Weiss H, Changalucha J, Todd J, Mugeye K, Buvé A, Kanga Z, Ndeki L, Rusizoka M, Ross D, Marealle J, Balira R, Mabey D, Hayes R (2002). "Syphilis in pregnancy in Tanzania. II. The effectiveness of antenatal syphilis screening and single-dose benzathine penicillin treatment for the prevention of adverse pregnancy outcomes". J. Infect. Dis. 186 (7): 948–57. doi:10.1086/342951. PMID 12232835.
- ↑ Caddy SC, Lee BE, Sutherland K, Robinson JL, Plitt SS, Read R; et al. (2011). "Pregnancy and neonatal outcomes of women with reactive syphilis serology in Alberta, 2002 to 2006". J Obstet Gynaecol Can. 33 (5): 453–9. PMID 21639965.
- ↑ Ewing, C I; Roberts, C; Davidson, D C; Arya, O P (1985). "Early congenital syphilis still occurs". Archives of Disease in Childhood. 60 (12): 1128–1133. doi:10.1136/adc.60.12.1128. ISSN 0003-9888.
- ↑ Ferreira, Sara Tavares; Correia, Cátia; Marçal, Monica; Tuna, Madalena Lopo (2016). "Skin rash: a manifestation of early congenital syphilis". BMJ Case Reports: bcr2016216148. doi:10.1136/bcr-2016-216148. ISSN 1757-790X.
- ↑ Barron SD, Pass RF (1995). "Infectious causes of hydrops fetalis". Semin Perinatol. 19 (6): 493–501. PMID 8822333.
- ↑ Wendel GD, Sánchez PJ, Peters MT, Harstad TW, Potter LL, Norgard MV (1991). "Identification of Treponema pallidum in amniotic fluid and fetal blood from pregnancies complicated by congenital syphilis". Obstet Gynecol. 78 (5 Pt 2): 890–5. PMID 1923218.
- ↑ Muller, M; Ewert, I; Hansmann, F; Tiemann, C; Hagedorn, H J; Solbach, W; Roider, J; Nolle, B; Laqua, H; Hoerauf, H (2006). "Detection of Treponema pallidum in the vitreous by PCR". British Journal of Ophthalmology. 91 (5): 592–595. doi:10.1136/bjo.2006.110288. ISSN 0007-1161.
- ↑ Levine Z, Sherer DM, Jacobs A, Rotenberg O (1998). "Nonimmune hydrops fetalis due to congenital syphilis associated with negative intrapartum maternal serology screening". Am J Perinatol. 15 (4): 233–6. doi:10.1055/s-2007-993933. PMID 9565220.
- ↑ Russell, Peter (1974). "Placental Abnormalities of Congenital Syphilis". American Journal of Diseases of Children. 128 (2): 160. doi:10.1001/archpedi.1974.02110270034007. ISSN 0002-922X.
- ↑ Riley BS, Oppenheimer-Marks N, Radolf JD, Norgard MV (1994). "Virulent Treponema pallidum promotes adhesion of leukocytes to human vascular endothelial cells". Infect. Immun. 62 (10): 4622–5. PMC 303152. PMID 7927729.
- ↑ 29.0 29.1 29.2 Hollier LM, Harstad TW, Sanchez PJ, Twickler DM, Wendel GD (2001). "Fetal syphilis: clinical and laboratory characteristics". Obstet Gynecol. 97 (6): 947–53. PMID 11384701.
- ↑ https://radiopaedia.org/articles/in-utero-syphilis-infection. Accessed on September 28th, 2016.
- ↑ Reyna-Figueroa J, Esparza-Aguilar M, Hernández-Hernández Ldel C, Fernández-Canton S, Richardson-Lopez Collada VL (2011). "Congenital syphilis, a reemergent disease in Mexico: its epidemiology during the last 2 decades". Sex Transm Dis. 38 (9): 798–801. doi:10.1097/OLQ.0b013e31821898ca. PMID 21844732.
- ↑ Genc, M. (2000). "Syphilis in pregnancy". Sexually Transmitted Infections. 76 (2): 73–79. doi:10.1136/sti.76.2.73. ISSN 1368-4973.
- ↑ https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/syphilis-infection-in-pregnancy-screening Accessed on september 27,2016
- ↑ http://www.cdc.gov/std/tg2015/references.htm#424 Accessed on September 27, 2016
- ↑ 35.0 35.1 "Sexually Transmitted Diseases Treatment Guidelines, 2010". Retrieved 2012-12-19.
- ↑ Alexander JM, Sheffield JS, Sanchez PJ, Mayfield J, Wendel GD (1999) Efficacy of treatment for syphilis in pregnancy. Obstet Gynecol 93 (1):5-8. PMID: 9916946
- ↑ 37.0 37.1 Walker GJ (2001) Antibiotics for syphilis diagnosed during pregnancy. Cochrane Database Syst Rev (3):CD001143. DOI:10.1002/14651858.CD001143 PMID: 11686978
- ↑ Wendel GD, Sheffield JS, Hollier LM, Hill JB, Ramsey PS, Sánchez PJ (2002) Treatment of syphilis in pregnancy and prevention of congenital syphilis. Clin Infect Dis 35 (Suppl 2):S200-9. DOI:10.1086/342108 PMID: 12353207
- ↑ Klein VR, Cox SM, Mitchell MD, Wendel GD (1990) The Jarisch-Herxheimer reaction complicating syphilotherapy in pregnancy. Obstet Gynecol 75 (3 Pt 1):375-80. PMID: 2304710
- ↑ Nathan L, Bawdon RE, Sidawi JE, Stettler RW, McIntire DM, Wendel GD (1993). "Penicillin levels following the administration of benzathine penicillin G in pregnancy". Obstet Gynecol. 82 (3): 338–42. PMID 8355931.
- ↑ Stamm LV (2010). "Global challenge of atibiotic-resistant Treponema pallidum". Antimicrobial Agents and Chemotherapy. 54 (2): 583–9. doi:10.1128/AAC.01095-09. PMC 2812177. PMID 19805553. Retrieved 2012-02-21. Unknown parameter
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ignored (help) - ↑ Cameron CE, Lukehart SA (2014). "Current status of syphilis vaccine development: need, challenges, prospects". Vaccine. 32 (14): 1602–9. doi:10.1016/j.vaccine.2013.09.053. PMC 3951677. PMID 24135571.
- ↑ http://www.cdc.gov/std/tg2015/syphilis.htm Accessed on September 27, 2016
- ↑ Lago EG (2016). "Current Perspectives on Prevention of Mother-to-Child Transmission of Syphilis". Cureus. 8 (3): e525. doi:10.7759/cureus.525. PMC 4829408. PMID 27081586.
- ↑ Feliz MC, Prizybicien AR, Rossoni AM, Tahnus T, Pereira AM, Rodrigues C (2016). "Adherence to the follow-up of the newborn exposed to syphilis and factors associated with loss to follow-up". Rev Bras Epidemiol. 19 (4): 727–739. doi:10.1590/1980-5497201600040004. PMID 28146163.
- ↑ Wallace HE, Broomhall HM, Isitt CE, Miall LS, Wilson JD (2016). "Serological follow-up of infants born to mothers with positive syphilis serology - real-world experiences". Int J STD AIDS. 27 (13): 1213–1217. doi:10.1177/0956462415612394. PMID 26474815.
- ↑ Vallejo C, Cifuentes Y (2016). "Characterization and six-month follow-up on a cohort of newborns with congenital syphilis". Biomedica. 36 (1): 101–8. doi:10.7705/biomedica.v36i1.2661. PMID 27622443.