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Despite availability of simpler serologic tests for syphilis and near cure with penicillin, unacceptably high prevalence of infectious maternal syphilis exist in many developing countries, including Zambia. It is the foremost risk factor for mid-trimester abortions, stillbirths, prematurity and morbidity and mortality among infants born with congenital syphilis in Zambia. An intervention project was conducted in Lusaka aimed at demonstrating the effectiveness of new health education methods and prenatal screening for syphilis in reducing the adverse outcomes during pregnancy. During pre-intervention phase, approximately 150 consecutive pregnant women from each of the three study and the three control centres were recruited when they presented in labour at the University Teaching Hospital. The intervention phase lasted for one year at the three study centres during which new methods of health education were introduced to improve early attendances during pregnancy. Also, on-site syphilis screening was performed twice during pregnancy and seroreactive women, and in many cases their sexual partners, were treated by the existing prenatal clinic staff. During the post-intervention phase the steps of pre-intervention phase were repeated to evaluate the impact of intervention. Overall, 8.0% of women were confirmed seroreactive for syphilis; there was no difference between the study and the control centres (p greater than 0.05). Fifty seven percent (132/230) of syphilitic pregnancies ended with an adverse outcome, that is, abortion (RR 5.0), stillbirth (RR 3.6), prematurity (RR 2.6) and low birth weight (RR 7.8). The overall risk of adverse outcomes due to syphilis was 8.29 (95% confidence interval 6.53, 10.53). The new methods of health education were effective and the percentage of women who had their first prenatal visit under 16 weeks of gestation improved from 9.4 to 42.5. Although screening and treatment during intervention was suboptimal, the adverse outcomes attributable to syphilis were reduced to 28.3%; this is almost a two-third reduction when compared with 72.4% of adverse outcomes at control centres (p < less than 0.001). The intervention is culturally and politically acceptable in Zambia. The cost of each prenatal screening is US$0.60 and of averting each adverse outcome US$12. In countries with high rates of syphilis, there is an urgent need for STD control and Maternal and Child Health (MCH) programmes to pool their resources together to revitalise the prenatal care.

Objectives: Reported cases of congenital syphilis in the Russian Federation increased 26-fold from 1991–9. Our objectives were to describe the frequency, risk factors, and consequences of delivering an infant with congenital syphilis among pregnant women with active syphilis.

Methods: In a retrospective record review using consecutive sampling of logs at maternity hospitals in five geographic areas, data were abstracted for 850 women with active syphilis during pregnancy who had completed ≥20 weeks' gestation. Further information was abstracted from records in antenatal clinics, dermatovenereology clinics, and paediatric hospitals. We assessed the frequency of confirmed or probable congenital syphilis, used logistic modelling to identify independent predictors for delivering a baby with congenital syphilis, and calculated the proportion of infants with congenital syphilis who experienced late fetal death (20–27 weeks), stillbirth (≥28 weeks), or infant death.

Results: A total of 64% (n=544) of 850 pregnant syphilis infected women delivered an infant with confirmed or probable congenital syphilis; 40% of the sample had no prenatal care. Among women with no prenatal care, 77% received either no treatment or inadequate treatment and 86% delivered an infant with congenital syphilis. Important independent and modifiable risk factors for delivery of an infant with congenital syphilis included receiving no prenatal care (adjusted OR 2.8, 95% CI 1.7 to 4.7) and having the first test for syphilis at ≥28 weeks' gestation (adjusted OR 4.0, 95% CI 2.6 to 6.0). Fatal outcomes were observed in 26% of infants with congenital syphilis, including late fetal death (7%), stillbirth (16%), or neonatal death (3%).

Conclusions: In the Russian Federation, the frequency of congenital syphilis is high, risk factors for congenital syphilis are modifiable, and the consequences of congenital syphilis are severe.

Between 1983 and 1987, 62 out of 76519 pregnancies in 51 mothers had a positive miniaturised Treponema pallidum haemagglutination assay (TPHA) test--1 in 1234, or 0.81 per 1000 births. About two thirds of these mothers had syphilis and the remainder non-venereal treponematoses such as yaws or pinta. Antenatal screening identified 13 patients with previously unknown acquired syphilis, 11 of whom were given antibiotics during pregnancy. There were six fetal losses among the 62 TPHA positive pregnancies, but none had evidence of congenital syphilis. No live born child in this study group showed stigmata of congenital syphilis. It is concluded that despite the current low incidence of syphilis in the United Kingdom it is imperative to continue antenatal serological screening and to emphasise the importance of early adequate treatment of the infection.

Seven cases of early congenital syphilis have been recorded in the past 10 years in the Mersey Regional Health Authority. Antenatal serology was initially negative in five mothers, who were either incubating or acquired the infection later, and treatment had probably failed in two women given erythromycin for syphilis during pregnancy. Serology should be repeated later in pregnancy in those at high risk. Social factors that define this group include women who book for antenatal care late in pregnancy, have a past history of sexually transmitted disease, and have multiple consorts. Clinical signs in the infant such as failure to thrive, hepatosplenomegaly, symmetrical rash, rhinitis, and osteochondritis should alert the clinician to the possibility of congenital syphilis. Adequate management of mother and baby requires close liaison between the genitourinary physician, microbiologist, obstetrician, and paediatrician. Penicillin remains the treatment of choice.

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Because of the high incidence of congenital syphilis at the University Teaching Hospital, Lusaka, Zambia, the potential risks of congenital infection and fetal loss due to syphilis were assessed by screening 202 antenatal patients, 340 pregnant women admitted to the hospital whose pregnancies ended in either spontaneous abortion or stillbirth, and 469 consecutive babies delivered at the hospital. Primary serological screening was performed with the rapid plasma reagin test, and reactive sera were confirmed by the Treponema pallidum haemagglutination test. In all cases detailed histories were obtained and patients were examined for clinical signs of syphilis. The TPHA test result was reactive in 12.5% of antenatal patients and in 42% of women who aborted in the later half of pregnancy. Among 469 consecutive babies delivered at the hospital, 30 had reactive results to the TPHA test; of these two were stillborn and four had signs of congenital syphilis at birth. Thus, syphilis appears to affect adversely an appreciably high number of pregnant women in Zambia. For this reason a special campaign to screen adequately and treat pregnant women and neonates is needed.

Routine serologic tests for syphilis (as required by California law governing prenatal examination) and penicillin therapy during pregnancy for infected mothers have been major factors in the prevention of congenital syphilis in California during the past ten years. In 1940 one of each 822 infants had the disease, as indicated by morbidity reports of congenital syphilis in infants under the age of one year. In 1950 the ratio was one in 8,148. To determine why congenital syphilis continues to occur, a study of the 134 cases reported over a two-year period was made with the cooperation of local health officers and practicing physicians. It showed that in 76 per cent of cases the mother did not consult a physician prior to delivery or reported so late in pregnancy that the infant was born before adequate penicillin therapy could be given. In another 15 per cent syphilis developed in the mother during pregnancy after a negative reaction to a prenatal serologic test. The other 9 per cent of cases were due to various factors, such as infectious relapse or reinfection in previously adequately treated mothers. The study indicated that most cases occur in the lower socioeconomic population groups. Seventy-four per cent of cases were in infants delivered in county hospitals.

Syphilis can seriously complicate pregnancy and result in spontaneous abortion, stillbirth, non-immune hydrops, intrauterine growth restriction, and perinatal death, as well as serious sequelae in liveborn infected children. While appropriate treatment of pregnant women often prevents such complications, the major deterrent has been inability to identify the infected women and get them to undergo treatment. Screening in the first trimester with non-treponemal tests such as rapid plasma reagin (RPR) or venereal disease research laboratory (VDRL) test combined with confirmation of reactive individuals with treponemal tests such as the fluorescent treponemal antibody absorption (FTA-ABS) assay is a cost effective strategy. Those at risk should be retested in the third trimester. Treatment during pregnancy should be with penicillin. In determining a penicillin regimen, the clinician must consider the stage of the maternal infection and the HIV status of the mother. Patients who are allergic to penicillin should be desensitised before treatment. Despite appropriate treatment, as many as 14% will have a fetal death or deliver infected infants. Treatment may further be complicated by the Jarich–Herxheimer reaction, a complex allergic response to antigens released from dead micro-organisms, which can cause fetal distress and uterine contractions. Thanks to effective intervention strategies and inexpensive penicillin, syphilis rarely complicates pregnancy in the Western world today. In parts of the world where the traditional sexually transmitted diseases have not been controlled, the magnitude of problems associated with syphilis during pregnancy is reminiscent of that faced by the West during the early 1900s.

Key Words: syphilis; pregnancy

BACKGROUND: Although congenital syphilis usually occurs as a result of a failure to detect and treat syphilis in pregnant women, failures of the currently recommended regimen to prevent congenital syphilis have been reported. CASE: This report describes an infant with congenital syphilis despite maternal treatment with a regimen exceeding current CDC guidelines. CONCLUSION: Regardless of the regimen used to treat syphilis during pregnancy, clinicians should recognize the possibility of occasional treatment failures and the importance of adequate follow-up of infants at risk for congenital syphilis.

Congenital syphilis is the oldest recognized congenital infection, and continues to account for extensive global perinatal morbidity and mortality today. Serious adverse pregnancy outcomes caused by maternal syphilis infection are prevented with screening early in pregnancy and prompt treatment of women testing positive. Intramuscular penicillin, an inexpensive antibiotic on the essential medicine list of nations all over the world, effectively cures infection and prevents congenital syphilis. In fact, at a cost of $11–15 per disability adjusted life year (DALY) averted, maternal syphilis screening and treatment is among the most cost-effective public health interventions in existence. Yet implementation of this basic public health intervention is sporadic in countries with highest congenital syphilis burden. We discuss the global burden of this devastating disease, current progress and ongoing challenges for its elimination in countries with highest prevalence, and next steps in ensuring a world free of preventable perinatal deaths caused by syphilis.

BACKGROUND--IgG antibodies from mothers adequately treated for syphilis can cross the placenta and appear in the sera of healthy newborns without infection. In such infants, a false diagnosis of congenital syphilis is often made. We have designed a retrospective survey to determine the time of seroreversion of the serological tests for syphilis (STS) in uninfected newborns born to mothers who were adequately treated for syphilis. MATERIALS AND METHODS--Fifty two seropositive, untreated newborns born to 51 mothers treated for syphilis were studied. The newborns were followed at 1, 3, 6, 9, and 12 months of age until seroreversion was detected. The VDRL test was followed until 12 months in 12 of the 22 newborns who were positive at birth, the TPHA in 21 of the 46 newborns, and the FTA-ABS test in 22 of the 48 newborns. RESULTS--In the first serological tests done within 1 month after birth, the VDRL was positive in 22 newborns (42%), the TPHA in 46 (88%), and FTA-ABS in 48 (92%). The VDRL seroreverted within 6 months after birth in 84%, and within 1 year in 100%. The TPHA test seroreverted in 95% within 1 year after birth. The FTA-ABS test seroreverted in 100% within 1 year after birth. CONCLUSIONS--In most seropositive, untreated newborns born to treated mothers the VDRL became negative within 6 months after birth and the TPHA and FTA-ABS within 1 year. This result is consistent with current Centers for Disease Control (CDC) guidelines. However, although the CDC guidelines are adequate in general, we think that some revision is desirable concerning the IgM test and combination of the test results in order to rule out congenital syphilis in seropositive, nonsymptomatic newborns born to the treated mothers.

In six cases of congenital syphilis in newborn at Los Angeles County-USC Medical Center over a seven-month period the clinical findings fell into two categories related to the time of onset of symptoms. Infants ill in the nursery presented evidence of transplacental infection; infants who became ill later showed the “classic” findings of rash, rhinorrhea and pseudoparalysis.

No single clinical symptom was present in all cases but all symptomatic infants had radiographic evidence of bone disease. Respiratory distress was present at the onset of symptoms in three of four infants with neonatal disease, and all three had evidence of interstitial pneumonia in chest radiographs.

Serologic testing may be difficult to evaluate in the newborn period, but more recent and specific tests are helpful in diagnosis. Penicillin remains the drug of choice. The only death occurred at five hours of life in a premature infant. Growth and development in surviving infants appeared normal.

Experiments were performed to further elaborate on our congenital syphilis rabbit model. Attempts were made to determine whether in utero exposure to Treponema pallidum would stimulate immune reactivity and whether this activity would, in turn, affect lesion development upon challenge infection. Newborn rabbits aged 2 or 5 weeks were obtained from control does or from does infected intravenously with T. pallidum during pregnancy. Congenitally infected newborns exhibited increased immunologic functions. Concanavalin A-induced T-lymphocyte proliferation was elevated at both 2 and 5 weeks. In addition, macrophage Ia expression and RPR antibody titers were increased at 5 weeks. In separate experiments, newborn rabbits from control does or from does infected during pregnancy were challenged intradermally with viable organisms at either 2 or 5 weeks of age. Subsequent lesion severity was markedly increased in those newborns previously exposed to treponemes in utero. These observations further strengthen our model for congenital transmission of T. pallidum during pregnancy. We propose that at least some of the tissue pathology in syphilitic infection is associated with activated host defenses.

During 1982-5 the 19S (IgM) fluorescent treponemal antibody absorption (19S (IgM) FTA-ABS) test gave positive results in 19 children. The parental histories were analysed. As five of the children were adopted, 14 pregnancies were evaluated. Mothers of foreign origin and extramarital pregnancies were found to be over-represented. Of 13 women who attended for pregnancy checkup, three were not serologically screened for syphilis. In four the infection had developed late in the course of pregnancy. In at least four treatment had not been given or had been inadequate or too late. At least two had positive 19S (IgM) FTA-ABS test results that did not indicate congenital syphilis. The possibility of false positive 19S (IgM) FTA-ABS test results is pointed out. As the male sexual partners of four of the 14 mothers had presented elsewhere with early syphilis at the time of their partner's pregnancy, adequate contact tracing appears to be important to prevent congenital syphilis in future.

Syphilis is a sexually transmitted disease with protean manifestations resulting from infection by Treponema pallidum. It is systemic early from the outset, the primary pathology being vasculitis. Acquired syphilis can be divided into primary, secondary, latent, and tertiary stages. The infection can also be transmitted vertically resulting in congenital syphilis, and occasionally by blood transfusion and non-sexual contact. Diagnosis is mainly by dark field microscopy in early syphilis and by serological tests. The management in the tropics depends on the diagnostic facilities available: in resource poor countries, primary syphilis is managed syndromically as for anogenital ulcer. The introduction of rapid "desktop" serological tests may simplify and promote widespread screening for syphilis. The mainstay of treatment is with long acting penicillin. Syphilis promotes the transmission of HIV and both infections can simulate and interact with each other. Treponemes may persist despite effective treatment and may have a role in reactivation in immunosuppressed patients. Partner notification, health education, and screening in high risk populations and pregnant women to prevent congenital syphilis are essential aspects in controlling the infection.

Female LSH hamsters infected with Treponema pallidum subsp, endemicum before pregnancy or during early pregnancy transmit a form of syphilis to the fetus that is similar to human congenital syphilis. The offspring develops rhinitis, skin rash, failure to thrive, and hepatosplenomegaly. T. pallidum is detectable in their livers, spleens, and nasal secretions. Immunoglobulin M antibodies are detected in the serum.

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Acute primary maternal infection with rubella virus during pregnancy often, but not invariably, leads to the congenital rubella syndrome. Diagnosis by detection of virus specific IgM in the mother is not always possible, and in those cases in which IgM is detected the fetus has not necessarily also been infected. A method for direct, prenatal detection of fetal infection would allow more accurate early diagnosis of congenital rubella syndrome. In this study a case of suspected preconception rubella infection that was not referred until 14 weeks after the appearance of a rash was studied to determine whether a retrospective serological diagnosis of primary rubella could be made, and whether direct evidence of fetal infection could be obtained from a chorionic villus biopsy specimen by detecting virus specific antigens or ribonucleic acid (RNA) sequences. Monoclonal antibodies and a cloned complementary deoxyribonucleic acid probe were used successfully to detect antigens to rubella virus antigens and RNA sequences in the chorionic villus biopsy specimen, which was taken at 15 weeks' gestation. This method should serve as a new approach to the diagnosis of congenital rubella syndrome in utero.

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Background

Globally syphilis is an important yet preventable cause of stillbirth, neonatal mortality and morbidity.

Objectives

This review sought to estimate the effect of detection and treatment of active syphilis in pregnancy with at least 2.4MU benzathine penicillin (or equivalent) on syphilis-related stillbirths and neonatal mortality.

Methods

We conducted a systematic literature review of multiple databases to identify relevant studies. Data were abstracted into standardised tables and the quality of evidence was assessed using adapted GRADE criteria. Where appropriate, meta-analyses were undertaken.

Results

Moderate quality evidence (3 studies) supports a reduction in the incidence of clinical congenital syphilis of 97% (95% c.i 93 – 98%) with detection and treatment of women with active syphilis in pregnancy with at least 2.4MU penicillin. The results of meta-analyses suggest that treatment with penicillin is associated with an 82% reduction in stillbirth (95% c.i. 67 – 90%) (8 studies), a 64% reduction in preterm delivery (95% c.i. 53 – 73%) (7 studies) and an 80% reduction in neonatal deaths (95% c.i. 68 – 87%) (5 studies). Although these effect estimates were large and remarkably consistent across studies, few of the studies adjusted for potential confounding factors and thus the overall quality of the evidence was considered low. However, given these large observed effects and a clear biological mechanism for effectiveness the GRADE recommendation is strong.

Conclusion

Detection and appropriate, timely penicillin treatment is a highly effective intervention to reduce adverse syphilis-related pregnancy outcomes. More research is required to identify the most cost-effective strategies for achieving maximum coverage of screening for all pregnant women, and access to treatment if required.

Although congenital syphilis is a rare disease in Canada, infected infants may experience severe sequelae, including cerebral palsy, hydrocephalus, sensorineural hearing loss and musculoskeletal deformity. Timely treatment of congenital syphilis during pregnancy may prevent all of the above sequelae. However, the diagnosis of suspected cases and management of congenital syphilis may be confusing, and the potential for severe disability is high when cases are missed. The present review provides assistance to practitioners in the diagnosis of suspected cases and management of children with presumed or confirmed infection.

In a survey of 283 deliveries in Swaziland, active syphilis (positive results in the Treponema pallidum haemagglutination assay (TPHA) and the rapid plasma reagin (RPR) test) was found in 37 (13.1%) and possibly active infection (positive TPHA but negative RPR test results) in a further 87 (30.7%). The perinatal mortality of untreated mothers with active disease was 21.9% (7/32). The RPR test carried out antenatally by nurses had a sensitivity of 36% (13/36) and predictive accuracy of 48% (13/27). Awareness of this incidence of syphilis led to improved antenatal clinic measures and the prophylactic treatment of all newborn infants. More comprehensive serology is discussed and the prophylactic treatment of mothers considered. The need for health education aiming at safer sexual practices is of paramount importance in a society facing the arrival of the human immunodeficiency virus.

Congenital syphilis occurs when Treponema pallidum crosses the placenta during pregnancy or from contact with an infectious genital lesion during delivery. Cutaneous manifestations of congenital syphilis are relatively common, occurring in approximately 30% to 70% of patients. Maculopapular lesions, vesiculobullous lesions, condylomata lata lesions, annular lesions, and erythema multiforme-like targetoid lesions have been reported. We report on a premature newborn with congenital syphilis who presented with generalized bullous and pustular eruption and desquamation at birth.

Syphilis remains a serious cause of neonatal morbidity and mortality worldwide. In this paper, we describe a case of congenital syphilis that was fully supported by abnormal fetal heart rate patterns and placental histopathological evidence. A 24-year-old para 4 woman, who did not attend antenatal care, was admitted to our hospital with a complaint of abdominal discomfort at an estimated 31-week gestation. Fetal heart rate monitoring showed prolonged bradycardia. A neonate weighting 1,423 g with severe birth asphyxia was immediately delivered by cesarean section. Following delivery, the mother and the neonate were diagnosed with syphilis. Histopathological examination confirmed severe chorioamnionitis and necrotizing funisitis with numerous Treponema pallidum. Conclusions. Challenges in establishing the diagnosis of necrotizing funisitis are essential for optimal management of a fetus with a systemic inflammatory response in utero.

We have developed a model for congenital syphilis in the rabbit. This report provides additional information on newborn tissue pathology in animals that were infected in utero. A total of 35 pregnancies were evaluated, each containing 6 to 12 newborns. In the infected group, the mortality was approximately 50%; of the live newborns, half appeared normal and half were hyperreflexic, weak, and runty. Gross pathology in the sickly newborns was quite prevalent and involved enlarged spleens with isolated spots of necrosis; enlarged livers that were overtly congested and hemorrhagic and had numerous granular, white spots; and brains with hemorrhage in the occipital area. Histopathology was apparent in different tissues. Lymphocytes, plasma cells, and vacuolated macrophages were prominent in livers, spleens, brains, and bones. A few actively motile treponemes were visualized by dark-field microscopy within extracts of spleen and within cerebrospinal fluid. Low numbers of treponemes were also demonstrated in sections of brain and liver by using the Warthin-Starry silver stain technique. Blood hematocrits were decreased, and extramedullary hematopoiesis was prominent within spleens and livers; this is consistent with anemia. This rabbit model exhibits many of the same pathologic features commonly found in human congenital syphilis.

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Objective: The purpose of this study was to assess the effect of several maternal variables on the serologic response following the treatment of syphilis in pregnancy.

Methods: A 5-year chart review identified 95 patients coded with syphilis at Hermann Hospital. Inclusion criteria were 1) serologically confirmed syphilis infection during the index pregnancy, 2) complete treatment during the index pregnancy, and 3) minimum of one follow-up rapid plasma reagin (RPR) titer. Forty-nine of 95 patients met the inclusion criteria. Treatment response was evaluated by comparing each post-treatment titer of a patient to her pretreatment titer. Each comparison was considered an “observation.” Each observation was classified as either a positive response (≥4-fold titer decline) or a negative response (<4-fold titer decline). Maternal variables assessed included 1) prior history of syphilis untreated or incompletely treated prior to the index pregnancy, 2) gestational age, 3) titer level, 4) unknown duration, 5) positive response at 1 month, 6) positive response at 2 months, 7) positive response at >3 months, and 8) race.

Results: A positive response following treatment was significantly more likely if there was no prior history of syphilis or if there was a high initial RPR titer (>32). Only 33/54 (61%) observations at or greater than 3 months had a positive response.

Conclusions: Our study suggests that an absence of a history of syphilis and an initial high RPR titer are predictive of a positive response following appropriate treatment. Given the low percentage of observations with a positive response at 3 months, we speculate that we may be undertreating our pregnant patients with syphilis infection.

IgM-FTA tests have been carried out on 209 sera from 169 patients with treated or untreated syphilis at various stages and on 128 sera from 109 patients, born in areas where yaws is or was prevalent, with treated or untreated latent treponemal disease. IgM anti-treponemal antibody was found in virtually all cases of untreated early or early latent syphilis but in only 23 per cent. of sera from patients with untreated late latent syphilis. After treatment the antibody usually disappeared within one year, but it persisted in a minority of patients, including some treated for late symptomatic or congenital syphilis. Except in isolated cases there was no clinical evidence to suggest continued disease activity, although a third of the patient in whom the antibody persisted for more than 2 years after treatment were noted to be homosexuals. The test may assist in differentiating untreated early latent from late latent syphilis.

To determine the prevalence of cerebrospinal fluid abnormalities in Southeast Asian refugees with reactive serologic tests for syphilis, we evaluated 65 patients, 36 prospectively and 29 retrospectively, in a primary care clinic. Information was collected on history of treponemal infections, neurologic symptoms and signs, and total protein concentration, leukocyte count, and the VDRL test in the cerebrospinal fluid. Neurologic symptoms were reported by all patients for whom data were available. Abnormal neurologic signs were found or noted in medical records in 15 (42%) prospectively evaluated patients and 9 (64%) of 14 retrospectively evaluated patients for whom data were available. No patient had evidence of congenital or non-neurologic sequelae such as cutaneous or cardiovascular manifestations of syphilis. No patient had a positive cerebrospinal fluid VDRL test, 1 had more than 5 x 10(6) leukocytes per liter (5 leukocytes per mm3), and 6 (9%) had elevated total protein levels in the cerebrospinal fluid. Previous therapy for syphilis was not associated with lower serum VDRL reactions, neurologic symptoms and signs, or cerebrospinal fluid findings. In the absence of other indications, routine examination of the cerebrospinal fluid in seropositive Southeast Asian refugees who have nonspecific neurologic symptoms has a low yield, perhaps because of the high prevalence of yaws in this population, and may not be warranted.