Imperfect vaccine-induced immunity and whooping cough transmission to infants
Introduction
Whooping cough remains an important public health problem worldwide and a major cause of infant mortality. Despite routine and mass vaccination campaigns for over 50 years incidence in many developed countries has been increasing since the 1980s [1], with a marked rise in cases in teenagers and adults [2], [3]. Infections in adults and/or teenagers have been shown to be responsible for transmission to non-fully immunized infants [4], [5], [6], who have close to a 1% case-fatality rate [7]. The rise in cases in older, vaccinated individuals raises the concern that infants receive decreasing protection by vaccine-induced herd immunity. We explore the population-level effects of imperfect or temporary vaccine-induced immunity against both dominant etiological agents, Bordetella pertussis and B. parapertussis, and the impact of the resultant cases in teenagers and adults on transmission to infants through analysis of temporal and age-related patterns of B. pertussis and B. parapertussis infections in Massachusetts from 1990 through 2008.
The Massachusetts Department of Public Health (MDPH) provides most childhood vaccinations free of charge, and has very high immunization rates. It provides pertussis diagnostic services statewide and operates a robust pertussis surveillance program, which, since 1999, includes contact tracing to identify the source for cases in infants less than one year old. The MDPH recommends administering five doses at ages two, four, six and 15–18 months, and the last one between ages four and six years. In October 1995, the immunization guidelines changed from recommending the whole cell to the acellular pertussis vaccine for all five doses [2]. However, the transition between the vaccines was prolonged, precluding analysis of vaccine efficacy based solely on time period, and necessitating the use of individuals’ vaccine histories, as we use here. Teenage and adult boosters (TDaP) are recommended as well and have been available since 2005.
The duration of immunity against B. pertussis provided by the pertussis vaccines has been estimated to be a maximum of 15 years [8]. This implies that in a highly vaccinated population, without any boosters, there are wide age-classes in which B. pertussis can circulate, and from which it can escape to cause infections in infants. Two hypotheses have been put forward regarding the impact of teenage- and adult-cases on infections in infants. Either epidemics among teenagers lead to infections in infants [9], or subclinically infected adults are responsible for infection of prevaccine-age infants [10]. Subclinical infections are often not diagnosed until long after the infection took place because the symptoms were not severe enough to bring a patient to the doctor’s office right away. Additionally, the contact tracing program in Massachusetts identified some cases that were too mild to be identified except through contact tracing from an infant infection. It is suspected that these individuals were actually the cause of the infant case, despite the fact that their date of diagnosis was later.
Whooping cough can be caused by other etiological agents as well and the vaccine does not fully prevent infection and disease from all of them. In particular, B. parapertussis can cause similar symptoms and has been reported to be the dominant species at times in several European countries [11]. We investigate the impact of imperfect vaccine-induced immunity on whooping cough epidemiology by examining (1) the duration of immunity provided by the vaccine, (2) the likely role of infections in teenagers and adults on transmission to infants through investigating the relative timing of cases in the different groups and (3) the effectiveness of B. pertussis vaccines, both acellular and whole cell, against disease caused by B. parapertussis.
Age distributions, time series analysis and correlation tests were used to compare B. pertussis and B. parapertussis prevalence and dynamics and confirmed that the B. pertussis vaccine is not strongly protective against B. parapertussis. We further showed that (1) the time between vaccination and infection has been decreasing, (2) teenagers are disproportionately affected during outbreaks, and (3) teenage outbreaks are consistently out of phase with prevaccine-age infants, whereas adult cases are largely in phase with infant outbreaks suggesting that the chain of transmission in teenagers is somewhat separate from the very young.
Section snippets
Study design
The Massachusetts State Laboratory Institute (SLI) is the standard provider of Bordetella cultures in Massachusetts, in addition to performing serology and PCR tests. A serum test for IgG to pertussis toxin was performed if the patient was ≥11 years old and had a cough for more than 14 days. Because B. parapertussis does not produce pertussis toxin, the serology test was not sensitive to infection with B. parapertussis. In all other cases (<11 years old or ≤14 days of cough) a nasopharyngeal
Time between vaccination and infection (disease-free duration)
The whole cell and acellular vaccines provided very similar disease-free durations for cohorts first vaccinated between 1994 and 1996, with similar shapes, and the mean and median times from last vaccination to infection between 6.5 and 7 years for both (t-test for comparison of means: P-value = 0.61. Fig. 1a). However, among all other cohorts whose first dose of vaccine was whole cell, the mean time to infection was ∼10.5 years (Supplemental Fig. S1).
The discrepancy between the two estimates of
Discussion
We contribute new insights into the duration and epidemiological importance of waning immunity to the pertussis vaccines, and quantify the disease-free duration from both B. pertussis and B. parapertussis. The estimates of mean duration of vaccine-induced immunity against B. pertussis are consistent with previous estimates that range from 5 to 15 years [20], [21]. Additionally, we show that the time between vaccination and infection has steadily decreased over the past decade. However, the
Acknowledgments
This work was funded from the Bill and Melinda Gates Foundation (ONB), the RAPIDD program of the Science & Technology Directorate (ONB), the National Institute of Health (ONB; grant NIH/GM R01-GM083983-01, ONB and ETH; grants NIH/NIAID R56-AI065507-01A2 and NIH/GM R01-GM083113-01), NSF GREATT fellowship (JL) and the intramural Research Group at Fogarty International Center, at the NIH (HB).
We thank the Massachusetts State Laboratory Institute and the Massachusetts Department of Public Health’s
References (38)
- et al.
Pertussis in adults: frequency of transmission after household exposure
Lancet
(1995) - et al.
Loss of immunity to pertussis in a rural community in senegal
Vaccine
(2004) Epidemics of parapertussis: 20 years’ observations in denmark
The Lancet
(1971)- et al.
Efficacies of whole cell and acellular pertussis vaccines against bordetella parapertussis in a mouse model
Vaccine
(2004) - et al.
The efficacy of a whole cell pertussis vaccine and fimbriae against bordetella pertussis and bordetella parapertussis infections in a respiratory mouse model
Vaccine
(1998) The science and fiction of the “resurgence” of pertussis
Pediatrics
(2003)- et al.
The increasing incidence of pertussis in massachusetts adolescents and adults, 1989–1998
J Infect Dis
(2000) - et al.
The changing age and seasonal profile of pertussis in canada
J Infect Dis
(2002) - et al.
Infant pertussis: who was the source?
Pediatr Infect Dis J
(2004) - et al.
Household contact study of bordetella pertussis infections
Clin Infect Dis
(1995)
Duration of immunity against pertussis after natural infection or vaccination
Pediatr Infect Dis J
Population-based incidence of pertussis among adolescents and adults, minnesota, 1995–1996
J Infect Dis
Pertussis vaccines for adolescents and adults
Pediatrics
Whooping cough due to bordetella parapertussis: an unresolved problem
Expert Rev Anti Infect Ther
Recovery of bordetella holmesii from patients with pertussis-like symptoms: use of pulsed-field gel electrophoresis to characterize circulating strains
J Clin Microbiol
The elements of statistical learning: data mining, inference, and prediction: with 200 full-color illustrations
Travelling waves and spatial hierarchies in measles epidemics
Nature
Cited by (51)
Vaccination strategies and virulent mutation spread: A game theory study
2023, Chaos, Solitons and FractalsSpecies interactions may help explain the erratic periodicity of whooping cough dynamics
2018, EpidemicsCitation Excerpt :This is an interesting future question that vaccination, which may have an asymmetric effect on the system, can impact the interactions of these two species. For example, offset of age-distribution and positive correlation of pertussis and parapertussis incidence in Massachusetts (1990–2008) are likely due to pertussis vaccine-induced immunity in the population (Lavine et al., 2010). Many reported diseases can result from multiple etiological agents: e.g. diarrheal disease, influenza like illness, meningococcal meningitis.
Age-specific effectiveness following each dose of acellular pertussis vaccine among infants and children in New Zealand
2017, VaccineCitation Excerpt :Still, the effect estimates for older age groups are steady with heavily overlapping confidence intervals, meaning it is unlikely that there was any true but undetected decrease in VE as children aged. Adults and older siblings are the most important reservoir for transmission of pertussis to infants and young children [18,42,43]. Because whole-cell vaccine was discontinued only 6 years prior to the beginning of our study period, residual population immunity among adolescents who received whole-cell vaccine in the 1990s may have provided indirect protection for infants and children during our study period.
ADVICE for a healthier life: Adult Vaccination Campaign in Europe
2016, European Journal of Internal MedicinePertussis in the Newborn: Certainties and uncertainties in 2014
2015, Paediatric Respiratory ReviewsCitation Excerpt :Neonates may therefore have been partly protected by maternal antibodies [63]. Pertussis in adolescents and adults may represent an important reservoir for transmission to unvaccinated infants [64]. Teenagers booster immunization, although certainly of benefit for the teenage population, may have little impact on protection against infant pertussis.