Alexander McMillan1, 2
(1)
Department of Genitourinary Medicine, NHS Lothian, Edinburgh Royal Infirmary, Edinburgh, Uk
(2)
University of Edinburgh, Edinburgh, Uk
Alexander McMillanFormerly, Consultant Physician, part-time Senior Lecturer
Email: a.amcmm@btinternet.com
Abstract
Infection of the fetus is more likely to occur when the mother’s infection is in the early stage, as at this time considerable numbers of treponemes are present in the circulation. During the first year of infection in an untreated woman there is an 80–90% probability that the infection will be transmitted to the fetus. The chance of fetal infection declines rapidly after the second year of infection in the mother and becomes rare after the fourth year. In general, the greater the duration of syphilis in the mother, the less chance there is of the fetus being affected. If a mother with early-stage syphilis is not treated, 25–30% of fetuses die in utero; 25–30% die after birth; and of the infected survivors 40% develop late symptomatic syphilis.
Charles’s wife (Case 19), who is 4 month’s pregnant joins her husband in the United Kingdom 1 week after he is diagnosed as having secondary syphilis. He tells her his diagnosis and persuades her to attend the Sexual Health clinic.
33.1 What Are the Risks of Untreated Early Syphilis in a Pregnant Woman?
Infection of the fetus is more likely to occur when the mother’s infection is in the early stage, as at this time considerable numbers of treponemes are present in the circulation. During the first year of infection in an untreated woman there is an 80–90% probability that the infection will be transmitted to the fetus. The chance of fetal infection declines rapidly after the second year of infection in the mother and becomes rare after the fourth year. In general, the greater the duration of syphilis in the mother, the less chance there is of the fetus being affected. If a mother with early-stage syphilis is not treated, 25–30% of fetuses die in utero; 25–30% die after birth; and of the infected survivors 40% develop late symptomatic syphilis.
Charles’s wife attends the clinic. She is symptomless, and in particular she has not noticed any genital lesions suggestive of infection. The pregnancy is progressing satisfactorily. There is no past history of syphilis. She has documented allergy to penicillin. Clinical examination confirms the absence of external genital ulceration, and lesions of the vagina or uterine cervix are not found. Serological tests for treponemal infection are performed and the results are shown in Table 33.1 .
Table 33.1.
Results of serological tests for syphilis at initial clinic attendance.
Screening anti-treponemal EIAa: POSITIVE |
Venereal Diseases Research Laboratory (VDRL) test: POSITIVE at a titer of 4 |
Treponema pallidum particle agglutination test (TPPA): POSITIVE at a titer of 2560 |
Anti-treponemal IgM EIAa: POSITIVE |
aEnzyme immunoassay.
An HIV antigen/antibody EIA is negative.
33.2 How Do You Interpret These Results?
These results confirm treponemal infection, and as she is a recent sexual contact of a man with secondary syphilis, the diagnosis of early-latent infection is made.
Note: The endemic treponematoses – yaws, pinta, and endemic syphilis (bejel) – that are transmissible by direct skin contact most commonly infect young children produce results in the serological tests fro syphilis that resemble those found in venereal syphilis. Yaws, caused by Treponema pallidum, subspecies pertenue, is found in tropical Africa. Endemic syphilis, caused by Treponema pallidum subspecies endemicum, occurs in the Arabian peninsula and along the southern border of the Sahara desert, and pinta, caused by Treponema carateum is found in scattered foci in northern South America. It may not be possible to differentiate the non-venereal treponematoses from venereal syphilis in individuals from geographical areas where these infections are prevalent, and in whom there are no clinical features of past or current infection. It is better to treat the person as if he or she had syphilis.
33.3 How Would You Treat This Patient?
Treatment of pregnant women with syphilis who are allergic to penicillin is difficult. The tetracyclines are contraindicated in pregnancy. Ceftriaxone has been used in the treatment of small numbers of patients with early syphilis with apparent success. However, there are concerns about cross-hypersensitivity with the penicillins (see Case 28). Treatment failures have been described following treatment with erythromycin. Although azithromycin has been used in the treatment of pregnant women with syphilis, efficacy is uncertain, and infection with strains of Treponema pallidum that are resistant to the macrolides is well documented. It is recommended that babies born to mothers who have been treated with the macrolides should be treated with penicillin after birth. For this reason, desensitization to penicillin is recommended followed by treatment with penicillin.
Charles’s wife is admitted to hospital for desensitizing to penicillin and is treated with benzathine penicillin thereafter. She is followed-up at monthly intervals with clinical examination and serological testing. Two weeks before delivery, the results of serological tests are shown in Table 33.2 .
Table 33.2.
Results of serological tests for syphilis before delivery.
Screening anti-treponemal enzyme immunoassay (EIA): POSITIVE |
Venereal Disease Research Laboratory (VDRL) test: NEGATIVE |
Treponema pallidum particle agglutination (TPPA) test: POSITIVE at a titer of 640 |
Anti-treponemal IgM EIA: NEGATIVE |
33.4 How Do You Interpret These Results, and How Would You Manage the Neonate?
These results are in keeping with adequately treated early syphilis (see Case 19). (A four-fold rise in VDRL titer would have been an indication for re-treatment). However, follow-up of the newborn child is recommended with clinical examination and the undertaking of serological tests to ensure that the child is uninfected.
The diagnosis of congenital syphilis can be difficult because most affected neonates are symptomless at birth. The screening EIA, the VDRL test, and the TPPA may be positive in the neonate’s blood in the absence of active infection. The IgG found in the serum of neonates is largely passively acquired through the placenta and does not represent the infant’s own response. A rising or higher titer in the neonate’s blood than in the mother is suggestive of infection; lower titers in neonates when compared to their mothers are suggestive of passively transferred antibody. In the absence of infection passively transferred antibody detected by the VDRL (or rapid plasma regain test [RPR]) will decrease and the tests will become negative in approximately 3 months. In the case of the treponemal antigen tests it may take up to 6 or 9 months for the test to become negative. The demonstration of anti-treponemal IgM in neonatal serum correlates well with congenital infection. Because of the possibility of a delayed IgM response or suppression of IgM synthesis in the neonate due to high levels of circulating maternal anti-treponemal IgG, IgM testing should be repeated after 4, 8, and 12 weeks.