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"Whooping Cough"
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Vaccine innovators Pearl Kendrick and Grace Eldering
Discusses how the research efforts of Grace Eldering and Pearl Kendrick helped to treat and prevent whooping cough, a deadly disease that mostly affected children.
Book
A Phase I Clinical Study of a Live Attenuated Bordetella pertussis Vaccine - BPZE1; A Single Centre, Double-Blind, Placebo-Controlled, Dose-Escalating Study of BPZE1 Given Intranasally to Healthy Adult Male Volunteers
Acellular pertussis vaccines do not control pertussis. A new approach to offer protection to infants is necessary. BPZE1, a genetically modified Bordetella pertussis strain, was developed as a live attenuated nasal pertussis vaccine by genetically eliminating or detoxifying 3 toxins.
We performed a double-blind, placebo-controlled, dose-escalating study of BPZE1 given intranasally for the first time to human volunteers, the first trial of a live attenuated bacterial vaccine specifically designed for the respiratory tract. 12 subjects per dose group received 10³, 10⁵ or 10⁷ colony-forming units as droplets with half of the dose in each nostril. 12 controls received the diluent. Local and systemic safety and immune responses were assessed during 6 months, and nasopharyngeal colonization with BPZE1 was determined with repeated cultures during the first 4 weeks after vaccination.
Colonization was seen in one subject in the low dose, one in the medium dose and five in the high dose group. Significant increases in immune responses against pertussis antigens were seen in all colonized subjects. There was one serious adverse event not related to the vaccine. Other adverse events were trivial and occurred with similar frequency in the placebo and vaccine groups.
BPZE1 is safe in healthy adults and able to transiently colonize the nasopharynx. It induces immune responses in all colonized individuals. BPZE1 can thus undergo further clinical development, including dose optimization and trials in younger age groups.
ClinicalTrials.gov NCT01188512.
Journal Article
Efficacy of an Acellular Pertussis Vaccine among Adolescents and Adults
In this randomized trial in subjects between 15 and 65 years old, a new acellular pertussis vaccine was safe and had an efficacy of 92 percent against documented, symptomatic
Bordetella pertussis
infections. Among controls, the incidence of pertussis was 370 per 100,000 person-years. Vaccination of adults and adolescents could prevent pertussis and reduce the transmission of
B. pertussis
to young children.
In subjects between 15 and 65 years old, a new acellular pertussis vaccine was safe and had an efficacy of 92 percent against documented, symptomatic
Bordetella pertussis
infections.
Bordetella pertussis
infects the human respiratory tract and in nonimmune persons causes whooping cough, a severe illness associated with prolonged cough.
1
,
2
The severity of illness varies with age, immune status (prior immunization or infection), and probably such factors as the extent of exposure and the virulence of the organism. Disease risk and severity are greatest in unimmunized infants.
3
–
5
During the past 50 years, routine pediatric pertussis immunization has dramatically decreased the pediatric disease burden.
1
,
2
In the United States, the annual incidence of pertussis fell from 157 per 100,000 persons in the prevaccine era to less than 1 . . .
Journal Article
An update of the global burden of pertussis in children younger than 5 years: a modelling study
Since the publication in 2003 of a model to estimate the disease burden of pertussis, new evidence of the protective effect of incomplete pertussis vaccination against severe pertussis has been reported. We revised the model to provide new estimates of regional and global pertussis cases and deaths for children younger than 5 years.
We developed a revised model with data from 2014 to estimate pertussis cases and deaths. Pertussis cases were defined according to the WHO clinical case definition, as a coughing illness lasting at least 2 weeks with paroxysms of coughing, inspiratory whooping, or post-tussive vomiting. We used UN population estimates and WHO and UNICEF data on national pertussis immunisation coverage. Estimates were made for vaccine effectiveness against pertussis cases and deaths for one, two, and three doses of vaccination, probability of infection in low and high coverage countries, and case fatality ratios in low and high mortality countries in two age groups: infants younger than 1 year and children aged 1–4 years. We did sensitivity analyses with a range of input parameters to assess the effect of uncertainty of the input parameters on the model outputs.
We estimated that there were 24·1 million pertussis cases and 160 700 deaths from pertussis in children younger than 5 years in 2014, with the African region contributing the largest proportions (7·8 million [33%] cases and 92 500 [58%] deaths). 5·1 million (21%) estimated pertussis cases and 85 900 (53%) estimated deaths were in infants younger than 1 year. In the sensitivity analyses, the estimated number of cases ranged from 7 million to 40 million and deaths from 38 000 to 670 000.
Our estimates suggest that, compared with the 1999 estimates published in 2003 (30·6 million pertussis cases and 390 000 deaths from pertussis in children younger than 5 years), the numbers of cases and deaths of pertussis have fallen substantially. Model sensitivity emphasised the importance of better surveillance to improve country-level decision making and pertussis control.
None.
Journal Article
Seroprevalence of Bordetella pertussis antibodies and anti-pertussis antibody response after a single dose of reduced-antigen combined diphtheria, tetanus, and acellular pertussis vaccine (Tdap) in pregnant Thai women
Maternal immunization with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) has recently been implemented to prevent infant pertussis. Tdap is still not routinely recommended in Thailand, and there are limited data to support or challenge this strategy.
The primary aim was to determine the seroprevalence of anti-pertussis toxin antibodies (anti-PT IgG) among pregnant Thai women. The secondary aims were to evaluate antibodies response after Tdap vaccination between seronegative and seropositive mothers and to compare the different antibody titers at delivery among seropositive mothers who received Tdap to those who received tetanus-diphtheria vaccine (Td).
This randomized clinical trial was conducted during April 2018 to April 2019 at Siriraj Hospital, Bangkok, Thailand. A total of 129 pregnant women were included. Paired blood samples for anti-PT IgG levels were obtained during the first antenatal visit and at delivery. A baseline cut-off value of <5 IU/ml indicated seronegativity. There were 29 exclusions from the original 129 enrollment. All seronegative participants (n = 69) received Tdap, while the seropositive group were randomized 1:1 to receive either Tdap (n = 18) or Td (n = 13) during 27–36 weeks’ gestation. The antibody levels from both sera were compared between groups.
The seroprevalence of maternal anti-PT IgG was 33.3% (43/129). There was no significant difference in the increment of antibody levels after Tdap vaccination between the seronegative and seropositive groups (30.2 vs. 42 IU/ml; p = 0.183). Among seropositive groups, all Tdap recipients had increased antibody titers at delivery, while all Td recipients showed waning of immunity throughout gestation. (42 IU/ml vs. −7.4 IU/ml; p < 0.001).
Most pregnant Thai women have seronegative against pertussis. Most seropositive mothers had initial low antibody titers and their immunity significantly decreased before delivery. Our findings highlight the need for universal pertussis immunization in pregnancy regardless of individual baseline immunity.
Journal Article
Epidemic Pertussis in 2012 — The Resurgence of a Vaccine-Preventable Disease
According to the Centers for Disease Control and Prevention, the United States is currently experiencing what may turn out to be the largest outbreak of reported pertussis in 50 years. Why has this theoretically vaccine-preventable disease been on the upswing?
According to the Centers for Disease Control and Prevention, the United States is currently experiencing what may turn out to be the largest outbreak of reported pertussis (whooping cough) in 50 years. Why has this theoretically vaccine-preventable disease been on the upswing?
The past 45 years have seen concern about the safety of the diphtheria–tetanus–pertussis (DTP) vaccine, epidemics stemming from the vaccine's decreased use, and the development of new vaccines using acellular pertussis components (DTaP). In the prevaccine era, the number of reported cases of pertussis reached epidemic proportions every 2 to 5 years.
1
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2
Pertussis immunization in the United . . .
Journal Article
Maternal Vaccination in Argentina
Abstract
Background
In 2011, Argentina experienced its highest pertussis incidence and mortality rates of the last decade; 60% of deaths were among infants aged <2 months. In response, a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine was recommended for all pregnant women at ≥20 weeks of gestation. Although recent studies suggest that maternal Tdap vaccination is effective at preventing infant disease, no data have come from low- or middle-income countries, nor from ones using whole-cell pertussis vaccines for primary immunization.
Methods
We conducted a matched case-control evaluation to assess the effectiveness of maternal Tdap vaccination in preventing pertussis among infants aged <2 months in Argentina. Pertussis case patients identified from September 2012 to March 2016 at 6 hospital sites and confirmed by polymerase chain reaction testing were included. Five randomly selected controls were matched to each case patient by hospital site and mother’s health district. We used multivariable conditional logistic regression to calculate odds ratios (ORs). Vaccine effectiveness (VE) was estimated as (1 – OR) × 100%.
Results
Seventy-one case patients and 300 controls were included in the analysis. Forty-nine percent of case patients and 78% of controls had mothers who were vaccinated during pregnancy. Overall Tdap VE was estimated at 80.7% (95% confidence interval, 52.1%–92.2%). We found similar VE whether Tdap was administered during the second or third trimester.
Conclusions
Tdap vaccination during pregnancy is effective in preventing pertussis in infants aged <2 months in Argentina, with similar effectiveness whether administered during the second or third trimester of pregnancy.
Effectiveness of maternal Tdap vaccination in preventing infant pertussis has not been well studied in middle-income countries. Our findings demonstrate that Tdap vaccination during the second or third trimester of pregnancy protects against pertussis in infants aged <2 months in Argentina.
Journal Article
PERISCOPE: road towards effective control of pertussis
The resurgence and changing epidemiology of pertussis in high-income countries, the high infant mortality caused by pertussis in low-income countries, and the increasing morbidity in all age groups worldwide call for a concerted effort to both improve the current vaccines and develop new vaccines and vaccination strategies against pertussis. In this Personal View, we identify several key obstacles on the path to developing a durable solution for global control of pertussis. To systematically address these obstacles, the PERtussIS Correlates Of Protection Europe (PERISCOPE) Consortium was established in March, 2016. The objectives of this consortium are to increase scientific understanding of immunity to pertussis in humans induced by vaccines and infections, to identify biomarkers of protective immunity, and to generate technologies and infrastructure for the future development of improved pertussis vaccines. By working towards the accelerated licensure and implementation of novel, well tolerated, and effective pertussis vaccines, we hope to strengthen and stimulate further collaboration and transparency between the key stakeholders, including the public, the scientific community, public health institutes, regulatory authorities, and vaccine manufacturers.
Journal Article
Severe pertussis infections in pediatric intensive care units: a multicenter study
This study aims to evaluate the clinical course of critical pertussis illness to the pediatric intensive care unit in Istanbul. The study was conducted as a multicenter, retrospective study between January 1, 2023, and December 31, 2023. Cases with positive polymerase chain reaction testing for
Bordetella pertussis
of nasopharyngeal swab samples within the first 24 h of pediatric intensive care unit admission were recorded. We divided the patients into exchange blood transfusion group and non-exchange blood transfusion group, comparing related factors and clinical characteristics among each group. A total of 50 children with severe pertussis were enrolled in the study, including 29 males (58%), with a median age of 9.14 weeks (range, 7.29–15.3 weeks). The mortality rate for severe pertussis was 8%. Exchange blood transfusion was performed in eight patients (16%). There were no significant differences between patients who received exchange blood transfusion and those who did not in terms of age, male gender, gestational age, birth weight, comorbidities, presenting symptoms, duration of cough, prior antibiotic use, vaccination status, coinfections, PICU length of stay, or mortality (
p
> 0.05). Children who underwent exchange blood transfusion had significantly higher white blood cell (WBC) counts, lymphocyte counts, neutrophil counts, and C-reactive protein (CRP) levels compared to those who did not receive the procedure (
p
< 0.05). Pulmonary hypertension was observed in 50% of the children who received exchange blood transfusion, while it was present in only 11.8% of those who did not undergo the procedure (
p
< 0.05). Additionally, patients who received exchange blood transfusion had higher incidences of respiratory failure, cardiac failure or arrest, inotrope requirement, and mechanical ventilation compared to those who did not receive the transfusion (
p
< 0.05).
Conclusions
: Pertussis can lead to severe complications and mortality in critically ill infants. Most severe pertussis occurred in young, unimmunized infants. Children admitted with pertussis with high CRP level, high WBC and lymphocyte, and cardiac and respiratory failure can need exchange blood transfusion.
What is Known:
•
Pertussis is a highly contagious respiratory infection caused by Bordetella pertussis, which primarily affects infants. Despite vaccination efforts, pertussis remains a significant cause of morbidity and mortality in infants, particularly those too young to be fully vaccinated.
What is New:
•
In pertussis, exchange blood transfusion may be considered in cases of severe pulmonary hypertension or cardiogenic shock, as indicated by echocardiographic findings, in conjunction with leukocytosis observed on laboratory tests.
Journal Article
Reemergence of Bordetella parapertussis , United States, 2019–2023
To determine changes in Bordetella pertussis and B. parapertussis detection rates, we analyzed 1.43 million respiratory multiplex PCR test results from US facilities from 2019 through mid-2023. From mid-2022 through mid-2023, Bordetella spp. detection increased 8.5-fold; 95% of detections were B. parapertussis. While B. parapertussis rates increased, B. pertussis rates decreased.
Journal Article