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Vaccine Jan 2021This issue of Vaccine is devoted to papers from a research project that developed two types of simulation models, static and dynamic transmission, to evaluate the...
This issue of Vaccine is devoted to papers from a research project that developed two types of simulation models, static and dynamic transmission, to evaluate the cost-effectiveness of maternal immunization to prevent pertussis in infants in low- and middle-income countries (LMICs). The research was conducted by a multinational team of investigators and funded by the Bill & Melinda Gates Foundation to gain an understanding of when and where maternal immunization might be a good public health investment for LMICs. Here we review the project's central lessons for vaccine policy and research. Models require a lot of data. As most LMICs lack good data, the models were built using pertussis disease burden data from Brazil, a middle-income country with three long-established, independent information systems (disease surveillance, hospitalization, and mortality), on the hypothesis that the disease process is similar across countries. Values for key parameters, particularly infant mortality, infant vaccine coverage, and costs of vaccination and treatment, were then varied to represent other LMICs. The results show that coverage levels of infant whole cell pertussis (wP) vaccine are key to the cost-effectiveness of maternal pertussis immunization. In settings where infant wP coverage is below the threshold thought necessary to eliminate pertussis in the population, 90-95%, maternal immunization is cost-effective, even cost-saving. By contrast, it is very expensive in countries capable of maintaining infant vaccination in or above the threshold range. The research also suggests that, while static models may serve to explore an intervention's cost-effectiveness initially, dynamic transmission models are essential for more accurate estimates. These findings can help guide policies toward maternal pertussis immunization, but also show that developing better data on neonatal pertussis mortality burden and infant vaccine coverage in LMICs, and on the duration of immunity of currently available pertussis vaccines, are key priorities to support better vaccine policy.
Topics: Humans; Infant; Brazil; Cost-Benefit Analysis; Developing Countries; Immunization Programs; Pertussis Vaccine; Vaccination; Whooping Cough; Maternal Health Services
PubMed: 33303179
DOI: 10.1016/j.vaccine.2020.10.054 -
BMC Infectious Diseases Oct 2019Pertussis causes severe disease in young unvaccinated infants, with preterms potentially at highest risk. We studied pertussis in hospitalized infants as related to... (Observational Study)
Observational Study
BACKGROUND
Pertussis causes severe disease in young unvaccinated infants, with preterms potentially at highest risk. We studied pertussis in hospitalized infants as related to gestational age (GA) and vaccination history.
METHODS
Medical record data of 0-2y old patients hospitalized for pertussis during 2005-2014 were linked to vaccination data. Multivariable logistic regression was used to study the association between GA and vaccination history on the clinical disease course. We compared vaccine effectiveness (VE) against hospitalization for pertussis between term and preterm infants (i.e., <37w GA) using the screening method as developed by Farrington.
RESULTS
Of 1187 records, medical data from 676 were retrieved. Of these, 12% concerned preterms, whereas they are 8% of Dutch birth cohorts. Median age at admission was 3 m for preterms and 2 m for terms (p < 0.001). Preterms more often had received pertussis vaccination (62% vs 44%; p = 0.01) and more often had coinfections (37% vs 21%; p = 0.01). Preterms tended more often to have complications, to require artificial respiration or to need admittance to the intensive care unit (ICU). Preterms had longer ICU stays (15d vs 9d; p = 0.004). Vaccinated preterms and terms had a lower median length of hospital stay and lower crude risks of apneas and the need for artificial respiration, additional oxygen, and ICU admittance than those not vaccinated. After adjustment for presence of coinfections and age at admittance, these differences were not significant, except the lower need of oxygen treatment in vaccinated terms. Effectiveness of the first vaccination against pertussis hospitalizations was 95% (95% CI 93-96%) and 73% (95% CI 20-91%) in terms and preterms, respectively. Effectiveness of the second dose of the primary vaccination series was comparable in both groups (86 and 99%, respectively).
CONCLUSIONS
Infants hospitalized for pertussis suffer from severe disease. Preterms were overrepresented, with higher need for intensive treatment and less VE of first vaccination. These findings stress the need for alternative prevention, in particular prenatal vaccination of mothers, to reduce pertussis in both groups.
Topics: Apnea; Child, Hospitalized; Child, Preschool; Cohort Studies; Female; Gestational Age; Hospitalization; Humans; Infant; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Length of Stay; Logistic Models; Male; Mothers; Netherlands; Pertussis Vaccine; Pregnancy; Respiration, Artificial; Retrospective Studies; Treatment Outcome; Vaccination; Whooping Cough
PubMed: 31664950
DOI: 10.1186/s12879-019-4563-5 -
MMWR. Morbidity and Mortality Weekly... Feb 2002Pertussis was a major cause of morbidity and mortality among infants and children in the United States during the prevaccine era (i.e., before the mid-1940s). Following...
Pertussis was a major cause of morbidity and mortality among infants and children in the United States during the prevaccine era (i.e., before the mid-1940s). Following the introduction and widespread use of whole-cell pertussis vaccine combined with diphtheria and tetanus toxoids (DTP) among infants and children in the late 1940s, the incidence of reported pertussis declined to a historic low of 1,010 cases in 1976 (Figure 1). However, since the early 1980s, reported pertussis incidence has increased cyclically with peaks occurring every 3-4 years. In 1996, less reactogenic acellular pertussis vaccines (DTaP) were licensed and recommended for routine use among infants. This report summarizes national surveillance data for pertussis during 1997-2000 and assesses the effectiveness of pertussis vaccination in the United States during this period. The findings indicate that pertussis incidence continues to increase in infants too young to receive 3 doses of pertussis-containing vaccine and in adolescents and adults. Prevention efforts should be directed at maintaining high vaccination rates and managing pertussis cases and outbreaks.
Topics: Adolescent; Adult; Age Distribution; Child; Child, Preschool; Humans; Infant; Pertussis Vaccine; United States; Vaccination; Whooping Cough
PubMed: 11837909
DOI: No ID Found -
Indian Pediatrics Aug 2016Though vaccines have been in use for over seventy years, we have been unable to eradicate or control pertussis. This disease is a worldwide problem, and recently has...
Though vaccines have been in use for over seventy years, we have been unable to eradicate or control pertussis. This disease is a worldwide problem, and recently has been occurring in outbreaks even in places with good immunization coverage. The debate about the use of acellular or whole cell vaccine has taken attention away from the other significant issues. The high rate of serious disease and death in young infants, and the repeated outbreaks of pertussis even in highly-vaccinated populations is a matter for grave concern. Finding strategies to protect the most vulnerable is a priority. Newer vaccines are under development, and will be welcome, but may be too expensive for mass use in resource-poor nations. It is important to adopt cost-effective strategies to deal with this disease.
Topics: Child; Child, Preschool; Diphtheria-Tetanus-Pertussis Vaccine; Humans; Infant; Infant, Newborn; Mothers; Pertussis Vaccine; Whooping Cough
PubMed: 27567644
DOI: 10.1007/s13312-016-0909-x -
Human Vaccines & Immunotherapeutics 2018Young infants contribute to relatively high burden of vaccine-preventable diseases, including infections by influenza virus and Bordetella pertussis. Vaccination of... (Review)
Review
Young infants contribute to relatively high burden of vaccine-preventable diseases, including infections by influenza virus and Bordetella pertussis. Vaccination of pregnant women can enhance transplacental transfer of protective antibody to the fetus and protect the infant against disease during the first few months of life. Pregnant women are a priority group for seasonal influenza vaccination, due to third-trimester pregnancy being a risk-factor for severe influenza illness. Furthermore, randomized controlled trials confirmed that influenza vaccination during pregnancy confers protection against influenza-confirmed illness in the women, and their infants up to 3 months of age; and is also associated with 20% reduction in all-cause pneumonia among young-infants. Maternal influenza vaccination might also reduce the risk of low-birth weight, preterm births, and stillbirths however, data on this is conflicting. Vaccination of pregnant women with acellular pertussis vaccines reduces pertussis in their young infants by up to 93%. The increase in specific pertussis antibody among the infants born to vaccinated women might, however, interfere with the active pertussis vaccination of the infant following the primary series of vaccines. The clinical implication of this is yet to be ascertained, particularly since immune responses following the booster vaccine are unaffected. Vaccination of pregnant women with inactivated influenza vaccine and acellular pertussis vaccine have been demonstrated to confer protection to their young infants, and warrants consideration for inclusion into public health immunization programs, including in low and middle income countries.
Topics: Female; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Influenza Vaccines; Influenza, Human; Pertussis Vaccine; Pregnancy; Pregnancy Complications, Infectious; Vaccines, Acellular; Vaccines, Inactivated; Whooping Cough
PubMed: 30024822
DOI: 10.1080/21645515.2018.1483810 -
MBio Jun 2014The resurgence of pertussis (whooping cough) in countries with high vaccination coverage is alarming and invites reconsideration of the use of current acellular...
The resurgence of pertussis (whooping cough) in countries with high vaccination coverage is alarming and invites reconsideration of the use of current acellular pertussis (aP) vaccines, which have largely replaced the old, reactogenic, whole-cell pertussis (wP) vaccine. Some drawbacks of these vaccines in terms of limited antigenic composition and early waning of antibody levels could be anticipated by the results of in-trial or postlicensure human investigations of B- and T-cell responses in aP versus wP vaccine recipients or unvaccinated, infected children. Recent data in experimental models, including primates, suggest that generation of vaccines capable of a potent, though regulated, stimulation of innate immunity driving effective, persistent adaptive immune responses against Bordetella pertussis infection should be privileged. Adjuvants that skew Th1/Th17 responses or new wP (detoxified or attenuated) vaccines should be explored. Nonetheless, the high merits of the current aP vaccines in persuading people to resume vaccination against pertussis should not be forgotten.
Topics: Animals; Bordetella pertussis; Humans; Pertussis Vaccine; Th1 Cells; Th17 Cells; Vaccination; Whooping Cough
PubMed: 24917600
DOI: 10.1128/mBio.01339-14 -
Vaccine Jul 2015The limited durability of pertussis vaccine-induced protection requires novel approaches to reactivate immunity and limit pertussis resurgence in older children and...
The limited durability of pertussis vaccine-induced protection requires novel approaches to reactivate immunity and limit pertussis resurgence in older children and adults. We propose that periodic boosters could be delivered using a novel epicutaneous delivery system (Viaskin) to deliver optimized pertussis antigens such as genetically-detoxified pertussis toxin (rPT). To best mimic the human situation in which vaccine-induced memory cells persist, whereas antibodies wane, we developed a novel adoptive transfer murine model of pertussis immunity. This allowed demonstrating that a single application of Viaskin delivering rPT and/or pertactin and filamentous hemagglutinin effectively reactivates vaccine-induced pertussis immunity and protects against Bordetella pertussis challenge. Recalling pertussis immunity without needles nor adjuvant may considerably facilitate the acceptance and application of periodic boosters.
Topics: Administration, Cutaneous; Animals; Antigens, Bacterial; Bordetella pertussis; Female; Immunization, Secondary; Mice, Inbred BALB C; Pertussis Vaccine; Whooping Cough
PubMed: 26067183
DOI: 10.1016/j.vaccine.2015.05.089 -
Toxins Sep 2019is a human-specific pathogen and the causative agent of whooping cough. The ongoing resurgence in pertussis incidence in high income countries is likely due to faster... (Review)
Review
is a human-specific pathogen and the causative agent of whooping cough. The ongoing resurgence in pertussis incidence in high income countries is likely due to faster waning of immunity and increased asymptomatic colonization in individuals vaccinated with acellular pertussis (aP) vaccine relative whole-cell pertussis (wP)-vaccinated individuals. This has renewed interest in developing more effective vaccines and treatments and, in support of these efforts, defining pertussis vaccine correlates of protection and the role of vaccine antigens and toxins in disease. Pertussis and its toxins have been investigated by scientists for over a century, yet we still do not have a clear understanding of how pertussis toxin (PT) contributes to disease symptomology or how anti-PT immune responses confer protection. This review covers PT's role in disease and evidence for its protective role in vaccines. Clinical data suggest that PT is a defining and essential toxin for pathogenesis and, when formulated into a vaccine, can prevent disease. Additional studies are required to further elucidate the role of PT in disease and vaccine-mediated protection, to inform the development of more effective treatments and vaccines.
Topics: Animals; Hemagglutinins; Humans; Immunoglobulins, Intravenous; Pertussis Toxin; Pertussis Vaccine; Vaccination
PubMed: 31546599
DOI: 10.3390/toxins11100557 -
Clinical Microbiology and Infection :... Dec 2016Pertussis is a severe respiratory disease that can be fatal in young infants. Its main aetiological agent is the Gram-negative micro-organism Bordetella pertussis.... (Review)
Review
Pertussis is a severe respiratory disease that can be fatal in young infants. Its main aetiological agent is the Gram-negative micro-organism Bordetella pertussis. Vaccines against the disease have been in use since the 1950s, and global vaccination coverage has now reached more than 85%. Nevertheless, the disease has not been controlled in any country, and has even made a spectacular come-back in the industrialized world, where the first-generation whole-cell vaccines have been replaced by the more recent, less reactogenic, acellular vaccines. Several hypotheses have been proposed to explain these observations, including the fast waning of acellular vaccine-induced protection. However, recent mathematical modelling studies have indicated that asymptomatic transmission of B. pertussis may be the main reason for the current resurgence of pertussis. Recent studies in non-human primates have shown that neither whole-cell, nor acellular vaccines prevent infection and transmission of B. pertussis, in contrast to prior exposure. New vaccines that can be applied nasally to mimic natural infection without causing disease may therefore be useful for long-term control of pertussis. Several vaccine candidates have been proposed, the most advanced of which is the genetically attenuated B. pertussis strain BPZE1. This vaccine candidate has successfully completed a first-in-man phase I trial and was shown to be safe in young male volunteers, able to transiently colonize the nasopharynx and to induce antibody responses to B. pertussis antigens in all colonized individuals. Whether BPZE1 will indeed be useful to ultimately control pertussis obviously needs to be assessed by carefully conducted human efficacy trials.
Topics: Animals; Carrier State; Clinical Trials as Topic; Disease Models, Animal; Disease Transmission, Infectious; Humans; Pertussis Vaccine; Primates; Vaccines, Attenuated; Whooping Cough
PubMed: 28341014
DOI: 10.1016/j.cmi.2016.05.029 -
The Journal of Infectious Diseases Apr 2014The significant burden of disease due to pertussis, which predominantly affects newborns during their first few months of life, was substantially decreased following the... (Review)
Review
The significant burden of disease due to pertussis, which predominantly affects newborns during their first few months of life, was substantially decreased following the introduction of inactivated whole-bacterial-cell vaccines in the middle of the 20th century. Although these vaccines were effective in reducing the incidence of pertussis in the countries that implemented their widespread use, increasing concerns about pertussis vaccine-associated adverse events led the development of acellular pertussis vaccines containing 1 or more purified Bordetella pertussis proteins. During the 1990s, collaborative international clinical trials were conducted to evaluate the safety, immunogenicity, and/or efficacy of different acellular vaccines.
Topics: Clinical Trials as Topic; History, 20th Century; Humans; Pertussis Vaccine; Vaccination; Vaccines, Acellular; Whooping Cough
PubMed: 24626871
DOI: 10.1093/infdis/jit592