Effectiveness of maternal pertussis vaccination in England: an observational study

doi:10.1016/S0140-6736(14)60686-3

The Lancet

Volume 384, Issue 9953, 25–31 October 2014, Pages 1521-1528

https://doi.org/10.1016/S0140-6736(14)60686-3 Get rights and content

Summary

Background

In October, 2012, a pertussis vaccination programme for pregnant women was introduced in response to an outbreak across England. We aimed to assess the vaccine effectiveness and the overall effect of the vaccine programme in preventing pertussis in infants.

Methods

We undertook an analysis of laboratory-confirmed cases and hospital admissions for pertussis in infants between Jan 1, 2008, and Sept 30, 2013, using data submitted to Public Health England as part of its enhanced surveillance of pertussis in England, to investigate the effect of the vaccination programme. We calculated vaccine effectiveness by comparing vaccination status for mothers in confirmed cases with estimates of vaccine coverage for the national population of pregnant women, based on data from the Clinical Practice Research Datalink.

Findings

The monthly total of confirmed cases peaked in October, 2012 (1565 cases), and subsequently fell across all age groups. For the first 9 months of 2013 compared with the same period in 2012, the greatest proportionate fall in confirmed cases (328 cases in 2012 vs 72 cases in 2013, −78%, 95% CI −72 to −83) and in hospitalisation admissions (440 admissions in 2012 vs 140 admissions in 2013, −68%, −61 to −74) occurred in infants younger than 3 months, although the incidence remained highest in this age group. Infants younger than 3 months were also the only age group in which there were fewer cases in 2013 than in 2011 (118 cases in 2011 vs 72 cases in 2013), before the resurgence. 26 684 women included in the Clinical Practice Research Datalink had a livebirth between Oct 1, 2012 and Sept 3, 2013; the average vaccine coverage before delivery based on this cohort was 64%. Vaccine effectiveness based on 82 confirmed cases in infants born from Oct 1, 2012, and younger than 3 months at onset was 91% (95% CI 84 to 95). Vaccine effectiveness was 90% (95% CI 82 to 95) when the analysis was restricted to cases in children younger than 2 months.

Interpretation

Our assessment of the programme of pertussis vaccination in pregnancy in England is consistent with high vaccine effectiveness. This effectiveness probably results from protection of infants by both passive antibodies and reduced maternal exposure, and will provide valuable information to international policy makers.

Funding

Public Health England.

Introduction

In the UK, pertussis-containing vaccines have been used in infancy since 1957, at an accelerated schedule (at 2, 3, and 4 months of age) since 1990, and with acellular pertussis since 2004.¹ High coverage during the past two decades, combined with the 2001 introduction of a preschool booster for acellular pertussis from 3 years and 4 months of age, has achieved good disease control without additional boosters at older ages.¹ However, in late 2011, a national increase in confirmed pertussis cases was reported, initially restricted to adolescents and adults, but extending to young infants in 2012.² Resurgence of pertussis has recently been reported in several countries,3, 4, 5 but the reasons are not yet fully understood. The improved availability of methods to confirm diagnosis (eg, serology and PCR), increased awareness among health professionals, and waning natural or vaccine immunity during periods of low pertussis activity have been suggested.⁵ Changes in Bordetella pertussis organisms and decreased duration of protection or effectiveness against transmission with acellular pertussis vaccines (by comparison with whole-cell vaccines) have also been described.⁵

The high rates of disease in infants younger than 3 months and a concomitant increase in pertussis-related infant deaths led to an urgent review of potential control strategies by the UK's Joint Committee on Vaccination and Immunisation. In September, 2012, the UK Department of Health recommended a temporary programme to offer a five-component acellular-pertussis-containing vaccine, Repevax (Sanofi Pasteur MSD, Maidenhead, UK)—a diphtheria, tetanus, pertussis (acellular, component), and poliomyelitis (inactivated) vaccine, also known as dTaP/IPV—to all women between 28 and 38 weeks of pregnancy.⁶ Repevax was available without delay in sufficient quantities required for the UK programme. Although the WHO Global Advisory Committee on Vaccine Safety has pronounced the safety of vaccination with inactivated vaccines in pregnancy, the effectiveness of a maternal immunisation programme for pertussis has not been shown.⁷ We aimed to provide the first estimates of the effectiveness of a maternal pertussis vaccination programme in prevention of infant disease in England.

Section snippets

Participants and data sources

For vaccine effectiveness calculations, we used data from the Clinical Practice Research Datalink (CPRD), a primary care dataset containing anonymised information for patients registered at 520 English general practices, which are representative of the population of England in terms of geographical distribution.⁸ For each patient, basic demographic information, details of every consultation and diagnosis, and vaccination history are recorded. We estimated maternal vaccine coverage using CPRD

Results

We estimated maternal vaccine coverage from English practices in the CPRD based on 26 684 women with a livebirth from Oct 1, 2012 (week 40, 2012) until Sept 3, 2013 (week 36, 2013). This figure represents about 4% of all livebirths in England in 2012 (694 241).¹² Maternal coverage by week of delivery peaked at 500 (78%) of 638 women in week 2, 2013, then fell gradually to 144 (60%) of 241 women giving birth in week 35, 2013 (end of August; figure 1). We compared these data with national data,

Discussion

In the UK, pertussis vaccination for pregnant women was introduced at a time of heightened pertussis activity and a substantial rise in infant deaths.⁶ The programme rapidly achieved coverage approaching 60%.⁹ Although efficient placental transfer of pertussis antibodies has been shown after recent maternal immunisation with acellular vaccine,13, 14, 15 we provide the first evidence of the effectiveness of pertussis vaccination in pregnancy to prevent infant disease (panel).

In England,

References (31)

KE Wiley et al.
Sources of pertussis infection in young infants: a review of key evidence informing targeting of the cocoon strategy
Vaccine
(2013)
H Campbell et al.
Accelerating control of pertussis in England and Wales
Emerg Infect Dis
(2012)
G Amirthalingam
Strategies to control pertussis in infants
Arch Dis Child
(2013)
SC de Greeff et al.
Seroprevalence of pertussis in The Netherlands: evidence for increased circulation of Bordetella pertussis
PLoS One
(2010)
P Campbell et al.
Increased population prevalence of low pertussis toxin antibody levels in young children preceding a record pertussis epidemic in Australia
PLoS One
(2012)
DL Burns et al.
Pertussis resurgence: perspectives from the working group meeting on pertussis on the causes, possible paths forward, and gaps in our knowledge
J Infect Dis
(2014)
SC Davies
Temporary programme of pertussis (whooping cough) vaccination of pregnant women
Wkly Epidemiol Rec
(2013)
IJ Douglas et al.
Orlistat and the risk of acute liver injury: self controlled case series study in UK Clinical Practice Research Datalink
BMJ
(2013)
Pertussis vaccination programme for pregnant women: vaccine coverage estimates in England, October 2012 to September 2013. Health Protection Report 2013, Volume 7 Number 51

NK Fry et al.

Modelling anti-pertussis toxin IgG antibody decay following primary and preschool vaccination with an acellular pertussis vaccine in UK subjects using a modified oral fluid assay

J Med Microbiol

(2013)

CP Farrington

Estimation of vaccine effectiveness using the screening method

Int J Epidemiol

(1993)

Statistical bulletin: births in England and Wales, 2012

CM Healy et al.

Prevalence of pertussis antibodies in maternal delivery, cord, and infant serum

J Infect Dis

(2004)

CM Healy et al.

Importance of timing of maternal combined tetanus, diphtheria, and acellular pertussis (Tdap) immunization and protection of young infants

Clin Infect Dis

(2013)

Cited by (586)

Vaccination coverage during pregnancy and factors associated with refusal of recommended vaccinations: An Italian cross sectional study
2024, Vaccine: X
The vaccines recommended during pregnancy are the Tdap, the influenza vaccine, and, during the SARS-CoV-2 pandemic, the vaccine against COVID-19. This survey aimed at determining vaccination coverage among pregnant women and adverse events, reasons for vaccine refusal, and factors associated with vaccine uptake.
A single-center cross-sectional study was conducted on women who delivered between March and April 2022 at Careggi University Hospital in Florence, Italy. Information on the vaccinations (Tdap, influenza and COVID-19) received during pregnancy were collected through in-person interviews.
Among 307 enrolled women (response rate 99 % on a study population of 310 eligible women), 74 % of patients were vaccinated with Tdap, 82 % against COVID-19, and only 33 % against influenza. Vaccination coverage for Tdap and COVID-19 was significantly higher among Italian than foreign patients (80 % vs 51 %, p < 0.001 and 86 % vs 69 %, p = 0.002, respectively), and for Tdap was higher among patients followed in the private vs public care setting. The main reasons behind refusal of vaccinations were low risk perception of influenza (41 %), insufficient information received from the prenatal care provider regarding the Tdap (35 %), and, for the COVID-19, fear of vaccine side effects (64 %), and concerns about effects on the fetus (70 %).
Adherence to the influenza vaccine was low because of reduced perception of the disease risks. The difference in vaccination coverage between Italians and foreigners is an example of healthcare disparity. Better information provided to patients about vaccines’ efficacy and safety is advisable to increase acceptance of recommended vaccines.
Safety and immunogenicity of a single dose of Tdap compared to Td in pregnant women in Mali and 3 its effect on infant immune responses: a single-centre, randomised, double-blind, active-controlled phase 2 study
2024, eClinicalMedicine
While maternal pertussis vaccination is a strategy to reduce infant morbidity, safety and immunogenicity data are limited in sub-Saharan Africa. We aimed to evaluate the safety of a single dose of tetanus, diphtheria and acellular pertussis vaccine (Tdap) vaccine compared to tetanus and diphtheria vaccine (Td) vaccine in pregnant women in Bamako, Mali and to assess the pertussis toxin (PT) antibody response at birth.
In this phase 2, single-centre, randomised, double-blind, active-controlled study, from 23 January 2019 to 10 July 2019, healthy 18–39 year old women in the second trimester of a singleton pregnancy were randomised 2:1 to receive Tdap or Td. Blood was tested for serum immunoglobulin G (IgG) against PT and other vaccine antigens using a qualified Meso Scale Discovery multiplex immunoassay. The co-primary objectives evaluated safety and birth anti-PT levels. Infant immune responses to whole-cell pertussis vaccine (DTwP) were assessed. Statistical analysis was descriptive. This trial is registered with clinicaltrials.gov, NCT03589768.
133 women received Tdap and 67 received Td, with 126 and 66 livebirths, respectively. In the Tdap group, 22 serious adverse events (SAEs) including one maternal death occurred in 20 participants (15·0%), with 10 SAEs in 10 participants (14·9%) in the Td group. Among infants, 18 events occurred among 13 participants (10.3%) and 8 SAEs in 6 participants (9.1%), including three and two infant deaths, occurred in Tdap and Td groups, respectively. None were related to study vaccines. Anti-PT geometric mean concentration (GMC) at birth in the Tdap group was higher than in the Td group (55.4 [46.2–66.6] IU/ml vs 7.9 [5.4–11.5] IU/ml). One month after the third dose of DTwP, the GMC in infants born to mothers in the Tdap group were lower compared to the Td group (20.2 [13.7–29.9] IU/ml vs 77.2 [32.2–184.8] IU/ml). By 6 months of age, the anti- PT GMCs were 17.3 [12.8–23.4] IU/ml and 67.1 [35.5–126.7] IU/ml in Tdap and Td groups, respectively. At birth, anti-tetanus toxin (TT) GMCs were higher in infants in the Td vs Tdap group (5.9 [5.0–7.0] IU/ml vs 4.1 [3.5–4.8] IU/ml). Anti-diphtheria toxin GMCs were similar in both groups.
Tdap administered to pregnant women in Mali is safe and well-tolerated. Infants of mothers who received Tdap were born with high PT and protective anti-TT antibody levels. By six months of age, after primary vaccination, the PT levels were lower in the Tdap group compared to the Td group. The blunted immune responses to primary DTwP vaccination in the Tdap infant group warrant further study.
This project was funded by National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), under contract numbers 75N93021C00012 (The Emmes Company), and HHSN27220130000221 (University of Maryland, Baltimore). Dr. Susana Portillo was supported by NIH award no. T32AI007524. NIAID, NIH provided Tdap vaccine (BOOSTRIX).
The immunogenicity and safety of Group B Streptococcal maternal vaccines: A systematic review
2024, Vaccine
To systematically review immunogenicity and safety data of maternal group B streptococcal (GBS) vaccines in published clinical trials until July 2023.
EMBASE, MEDLINE, Cochrane Library and clinicaltrial.gov. databases were searched for clinical studies that reported immunogenicity and/or safety of GBS vaccine in non-pregnant adults, pregnant women and infants between 1st of January 1996 to 31st of July 2023. Pairs of reviewers independently selected, data extracted, and assessed the risk of bias of the studies. Discrepancies were resolved by consensus. (PROSPERO CRD42020185213).
We retrieved 1472 records from the literature search; 20 studies and 6 sub-studies were included, involving 4440 non-pregnant participants and 1325 pregnant women with their newborns. There was a significantly higher IgG Geometric Mean Concentration (GMC) and IgG placental transfer ratios in vaccinated compared to placebo groups, with peak response 4–8 weeks after vaccination. Placental transfer ratio varied from 0.4 to 1.4 across five studies. The different clinical trials used different assays that limited direct comparison. There were no significant differences in the risk of serious adverse events (adjusted OR 0.73; 95 % CI 0.49–1.07), serious adverse events leading to withdrawal (adjusted OR 0.44; 95 % CI 0.13–1.51), and systemic illness or fever (adjusted OR 1.05; 95 % CI 0.26–4.19) between the vaccine and placebo groups.
The published clinical trials show significant IgG GMC response in subjects receiving the conjugated capsular polysaccharide and surface subunit protein vaccines compared to placebo. In current clinical trials of experimental GBS maternal vaccines, there have been no observed serious adverse events of special interest directly linked to vaccination.
Effective and safe transfer of maternal antibodies persisting two months postpartum following maternal immunization with different doses of recombinant pertussis-containing vaccines
2024, Vaccine
Recombinant acellular pertussis (ap) vaccines containing genetically inactivated pertussis toxin (PT_gen) and filamentous hemagglutinin (FHA) with or without tetanus (TT) and diphtheria (DT) vaccines (Td) were found safe and immunogenic in non-pregnant and pregnant women. We report here maternal antibody transfer and safety data in mothers and neonates.
This is the follow up of a phase 2 trial in 2019 among 400 pregnant women who randomly received one dose of recombinant pertussis-only vaccine containing 1 µg PT_gen and 1 µg FHA (ap1_gen), or Td combined with ap1_gen (Tdap1_gen), or with 2 µg PT_gen and 5 µg FHA (Tdap2_gen), or with 5 µg PT_gen and 5 µg FHA (TdaP5_gen, Boostagen®, BioNet, Thailand) or chemically-inactivated acellular pertussis comparator (Tdap8_chem, Boostrix™, GSK, Belgium), either in the second or third trimester of gestation. IgG against PT, FHA, TT and DT were assessed by ELISA, PT-neutralizing antibodies (PTNA) by Chinese Hamster Ovary cell assay and safety outcomes at delivery in mothers and at birth.
Anti-PT and anti-FHA geometric mean concentration (GMC) ratio between infants at birth and mothers at delivery was above 1 in all groups. PT GMC in infants at birth were ≥30 IU/mL in all groups with the highest titers in infants found in TdaP5_gen group at birth (118.8 [95% CI 93.9–150.4]). At 2 months, PT GMC ratio to Tdap8_chem (98.75% CI) was significantly higher for TdaP5_gen (2.6 [1.7–4.0]) and comparable for other recombinant vaccines. No difference in PTNA titers at birth was observed between all groups nor between time of vaccination. Adverse events were comparable in all vaccine groups.
BioNet licensed (TdaP5_gen and Tdap2_gen) and candidate vaccines (Tdap1_gen and ap1_gen) when given to pregnant women in the second or third trimester of gestation are safe and have induced passive pertussis immunity to infants.
Maternal immune factors involved in the prevention or facilitation of neonatal bacterial infections
2024, Cellular Immunology
Newborns, whether born prematurely or at term, have a fully formed but naive immune system that must adapt to the extra-uterine environment to prevent infections. Maternal immunity, transmitted through the placenta and breast milk, protects newborns against infections, primarily via immunoglobulins (IgG and IgA) and certain maternal immune cells also known as microchimeric cells.
Recently, it also appeared that the maternal gut microbiota played a vital role in neonatal immune maturation via microbial compounds impacting immune development and the establishment of immune tolerance.
In this context, maternal vaccination is a powerful tool to enhance even more maternal and neonatal health. It involves the transfer of vaccine-induced antibodies to protect both mother and child from infectious diseases.
In this work we review the state of the art on maternal immune factors involved in the prevention of neonatal bacterial infections, with particular emphasis on the role of maternal vaccination in protecting neonates against bacterial disease.
Antibody and B-cell Immune Responses Against Bordetella Pertussis Following Infection and Immunization
2023, Journal of Molecular Biology
Neither immunization nor recovery from natural infection provides life-long protection against Bordetella pertussis. Replacement of a whole-cell pertussis (wP) vaccine with an acellular pertussis (aP) vaccine, mutations in B. pertussis strains, and better diagnostic techniques, contribute to resurgence of number of cases especially in young infants. Development of new immunization strategies relies on a comprehensive understanding of immune system responses to infection and immunization and how triggering these immune components would ensure protective immunity. In this review, we assess how B cells, and their secretory products, antibodies, respond to B. pertussis infection, current and novel vaccines and highlight similarities and differences in these responses. We first focus on antibody-mediated immunity. We discuss antibody (sub)classes, elaborate on antibody avidity, ability to neutralize pertussis toxin, and summarize different effector functions, i.e. ability to activate complement, promote phagocytosis and activate NK cells. We then discuss challenges and opportunities in studying B-cell immunity. We highlight shared and unique aspects of B-cell and plasma cell responses to infection and immunization, and discuss how responses to novel immunization strategies better resemble those triggered by a natural infection (i.e., by triggering responses in mucosa and production of IgA). With this comprehensive review, we aim to shed some new light on the role of B cells and antibodies in the pertussis immunity to guide new vaccine development.

View all citing articles on Scopus

View full text

ArticlesEffectiveness of maternal pertussis vaccination in England: an observational study

Summary

Background

Methods

Findings

Interpretation

Funding

Introduction

Section snippets

Participants and data sources

Results

Discussion

Vaccine

Accelerating control of pertussis in England and Wales

Emerg Infect Dis

Strategies to control pertussis in infants

Arch Dis Child

Seroprevalence of pertussis in The Netherlands: evidence for increased circulation of Bordetella pertussis

PLoS One

Increased population prevalence of low pertussis toxin antibody levels in young children preceding a record pertussis epidemic in Australia

PLoS One

Pertussis resurgence: perspectives from the working group meeting on pertussis on the causes, possible paths forward, and gaps in our knowledge

J Infect Dis

Temporary programme of pertussis (whooping cough) vaccination of pregnant women

Wkly Epidemiol Rec

Orlistat and the risk of acute liver injury: self controlled case series study in UK Clinical Practice Research Datalink

BMJ

Pertussis vaccination programme for pregnant women: vaccine coverage estimates in England, October 2012 to September 2013. Health Protection Report 2013, Volume 7 Number 51

Modelling anti-pertussis toxin IgG antibody decay following primary and preschool vaccination with an acellular pertussis vaccine in UK subjects using a modified oral fluid assay

J Med Microbiol

Estimation of vaccine effectiveness using the screening method

Int J Epidemiol

Statistical bulletin: births in England and Wales, 2012

Prevalence of pertussis antibodies in maternal delivery, cord, and infant serum

J Infect Dis

Importance of timing of maternal combined tetanus, diphtheria, and acellular pertussis (Tdap) immunization and protection of young infants

Clin Infect Dis

Articles
Effectiveness of maternal pertussis vaccination in England: an observational study