Pediatrics International (2015) 57, 1112–1115

doi: 10.1111/ped.12663

Original Article

Recent change in congenital syphilis in Korea: Retrospective 10year study Sung-Han Kang,1 Ji-Hyun Lee,2 Sun-Hee Choi,2 Jin Lee,3 Hoi Soo Yoon,2 Sung-Ho Cha2 and Yong-Sung Choi2 1 Department of Pediatrics, Chungju Medical Center, Chungju, 2Department of Pediatrics, Kyung Hee University School of Medicine and 3Department of Pediatrics, Korea Electric Power Corporation (KEPCO) Hospital, Seoul, Korea Abstract

Background: This study was conducted to evaluate recent clinical and anthropologic features of neonates with reactive serology for syphilis and their mothers from three institutions in Korea over an 11-year-period. Method: The medical records of 20 neonates with reactive serology for syphilis and their mothers at three centers (Kyung Hee University Hospital, Kyung Hee University Hospital at Gangdong, and Korea Electric Power Corporation Hospital) seen between January 2000 and December 2010 were reviewed retrospectively. Results: Among 20 mothers, 16 (80%) were native Korean and four (20%) were foreign-born immigrants. Two mothers (10%) were unmarried. The annual distribution of cases was three (15%) in 2000, one each (5%) in 2005 and 2006, respectively, two each (10%) in 2007 and 2008, respectively, six (30%) in 2009, and five (25%) in 2010. Just over half (55%) occurred across 2009 and 2010. All neonates, by definition, were diagnosed with presumptive congenital syphilis (CS). Among the neonates, four had positive cerebrospinal fluid venereal disease research laboratory test, and three exhibited symptoms and signs. Conclusions: In three centers in Seoul, Korea, the observed number of CS cases was higher in 2009 and 2010 than in previous years. This finding is consistent with a trend toward increasing prevalence of international marriage and suggests that more meticulous screening of CS is needed.

Key words congenital syphilis, medical anthropology, serology. Untreated or inadequately treated pregnant women are a source of intrauterine Treponema pallidum (T. pallidum) infection. The transmission rate of primary syphilis in untreated mothers has been estimated to range from 70% to 100%1 and approximately 40% of these pregnancies will result in perinatal death including stillbirth, fetal loss, and neonatal death.2 The World Health Organization has estimated that the number of annual cases ranges from 728 000 to 1 528 000.3 Furthermore, according to recent data from the USA, there has been a rebound increase in the incidence of congenital syphilis (CS) from 8.2 cases per 100 000 live births in 2005 to 10.1 in 2008.4 Other Asian countries, such as China and Thailand, have also been experiencing rapid increase of both syphilis and CS during the past few years.5,6 The incidence and prevalence of CS observed in Korea has recently started to show a pattern similar to that observed in Western countries.7 Congenital syphilis has been included in the sentinel surveillance system in Korea since 2001. A total of 94 cases of CS have been reported between 2001 and 2010, but 40 cases were reported in the year 2011 alone.8 With the exception of several case reports, there have been no published studies on recent trends pertaining to CS in Korea. In the current study, features of neonates with CS and their mothers reported from 2000 to 2010 were examined. Correspondence: Yong-Sung Choi, MD, PhD, 23 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-872, Korea. Email: [email protected] Received 11 August 2014; revised 2 March 2015; accepted 9 April 2015. © 2015 Japan Pediatric Society

Methods A retrospective study was performed through a review of patient charts from January 2000 to December 2010 in Kyung Hee University Hospital, Kyung Hee University Hospital at Gangdong, and Korea Electric Power Corporation (KEPCO) Hospital. Infants positive for T. pallidum (T. pallidum hemagglutination assay [TPHA] or fluorescent treponemal antibody absorption [FTA-ABS IgM]) were eligible for participation in this study. Patient data on gestational age, birthweight, clinical manifestations, cerebrospinal fluid (CSF), radiology, and history of maternal treatment were analyzed. The medical records of each infant’s mother were also reviewed for nationality, marital status, laboratory findings, and history of treatment. For laboratory tests of syphilis, Kyung Hee University Hospital and Kyung Hee University Hospital at Gangdong used rapid plasma reagin (RPR) for the non-treponemal test while TPHA and FTA-ABS IgM were used for treponemal tests. KEPCO Hospital used the Veneral Disease Research Laboratory (VDRL) test for the non-treponemal test and TPHA for treponemal tests. Congenital syphilis was defined in accordance with guidelines published by the US Centers for Disease Control and Prevention (US CDC).4 CS was confirmed when T. pallidum was detected on darkfield microscopy, antibody fluorescence, or other specific stains in lesions, placenta, umbilical cord, or autopsy material specimens. Presumptive CS was defined as a condition affecting an infant whose mother was untreated or inadequately treated prior to delivery, regardless of signs in infants with a positive treponemal

Recent change in congenital syphilis 1113 test for syphilis; and any one of the following: (i) any evidence of CS on physical examination (condyloma lata, rhinitis, skin rash, hepatosplenomegaly, jaundice due to syphilis, pseudoparalysis, malnutrition, edema due to nephritis); (ii) any evidence of CS on radiography of long bones (osteitis); (iii) positive CSF VDRL; (iv) elevated CSF cell count or protein without other cause (>5/mm3 or CSF protein >40 mg/dL); (v) positive FTA-ABS 19S IgM antibody test (a treponemal test that detects a specific subunit of antitreponemal IgM) or positive FTA-ABS IgM ELISA. Treatment of mothers was classified according to the US CDC treatment guideline published in 2010.4 Mothers were considered treated when penicillin was given in a manner consistent with the stage of syphilis, provided that treatment was finished at least 30 days before delivery. Recommended and appropriate treatment for first and second stage syphilis is i.m. benzathine penicillin G administered as a single dose of 720 000 000 U. For late or unknown stages of syphilis, three doses of benzathine penicillin administered by i.m. injection are recommended and considered as appropriate treatment. Those receiving anything other than benzathine penicillin G or those not finishing treatment at least 30 days prior to delivery were considered to have received inappropriate treatment.

Results Infant clinical characteristics

Twenty infants had positive treponemal results and 10 (50%) were male. The mean gestational age of presumptive CS infants was 38.3 ± 4.8 weeks and the mean birthweight was 2942 ± 758 g. Three infants were born prematurely (gestational age < 37 weeks),

and four were considered low birthweight (birthweight < 1500 g). The mean 1 min and 5 min Apgar scores were 6.9 ± 1.4 and 8.5 ± 0.9, respectively, in 11 neonates. All infants were defined as having presumptive CS because they were all delivered from inappropriately treated mothers, and because direct identification of T. pallidum was negative. Three infants had clinical findings of CS. One had hepatosplenomegaly with jaundice; another had pneumonia with pleural effusion and radiologic findings of osteolysis in the tibia metaphysis; and the third had desquamation of fingers and toes with thrombocytopenia (Table 1). Positive CSF VDRL test was noted in four patients (Table 2). Maternal characteristics

All mothers were positive on prenatal VDRL or RPR screening tests for syphilis. The majority of mothers (n = 16; 80%) were Korean, while four (20%) were foreign born (Southeast Asian, n = 2; Chinese–Korean, n = 2). All fathers were Korean. On assessment of maternal treatment history for syphilis, half of the histories were documented and the other half were not clear because the infants were admitted apart from their mothers out of the hospitals (Table 3). Seven mothers (35%) were classified as inappropriately treated. Of these, six received benzathine penicillin G (3–4 times) and one was treated with erythromycin. The timing of treatment during pregnancy, however, was not clear and therefore it could not be determined whether it had been finished >30 days before delivery or not. Three mothers (15%) did not receive treatment for syphilis during pregnancy.

Table 1 Mothers with positive syphilis serology: Clinical characteristics Infants Non-treponemal test VDRL test 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Treponemal test

RPR

TPHA

Negative Negative Reactive Reactive Reactive Negative Reactive

Reactive Reactive Reactive Reactive Reactive Reactive Reactive Reactive Reactive Reactive Reactive Reactive Reactive Reactive Reactive Reactive Reactive Reactive Reactive Reactive

Negative Negative Reactive Negative Reactive Reactive Negative Reactive Reactive Negative Reactive Reactive Reactive

Symptoms

Maternal treatment status

Nationality

– – – – – – – – – – – +† – – –

Untreated Inadequate Inadequate Inadequate Not confirmed Inadequate Not confirmed Not confirmed Not confirmed Not confirmed Not confirmed Not confirmed Not confirmed Inadequate Inadequate Inadequate Not confirmed Not confirmed Untreated Untreated

Non-Korean Non-Korean Korean Korean Korean Korean Non-Korean Korean Korean Korean Korean Non-Korean Korean Korean Korean Korean Korean Korean Korean Korean

CSF VDRL

FTA-ABS IgM Negative Negative Negative Negative Negative Negative Negative

Negative Negative Negative Negative Negative Negative Reactive

Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Reactive Reactive Negative Negative Negative weakly Reactive Negative Negative Negative Reactive

– – +‡ +§



Hepatosplenomegaly;‡pneumonia with pleural effusion, abnormality in tibia X-ray;§desquamation on tips of fingers and toes, thrombocytopenia. CSF, cerebrospinal fluid; FTA-ABS, fluorescent treponemal antibody absorption; RPR, rapid plasma regain; TPHA, Treponema pallidum hemagglutination assay; VDRL, venereal disease research laboratory. © 2015 Japan Pediatric Society

1114 S-H Kang et al. 8

Table 2 Neonates with positive syphilis CSF serology

Positive VDRL test (n) WBC (/mm3), mean ± SD Protein (mg/dL), mean ± SD

4 26 ± 64 117 ± 62

CSF, cerebrospinal fluid; VDRL, venereal disease research laboratory; WBC, white blood cells. Table 3 Positive neonatal serology for syphilis: Maternal characteristics n (%) †

Maternal age (years), mean(±SD) Marital status Married Single Nationality Korean Foreign born‡ Positive non-treponemal test First trimester Second trimester Third trimester Positive treponemal test First trimester Second trimester Third trimester Treatment Adequately treated Inadequately treated Treatment undocumented Untreated

26.5 ± 6.2 (years) 18 (90) 2 (10) 16 (80) 4 (20) 10 (50) 5 1 4 6 (30) 2 2 2 0 (0) 7 (35) 10 (50) 3 (15)

n = 11. ‡Two mothers were from Southeast Asia and two were from China.



Annual incidence of positive treponemal infants

The annual distribution of the 20 cases was three (15%) in 2000, one each (5%) in 2005 and 2006, respectively, two each (10%) in 2007 and 2008, respectively, six (30%) in 2009, and five (25%) in 2010. Slightly more than half (55%) of the cases occurred in 2009 and 2010. Crude positive rate among total births was calculated in the three different districts to which each hospital belonged. Crude positive rate among total births was 0.020% in 2000, 0.010% in 2005, 0.009% in 2006, 0.019% in 2007, 0.019% in 2008, 0.060% in 2009, and 0.047% in 2010, suggestive of a recent trend toward rebound increase in the incidence of CS (Fig. 1).

Discussion Approximately 2 million pregnant women per year are identified as serologically positive to syphilis in the world, accounting for 1.5% of total pregnancies. Of these pregnancies, 692 000–1 527 600 neonates will be born with CS.9 In the USA, the incidence of syphilis has been gradually decreasing from a peak in 1989, but a rebound increase in incidence has been observed recently.10 In Korea, results from a single center report originating in Seoul indicated that maternal VDRL positivity had decreased from 2.8% in 1927 to 0.2% in 2005. The VDRL positivity of the general population has © 2015 Japan Pediatric Society

N cases

6

CSF

4 2 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Year

Fig. 1 Annual cases of neonates with positive syphilis serology. Positive rates from hospitals located in three different districts in Seoul showed a trend towards rebound increase.

also decreased gradually from 4.8% in 1972 to 0.2% in 2000.11–13 In 2007, however, the positivity increased up to 0.7%.11 Originally, only pediatricians in specifically designated hospitals were obligated to report cases of syphilis, because it had been included in the sentinel surveillance system in 2001, and this obligation was expanded to all medical centers in 2011.8 Therefore, the change in obligatory reporting practices could be considered a confounding factor regarding the observation of an increasing trend of syphilis and CS, due to the potential for missing cases prior to 2011. Nonetheless, the incidence of both syphilis and CS has obviously increased. According to the current study, CS in 2009 and 2010 accounted for 55% of total cases, suggesting that the incidence of syphilis and CS is increasing in Korea as in other Asian and Western developed countries. Additionally, according to Korean Centers for Disease Control, the incidence of first and second stage syphilis has increased since 2012 (2012, n = 562 199; 2013, n = 566 210; 2014, , n = 735 253). Such an increase of syphilis was followed by a rapid increase of CS during 2013–2014 (2013, n = 22; 2014, n = 31). Congenital syphilis, transmitted vertically, is closely related to the prevalence of the adult disease and the present results may reflect this relationship. Therefore, meticulous screening and aggressive treatment should be guaranteed. In the case of infants born to untreated mothers (three in the present study), thorough evaluation is needed immediately after birth, including CSF evaluation. If any part of the infant’s evaluation is abnormal, 10 day penicillin is required.4 Interestingly, it has been inferred that recent anthropological changes in Korea parallel the rebound increase in CS incidence. In the current study, four of 20 serologically positive mothers (20%) were foreign-born immigrants who subsequently married native Korean men. Two of these mothers were Southeast Asian, and two were Chinese–Korean. For centuries, Korea was a single ethnic group. Currently, the prevalence of international marriage is rising steeply. In 2000, international marriages accounted for only 3.5% of total marriages in Korea. By 2005, international marriages increased to up to 13.5% of total marriages in Korea, showing a rapid increase that has been maintained at up to 10.8% in 2009, suggesting that Korea is now a multiracial or multicultural country.14,15 According to the present study of CS in three different districts in Seoul, no cases were observed in 2001–2004, one case each was observed in 2005 and 2006, and two cases each were observed in 2007 and 2008. A sudden increase of up to six cases, however, was observed in 2009, and five cases were observed in

Recent change in congenital syphilis 1115 2010. Although a nationwide CS surveillance system was only completely established in 2011, according to a report from the Korea Center for Disease Control and Prevention, 40 and 26 cases of CS have been reported in 2011 and 2012, respectively, in Korea.16 Considering that 20% of the present infants with presumptive CS were born to immigrants, the increasing incidence could be related to the increasing prevalence of international marriage in Korea. Park et al. also reported that the incidence of CS had gradually increased from 2000 to 2007 and was more frequent in infants born to immigrant mothers.17 According to a multicultural family health care survey in 2009, 10.6% of families were not able to use medical institutions despite the need for medical care, due to high cost or difficulty in communication. Insufficient prenatal care and increased number of syphilis cases both have the potential to affect increases in CS.18 In addition to Korea, the USA and Europe have also experienced increases in CS during the last decade.19 Therefore, the Korean Ministry of Health should focus on more intense prenatal screening and proper health care. Limitations of the current study include its retrospective design and the review of patient medical records from three different hospitals, which may have introduced variation due to differences in laboratory facilities and availability of detailed medical records of mothers who had their infants transferred from other hospitals. In Korea, several case reports have been published, but, to the best of our knowledge, a multicenter study of CS and maternal clinical manifestations has not been reported. This report may be used as a baseline study for screening and following CS and syphilis control.

Acknowledgment The authors declare no conflict of interest.

References 1 Herremans T, Kortbeek L, Notermans DW. A review of diagnostic tests for congenital syphilis in newborns. Eur. J. Clin. Microbiol. Infect. Dis. 2010; 29: 495–501. 2 Gomez GB, Kamb ML, Newman LM, Mark J, Broutet N, Hawkes SJ. Untreated maternal syphilis and adverse outcomes of pregnancy: A systematic review and meta-analysis. Bull. World Health Organ. 2013; 91: 217–26.

3 Schmid GP, Stoner BP, Hawkes S, Broutet N. The need and plan for global elimination of congenital syphilis. Sex. Transm. Dis. 2007; 34: S5–10. 4 Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines, 2010. MMWR 2010; 59: 26–39. 5 Leeyaphan C, Jiamton S, Prasertworonun N, Maneeprasopchoke P, Omcharoen V. Clinical and epidemiological characteristics of patients with syphilis: 5 year-case study from Thailand. J. Med. Assoc. Thai. 2014; 97: 963–8. 6 Tucker JD, Chen XS, Peeling RW. Syphilis and social upheaval in China. N. Engl. J. Med. 2010; 362: 1658–61. 7 Kim HY, Kim BJ, Kim JH, Yoo BH. Early congenital syphilis presenting with skin eruption alone: A case report. Korean J. Pediatr. 2011; 54: 512–4. 8 KCDC. Infectious Disease Surveillance Yearbook, 2011. Publ. Health Wkly Rep. KCDC 2012; 5: 1–621. 9 Kamb ML, Newman LM, Riley PL et al. A road map for the global elimination of congenital syphilis. Obstet. Gynecol. Int. 2010; 2010: 1–6. 10 Patterson MJ, Davies HD. Syphilis. In: Kliegman RM, Stanton BF, St Geme JW, Schor NF, Behrma RE (eds). Nelson Textbook of Pediatrics. WB Saunders, Philadelphia, 2011; 1016–22. 11 Baek JO, Jee HJ, Kim TK, Kim HS, Lee MG. Recent trends of syphilis prevalence in normal population in Korea: A single center study in Seoul. Korean J. Dermatol. 2011; 49: 106–10. 12 Kim HS, Lee HS, Lee MG, Lee JB. Recent trends of syphilis prevalence in the normal population in Korea – 1995. Korean J. Dermatol. 1997; 35: 514–19. 13 Cho YH, Kim HO, Lee JB, Lee MG. Syphilis prevalence has rapidly decreased in South Korea. Sex. Transm. Infect. 2003; 79: 323–4. 14 Cho AJ. Findings from the marriage and family life on the multicultural families. Health-Welfare Policy Forum, Korea Institute for Health and Social Affairs 2010; 165: 19–35. 15 Lee JH, Hahn MH, Chung SH et al. Statistic observation of marriages, births, and children in multi-cultural families and policy perspectives in Korea. Korean J. Perinatol. 2012; 23: 76–86. 16 KCDC. Infectious Disease Surveillance Yearbook, 2012. Publ. Health Wkly Rep. KCDC 2013; 6: 1–580. 17 Park HO, Lim JW, Jin HS et al. Comparative study of newborns of Asian immigrant and Korean women. Korean J. Pediatr. 2009; 52: 1119–26. 18 Simms I, Ward H. Congenital syphilis in the United Kingdom. Sex. Transm. Infect. 2006; 82: 1. 19 Rodríguez-Cerdeira C, Silami-Lopes VG. Congenital syphilis in the 21st century. Actas Dermosifiliogr. 2012; 103: 679–93.

© 2015 Japan Pediatric Society

Recent change in congenital syphilis in Korea: Retrospective 10 year study.

This study was conducted to evaluate recent clinical and anthropologic features of neonates with reactive serology for syphilis and their mothers from...
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