Archived: Update on Pertussis Vaccination in Pregnancy

An Advisory Committee Statement (ACS) National Advisory Committee on Immunization (NACI)^{Footnote †}

1. What

Bordetella pertussis is a respiratory pathogen which has the heaviest burden of mortality and morbidity in the first 6 months of life. In Canada, we have seen an increase in the total number of cases of pertussis reported nationally in 2012.

2. Who

In order to protect newborn infants against pertussis, this statement addresses pregnant women who are 26 weeks of gestation or greater.

3. How

NACI does not recommend a universal program for vaccination of pregnant women given the current epidemiology in Canada

In special circumstances, such as a regional outbreak situation, immunization with Tdap may be offered to pregnant women (≥26 weeks of gestation) irrespective of their immunization history.

Every effort should be made to administer one dose of pertussis containing vaccine in adulthood. Therefore, one dose of combined diphtheria, tetanus, acellular pertussis containing vaccine (Tdap) can be offered to pregnant women (≥26 weeks of gestation) who have not been previously vaccinated against pertussis in adulthood.

4. Why

Pertussis continues to occur in a cyclic pattern every 2-5 years. The greatest morbidity and mortality occurs in children under 6 months of age. When an outbreak is occurring, vaccinating pregnant woman increases maternal antibody transfer. This provides immediate protection to infants who are at the greatest risk of morbidity and mortality, prior to the completion of their primary series. Vaccinating pregnant women also prevents them from acquiring infection that they may pass onto their newborn baby.

I. Introduction

In 2012, a number of Canadian provinces and territories reported an increase in pertussis with a total of more than 4,800 cases reported nationally. This represents an approximate three-fold increase from the mean number of cases reported between 2005 and 2011.

The observed outbreaks in Canada as well as the recently adopted recommendations for immunization of pregnant women in other countries have prompted a review of existing advice to immunize pregnant women as a means of protecting infants prior to completion of their primary immunization series. In 2011, US Center for Disease Control and Prevention's (CDC's) Advisory Committee on Immunization Practices (ACIP) recommended that an acellular pertussis vaccine be administered to all pregnant women after 20 weeks gestation and in 2012 expanded this to recommend revaccination with every pregnancy between 27 and 36 weeks gestation.^{Footnote 1Footnote 2} In 2012, UK's Department of Health announced the introduction of a temporary immunization programme for all pregnant women between 28-38 weeks of pregnancy during one of the country's largest pertussis outbreaks in several decades, which was associated with significant infant mortality.^{Footnote 3} Compared to postpartum vaccination, vaccination in pregnancy could potentially reduce annual infant pertussis incidence by 33% versus 20%, hospitalizations by 38% versus 19%, and deaths by 49% versus 16%.^{Footnote 4}

Since 1998, immunization with an acellular pertussis vaccine has been recommended at 2, 4, 6 months of age and at 12 to 23 months of age (generally given at 18 months of age); in cases where rapid protection is required, the first dose can be given at 6 weeks of age. DTaP-IPV or Tdap-IPV should be used as the booster dose for children 4-6 years of age. Also, a booster dose of Tdap vaccine should be administered at 14-16 years of age. The National Advisory Committee on Immunization (NACI) recommends that all adults receive one dose of Tdap vaccine if not previously immunized in adulthood (18 years of age and older), with particular attention given to those who anticipate having regular contact with infants. Several Canadian jurisdictions including British Columbia,^{Footnote 5Footnote 6} the Yukon^{Footnote 7} and New Brunswick^{Footnote 8} have issued temporary provincial advisories recommending pregnant women be immunized in the last trimester of pregnancy or prior to discharge from hospital after delivery. Saskatchewan^{Footnote 9} has also recommended that in certain high risk circumstances (such as outbreaks) pregnant women can be offered Tdap any time after 20 weeks gestation if they have not received an adult dose of Tdap.

At the NACI meeting in October 2012, NACI requested the Pertussis Working Group to review the evidence related to vaccination in pregnancy and consider the following questions:

• Review the epidemiology of pertussis in Canada
• Are pertussis vaccines safe for pregnant woman and their fetus if given during pregnancy?
• Do pertussis vaccines provide effective protection to pregnant women if given during pregnancy?
• Does vaccinating mothers increase the protection of infants?
• Does maternal antibody transferred across the placenta interfere with neonatal immune response to immunization?

NACI did not consider other public health strategies for preventing infant disease, such as vaccinating those in contact with infants (cocooning), due to the significant programmatic issues associated with its implementation.^{Footnote 4Footnote 10-14}

II. Methods

The Pertussis Working Group reviewed the key questions for the literature review as proposed by NACI, including such considerations as the burden of disease to be prevented and any evidence of change in the burden amongst different populations; safety, immunogenicity, efficacy, and effectiveness of the vaccines; vaccine schedules; and other aspects of the overall immunization strategy. Building on the work conducted by US CDC^{Footnote 1Footnote 15} and UK Joint Committee on Vaccination and Immunisation (JCVI)^{Footnote 3} a further literature search and review of articles published between January 1, 2011 to February 15, 2013 was completed. A total of 44 articles were identified, retrieved and included in the literature review to inform this statement. The knowledge synthesis was performed by two medical advisors at the Agency, and supervised by the Working Group. Following critical appraisal of individual studies, summary tables with ratings of the quality of the evidence using NACI's methodological hierarchy (Table 1 to 4) were prepared, and proposed recommendations for vaccine use developed. The Working Group Chair and PHAC medical advisors presented the evidence and proposed recommendations to NACI on May 15, 2013. Following thorough review of the evidence and consultation at the NACI meeting of June 6, 2013, the committee voted on specific recommendations. The description of relevant considerations, rationale for specific decisions, and knowledge gaps are described in the text below.

III. Epidemiology

For information on symptoms and natural progression of disease please refer to the Canadian Immunization Guide (CIG).^{Footnote 16}

Pertussis is an endemic and cyclical disease, which peaks at two to five year intervals. Pertussis cycles are asynchronous in Canada, with the timing of cyclic peaks in activity varying by province and territory. Despite periodic increases in disease activity, Canada has experienced an overall decline in the incidence of pertussis since 1998, from a high of 29.5 cases per 100,000 population to a low of 2.0 cases per 100,000 population in 2011. However, the severity of illness and complications following infection remain greatest among infants too young to be protected by a complete vaccine series. Average incidence rates from 2005 to 2011 were highest among infants less than 1 year of age at 72.2 cases per 100,000 population, followed by 1 to 4 year olds (25.6 cases per 100,000), and 10 to 14 year olds (16 cases per 100,000). For further details on the overall epidemiology of pertussis in Canada, please see the pertussis chapter of the Canadian Immunization Guide webpage or PHAC's Vaccine Preventable Diseases (VPD) web page.

Based on preliminary data, in 2012, increased incidence rates relative to the annual average from 2005-2011 occurred in 8 provinces and territories with the largest increases being observed in New Brunswick and the Yukon. Other provinces with notable increases in pertussis infection included British Columbia, Manitoba, and Quebec. Among the 5 provinces/territories which experienced decreases in pertussis activity in 2012 relative to the annual average from 2005-2011, many had experienced peaks in activity in 2010 and/or 2011. In 2012, due to the increase in incidence across multiple jurisdictions, the national incidence of disease increased by almost 7-fold from what was reported in 2011 to 13.9 cases per 100,000 (n=4,845). The increase in incidence was observed across all age groups (range of 1.7 to 5.6 times greater relative to the mean 2005-2011) with the highest incidence rates in those less than one (120.8 per 100,000; n=460) and those 10-14 years of age (64.1 per 100,000; n=1203). As well in 2012, preliminary data show a total of 104 pertussis related hospitalizations that were reported through the Immunization Monitoring Program Active (IMPACT), an almost 2-fold increase from the number of hospitalizations in 2011 (n=55) and a 64% increase from the average annual number of hospitalization reported between 2005-2011 (n=63.5). Three deaths were reported in 2012, all in previously well infants without underlying medical conditions, who were less than two months of age. The number of reported deaths is in keeping with historical trends.

In general, adolescents and adults who have not been optimally protected through recommended immunization are at risk of infection and are at risk for passing the infection onto infants. Parents are an important source of pertussis transmission to young infants. ^{Footnote 17-24} Specifically, the lack of maternal immunity increases susceptibility to pertussis infection in very young infants both by increasing the risk of infection in mothers and subsequent transmission to the infant, as well as by not providing the infant with sufficient passive protection transplacentally in the third trimester or through breast milk. Before completing the primary series of pertussis immunization, which is the period of highest risk for pertussis complications, infants rely on maternally transferred antibodies for protection. In Canada in 2011, the mean age of mothers at birth was 29.7 years and there were approximately 380,000 live births.^{Footnote 25Footnote 26}

IV. Vaccine

IV.1 Adult pertussis vaccine preparations authorized for use in Canada

IV.2 Effectiveness and duration of protection

The vaccine efficacy following the primary series with acellular pertussis vaccines is estimated to be about 85%, and approximately 90% following booster immunization.^{Footnote 27Footnote 28-30} However, the true vaccine effectiveness of acellular pertussis vaccines is difficult to determine because few surveillance systems have the capacity or data quality to calculate this accurately (including Canada). In addition, the clinical trials case definition provided by the World Health Organization (WHO) does not account for milder cases, and may artificially inflate efficacy.^{Footnote 31}

Although the duration of protection remains unknown, available data suggests that protection does not significantly decline in the first four years following the primary and booster immunization with an acellular pertussis vaccine. ^{Footnote 28-30} Two recent studies indicate waning of immunity over the five years after the fifth dose of DTaP. In the Klein et al study (2012), after the fifth dose of DTaP, the odds of acquiring pertussis increased by an average of 42% per year in those vaccinated over 5 years before.^{Footnote 32} Misegades et al (2012) also investigated the vaccine effectiveness (VE) in children after receipt of five doses of pertussis containing vaccine.^{Footnote 33} Using a case-control design, they showed that VE declined each year after the fifth dose of DTaP. Their estimates of VE based on time since the fifth dose were as follows: 98.1% (95% CI 96.1-99.1) for those within one year of receipt; 95.3% (95% CI 91.2-97.5) for those 12-23 months since last dose; 92.3% (95% CI 86.6-95.5%) for those 24-35 months since last dose; 87.3% (95% CI 76.2-93.2) for those 36-47 months since last dose; 82.8% (95% CI 68.7-90.6) for those 48-59 months since last dose; and 71.2% (95% CI 45.8-84.8) in those greater than 60 months since last dose of DTaP.

Effectiveness and duration of maternal and infant protection following vaccination in pregnancy has not been studied.

IV.3 Immunogenicity

Immunologic correlates of protection against pertussis are not well defined, but higher levels of antibodies (pertussis toxin (PT); pertactin (PRN); fimbriae (FIM)) seem to be associated with greater protection.^{Footnote 34-37} In previously immunized adults, booster vaccination produces antibody responses to pertussis after 7 days and peak antibody levels are reached 10-14 days after vaccination.^{Footnote 38Footnote 39} Following vaccination with acellular pertussis vaccines, antibody levels rapidly decrease in the first year and approach pre-vaccination levels by end of third year.^{Footnote 40Footnote 41}

Although pregnancy is considered to be an immunomodulatory condition, conducted serological studies indicate that the immune response following vaccination with Tdap is comparable between pregnant and non-pregnant women.^{Footnote 42} Studies measuring the levels of anti-pertussis antibody in maternal sera after immunization have demonstrated similar trends to those seen in non-pregnant women following vaccination.^{Footnote 10Footnote 38Footnote 41Footnote 43Footnote 44}

Administration of Tdap immediately before or during pregnancy has demonstrated significantly higher concentrations of antibodies in the cord blood of newborn infants as compared to infants whose mothers were not vaccinated in this time period.^{Footnote 34Footnote 42Footnote 43Footnote 45-48} Several studies provide evidence of effective maternal antibody transfer via the placenta to the newborn with the degree of transfer appearing to be dependent on the amount of maternal antibody in circulation.^{Footnote 34Footnote 43Footnote 46} Passive transfer of maternal antibodies begins after 28 weeks of gestation and is followed by active/preferential antibody transfer after 32-33 weeks of gestation leading to higher antibody levels in infants than in mothers at birth.^{Footnote 44} Following birth, the level of pertussis antibodies declines in the newborn. The half-life of transferred maternal pertussis antibodies has been estimated to be between 5 and 6 weeks and the majority of infants will not have any detectable maternal pertussis antibodies by the age of 2 to 6 months.^{Footnote 44Footnote 47}

Does transplacental transfer of pertussis antibody from mother to child interfere with the infant immune response to the active pertussis immunization primary series?

Van Savage et al investigated a small group of infants (n=23) who had either 'high' or 'low' levels of transplacental antibodies - both groups were able to mount similar antibody responses to their primary series acellular pertussis vaccine.^{Footnote 47} Englund et al found that there was no adverse relationship with the PT antibody level measured pre immunization and an infants' post immunization antibody level after three doses of pertussis containing vaccine. However, higher pre immunization levels of FHA, PRN, FIM antibodies did show a statistically significant negative effect on the level of antibody measured in infants one month after a three-dose schedule (i.e. at 2,4, and 6 months).^{Footnote 49} Hardy-Fairbanks et al compared the immune responses of 16 infants whose mothers received Tdap during pregnancy to controls and found that they had substantially higher pertussis antibodies from birth through the first few months of life, slightly lower levels at 7 months (after third DTaP), but similar levels before and after the booster dose of DTaP at 12-18 months.^{Footnote 50} A randomized controlled trial of 48 mother/infants pairs by Munoz et al^{Footnote 42} showed there was no difference in antibody levels after the primary series and following the first booster dose at 12 months in infants of mothers vaccinated compared to infants whose mothers did not receive Tdap in pregnancy.

Preliminary, blinded results from an ongoing trial by Halperin et al^{Footnote 51} have suggested an increased level of antibodies in one group at 2 months of age prior to receiving the first dose of the primary series. Interim immunogenicity analysis of 50 infants demonstrated significant differences in antibody levels at 7 months of age, particularly for the FIM antibody. In the group that had had an increased level of antibody at 2 months of age, there was a decreased level of antibodies at 7 months of age suggesting possible interference in the immune response. This study expects to complete enrolment in December 2013. In comparing the data reported by Munoz et al^{Footnote 42Footnote 52} and Halperin et al,^{Footnote 51} the absolute values of antibody levels measured between the two studies were quite similar. It is possible that the Munoz et al^{Footnote 42Footnote 52} study was underpowered to detect a difference in antibody levels. Further information will be available from the Halperin et al^{Footnote 51} study after completion and unblinding of the treatment versus control group.

In general, immunization following 26 weeks' of gestation has been shown to be immunogenic and maximizes the transfer of maternal antibodies to the fetus. However, there is limited evidence regarding the effect of maternal antibodies on the infant immune response to routine infant DTaP vaccination and the potential for increased risk of pertussis later in life.

IV.4 Adverse events

In non-pregnant healthy adolescents and adults Tdap is a safe and well tolerated vaccine with some injection-site reactogenicity. Most common adverse events following vaccination include pain, redness, swelling and headache. Receipt of a second dose of Tdap at a 5- or 10-year interval in healthy non-pregnant adolescents and adults does not seem to increase the frequency or intensity of adverse events;^{Footnote 53-55} Safety data on use of Tdap during multiple pregnancies have not been published, but may be available in the coming years following the ACIP recommendation to administer Tdap during every pregnancy. For a more detailed discussion on adverse events related to Tdap, please see the CIG.^{Footnote 53-55Footnote 57Footnote 16}

Data on the safety of administering Tdap to pregnant women and the fetus are available through several small studies, the US Vaccine Adverse Event Reporting System (VAERS), the UK Clinical Practice Research Datalink (CPRD), and published and unpublished data from Sanofi Pasteur's (Adacel^®) and GlaxoSmithKline's (Boostrix^®) registries.

Correct interpretation of adverse events following vaccination in pregnancy using registry data requires adequate knowledge of background or expected rates of complications that are not related to immunization.^{Footnote 58} In a population of pregnant women it is expected that there would be 12 to 14.5 spontaneous abortions per 100 pregnancies,(58) 10.4 - 11.5% of babies would be born prematurely and 1-3% of babies would be born with congenital anomalies.^{Footnote 59}

In a self-reported survey following a mass immunization program of health care workers in a tertiary hospital with a pertussis outbreak, Talbot et al (2010)^{Footnote 60} reported that out of 16 women pregnant at the time of vaccination only one reported severe swelling at the injection site and two reported fever (not documented) in the 2 weeks after Tdap. None of the respondents reported serious adverse events. All 16 women reported delivering healthy term newborns. Similarly, in a trial conducted by Gall et al (2011)^{Footnote 48} there were no adverse reactions to pertussis vaccine administration reported by the 52 women participating in the trial.^{Footnote 48} This study did not specifically report on infant related safety outcomes. A post-marketing safety evaluation study was reported by Klein et al (2010)^{Footnote 61}; in their cohort of 6550 female adolescents from 10-18 years of age, three pregnancies were reported in Tdap recipients.^{Footnote 61} One reported pregnancy ended in miscarriage at 8 weeks gestation and was not considered to be related to vaccination, while the other 2 pregnancies resulted in normal healthy offspring. In a randomized control trial (RCT) conducted by Munoz et al,^{Footnote 42} 33 women received Tdap during the 3rd trimester and 15 women received placebo. There were no significant differences in adverse events reported and all pregnant women delivered healthy infants, 92% at term. In another RCT, an interim blinded safety analysis of 50 women by Halperin et al^{Footnote 51} showed similar results with no significant adverse events reported in either of the groups.

Zheteyeva et al (2012)^{Footnote 62} conducted a search of VAERS from January 2005 through June 2010. This surveillance system provides passive data on adverse events that are reported following vaccination. The study identified 132 reports of Tdap administered to pregnant women. Of the reports, 55 (42%) reported on vaccine administered to a pregnant woman with no adverse events having occurred. Spontaneous abortion was reported in 22 (16.7%) with injection site reaction being reported by 6 (4.5%). There were six adverse events reported in infants with only one serious adverse event (gastroschisis). The authors concluded that there was no safety signal identified in pregnant women or infants when pertussis vaccine was given in pregnancy. The CDC is also planning on reviewing the Vaccine Safety Data link (VSD) for adverse events related to immunizing pregnant women with Tdap. The VSD includes a large linked database that uses administrative data sources at nine managed care organizations which gather data on vaccination (vaccine type, date of vaccination, concurrent vaccinations), medical outcomes (outpatient visits, inpatient visits, urgent care visits), birth data, and census data. It is anticipated these data will not be available for approximately 5 years from introduction of their maternal pertussis immunization program in 2010.

Following the implementation of the UK outbreak-related maternal pertussis immunization program, an analysis of the Clinical Practice Research Datalink (CPRD) data was conducted. A total of 12 000 vaccinated women with at least 2 weeks post vaccination follow up data was analysed. This research database, using vaccination and clinical data, did not detected an increased immediate or later pregnancy risk of any of the pre-specified events (intrauterine death, stillbirth, pre-eclampsia, eclampsia, ante-/ post-partum haemorrhage, uterine rupture, placenta praevia, vasa praevia, fetal distress and pre-term birth).^{Footnote 63}

The Sanofi Pasteur Adacel^® pregnancy registry has previously been used to review clinical trial or spontaneously reported adverse events following Tdap vaccination in pregnancy.^{Footnote 64Footnote 65} The most recent review of registry data conducted in October 2012 analyzed a total of 1083 reported cases with Tdap exposure in women within 30 days before last menstrual cycle or during pregnancy. Out of these, 270 were reported in clinical trials/phase IV studies, 1 case was retrieved in the literature and 812 were spontaneously reported to the manufacturer. Review of spontaneous abortion cases did not indicate any safety concern. In the few cases of the reported congenital anomalies, no pattern of anomaly was observed and the role of the vaccine was considered unlikely. Overall, available data through the registry does not suggest increased concern for maternal or infant health after receipt of Adacel^®.

The GlaxoSmithKline (GSK) product Boostrix^® related information is collected through the Worldwide Safety database and the GSK Pregnancy Registry. The number of pregnancies and outcomes reported was deemed by GSK to be insufficient for reaching reliable and definitive conclusions about the safety of vaccination with Boostrix^® during pregnancy.

Overall, the current data suggests a good safety profile of Tdap vaccination in pregnancy, although it is not sufficient to exclude occurrence of rare adverse events in mother or newborn. However, this potential risk appears to be unlikely. Tetanus and combined tetanus and diphtheria vaccines have a well-established safety record when given during pregnancy. They have not been shown to adversely affect mothers or their infants.^{Footnote 66-69}

V. Recommendations

VI. Research priorities

Research to address the following outstanding questions related to immunization in pregnancy is encouraged:

• further work on determining the impact of maternal vaccination on an infant's immune response
• further work on determining the optimal timing of maternal vaccination
• vaccine effectiveness and immunogenicity studies for pertussis in women and their newborns when the women have been immunized in pregnancy
• knowledge and attitudes of physicians and parents related to immunization in pregnancy
• implementation and programmatic research related to the optimal process for delivering immunizations to pregnant women
• qualitative studies to understand a physicians'/patients' decision making around whether to offer/accept pertussis vaccine while pregnant

Additional research pertaining to broader knowledge gaps concerning immunization against pertussis is required to complement research related to immunization in pregnancy. Areas of particular interest include:

• determination of correlates and the duration of protection provided by acellular pertussis vaccine in adolescence and adulthood
• determining the optimal schedule for Tdap vaccination in adolescence and adulthood
• vaccine effectiveness studies for pertussis in adolescents and adults
• optimal outbreak prevention and control strategies/activities during periods of low/high disease activity
• improving the diagnosis of pertussis at the primary health care level

VII. Surveillance issues

Pertussis has been a nationally reported disease since 1924. Ongoing and systematic data collection, analysis, interpretation and timely dissemination is fundamental to planning, implementation, evaluation, and evidence-based decision-making. To support such efforts, NACI encourages surveillance improvements in the following areas:

• improved data quality, including completeness of information particularly immunization status
• surveillance on mother-infant dyads that have received vaccine
• enhanced pertussis surveillance to detect outbreaks quickly and understand the burden of disease in different age groups
• disease surveillance to determine the impact of changing immunization programs
• investigate the use of a case definition which allows for milder cases of pertussis^{Footnote 70}
• active safety evaluation and surveillance including use of linked administrative data
• improving methods of assessing vaccine coverage (comprehensive immunization registries)
• improving collaboration between public health and industry in Canada and internationally on monitoring disease activity, vaccine safety and program outcomes
• use of surveillance data as part of program evaluation

Tables

Table 1. Summary of evidence related to immunogenicity of acellular pertussis vaccination in pregnancy (mother)

Table 2. Summary of evidence related to immunogenicity of acellular pertussis vaccination in pregnancy (baby)

Table 3. Summary of evidence related to safety of acellular pertussis vaccine in pregnancy (mother)

Table 4. Summary of evidence related to safety of acellular pertussis vaccine in pregnancy (baby)

Table 5. Levels of evidence based on research design

Table 6. Quality (internal validity) rating of evidence

Table 7. NACI recommendation for immunization - grades

List of abbreviations

Acknowledgements

Former NACI Members: Dr. N. Crowcroft, Dr. S. McNeil.

Liaison Representatives: Dr. J. Blake (Society of Obstetricians and Gynaecologists of Canada), Dr. S. Deeks (Canadian Public Health Association), Dr. A. Mawle (Centers for Disease Control and Prevention), Dr. D. Moore (Canadian Paediatric Society), Dr. A. Pham-Huy (Canadian Association for Immunization Research and Evaluation).

Former Liaison Representatives: Dr. A. Corriveau (Council of Chief Medical Officers of Health), Dr. H. Morrison (Council of Chief Medical Officers of Health), Dr. A. Opavsky (Association of Medical Microbiology and Infectious Disease Canada), Dr. S. Rechner (College of Family Physicians of Canada).

Ex-Officio Representatives: Lt.-Col. (Dr.) P. Eagan (Canadian Forces Health Service Group, National Defence), Dr. A. Klein (Biologics and Genetic Therapies Directorate, Health Canada), Dr. B. Law (Centre for Immunization and Respiratory Infectious Diseases, Public Health Agency of Canada), Dr. B. Raymond (Centre for Immunization and Respiratory Infectious Diseases, PHAC/Canadian Immunization Committee), Dr. E. Taylor (Marketed Health Products Directorate, Health Canada), Ms. M. St-Laurent (Centre for Immunization and Respiratory Infectious Diseases, Public Health Agency of Canada).

Former Ex-Officio Representatives: Dr. M. Carew (First Nations and Inuit Health Branch, Health Canada), Dr. C. Légaré (Marketed Biologicals, Biotechnology and Natural Health Products Bureau, Health Canada).

This statement was prepared by: Dr. S. Desai, Dr. O. Baclic, Ms T. Smith and approved by NACI.

NACI gratefully acknowledges the contribution of the Meningococcal B Project Pilot Task Group: Dr. N. Crowcroft (Co-Chair), Dr. P. De Wals (Co-Chair), Ms. H. Deehan, Dr. S. Deeks, Dr. S. Desai, Dr. S. Halperin, Dr. C. Kennedy, Dr. M. Landry, Dr. M. Naus, Dr. R. Tsang, Dr. W. Vaudry.

NACI gratefully acknowledges the contribution of: Dr. C. Baker, Dr. E. Castillo, Dr. T. Clark, Dr. K. Donegan, Dr. A. Doroshenko, Dr. S. Halperin and Dr. P. McIntryre.

References