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were identifi ed. The three obstetric ultrasounds were described as normal.

The pregnant mother and her current partner are both white and have Portuguese nationality. She had several sexual partners (not identifi ed through this study), but no relation to Africa could be established. As the source of the infection remains unknown, the hypothetical and logical scenario described by Wright cannot be validated.

The maternal syphilis infection was successfully treated and no signs of reinfection were seen. However, T pallidum survived in the fetal cerebrospinal fl uid (CSF). Early CNS infection by T pallidum has been described, and some strains might have a greater propensity for neuroinvasion.3 Nevertheless, T pallidum molecular subtyping was not possible because of the small amount of DNA available in the CSF sample.

Penicillin is the most effi cient treatment for syphilis during pregnancy, preventing congenital disease in most cases. However, our case showed that benzathine benzylpenicillin did not treat the fetus. T pallidum might be able to survive in fetal CNS because of the poor penetration of the blood–brain barrier by benzathine benzylpenicillin.3,4

Considering potential causes of therapeutic failure, a careful assess-ment of therapeutic guidelines should be done. Further randomised clinical studies exploring diff erent penicillin regimens during pregnancy (investigating dose, treatment dur-ation, and formulations) will also be important. Maybe in the near future we will be able to systematically sequence the T pallidum genome from clinical isolates to identify putative neurotropic strains needing further research.We declare that we have no confl icts of interest.

*Sónia Silva, Raquel Henriques, Maria José Borrego, João Paulo Gomes, Eulália Afonsosoniasilva81@sapo.pt

possibility of secondary syphilis due to high spirochete load;5 and late treatment during pregnancy, when maternal pharmacokinetics are changed because of augmented renal blood fl ow and a larger volume of distribution for penicillin.6

We therefore disagree with the proposal of screening with trans-fontanellar ultrasound and lum bar puncture for T pallidum-specifi c PCR of every newborn baby from mothers given appropriate treatment. Treat-ment failure for syphilis should always be con sidered in mothers who undergo sero conversion during pregnancy and who are given treatment late. In these cases, babies who are negative according to non-treponemal tests should be rigorously followed up. In settings in which this follow-up is not possible, infants should be immediately investigated, with the inclusion of a cerebrospinal fl uid study by VDRL or rapid plasma reagin.We declare that we have no confl icts of interest.

*Regina Célia de Souza Campos Fernandes, Enrique Medina-Acostareg.fernandes@bol.com.br

Faculty of Medicine of Campos (RCdSCF), Municipal Program for the Surveillance of Sexually Transmitted Diseases and Acquired Immunodefi ciency Syndrome (RCdSCF), and Molecular Identifi cation and Diagnosis Unit (EM-A), Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, CEP 28013-602, Brazil

1 Silva S, Henriques R, Gomes JP, Borrego MJ, Afonso E. Could we miss congenital neurosyphilis? Lancet Infect Dis 2012; 12: 816.

2 Brazilian Ministry of Health. Diretrizes para o controle da sífi lis congênita. Brasília: Brazilian Ministry of Health, 2005.

3 Tagarro A, Garcia-Alix A, Alarcon A, Hernanz A, Quero J. Congenital syphilis: beta2-microglobulin in cerebrospinal fl uid and diagnosis of neurosyphilis in an aff ected newborn. J Perinat Med 2005; 33: 79–82.

4 Brazilian Ministry of Health. Boletim epidemiológico sífi lis 2012. Brasília: Brazilian Ministry of Health, 2012.

5 Rawstron SA, Bromberg K. Failure of recommended maternal therapy to prevent congenital syphilis. Sex Transm Dis 1991; 18: 102–06.

6 Alexander JM, Sheffi eld JS, Sanchez PJ, Mayfi eld J, Wendel GD Jr. Effi cacy of treatment for syphilis in pregnancy. Obstet Gynecol 1999; 93: 5–8.

Authors’ replyWe agree with Fernandes and Medina-Acosta’s comments regarding the lack of specifi city 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-specifi c changes, to help to diagnose cases of neurosyphilis. In this case, it led to additional examinations that confi rmed our neurosyphilis suspicion, and the baby was then treated accordingly.

Regarding the concerns of Fernandes and Medina-Acosta about IgM false-positives, the European Commission implementing decision (2012/506/EU) defi nes a laboratory-confi rmed case as any case in which a reactive non-treponemal test (eg, venereal disease research laboratory test, rapid plasma reagin) of the child’s serum occurs in addition to the detection of Treponema pallidum by one of the following: T pallidum-specifi c IgM (fl uorescent treponemal antibody– absorption test, enzymeimmuno assay); dark fi eld micro-scopy; or direct fl uorescent antibody test.1

We share Wright’s concerns about the possibility of syphilis treatment failure in the fetus, even when recommended treatment is given to the pregnant mother. In our case, the asymptomatic pregnant woman had syphilis seroconversion in the second trimester and was given three doses of benzathine benzylpenicillin at weekly intervals, although the Portuguese protocol recommends one dose only (at 2·4 million IU).2 Maternal HIV serologies were negative and no other signs of immunosuppression

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1 Hamers RL, Schuurman R, Sigaloff KCE, et al, for the PharmAccess African Studies to Evaluate Resistance (PASER) Investigators. Eff ect of pretreatment HIV-1 drug resistance on immunological, virological, and drug-resistance outcomes of fi rst-line antiretroviral treatment in sub-Saharan Africa: a multicentre cohort study. Lancet Infect Dis 2012;12: 307–17.

2 Lynen L, Fransen K, Van Griensven J, Colebunders R. Pretreatment HIV-1 drug resistance testing in sub-Saharan Africa. Lancet Infect Dis 2012; 12: 911.

3 Roberts T, Bygrave H, Fajardo E, Ford N. Challenges and opportunities for the implementation of virological testing in resource-limited settings. J Int AIDS Soc; 15: 17324.

4 Hamers RL, Sawyer AW, Tuohy M, Stevens WS, Rinke de Wit TF, Hill AM. Cost-eff ectiveness of laboratory monitoring for management of HIV treatment in sub-Saharan Africa: a model-based analysis. AIDS 2012; 26: 1663–72.

5 Sigaloff KC, Hamers RL, Wallis CL, et al. Unnecessary antiretroviral treatment switches and accumulation of HIV resistance mutations; two arguments for viral load monitoring in Africa. J Acquir Immune Defi c Syndr 2011; 58: 23–31.

6 Nichols BE, Sigaloff KC, Kityo C, et al. Benefi ts of early antiretroviral treatment initiation outweigh risk of transmitted HIV drug resistance: a modelling study of two east African settings. 20th Conference on Retroviruses and Opportunistic Infections; March 3–6, 2013; Atlanta, GA. Abstr 1116.

7 Phillips AN, Pillay D, Garnett G, et al. Eff ect on transmission of HIV-1 resistance of timing of implementation of viral load monitoring to determine switches from fi rst to second-line antiretroviral regimens in resource-limited settings. AIDS 2011; 25: 843–50.

8 Gupta RK, Jordan MR, Sultan BJ, et al. Global trends in antiretroviral resistance in treatment-naive individuals with HIV after rollout of antiretroviral treatment in resource-limited settings: a global collaborative study and meta-regression analysis. Lancet 2012, 380: 1250–58.

test ing and alternative fi rst-line regimens. Accurate ident ifi cation of virological failure will preserve drug options by avoiding the incremental cost of unnecessary switches and reducing drug-resistance accumulation.4,5 Moreover, mathematical models predict that access to viral-load monitoring and second-line regimens might mitigate transmitted drug resistance.6,7 A shift to protease inhibitors in fi rst-line ART is regarded as a last resort by many experts, since this would have major programmatic implications, increase drug cost, and restrict options for constructing eff ective second-line regimens. Routine pretreatment drug-resistance testing is not feasible for most ART programmes because of restricted resources and laboratory capacity.

As levels of transmitted drug resistance increase in east and southern Africa,8 we argue that improved functioning of national HIV treatment programmes will be crucial to preserve the long-term eff ectiveness of available ART regimens. Functioning would be improved by an uninterrupted drug supply, optimised patient adherence and retention, and access to viral-load monitoring.We declare that we have no confl icts of interest.

*Raph L Hamers, Cissy Kityo, Kim C E Sigaloff , Tobias F Rinke de Witr.hamers@aighd.org

PharmAccess Foundation, Department of Global Health, Amsterdam Institute for Global Health and Development, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands (RLH, KCES, TFdW); and Joint Clinical Research Centre, Kampala, Uganda (CK)

Neonatal Intensive Care Unit, Coimbra University Hospitals, 3000–075 Coimbra, Portugal (SS, RH, EA); and National Health Institute Doutor Ricardo Jorge, Lisbon, Portugal (MJB, JPG)

1 European Commission. Commission implementing decision 2012/506/EU of 8 August 2012. Offi cial Journal of the European Union 2012; L262: 1–57.

2 Secção de Neonatologia da Sociedade Portuguesa de Pediatria. Sífi lis. In: Protocolos de diagnóstico e terapêutica em infecciologia perinatal. Porto: Angelini Farmacêutica; 2007; 29–33.

3 Stamm LV. Global challenge of antibiotic-resistant Treponema pallidum. Antimicrob Agents Chemother 2010; 54: 583–89.

4 Walker GJA. Antibiotics for syphilis diagnosed during pregnancy. Cochrane Database Syst Rev 2001; 3: CD001143.

Pretreatment HIV-1 drug resistance in AfricaWe recently showed that pretreat-ment antiretroviral resistance more than doubled the risk of virological failure and further acquisition of drug-resistance mutations in patients receiving standard fi rst-line antiretroviral therapy (ART) from a large sub-Saharan African cohort of people infected with HIV.1 Debate about what the public health response should be to high levels of pretreatment resistance in any given setting is ongoing, and a level at which a policy change would be appropriate has not yet been defi ned.

We agree with Lutgarde Lynen and colleagues2 that viral-load monitoring seems to be the most feasible option to manage emerging pretreatment anti-retroviral resistance as simple, low-cost technologies become available,3 rather than investment in pretreatment drug-resistance