Sónia Silva and colleagues1Silva S Henriques R Gomes JP Borrego MJ Afonso E Could we miss congenital neurosyphilis?.Lancet Infect Dis. 2012; 12: 816Summary Full Text Full Text PDF PubMed Scopus (6) Google Scholar describe a case of a Portuguese pregnant mother whose syphilis serology became positive during pregnancy. She was treated during the second trimester with 2·4 million IU of benzathine benzylpenicillin, given intramuscularly, three times at weekly intervals. The mother's serology became negative during treatment, but the newborn child was discovered to have neurosyphilis on the basis of clinical and sonographic findings, with treponemal sequences detected in the cerebrospinal fluid by PCR. The standard use of benzathine benzylpenicillin has been advocated for treatment of syphilis during pregnancy and is recommended in the local treatment protocol in Portugal, but reservations have been expressed about the use of this penicillin formulation.2Walker GJA Antibiotics for syphilis diagnosed during pregnancy.Cochrane Database Syst Rev. 2001; 3 (CD001143)PubMed Google Scholar Firstly, benzathine benzylpenicillin does not produce adequate treponemacidal concentrations of penicillin in the cerebrospinal fluid, hence the reluctance to treat neurosyphilis with this antibiotic; and secondly, when concurrent immunosuppression occurs, as in patients with HIV, syphilis is thought to resolve slowly, and even relapse, if the patient is given benzathine benzylpenicillin. The question arises as to whether the embryo or fetus is naturally in a state of immunosuppression. Certainly, when a baby is born, its cellular immunity to syphilis does not seem to be impaired,3Friedmann PS Cell-mediated immunological reactivity in neonates and infants with congenital syphilis.Clin Exp Immunol. 1977; 30: 271-276PubMed Google Scholar, 4Samson GR Beatty DW Malan AF Immune studies in infants with congenital syphilis.Clin Exp Immunol. 1990; 81: 315-318Crossref PubMed Scopus (7) Google Scholar by contrast with the cellular immunity of the placenta. Immune tolerance to paternal fetal antigens by the mother—and, inadvertently, to microbes by the placenta—depends on a reduction in T4-helper cells5Nahamias AJ Schollin J Abramowsky C Evolutionary and developmental perspectives in immune system of pregnant women, placenta and foetus, and responses to sexually transmitted infection.Ann NY Acad Sci. 2011; 1230: 25-47Crossref PubMed Scopus (23) Google Scholar (more Th2 than Th1), particularly by the peripheral regulatory T4 cells.6Williams Z Immune tolerance in pregnancy.N Engl J Med. 2012; 367: 1159-1161Crossref PubMed Scopus (86) Google Scholar Thus, in the case described by Silva and colleagues, the treponeme might not have been recognised as a foreign antigen and was allowed to cause damage to the placenta and subsequently infect the embryo. In fact, in about 70% of miscarriages associated with syphilis, syphilitic placental infection with severe restriction in fetal blood flow occurs. Therefore, the sensible option might be to restrict the use of benzathine benzylpenicillin in maternal syphilis to cases in which ultrasonic scans of the fetus and placenta are normal. One theory of how syphilis arrived in Europe is that it was imported during the Portuguese colonisation of Africa in the latter part of the 15th century. Perhaps a new neurotropic strain of Treponema pallidum is similarly being transported to Portugal from Portuguese-speaking African countries where syphilis is endemic and where a new strain could have arisen among the multiplicity of circulating treponemal strains.7Castro R Prieto E Aguas MJ Manata MJ Botas J Pereira FM Molecular subtyping of Treponema pallidum subsp. pallidum in Lisbon, Portugal.J Clin Microbiol. 2009; 47: 2510-2512Crossref PubMed Scopus (36) Google Scholar I declare that I have no conflicts of interest. Could we miss congenital neurosyphilis?Portugal has the highest incidence of congenital syphilis in Europe, and employs a screening protocol during pregnancy of serological testing in every trimester and in all newborn babies whose mothers were treated during pregnancy. Full-Text PDF Congenital neurosyphilis – Authors' replyWe agree with Fernandes and Medina-Acosta's comments regarding the lack of specificity of CNS imaging in neurosyphilis diagnosis. Nevertheless, our case study has an interesting feature: because the results of the baby's serological tests did not suggest congenital syphilis, if the neurological signs—probably due to traumatic subdural bleeding—that prompted the ultrasound had not been apparent, the diagnosis of neurosyphilis would have been missed. Therefore, we emphasise the importance of transfontanellar ultrasound, even when results show non-specific changes, to help to diagnose cases of neurosyphilis. Full-Text PDF