Rapid antibody responses after challenge with oral polio vaccine provide evidence for poliovirus-specific memory immunity in seronegative elderly people. However, in contrast to preexisting immunity, memory immunity does not protect against virus excretion. These results have important implications for the poliomyelitis-eradication initiative, in particular for future immunization policies after eradication has been achieved.

ObjeCtiveTo determine the accuracy of non-invasive fetal testing for the RHD gene in week 27 of pregnancy as part of an antenatal screening programme to restrict anti-D immunoglobulin use to women carrying a child positive for RHD. DesignProspectively monitoring of fetal RHD testing accuracy compared with serological cord blood typing on introduction of the test. Fetal RHD testing was performed with a duplex real time quantitative polymerase chain reaction, with cell-free fetal DNA isolated from 1 mL of maternal plasma The study period was between 4 July 2011 and 7 October 2012. The proportion of women participating in screening was determined.setting Nationwide screening programme, the Netherlands. Tests are performed in a centralised setting.PartiCiPants 25 789 RhD negative pregnant women. Main OutCOMe MeasuresSensitivity, specificity, false negative rate, and false positive rate of fetal RHD testing compared with serological cord blood typing; proportion of technical failures; and compliance to the screening programme. resultsA fetal RHD test result and serological cord blood result were available for 25 789 pregnancies. Sensitivity for detection of fetal RHD was 99.94% (95% confidence interval 99.89% to 99.97%) and specificity was 97.74% (97.43% to 98.02%). Nine false negative results for fetal RHD testing were registered (0.03%, 95% confidence interval 0.01% to 0.06%). In two cases these were due to technical failures. False positive fetal RHD testing results were registered for 225 samples (0.87%, 0.76% to 0.99%). Weak RhD expression was shown in 22 of these cases, justifying anti-D immunoglobulin use. The negative and positive predictive values were 99.91% (95% confidence interval 99.82% to 99.95%) and 98.60% (98.40% to 98.77%), respectively. More than 98% of the women participated in the screening programme. COnClusiOnsFetal RHD testing in week 27 of pregnancy as part of a national antenatal screening programme is highly reliable and can be used to target both antenatal and postnatal anti-D immunoglobulin use.

Despite a vaccination coverage rate of 97%, several poliomyelitis outbreaks occurred in the Netherlands during the last three decades, all among sociogeographically clustered, unvaccinated persons. Therefore, to eradicate polio, insight into poliomyelitis immunity is particularly useful. In 1995-1996, the authors conducted a population-based study and determined neutralizing antibodies against poliovirus types 1, 2, and 3 in 9,274 sera from the general population and from religious groups rejecting vaccination. In the general population, the antibody prevalence (>/=1:8) was 96.6% (95% confidence interval (CI): 95.9, 97.2), 93.4% (95% CI: 92.3, 94.5), and 89.7% (95% CI: 88.3, 91.0) for poliovirus types 1, 2, and 3, respectively. Antibodies persisted for long periods in persons with natural immunity as well as in persons whose immunity was induced by inactivated polio vaccine. In Orthodox Reformed persons, the antibody prevalence of poliovirus types 1, 2, and 3 was 65.0% (95% CI: 57.2, 72.9), 59.0% (95% CI: 40.1, 77.9), and 68.7% (95% CI: 65.2, 72.2), respectively. The recent outbreaks clearly affected the seroprevalence profiles of Orthodox Reformed groups but not the general population. At present, there is an insufficient social and political basis for mandatory vaccination; therefore, global eradication of poliovirus seems to be the only way to protect these Orthodox Reformed persons against future poliomyelitis outbreaks.

1 report the results of a long-term, multicenter, randomized trial comparing fludarabine with chlorambucil in previously untreated patients with advanced chronic lymphocytic leukemia (CLL). In their study the treatments were repeated monthly for a maximum of 12 cycles unless patients had progressive disease, a complete remission, or a response that plateaued over two months of treatment. The hematologic toxicity of fludarabine is well established, and most prior studies have reported that fludarabine can be given for a maximum of six cycles. [2][3][4][5] In our experience, we have not been able to administer more than eight cycles of fludarabine therapy because of severe and prolonged myelosuppression. Rai et al. have not stated how many patients were able to receive 12 cycles of fludarabine, the median number of cycles of fludarabine administered, or the median number of courses of fludarabine needed to induce a complete remission. To the Editor: Rai et al. conclude that older patients with medical problems in addition to CLL should receive palliative treatment with chlorambucil and that fludarabine should be used in patients who can tolerate a more toxic treatment. Though this approach makes sense, the evidence underlying the decision is not presented. We believe that data concerning the rates of response and adverse effects stratified according to age would be invaluable to clinicians whose aim is to achieve the best risk-benefit ratio for their patients with CLL.Hacettepe University 06100 Ankara, TurkeyTo the Editor: The trial by Rai and colleagues demonstrates that fludarabine yields a higher rate of response as well as longer progression-free survival than chlorambucil in patients with CLL. However, the choice of therapy should also be considered from a health-policy perspective. Fludarabine is expensive; in Italy, a 40-mg dose of chlorambucil costs $8, whereas a 40-mg dose of fludarabine costs $296. In addition, fludarabine must be administered intravenously, and the cost for this procedure is $250 per day (charge based on diagnosis-related group code 473).We performed an economic comparison of fludarabine and chlorambucil as first-line therapy for CLL from the perspective of the Italian health care system. Using a Markov model, we followed the transition of treated patients from diagnosis (remission) to progression and death, according to the curves shown in the article by Rai et al. We calculated the incremental cost-effectiveness ratio of fludarabine as compared with chlorambucil by dividing the additional cost incurred by patients treated with fludarabine by theThe New England Journal of Medicine Downloaded from nejm.org on May 11, 2018. For personal use only. No other uses without permission.

In the Netherlands, since 1 July 2011, both antenatal anti‐D immunoprophylaxis (1000 IU in the 30th week of gestation) and postnatal prophylaxis (1000 IU) is administered to only those women for whom a fetal RHD typing, performed in week 27 of pregnancy, predicts the presence of a D‐positive child. The fetal RHD screening is part of the antenatal Screening Programme for Infectious diseases and Erythrocyte immunisation (PSIE), offered to all pregnant women early in pregnancy at their first antenatal visit, preferably before 12 weeks of gestation. Currently, the compliance to the fetal RHD screening programme and the performance of the fetal RHD typing test is evaluated in a nation‐wide study. At the start of the programme, it was determined that the number of false negative test results should be below 0·25%. In the first seven months after introduction of the fetal RHD screening programme, the number of false‐negative results was below the critical threshold and the number of false positives around 1·1%. The compliance to the programme was in this period >95%. Our first analysis confirms that, in a centralised setting, it is possible to guide both antenatal and postnatal anti‐D immunoprophylaxis by fetal RHD screening in maternal blood obtained at 27 week of gestation. The current analysis, however, is based on the cord blood samples received by Sanquin only. A longer period of nation‐wide evaluation of the fetal RHD screening programme, including all (also locally typed) cord blood serology results obtained in a one‐year time period, will provide insight in the robustness of the fetal RHD screening programme.