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5 Tucker JD, Chen XS, Peeling RW. Syphilis and social upheaval in China. N Engl J Med 2010; 362: 165861.

6 Lin CC, Gao X, Chen XS, Chen Q, Cohen MS. Chinas syphilis epidemic: a systematic review of seroprevalence studies. Sex Transm Dis 2006; 33: 72636.

7 Xinhua. China off ers free pre-marital medical check. http://www.chinadaily.com.cn/english/doc/2004-12/18/content_401393.htm (accessed Feb 7, 2012).

8 Xinhua. Shanghai: one-stop services signifi cantly increase the Voluntary pre-marital medical check-up rate. http://www.gov.cn/fwxx/jk/2008-12/04/content_1167916.htm (accessed Feb 7, 2012).

9 China Ministry of Health: notice of the Ministry of Health on issuing National Program for Prevention and Control of Syphilis in China (2010-2020). http://www.gov.cn/gzdt/2010-06/21/content_1632301.htm (accessed Feb 7, 2012).

for a comprehensive programme for prevention and elimination of congenital syphilis in the country. The Chinese Ministry of Health has already issued a 10-year plan for syphilis control and prevention, including elimination of congenital syphilis by 2020, in which integration of syphilis screening into voluntary premarital check-ups has been highlighted.9 More evidence needs to be collected and reviewed to show the benefi ts of present premarital syphilis screening practice for prevention of congenital syphilis in China.We declare that we have no confl icts of interest.

Xiang-Sheng Chen, Yue-Ping Yinchenxs@ncstdlc.org

National Center for STD Control and Chinese Academy of Medical Sciences Institute of Dermatology, 12 Jiangwangmiao Street, Nanjing 210042, China

1 Hawkes S, Matin N, Broutet N, Low N. Eff ectiveness of interventions to improve screening for syphilis in pregnancy: a systematic review and meta-analysis. Lancet Infect Dis 2011; 11: 684-91.

2 Standing Committee of the National Peoples Congress of China. Law of the Peoples Republic of China on Maternal and Infant Health Care. http://www.gov.cn/banshi/2005-08/01/content_18943.htm (accessed Feb 7, 2012).

3 China Ministry of Health. Chinas Health Statistical Yearbook 2008. Beijing: Peking Union Medical College Press, 2009: 20608.

4 State Council of the peoples Republic of China. Regulations Governing Marriage Registration. http://www.gov.cn/banshi/2005-08/21/content_25042.htm (accessed Feb 7, 2012).

screening. During the same period of time (20022009), an increase in the incidence of congenital syphilis was noted according to the national surveillance system (fi gure).5

Eff ective prevention of congenital syphilis depends on the identifi cation and treatment of syphilis in mothers before or during pregnancy. A higher prevalence of syphilis in prospective couples than pregnant women,6 and poor maternal care-seeking behaviours as shown by the absence or delay in maternal care has challenged the eff ectiveness of congenital syphilis interventions only during pregnancy. There has been a long debate on the reintroduction of premarital screening on a compulsory basis. Concerning the feasibility of reintroducing mandatory testing in China, exploration of the ways to ensure that screening is acceptable and aff ordable will be important. A free confi dential syphilis screening programme has been implemented in many areas in China, with encouraging results.7 Additionally, a model of one-stop servicesa similar strategy to provider-initiated testing and counsellinghas been introduced in some areas.8 The consensus that China has an expanding syphilis epidemic has already served as a call

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Figure: National rate of premarital health check-ups and national reported incidence of congenital syphilis cases in China

Authors replyWe are pleased to say that WHO and its partners are already taking the task-force approach to dealing with congenital syphilis, as suggested by Damian Walker and Godfrey Walker. We have established a global network of institutions and academics that are committed to tackling this health injustice. WHOs programme of work includes the development of a 5 year investment case for elimination of congenital syphilis and support to regional and national initiatives, particularly in areas with a high burden of disease. Our systematic review,1 which is part of the evidence base that supports the investment case, goes beyond listing what works by quantifying the eff ectiveness of interventions to prevent congenital syphilis and syphilis-associated neo-natal outcomes. At the moment all that is absent are funds to implement our proposed, evidence-informed activities.

We therefore welcome the arrival of Damian Walker to the Bill and Melinda Gates Foundation. We hope that he has more success in raising the profi le of congenital syphilis within the foun-dation than we have had in our several unsuccessful attempts to se cure funding from this important donor.

Xiang-Sheng Chen and Yue-Ping Yin link an increase in congenital syphilis

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measure of eff ect size. Therefore, based on the following simple correction formula given by Zhang and Yu,3 we estimated RR (95% CI) from OR (95% CI) with the data provided by authors in their report:

where P0 is the incidence of outcome of interest in the reference group.

Incidence of death (n=26) or any sequelae (serious neurological defi cit in fi ve patients and deafness in three) in patients in the reference group who had pneumococcal meningitis and who were given cefotaxime bolus with oral placebo (n=53) was 064 (ie, 34/53). With these values of OR 018 and P0 064, the RR was 038 (95% CI 006189). A much wider 95% CI crossing the null hypothesis value of 1 suggests that infusion of cefotaxime for the fi rst 24 h has no statistical superiority over bolus administration in the pneumococcal meningitis subgroup on intention-to-treat analysis. On the contrary, our analysis showed an absolute risk increase (ARI) of 164% (95% CI 1801 to 2035) in the outcome of mortality or any sequelae in patients given cefotaxime infusion with placebo (death in 16 patients, serious neurological sequelae in fi ve, and deafness in four: total 25/38) versus cefotaxime bolus with placebo (total 34/53) in the subgroup of patients with pneumococcal meningitis. Again, the 95% CI shows wide sampling variability in the outcome of combined mortality or any sequelae, with the interval crossing the null value of no diff erence. Additionally, the univariate OR of 107 (95% CI 045258) calculated by us (25/13 divided by 34/19) for the above outcome contradicts the authors conclusion about pneumococcal meningitis.

Finally, high-end dosing of oral paracetamol is also not consistent with recent evidence that favours

Organization, Geneva, Switzerland (NB); and Division of Clinical Epidemiology and Biostatistics, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland (NL)

1 Hawkes S, Matin N, Broutet N, Low N. Eff ectiveness of interventions to improve screening for syphilis in pregnancy: a systematic review and meta-analysis. Lancet Infect Dis 2011; 11: 68491.

2 Alswaidi FM, OBrien SJ. Premarital screening programmes for haemoglobinopathies, HIV and hepatitis viruses: review and factors aff ecting their success. J Med Screen 2009; 16: 2228.

3 Eng TR, Butler WT, eds. Prevention and control of sexually transmitted diseases. Washington DC: Institute of Medicine, National Academy Press, 1997.

4 UNAIDS. Global plan towards the elimination of new HIV infections among children by 2015 and keeping their mothers alive. UNAIDS, 2011. http://www.unaids.org/en/media/unaids/contentassets/documents/unaidspublication/2011/20110609_JC2137_Global-Plan-Elimination-HIV-Children_en.pdf (accessed Feb 3, 2012).

5 Kamb ML, Newman LM, Riley PL, et al. A road map for the global elimination of congenital syphilis. Obstet Gynecol Int 2010; published online July 14. DOI:10.1155/2010/312798.

reports in China to a reduction in the uptake of premarital syphilis screening. The ways in which other behavioural, health services, policy, and structural factors might have contributed to the recent resurgence in syphilis in China would be interesting to know. Premarital screening programmes are promoted by states (at national or subnational levels) for the prevention and con trol of several disorders, including the hereditary haemoglobinopathies (thalassaemia and sickle cell anaemia) and some infectious diseases such as syphilis, HIV, and hepatitis B and C.2 Evidence for the eff ectiveness of this approach for controlling congenital syphilis is mixed. A review3 by the US Institute of Medicine in 1997 reported that premarital syphilis screening was not likely to be cost eff ective and would have little eff ect on public health. By contrast, syphilis screening in pregnancy was reported to be cost-saving.3 We agree with Chen and Yin that more evidence is needed on the feasibility, acceptability, and cost eff ectiveness of this approach.

We note the success of the global movement to eliminate mother-to-child transmission of HIV,4 and hope that our Article goes some way to highlighting the similarities with the equally burdensome5 issue of mother-to-child transmission of syphilisa neglected and, at present, under-funded health problem. Screening (and treatment) of pregnant women for HIV or syphilis should not be a zero-sum game: both infections deserve to be prevented among future generations. NB is a staff member of WHO. She alone is responsible for the views expressed in this publication and they do not necessarily represent the decisions, policy or views of WHO. We declare that we have no confl icts of interest.

*Sarah Hawkes, Nathalie Broutet, Nicola Lows.hawkes@ucl.ac.uk

Institute of Global Health, University College London, London, UK (SH); Department of Reproductive Health Research, World Health

Antibiotics by bolus or infusion for bacterial meningitis? Tuula Pelkonen and colleagues1 investigated the superiority of infusion over bolus administration of cefotaxime in the management of acute bacterial meningitis. The reported subgroup analysis outcome of death or any sequelae (ie, severe neurological impairment or deafness) was statistically lower with infusion of cefotaxime (n=38) than its bolus administration (n=53) in children with pneumococcal meningitis in an intention-to-treat analysis (odds ratio [OR] 018; 95% CI 003090; p=004). However, the use of OR in this scenario comes with a caveat: the high incidence of the primary outcome in the study groups over infl ates the true treatment eff ect.2 In any prospective cohort study or trial in which the incidence of the primary endpoint exceeds 10%, the outcome eff ect is overestimated by the OR, particularly if the OR is more than 25 or less than 05.3 In this regard, relative risk (RR) outweighs OR as a statistically better

RR= OR(1 P0) + (P0 OR)

Syphilis: still a major cause of infant mortalityReferences