Congenital syphilis: A continuing but neglected problem

doi:10.1016/j.siny.2007.01.019

Seminars in Fetal and Neonatal Medicine

Volume 12, Issue 3, June 2007, Pages 198-206

https://doi.org/10.1016/j.siny.2007.01.019 Get rights and content

Summary

Congenital syphilis was rare in most affluent countries but there has been a slight resurgence recently in several European countries. In large parts of the world and particularly sub-Saharan Africa congenital syphilis is a significant public health problem. The cornerstone of congenital syphilis control is antenatal screening and treatment of mothers with penicillin, which is a cost-effective intervention. In affluent countries it should be strengthened among those at high risk. Clinicians should be more vigilant for the possibility of babies being born with congenital syphilis, which is often asymptomatic. In developing countries not only does antenatal care screening need to be strengthened by implementing point-of-care decentralised screening and treatment but alternative innovative approaches to controlling congenital syphilis should be explored. There is an urgent need for international health agencies to support focused approaches to tackling the tragedy of continuing congenital syphilis. This could be a part of a pro-poor strategy to meet the Millennium Development Goals.

Introduction

In much of the world congenital syphilis continues to present a significant public health problem. Untreated syphilis among pregnant women can profoundly affect pregnancy outcome. Syphilis is neither a new disease nor a newly-recognised one and humans are the sole natural host.1, 2 Many of the basic facts and characteristics of congenital involvement have been described for well over 100 years.

With the advent of penicillin in the 1940s and the establishment of its effectiveness in treating syphilis, antenatal syphilis screening services were introduced as part of national programmes for controlling congenital syphilis.³ To a great extent these programmes were responsible for almost eliminating congenital syphilis in more affluent countries and, until recently, it was considered a disease of the past. In poorer areas of the world congenital syphilis has persisted.⁴

Although there have been marked advances in other biomedical fields the tools for the management and control of syphilis have changed little over the past 60 or so years.⁵ Recently more attention has been given to congenital syphilis and there are indications that this is beginning to lead to some concerted action to tackle syphilis and, in particular, congenital syphilis.⁶ This chapter will give an overview of the situation regarding congenital syphilis, recent developments and continuing challenges.

Section snippets

Congenital syphilis: epidemiology and burden of disease

Congenital syphilis in different regions of the world reflects that of syphilis more generally.⁵ The World Health Organisation (WHO) estimates that 12 million people are infected with syphilis each year and more than 90% of infections occur in developing countries.⁷

In Western Europe the disease became very uncommon until recently, largely through effective treatment at genitourinary clinics with efficient partner tracing and treatment. In North America syphilis rates have historically been

The organism—microbiology

Syphilis is caused by Treponema pallidum but little is known about its mechanism of action or what determines virulence of infection.¹ Treponemes are macroaerophilic gram-negative bacteria that are 6–20 μm long and 0.1–0.5 μm in diameter.² The genome was sequenced in 1998 and the outer membrane is mostly lipid and contains little protein creating challenges for the development of accurate diagnostic tests and effective vaccines.8, 41

Maternal syphilis

Frequently women infected with syphilis are unaware of this. The painless genital sores (or chancres) of primary syphilis often go unnoticed and many women do not seek care. This is followed several weeks or months later by widespread cutaneous, mucosal and sometimes systemic indications of the dissemination of the spirochetes of secondary syphilis. Syphilis is most contagious at this stage, which can last up to a year. Again treatment might not be sought nor be accessible and even without

Congenital syphilis—clinical features

The consequences of infection with syphilis on affected babies are profound. Congenital syphilis is a multiorgan infection that may cause neurological or skeletal disabilities or death in the fetus or newborn. However, when mothers with syphilis are treated early in pregnancy the disease is almost entirely preventable.⁴²

Spirochetes can cross the placenta and infect the fetus from about 14 weeks’ gestation, with the risk of fetal infection increasing with gestational age.⁴³ During the first 4

Laboratory confirmation of a diagnosis of syphilis

Unlike most other common bacterial infections, T. pallidum cannot be cultured sufficiently quickly or cheaply to assist diagnosis.¹Treponema pallidum is very difficult to visualise using light microscopy and requires darkfield microscopy. Consequently serological testing remains the mainstay of syphilis screening and diagnosis.⁵

There are two main types of serological tests for syphilis: the non-treponemal and the treponemal tests.⁴⁰ The two commonly used non-treponemal tests are the Venereal

Recent developments in syphilis diagnostic tests

Several developments in diagnostic tests for syphilis promise to make screening and diagnosis of syphilis infection in pregnant women easier in antenatal clinics, particularly in developing countries. New RPR reagents that are stable at room temperature and simple, rapid treponemal tests that do not require electricity or other equipment are now available with sensitivities, specificities and costs similar to those of the TPPA.49, 54

Further rapid syphilis tests are now available in the

Treatment of maternal syphilis

The introduction of penicillin and its use in the treatment of syphilis was a notable early success and has remained the preferred treatment for all types of syphilis since its first use for this indication by Mahoney in 1943. As Ingraham noted in 1951, ‘the value of penicillin in preventing the passage of syphilis from mother to child approaches perfection’, and this remains true.⁵⁸ Fortunately T. pallidum, unlike pathogens causing most other sexually transmitted infections (STIs), has not

Treatment of congenital syphilis

The treatment of congenital syphilis with penicillin was established on the basis of a case series as the standard shortly after its discovery.⁴⁰ WHO, CDC and the UK recommend that infants with confirmed or highly probable congenital syphilis are treated with systemic benzylpenicillin 100,000 to 150,000 IU/kg/day for 10 days.56, 60, 63 WHO and CDC recommend asymptomatic babies born to seropositive mothers are treated with a single dose of benzathine benzylpenicillin 50,000 IU/kg.

Two randomised

Clinical follow-up evaluation

It is important that all babies treated for confirmed or suspected congenital syphilis are followed up to ensure treatment was effective. In symptomatic infants given appropriate treatment, clinical features resolve within 3 months and serological markers, such as RPR and FTA-IgM, disappear by 6 months. Therefore, infants born to mothers with positive RPR tests should be followed for 6 months.⁴⁰ Ideally non-treponemal antibody serological testing should be checked at 1, 3, 6, 12 and 24 months

Potential for control in affluent countries—strengthening screening

The prevention of congenital syphilis has traditionally depended on screening women during pregnancy to identify those infected particularly with primary and secondary syphilis. This has been the cornerstone for the control of congenital syphilis in affluent countries.

With the re-emergence of congenital syphilis in European countries12, 13 there have been calls for strengthening antenatal screening for maternal syphilis. Pregnant women who do not attend antenatal care, those from minority

Antenatal screening for maternal syphilis and treatment in developing countries

While antenatal coverage in affluent countries is extremely high, the situation is different for women in the developing world.⁷² In sub-Saharan Africa, where many pregnant women are infected with syphilis, about 60% contact antenatal care but tend to do this late, often not presenting until the third trimester and many do not have blood taken.72, 73

Screening and single dose treatment with benzathine benzylpenicillin are clinically effective and the procedures are straightforward implying that

Discussion

As has been repeatedly stated it is not difficult technically to prevent congenital syphilis, but in many parts of the world this is not happening. In affluent countries with a very low but increasing prevalence of congenital syphilis antenatal screening is cost-effective and affordable. However, clinicians need to be more aware and vigilant about the possibility of congenital syphilis. Particular attention needs to be given to pregnant women in high-risk groups and especially those seeking

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