What is congenital syphilis?
Syphilis is a bacterial infection caused by Treponema pallidum – primarily spread through sexual contact. World Health Organization (WHO) estimates that seven million people of reproductive age acquire syphilis globally each year.
Syphilis is transmitted from a woman to her baby during pregnancy or at birth. The infection in the baby is called congenital syphilis. If left untreated, congenital syphilis has a dramatic impact on pregnancy outcomes.
How is congenital syphilis spread?
Mother-to-child transmission may occur if the expectant mother has syphilis. Syphilis is highly transmissible during the first two years after infection. Mother-to-child transmission of syphilis (congenital syphilis) is usually devastating to the fetus in cases where maternal infection is not detected and treated sufficiently early in pregnancy (at least one month prior to delivery).1
How many people are affected by congenital syphilis?
Approximately one million women are infected with syphilis globally. There are an estimated 350,000 adverse pregnancy outcomes due to congenital syphilis per year.2 That includes 143,000 early fetal deaths and stillbirths, 61,000 neonatal deaths, 41,000 preterm or low-birth-weight births, and 109,000 infected infants (2016).3 Congenital syphilis affects significantly more newborns than are infected with HIV annually and the consequences for the baby are life long.4
The prevalence of syphilis differs by region but is highest in the WHO African Region where it affects almost 2% of the population at reproductive age. It is estimated that 64% of adverse syphilis outcomes globally occur in Africa.5
What is the link between maternal syphilis and congenital syphilis? How can congenital syphilis be prevented?
Congenital syphilis is preventable and elimination of mother-to-child transmission (or vertical transmission) of congenital syphilis can be achieved through implementation of effective early screening and treatment strategies during pregnancy. The fetus can be easily cured with treatment, and the risk of adverse outcomes to the fetus is minimal if the mother receives adequate treatment early, i.e., before the end of the second trimester.
To identify pregnant mothers infected with syphilis, the WHO Sexually Transmitted Infections (STI) guideline recommends screening all pregnant women for syphilis during the first antenatal care visit, regardless of where a woman lives and regardless of the time of this first visit relative to the pregnancy.1 Ensuring that pregnant women access antenatal care and receive screening is an essential step to preventing congenital syphilis.1
Screening can be done at the point-of-care using rapid tests that gives results in less than 20 minute and allow immediate treatment initiation.
Most syphilis-associated deaths in babies as well as syphilis in adults, could be prevented with a single dose of long-acting injectable penicillin (benzathine penicillin). Benzathine penicillin is an inexpensive, off-patent drug that is highly effective in the prevention and treatment of congenital syphilis.
Benzathine penicillin is the only antibiotic currently proven to prevent and treat congenital syphilis and is thus recommended for all pregnant women diagnosed with syphilis as early as possible in pregnancy. The WHO recommends between one and three doses of intramuscular benzathine penicillin 2.4MIU for pregnant women with syphilis depending on the state of the disease. One dose of benzathine penicillin will treat the great majority of fetuses. Additional doses may be required to fully treat the maternal infection; if the mother has early stage (less than one year of duration), one dose will be adequate to treat her infection. If the mother has late stage syphilis (more than one year of infection or unknown), three doses at weekly intervals are needed. When benzathine penicillin is not available, the WHO recommends daily procaine penicillin and probenecid for 10-14 days.6
In infants with confirmed congenital syphilis or infants who are clinically normal, but whose mothers had untreated syphilis, inadequately treated syphilis (including treatment within 30 days of delivery) or syphilis that was treated with non-penicillin regimens, the WHO STI guideline suggest infant treatment with aqueous benzyl-penicillin or procaine penicillin for 14 days, which means that the baby will remain in hospital for this period.7*
*In these cases, the provider should notify the case as congenital syphilis for the national authorities through its disease notification system
What is the link between HIV infection and syphilis?
There is an increase in mother-to-child transmission of HIV among pregnant women co-infected with syphilis and HIV.1 Therefore, the WHO strongly recommends screening all pregnant women for both HIV and syphilis at the first antenatal care visit in nearly all countries of the world. Despite WHO’s recommendation, HIV testing coverage has remained significantly higher than syphilis in most low- and middle-income countries (LMIC), due to under prioritization and underfunding of syphilis programs.8 Early diagnosis and treatment of both HIV and syphilis in pregnant women has been proven as an effective strategy in the prevention of both adverse outcomes of pregnancy and mother-to-child transmission.9
Recent advances in the development of dual HIV/syphilis rapid tests (rapid fingerstick tests that measure antibodies to both HIV and syphilis) means there are new testing options for dual elimination of HIV and syphilis.10
What does dual elimination of HIV and syphilis mean?
Dual elimination refers to the elimination of the mother-to-child transmission (or vertical transmission) of both HIV and syphilis. The use of dual elimination tools, such as dual rapid tests for HIV and syphilis, followed by appropriate treatment, can significantly reduce maternal and neonatal morbidity and mortality.
The prevention of mother-to-child transmission of HIV and syphilis infections can be addressed with similar strategies; therefore, combining the delivery and implementation of HIV and congenital syphilis services in antenatal care clinics can enhance the effectiveness of current programs on elimination of mother-to-child transmission of HIV and syphilis.
What is the role of a male partner in elimination?
Partner testing is an important strategy to address syphilis transmission and break the reinfection cycle. Pregnant women should be encouraged to counsel their male sexual partner(s) to present to the health facility for a syphilis test and be treated if positive to assuredly prevent congenital syphilis.
Is congenital syphilis elimination a good investment?
The World Health Organization published an investment case for the eliminating mother-to-child transmission of syphilis in 2012. The report concluded that congenital syphilis is relatively simple to eliminate and it is inexpensive to detect and treat, making it a possible “easy win” in terms of cost, feasibility, and speed of scale-up. This conclusion has been confirmed by additional studies since, for instance a 2020 modelling study examined the cost-effectiveness of dual maternal HIV and syphilis testing strategies in high and low HIV prevalence countries, concluding that routinely offering testing at the first antenatal care visit with a dual rapid diagnosis test was cost-saving measure.
With additional investment from development partners, this work could be expanded to support additional high-burden countries, dramatically reducing the global number of congenital syphilis cases and accelerating progress to global elimination.
Syphilis: Syphilis is a sexually transmitted infection (STI) caused by the bacterium Treponema pallidum. Syphilis is passed from person to person through direct contact with a syphilitic sore or chancre. Typically, painless chancres occur mainly on the external genitals, vagina, anus, or in the rectum but can also occur on the lips and in the mouth. Transmission of the organism occurs during vaginal, anal, or oral sex. Pregnant women with the disease can transmit it through the placenta to the fetus or at birth to the neonate.11
Congenital Syphilis: A condition caused by infection during pregnancy with Treponema pallidum. A wide spectrum of severity exists, from inapparent infection to severe cases that are clinically apparent at birth. An infant or child (aged less than 2 years) may have signs such as hepatosplenomegaly, rash, condyloma lata, snuffles, jaundice (nonviral hepatitis), pseudo paralysis, anemia, or edema (nephrotic syndrome and/or malnutrition). An older child may have stigmata (e.g., interstitial keratitis, nerve deafness, anterior bowing of shins, frontal bossing, mulberry molars, Hutchinson teeth, saddle nose, rhagades, or Clutton joints).11 However, many congenital syphilis cases may be unnoticed by the provider and later symptoms could occur such as developmental delay, neurologic manifestations, and late congenital syphilis physical signs.12
Syphilitic Stillbirth: A fetal death that occurs after a 20-week gestation or in which the fetus weighs greater than 500 g and the mother had untreated or inadequately treated syphilis at delivery.11
Elimination, as a public health problem: Elimination is defined as reduction in incidence of disease or infection to a level that no longer is considered a public health problem in a defined geographical area. The current goal for the WHO elimination of mother-to-child transmission (EMTCT) initiative is to reduce mother-to-child transmission of syphilis to a very low level (<50 cases per 100,000 per year), such that it is no longer a public health problem.13
Validation: The term “validation” of EMTCT of HIV and syphilis is a WHO initiative to attest that a country has successfully met elimination criteria for at least one year. “Validation of EMTCT of HIV and/or syphilis” implies that countries will also need to maintain ongoing, routine, effective programmatic interventions, assurance of quality laboratory services, and functional surveillance systems to monitor EMTCT of HIV and/or syphilis and allow immediate programmatic action when needed.14
1.World Health Organization. WHO Guideline on Syphilis screening and treatment for pregnant women. 2017. Available from: https://www.who.int/medical_devices/diagnostics/selection_in-vitro/selection_in-vitro-meetings/00007_02_WHO_Syphilis_SandT_Pregnant.pdf?ua=1
2.Newman L, Kamb M, Hawkes S, Gomez G, Say Lale, Seuc A, et al. Global estimates of syphilis in pregnancy and associated adverse outcomes: analysis of multinational antenatal surveillance data. 2013. Available from: https://doi.org/10.1371/journal.pmed.1001396
3.Korenromp EL, Rowley J, Alonso M, Mello MB, Wijesooriya NS, Mahiané SG, et al. Global burden of maternal and congenital syphilis and associated adverse birth outcomes – Estimates for 2016 and progress since 2021. 2019. Available from: https://doi.org/10.1371/journal.pone.0211720
4.UNAIDS. Global HIV & AIDS statistics – Fact Sheet. 2018. Available from: http://www.unaids.org/en/resources/fact-sheet
5.Wijesooriya NS, Rochat RW, Kamb ML, Turlapati P, Temmerman M, Broutet N, et al. Global burden of maternal and congenital syphilis in 2008 and 2012: a health systems modelling study. 2016. Available from: https://doi.org/10.1016/S2214-109X(16)30135-8
6.Centers for Disease Control and Prevention. Sexually Transmitted Infections Treatment Guidelines, 2021. 2021. Available from: https://www.cdc.gov/std/tg2015/syphilis.htm#Treatment
7.World Health Organization. WHO Guidelines for the Treatment of Treponema Pallidum (Syphilis). 2016. Available from: https://www.who.int/reproductivehealth/publications/rtis/syphilis-treatment-guidelines/en/
8.Storey A, Seghers F, Pyne-Mercier L, Peeling RW, Owirdeu MN, Taylor MM. Syphilis diagnosis and treatment during antenatal care: The potential catalytic impact of the dual HIV and syphilis rapid diagnostic test. 2019. Available from: https://doi.org/10.1016/S2214-109X(19)30248-7
9.World Health Organization. WHO Information Note on the Use of Dual HIV/Syphilis Rapid Diagnostic Tests (RDT). 2017. Available from: https://www.who.int/reproductivehealth/publications/rtis/dual-hiv-syphilis-diagnostic-tests/en/
10.Bristow CC, Vargas Rivera SK, Ramos Cordova LB, Qquellon Palacious LJ, Kona KA, et al. Dual rapid test for HIV and syphilis: A laboratory evaluation of the diagnostic accuracy of the Standard Q HIV/Syphilis Combo Test. 2019. Available from:https://doi.org/10.1016/j.diagmicrobio.2018.11.018
11.Centers for Disease Control and Prevention. National Notifiable Diseases Surveillance System (NNDSS). 2021. Available from: https://ndc.services.cdc.gov/case-definitions/syphilis-2018/
12.Centers for Disease Control and Prevention. Birth defects surveillance toolkit. 2021. Available from: https://www.cdc.gov/ncbddd/birthdefects/surveillancemanual/quick-reference-handbook/congenital-syphilis.html
13.Dowdle WR. The principles of disease elimination and eradication. 1998. Available from: https://apps.who.int/iris/handle/10665/260633
14.World Health Organization. WHO global guidance on criteria and processes for validation: Elimination of Mother-to-Child Transmission of HIV and syphilis. 2017. Available from: https://www.who.int/reproductivehealth/publications/emtct-hiv-syphilis/en/