Annals of Tropical Paediatrics International Child Health
ISSN: 0272-4936 (Print) 1465-3281 (Online) Journal homepage: http://www.tandfonline.com/loi/ypch19
Serological tests in cerebrospinal fluid for congenital syphilis in Central Africa Dominique Gendrel, Charles Mefane, Martine Nardou, Jean-Luc Moreno, Edouard Engohan, Andre Moussavou & Celestin Nguemby-Mbina To cite this article: Dominique Gendrel, Charles Mefane, Martine Nardou, Jean-Luc Moreno, Edouard Engohan, Andre Moussavou & Celestin Nguemby-Mbina (1992) Serological tests in cerebrospinal fluid for congenital syphilis in Central Africa, Annals of Tropical Paediatrics, 12:3, 273-276, DOI: 10.1080/02724936.1992.11747584 To link to this article: http://dx.doi.org/10.1080/02724936.1992.11747584
Published online: 13 Jul 2016.
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Citing articles: 3 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ypch19 Download by: [Australian Catholic University]
Date: 18 August 2017, At: 10:34
Annals of Tropical Paediatrics (1992) 12,273-276
Serological tests in cerebrospinal fluid for congenital syphilis in Central Africa
Downloaded by [Australian Catholic University] at 10:34 18 August 2017
DOMINIQUE GENDREL, CHARLES MEFANE, MARTINE NARDOU, JEAN-LUC MORENO, EDOUARD ENGOHAN, ANDRE MOUSSAVOU & CELESTIN NGUEMBY -MBINA Faculte de Medec£ne, Libreville, Gabon (Received 4 September 1991)
Summary Serological tests were performed in the cerebrospinal fluid (CSF) of 13 children with active congenital syphilis (presence of specific lgM FTA-ABS antibodies) and of seven seropositive children with no active syphilis (FTA-ABS IgM-negative) born to syphilitic treated mothers in Libreville, Gabon. Antibodies against treponema were measured by the Venereal Disease Research Laboratory test (VDRL), the Treponema pallidum haemagglutination assay (TPHA) and the fluorescent treponema antibody absorption tests (FTA-ABS lgG and lgM). Of the 13 children with active syphilis, seven had a positive FTA-ABS lgG in the CSF. The result of this test was not correlated with the severity of clinical features, CSF protein levels or number of CSF white blood cells. The CSFTPHA test was positive in four out of 12 children, and the CSF-VDRL test was negative in all the children with active congenital syphilis. One of the seven newborns with mother-transmitted antibodies had a positive FTA-ABS and TPHA in the CSF. These data show that the VDRL is not sensitive enough to diagnose congenital neurosyphilis, and that FTA-ABS or, at least, TPHA are convenient, sometimes with false-positive results, when a sophisticated method of detecting specific lgM in CSF is not available.
Introduction Suspected congenital neurosyphilis poses a diagnostic and therapeutic problem in seropositive newborns. Positive cerebrospinal fluid (CSF) serological studies will result in the use of high doses of penicillin to obtain local treponemicid levels. 1- 5 The CSF of infants with suspected central nervous system involvement must be checked every 6 months. }-5 In developing countries where congenital syphilis is endemic, the systematic
Reprint requests to: Dr D. Gendre!, Departement de Pediatrie, Hopital St Vincent de Paul, 82 Av. Denfert-Rochereau, 75014 Paris, France.
follow-up of seroposltlve infants is often difficult and incomplete. Futhermore, the laboratory evaluation of newborns from seropositive mothers using discriminatory tests easy to perform in secondary hospitals should lead to the most appropriate treatment being selected. Cerebrospinal fluid tests should be performed in suspected newborns, and Centers for Disease Control guidelines recommend the Venereal Disease Research Laboratory test (VDRL) in CSF. 4 However, the CSFVDRL can remain falsely negative in infants or adults with neurosyphilis. 6' 7 The aim of this field study was to compare the results of different CSF serology tests in newborns suspected of having congenital syphilis.
274
D. Gendre/ et al.
TABLE I. Serological tests in CSF of 13 newborns with and seven newborns without congenital syphilis in Gabon Cerebrospinal fluid
Downloaded by [Australian Catholic University] at 10:34 18 August 2017
No.
Age Clinical (days) manifestations
Prot g/1
WBC/ VDRL
mm'
TPHA
(a) Active congenital syphilis (blood FTA-ABS lgM-positive) 1 20 Cut-muc+bo ND ND 0 0 2 8 Cut-muc+bo 0.32 5 0 + 4 Cut+hepat 0.68 35 3 0 0 12 ND 4 Cut+bo ND 0 ND 4 Cut+muc 0.25 5 0 0 5 15 Cut+bo ND ND 0 6 0 7 8 Cut ND ND 0 0 20 Cut ND ND 8 0 0 6 Cut+bo 0.7 12 0 9 0 10 23 Hepat 0.85 3 0 + 15 Hepat 11 0.62 2 0 + 45 Hepat 15 12 0.5 0 0 13 Hepat ND ND 0 0 13 (b) Suspected newborns without syphilis (blood FTA-ABS lgM-negative) 14 8 0 ND ND 0 0 15 10 0 ND ND 0 0 16 5 0 0.25 4 0 ± 15 0 ND ND 17 0 0 10 0 18 5 0 0 0.5 12 0 ND 19 ND 0 0 ND 10 0 20 ND 0 0
lgM FTA/ABS
lgG FTA/ABS
0 0 0 0 0 0 0 0 0 0 0 0 0
++ ++ ++ + + 0 0 0 0 + + 0 0
0 0 0 0 0 0 0
0 0 + 0 0 0 0
Cut: cutaneous; muc: mucosal; bo: bones; hepat: hepatitis.
Patients and methods VDRL, haemagglutination assay for antibody to Treponema pallidum (TPHA) and the fluorescent Treponema antibody absorption test (FT A-ABS) for lgM and lgG were performed in the serum and CSF of 20 African newborns suspected of having congenital syphilis. The group consisted of 12 boys and 8 girls aged from 4 to 45 days, born to Gabonese mothers living in Libreville. All maternal sera were TPHA-positive. None of the women had received appropriate penicillin treatment in the first half of their pregnancies; one (patient no. 16) was treated at the end of the 7th month. The rest received no treatment. No infant was premature and all birthweights were over 2500 g. CSF and blood were taken on the infant's day of admission to the paediatric unit. The FTAABS, the TPHA and the VDRL were performed on blood and undiluted CSF, using
the WHO guidelines8 and commercial reagents (lnstitut Pasteur, Paris). The possibility of blood contamination was avoided by excluding CSF with more than 100 red blood cells per mm 3 • Oral consent was obtained from the parents in all cases.
Results The results are given in Table I. Thirteen newborns had active congenital syphilis, with specific lgM (FT A-ABS) demonstrated in the serum. The clinical findings are listed in Table I. None of the infants had neurological signs or other clinical evidence of neurosyphilis. There were no bacteria in the CSF, and agglutination against pathogens involved in newborn meningitis was negative. The CSF-VDRL and the CSF FT A-ABS lgM were non-reactive
Downloaded by [Australian Catholic University] at 10:34 18 August 2017
CSF serology in congenital syphilis
in the CSF in all cases. The CSF FTA-ABS IgG was reactive in seven cases and the CSF TPHA in three cases. These findings were not related to the CSF white blood cells or protein levels or to the severity of the disease. All the infants whose mothers had been treated for syphilis during their pregnancy (nos. 14-20) were serum FTA-ABS IgMnegative but IgG-positive. None of them had clinical signs of congenital syphilis, the positive IgG serology being merely the result of transplacental diffusion of maternal antibody, passively transmitted by the mother. In patient 16 (the infant whose mother's syphilis had been treated adequately but late in pregnancy), the CSF TPHA was borderline and the CSF FTA-ABS IgG was positive.
Discussion The results of this study show that the CSF VDRL is not very sensitive in infants with suspected congenital neurosyphilis. The CSF FTA-ABS, which screens for specific IgG antibodies, is more frequently positive than the VDRL: in our series seven out of 13 and in McCracken's series 12 out of 16 were positive, 1 whereas in both series the CSFVDRL was negative. CSF-TPHA is less sensitive but, as it is easy to perform, it could be quite useful in developing countries. As in adult neurosyphilis, the CSF-VDRL shows high specificity but low sensitivity. In Davis's series of 15 adults with clinical signs of neurosyphilis, only four had a positive CSF-VDRL. 7 From where does the IgG present in the CSF originate? Is it the result of intrathecal synthesis, or does it diffuse passively into the CSF across the blood brain barrier? The question is not an academic one because meningeal involvement in congenital syphilis will necessitate more intensive treatment and prolonged follow-up. I-S Inflammatory CSF reactions are oflittle help because of the wide variations in normal CSF protein and leucocyte levels in infancy. Confirmed cases of neurosyphilis in both adults and infants in
275
whom normal CSF protein and WBC counts have been recorded are well known. !,6-9 In our series, only one child whose mother had been treated by penicillin during pregnancy had traces of specific IgG in the CSF. This may have arisen by passive diffusion of IgG across the blood brain barrier. However, intrathecal synthesis cannot be excluded as the mother was treated late in her pregnancy. Furthermore, Treponema have been found in the CSF of adults who have received appropriate therapy. 10 The only definitive test is the demonstration of local IgM production, but FTA-ABS IgM is not a very sensitive technique. Recently, Sanchez & McCracken have demonstrated, using a blotting test, that IgM immunoglobulins specific for certain antigenic fragments of Treponema were present in the CSF of four of six children with clinical and laboratory signs of congenital syphilis. However, this type of test is usually performed in research-orientated laboratories. 11 ' 12 In developing countries, such antibody demonstrations will need to be done using the simple techniques and equipment available in the majority of hospital laboratories there. The FTA-ABS for the presence of IgG is very sensitive, but unfortunately is expensive. The TPHA is easy to perform and can therefore be recommended for use in developing countries in blood or CSF. 8 Congenital syphilis is becoming a major public health problem in Africa. In Libreville, the number of pregnant women with a positive test for syphilis has increased over 10 years from 4% to 14%? A study in Lusaka showed that more than 20% of pregnant women were seropositive. 14 Also, screening of CSF is necessary in choosing the therapeutic regime. TPHA in cerebrospinal fluid could provide a useful compromise solution in developing countries. It might possibly demonstrate the presence of passively diffused antibodies, which would lead to unnecessarily high treatment doses of penicillin being given. However, it is obvious that there would be benefit for the infant, as congenital neurosyphilis is frequently present
276
D. Gendre/ et al.
and often latent. Until sensitive and specific tests become available for the diagnosis of neurosyphilis, all newborns with congenital syphilis are best treated for neurosyphilis also. 5
Downloaded by [Australian Catholic University] at 10:34 18 August 2017
References 1 McCracken GH Jr, Kaplan JM. Penicillin treatment for congenital syphilis. JAMA 1974; 228:855-8. 2 Speer ME, Mason EO, Schamberg JT. Cerebrospinal fluid concentrations of aqueous procaine penicillin G in the neonate. Pediatrics 1981; 67:387-8. 3 American Academy of Pediatrics Committee of Infectious Diseases, (Red Book), 1986; 346-52. 4 Centers for Disease Control. Sexually transmitted diseases treatment guidelines, 1989. MMWR, 1989; 38: No S-8. 5 Ikeda MK, Jenson HB. Evaluation and treatment of congenital syphilis. J Pediatr 1990; 117:843-52. 6 Jaffe HW, Kabins SA. Examination of cerebrospinal fluid in patients with syphilis. Rev Infect Dis 1982; 4 (Suppl):842-7.
7 Davis LE, Schmitt JW. Clinical significance of cerebrospinal fluid tests for neurosyphilis. Ann Neurol1989; 25:5G-5. 8 Luger A. Diagnostic de Ia syphilis. Bull WHO 1981; 59:647-54. 9 Mascola L, Pelosi R, Blount JH, Alexander CE, Cates W Jr. Congenital syphilis revisited. Am J Commun Dis 1985; 139:575-80. 10 Tramont EC. Persistence of Treponema pallidum following penicillin G therapy. JAMA 1976; 236: 2206-7. 11 Sanchez PJ, McCracken GH Jr, Wendel GD, Olsen K, Threlkeld N, Norgard MV. lgM antibody to Treponema pallidum in CSF of infants with congenital syphilis. ICAAC, Los Angeles; Oct 1988, Abstr 745. 12 Sanchez PJ, McCracken GH Jr, Wendel GD, Olsen K, Threlkeld N, Norgard MV. Molecular analysis of the fetal IgM response to Treponema pallidum antigens: implications for improved serodiagnosis of congenital syphilis. J Infect Dis 1989; 159:508-17. 13 Mefane C, Toung-Mve M. Syphilis chez Ia femme enceinte a Libreville (Gabon). Bull Soc Pathol Exot 1987; 80:162-70. 14 Watts TE, Larsen SA, Brown ST. A case-control study of stillbirths at a teaching hospital in Zambia, 1979-80: serological investigations for selected infectious agents. Bull WHO 1984; 62:803-8.
ISSN: 0272-4936 (Print) 1465-3281 (Online) Journal homepage: http://www.tandfonline.com/loi/ypch19
Serological tests in cerebrospinal fluid for congenital syphilis in Central Africa Dominique Gendrel, Charles Mefane, Martine Nardou, Jean-Luc Moreno, Edouard Engohan, Andre Moussavou & Celestin Nguemby-Mbina To cite this article: Dominique Gendrel, Charles Mefane, Martine Nardou, Jean-Luc Moreno, Edouard Engohan, Andre Moussavou & Celestin Nguemby-Mbina (1992) Serological tests in cerebrospinal fluid for congenital syphilis in Central Africa, Annals of Tropical Paediatrics, 12:3, 273-276, DOI: 10.1080/02724936.1992.11747584 To link to this article: http://dx.doi.org/10.1080/02724936.1992.11747584
Published online: 13 Jul 2016.
Submit your article to this journal
View related articles
Citing articles: 3 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ypch19 Download by: [Australian Catholic University]
Date: 18 August 2017, At: 10:34
Annals of Tropical Paediatrics (1992) 12,273-276
Serological tests in cerebrospinal fluid for congenital syphilis in Central Africa
Downloaded by [Australian Catholic University] at 10:34 18 August 2017
DOMINIQUE GENDREL, CHARLES MEFANE, MARTINE NARDOU, JEAN-LUC MORENO, EDOUARD ENGOHAN, ANDRE MOUSSAVOU & CELESTIN NGUEMBY -MBINA Faculte de Medec£ne, Libreville, Gabon (Received 4 September 1991)
Summary Serological tests were performed in the cerebrospinal fluid (CSF) of 13 children with active congenital syphilis (presence of specific lgM FTA-ABS antibodies) and of seven seropositive children with no active syphilis (FTA-ABS IgM-negative) born to syphilitic treated mothers in Libreville, Gabon. Antibodies against treponema were measured by the Venereal Disease Research Laboratory test (VDRL), the Treponema pallidum haemagglutination assay (TPHA) and the fluorescent treponema antibody absorption tests (FTA-ABS lgG and lgM). Of the 13 children with active syphilis, seven had a positive FTA-ABS lgG in the CSF. The result of this test was not correlated with the severity of clinical features, CSF protein levels or number of CSF white blood cells. The CSFTPHA test was positive in four out of 12 children, and the CSF-VDRL test was negative in all the children with active congenital syphilis. One of the seven newborns with mother-transmitted antibodies had a positive FTA-ABS and TPHA in the CSF. These data show that the VDRL is not sensitive enough to diagnose congenital neurosyphilis, and that FTA-ABS or, at least, TPHA are convenient, sometimes with false-positive results, when a sophisticated method of detecting specific lgM in CSF is not available.
Introduction Suspected congenital neurosyphilis poses a diagnostic and therapeutic problem in seropositive newborns. Positive cerebrospinal fluid (CSF) serological studies will result in the use of high doses of penicillin to obtain local treponemicid levels. 1- 5 The CSF of infants with suspected central nervous system involvement must be checked every 6 months. }-5 In developing countries where congenital syphilis is endemic, the systematic
Reprint requests to: Dr D. Gendre!, Departement de Pediatrie, Hopital St Vincent de Paul, 82 Av. Denfert-Rochereau, 75014 Paris, France.
follow-up of seroposltlve infants is often difficult and incomplete. Futhermore, the laboratory evaluation of newborns from seropositive mothers using discriminatory tests easy to perform in secondary hospitals should lead to the most appropriate treatment being selected. Cerebrospinal fluid tests should be performed in suspected newborns, and Centers for Disease Control guidelines recommend the Venereal Disease Research Laboratory test (VDRL) in CSF. 4 However, the CSFVDRL can remain falsely negative in infants or adults with neurosyphilis. 6' 7 The aim of this field study was to compare the results of different CSF serology tests in newborns suspected of having congenital syphilis.
274
D. Gendre/ et al.
TABLE I. Serological tests in CSF of 13 newborns with and seven newborns without congenital syphilis in Gabon Cerebrospinal fluid
Downloaded by [Australian Catholic University] at 10:34 18 August 2017
No.
Age Clinical (days) manifestations
Prot g/1
WBC/ VDRL
mm'
TPHA
(a) Active congenital syphilis (blood FTA-ABS lgM-positive) 1 20 Cut-muc+bo ND ND 0 0 2 8 Cut-muc+bo 0.32 5 0 + 4 Cut+hepat 0.68 35 3 0 0 12 ND 4 Cut+bo ND 0 ND 4 Cut+muc 0.25 5 0 0 5 15 Cut+bo ND ND 0 6 0 7 8 Cut ND ND 0 0 20 Cut ND ND 8 0 0 6 Cut+bo 0.7 12 0 9 0 10 23 Hepat 0.85 3 0 + 15 Hepat 11 0.62 2 0 + 45 Hepat 15 12 0.5 0 0 13 Hepat ND ND 0 0 13 (b) Suspected newborns without syphilis (blood FTA-ABS lgM-negative) 14 8 0 ND ND 0 0 15 10 0 ND ND 0 0 16 5 0 0.25 4 0 ± 15 0 ND ND 17 0 0 10 0 18 5 0 0 0.5 12 0 ND 19 ND 0 0 ND 10 0 20 ND 0 0
lgM FTA/ABS
lgG FTA/ABS
0 0 0 0 0 0 0 0 0 0 0 0 0
++ ++ ++ + + 0 0 0 0 + + 0 0
0 0 0 0 0 0 0
0 0 + 0 0 0 0
Cut: cutaneous; muc: mucosal; bo: bones; hepat: hepatitis.
Patients and methods VDRL, haemagglutination assay for antibody to Treponema pallidum (TPHA) and the fluorescent Treponema antibody absorption test (FT A-ABS) for lgM and lgG were performed in the serum and CSF of 20 African newborns suspected of having congenital syphilis. The group consisted of 12 boys and 8 girls aged from 4 to 45 days, born to Gabonese mothers living in Libreville. All maternal sera were TPHA-positive. None of the women had received appropriate penicillin treatment in the first half of their pregnancies; one (patient no. 16) was treated at the end of the 7th month. The rest received no treatment. No infant was premature and all birthweights were over 2500 g. CSF and blood were taken on the infant's day of admission to the paediatric unit. The FTAABS, the TPHA and the VDRL were performed on blood and undiluted CSF, using
the WHO guidelines8 and commercial reagents (lnstitut Pasteur, Paris). The possibility of blood contamination was avoided by excluding CSF with more than 100 red blood cells per mm 3 • Oral consent was obtained from the parents in all cases.
Results The results are given in Table I. Thirteen newborns had active congenital syphilis, with specific lgM (FT A-ABS) demonstrated in the serum. The clinical findings are listed in Table I. None of the infants had neurological signs or other clinical evidence of neurosyphilis. There were no bacteria in the CSF, and agglutination against pathogens involved in newborn meningitis was negative. The CSF-VDRL and the CSF FT A-ABS lgM were non-reactive
Downloaded by [Australian Catholic University] at 10:34 18 August 2017
CSF serology in congenital syphilis
in the CSF in all cases. The CSF FTA-ABS IgG was reactive in seven cases and the CSF TPHA in three cases. These findings were not related to the CSF white blood cells or protein levels or to the severity of the disease. All the infants whose mothers had been treated for syphilis during their pregnancy (nos. 14-20) were serum FTA-ABS IgMnegative but IgG-positive. None of them had clinical signs of congenital syphilis, the positive IgG serology being merely the result of transplacental diffusion of maternal antibody, passively transmitted by the mother. In patient 16 (the infant whose mother's syphilis had been treated adequately but late in pregnancy), the CSF TPHA was borderline and the CSF FTA-ABS IgG was positive.
Discussion The results of this study show that the CSF VDRL is not very sensitive in infants with suspected congenital neurosyphilis. The CSF FTA-ABS, which screens for specific IgG antibodies, is more frequently positive than the VDRL: in our series seven out of 13 and in McCracken's series 12 out of 16 were positive, 1 whereas in both series the CSFVDRL was negative. CSF-TPHA is less sensitive but, as it is easy to perform, it could be quite useful in developing countries. As in adult neurosyphilis, the CSF-VDRL shows high specificity but low sensitivity. In Davis's series of 15 adults with clinical signs of neurosyphilis, only four had a positive CSF-VDRL. 7 From where does the IgG present in the CSF originate? Is it the result of intrathecal synthesis, or does it diffuse passively into the CSF across the blood brain barrier? The question is not an academic one because meningeal involvement in congenital syphilis will necessitate more intensive treatment and prolonged follow-up. I-S Inflammatory CSF reactions are oflittle help because of the wide variations in normal CSF protein and leucocyte levels in infancy. Confirmed cases of neurosyphilis in both adults and infants in
275
whom normal CSF protein and WBC counts have been recorded are well known. !,6-9 In our series, only one child whose mother had been treated by penicillin during pregnancy had traces of specific IgG in the CSF. This may have arisen by passive diffusion of IgG across the blood brain barrier. However, intrathecal synthesis cannot be excluded as the mother was treated late in her pregnancy. Furthermore, Treponema have been found in the CSF of adults who have received appropriate therapy. 10 The only definitive test is the demonstration of local IgM production, but FTA-ABS IgM is not a very sensitive technique. Recently, Sanchez & McCracken have demonstrated, using a blotting test, that IgM immunoglobulins specific for certain antigenic fragments of Treponema were present in the CSF of four of six children with clinical and laboratory signs of congenital syphilis. However, this type of test is usually performed in research-orientated laboratories. 11 ' 12 In developing countries, such antibody demonstrations will need to be done using the simple techniques and equipment available in the majority of hospital laboratories there. The FTA-ABS for the presence of IgG is very sensitive, but unfortunately is expensive. The TPHA is easy to perform and can therefore be recommended for use in developing countries in blood or CSF. 8 Congenital syphilis is becoming a major public health problem in Africa. In Libreville, the number of pregnant women with a positive test for syphilis has increased over 10 years from 4% to 14%? A study in Lusaka showed that more than 20% of pregnant women were seropositive. 14 Also, screening of CSF is necessary in choosing the therapeutic regime. TPHA in cerebrospinal fluid could provide a useful compromise solution in developing countries. It might possibly demonstrate the presence of passively diffused antibodies, which would lead to unnecessarily high treatment doses of penicillin being given. However, it is obvious that there would be benefit for the infant, as congenital neurosyphilis is frequently present
276
D. Gendre/ et al.
and often latent. Until sensitive and specific tests become available for the diagnosis of neurosyphilis, all newborns with congenital syphilis are best treated for neurosyphilis also. 5
Downloaded by [Australian Catholic University] at 10:34 18 August 2017
References 1 McCracken GH Jr, Kaplan JM. Penicillin treatment for congenital syphilis. JAMA 1974; 228:855-8. 2 Speer ME, Mason EO, Schamberg JT. Cerebrospinal fluid concentrations of aqueous procaine penicillin G in the neonate. Pediatrics 1981; 67:387-8. 3 American Academy of Pediatrics Committee of Infectious Diseases, (Red Book), 1986; 346-52. 4 Centers for Disease Control. Sexually transmitted diseases treatment guidelines, 1989. MMWR, 1989; 38: No S-8. 5 Ikeda MK, Jenson HB. Evaluation and treatment of congenital syphilis. J Pediatr 1990; 117:843-52. 6 Jaffe HW, Kabins SA. Examination of cerebrospinal fluid in patients with syphilis. Rev Infect Dis 1982; 4 (Suppl):842-7.
7 Davis LE, Schmitt JW. Clinical significance of cerebrospinal fluid tests for neurosyphilis. Ann Neurol1989; 25:5G-5. 8 Luger A. Diagnostic de Ia syphilis. Bull WHO 1981; 59:647-54. 9 Mascola L, Pelosi R, Blount JH, Alexander CE, Cates W Jr. Congenital syphilis revisited. Am J Commun Dis 1985; 139:575-80. 10 Tramont EC. Persistence of Treponema pallidum following penicillin G therapy. JAMA 1976; 236: 2206-7. 11 Sanchez PJ, McCracken GH Jr, Wendel GD, Olsen K, Threlkeld N, Norgard MV. lgM antibody to Treponema pallidum in CSF of infants with congenital syphilis. ICAAC, Los Angeles; Oct 1988, Abstr 745. 12 Sanchez PJ, McCracken GH Jr, Wendel GD, Olsen K, Threlkeld N, Norgard MV. Molecular analysis of the fetal IgM response to Treponema pallidum antigens: implications for improved serodiagnosis of congenital syphilis. J Infect Dis 1989; 159:508-17. 13 Mefane C, Toung-Mve M. Syphilis chez Ia femme enceinte a Libreville (Gabon). Bull Soc Pathol Exot 1987; 80:162-70. 14 Watts TE, Larsen SA, Brown ST. A case-control study of stillbirths at a teaching hospital in Zambia, 1979-80: serological investigations for selected infectious agents. Bull WHO 1984; 62:803-8.
