Incidence and mortality of pertussis disease in infants <12 months of age following introduction of pertussis maternal universal mass vaccination in Bogotá, Colombia

BackgroundMaternal immunization with tetanus, diphtheria, and acellular pertussis (Tdap) vaccine confers protection to young infants. We aimed to describe trends in pertussis incidence and associated mortality in children aged <12 months before and after introduction of maternal Tdap immunization in Bogotá, Colombia.MethodsData on pertussis-related cases/deaths in infants aged <12 months were collected from SIVIGILA for the period 2005–2016, and compared incidence for the pre-vaccine introduction (2005–2012) and post-maternal Tdap vaccination (2014–2016) periods in infants aged <12 months and in three distinct age-strata; ≤6 weeks, 7–<28 weeks, and 28–52 weeks. Mortality comparisons were performed in all infants <12 months.ResultsFrom 2005 to 2016, 2315 laboratory or clinically-confirmed pertussis cases were reported in infants <12 months of age (278 cases in young infants aged ≤6 weeks); 55 pertussis deaths were reported in children aged <12 months. No pertussis deaths were reported in the 2014–2016 period. Since maternal Tdap introduction in 2013, a consistent decline in pertussis incidence and mortality was observed. In the time-series analysis, incidence declined from 209.4/100,000 persons (2005–2012) to 49.1/100,000 persons (2014–2016) in all children <12 months; a 87.5% (95%CI: 77.2-93.2%) reduction. For these same period’s incidence in young infants ≤6 weeks declined from 196.7 to 89.6/100,000 person-years (an 54.4% [95% CI: 35.4–67.9%] reduction). Greater incidence reductions were observed in older infants; 73.4% (95% CI: 68.4–77.6%) in those aged 7–<28 weeks, and 100% in those aged 28–52 weeks. A 100% reduction in Pertussis mortality in infants <12 months was observed. Since Tdap introduction, maternal vaccine coverage rose from <60% in 2013–2015 to 80% in 2016.ConclusionsImplementation of maternal immunization in Bogotá may have contributed to the reduction in pertussis incidence and mortality among infants <12 months of age (ClinicalTrials.gov: NCT02569879).An Audio Summary linked to this article that can be found on Figshare https://doi.org/10.6084/m9.figshare.12943316     

Incidence of pertussis in subjects aged 50 years and older in France in 2013–2014

Objective

To assess the incidence of pertussis (whooping cough) in subjects aged 50 years and older in France.

What determines uptake of pertussis vaccine in pregnancy? A cross sectional survey in an ethnically diverse population of pregnant women in London

IntroductionFollowing the major outbreak of pertussis and 14 infant deaths across England in 2012, the Department of Health (DH) introduced the UK's first maternal pertussis vaccination programme. Data published by Public Health England (PHE) suggest uptake of the vaccine varies considerably across the country. The reasons for this heterogeneity need to be addressed to optimise the impact of the programme.ObjectiveTo assess uptake of antenatal pertussis and influenza vaccine in a leading NHS Trust in London and to explore awareness and attitudes of pregnant women towards the pertussis vaccination programme.DesignA cross sectional survey was conducted in an ethnically diverse group of 200 pregnant women accessing antenatal care at Imperial Healthcare NHS Trust. Quantitative data was tabulated and content analysis was carried out on the free text. Qualitative data was divided into themes for accepting or declining the vaccine.ResultsAwareness of the programme was 63% (126/200) with actual uptake of the vaccine only 26.0% (52/200). Women had received information from multiple sources, primarily General Practitioners (GP) and midwives. 34.0% (68/200) of women were offered the vaccine at their GP practice, only 24% reported a meaningful discussion with their GP about it. Uptake differed by up to 15.0% between ethnicities. Qualitative data showed that uptake could be significantly enhanced if vaccination was recommended by a familiar healthcare professional. Feeling uninformed, lack of professional encouragement and uncertainties of risk and benefit of the vaccine were the greatest barriers to uptake.ConclusionVaccine uptake in this cohort of pregnant women was poor. Understanding the target audience and engaging with key groups who influence women's decision-making is essential. Knowledgeable health care professionals need to recommend the vaccine and provide accurate and timely information to increase success of this important programme.     

Brand-specific rates of pertussis disease among Wisconsin children given 1–4 doses of pertussis Vaccine, 2010–2014

BackgroundAcellular pertussis vaccines were initially licensed based on placebo-controlled efficacy trials, but such trials are no longer ethical. The effectiveness of current pertussis vaccines among properly vaccinated children <5 years is so high that a randomized trial is infeasible. Fluctuations in pertussis incidence and characteristics of the US vaccine marketplace make selection of suitable controls for a case-control study problematic. To satisfy an FDA requirement to evaluate rates of pertussis following licensure of Pentacel® vaccine, we used a case-cohort study design with a novel method for characterizing the cohort population.MethodsThis prospective, observational study was conducted in Wisconsin from 2010 to 2014 among Wisconsin residents <60 months of age who received ≤four doses of pertussis vaccine (surveillance population). Cases were identified by the Wisconsin Division of Public Health. Characteristics and pertussis vaccinations of the surveillance population were estimated by ongoing random telephonic survey. The primary objective was to determine rates of pertussis disease among those who received only Pentacel vaccine (Group 1) vs those who received a single brand of vaccine other than Pentacel vaccine (Group 2).Results1195 pertussis cases were identified. It was estimated that the surveillance population accrued a total of 1,133,403 person-years (Group 1, 39%; Group 2, 41%; Group 3 [those not in Group 1 or Group 2], 20%). Pertussis rates were similar in Group 1 (98.9/100,000) and Group 2 (96.2/100,000); rate ratios were 1.03 (unadjusted; 90% CI, 0.92–1.15) and 0.99 (adjusted; 90% CI, 0.89–1.12). Persons with one or more delayed vaccinations had a 66% higher risk of pertussis (90% CI, 39–96%).DiscussionPertussis protection was not found to differ for recipients of the newly licensed vs other available pertussis vaccines. Delayed vaccination substantially increased risk of pertussis. Sample survey methodology was able to characterize the study cohort and enable an otherwise-infeasible study.Clinical Trial Registry number: ClinicalTrials.gov, NCT01129362.     

The induction of breast milk pertussis specific antibodies following gestational tetanus–diphtheria–acellular pertussis vaccination

Background

Center for Disease Control and Prevention recommends vaccination of pregnant women with tetanus–diphtheria–acellular pertussis (Tdap).

Aim

To measure pertussis specific antibodies, total protein and their ratio in breast milk following gestational Tdap vaccination.

Methods

Women who received Tdap after the 20th week of pregnancy were recruited and unvaccinated women served as controls. Breast milk total protein, immunoglobulin A (IgA) to pertussis toxin (PT), filamentous hemagglutinin (FHA) and immunoglobulin G (IgG) to PT, FHA and pertactin (PRN) were measured. To overcome the dilution that occurs in the transition from colostrum to mature breast milk, we calculated pertussis specific antibody to total protein ratio.

Results

Pertussis specific IgA was the predominant pertussis immunoglobulin in the colostrum of Tdap vaccinated women with the geometric mean concentrations (GMCs) of IgA to FHA higher than for IgA to PT, 24.12 ELISA units/milliliter (EU/mL) vs. 8.18 EU/mL, respectively, p < 0.004. There were differences between the vaccinated women and controls in the GMCs of IgA to FHA and IgG to PRN in the colostrum, 24.12 EU/mL vs. 6.52 EU/mL, p = 0.01 and 2.46 EU/mL vs. <0.6 EU/mL, p = 0.03, respectively. The GMCs of total protein showed significant decline over 8 weeks in the vaccinated women and controls, p < 0.004. Among vaccinated women, there was significant decline in the GMCs of IgA to PT and FHA over 8 weeks, p < 0.001. The geometric mean ratio of IgA to FHA to total protein also declined significantly over 8 weeks in the vaccinated women, p < 0.01, demonstrating a true decrease, however, pertussis IgA was measurable at 8 weeks.

Conclusions

Select colostrum pertussis antibody levels were significantly higher among women vaccinated with Tdap during pregnancy compared with unvaccinated women. Among vaccinated women, maximal levels of pertussis specific IgA were in the colostrum but still detected at 8 weeks. Lactation may augment infant's protection against pertussis.     

The resurgence of pertussis in developed countries: a problem for Brazil as well?

Pertussis is currently considered an important public health problem in developed countries. In most of these countries, mass immunization for pertussis was initiated in the 1950s and was followed by a marked decrease in disease incidence. In the 1970s, pertussis was apparently under control in countries were vaccine coverage was maintained high. However, in the last two decades of the 20th century, the number of reported cases increased in all age groups, including adolescents and adults, indicating resurgence of the disease. This brief note aims to present the possible reasons for resurgence of this disease and to discuss the prospects of its future dynamics in Brazil. There has been no evidence to date for the resurgence of pertussis in Brazil. However, since mass immunization in Brazil began only in the 1980s, one cannot rule out the possibility that pertussis will resurge in the near future. Therefore, it is important that public health services closely monitor the epidemiological situation of pertussis in order, if necessary, to rapidly update the current immunization strategy.     

Impact of Tdap vaccine during pregnancy on the incidence of pertussis in children under one year in Brazil – A time series analysis

Pertussis is a globally distributed infectious disease that is a significant cause of morbidity and mortality, especially in infants who are too young to be immunized. This disease is common in childhood, and when it occurs during the first few months of life, it leads to hospitalization and, sometimes, death. Brazil has adopted the strategy of maternal immunization against pertussis in late 2014. This study aims to analyze public data on the disease to determine whether there was an impact on the disease burden following the introduction of the vaccine Tdap in pregnant women and its magnitude. We performed a time-series analysis of the incidence of pertussis between October 2010 and January 2019. We stratified the population of interest into three groups: infants aged less than two months old, infants aged two to six months, and infants aged six months to one year, according to Brazil's vaccination schedule. We found a protective effect of maternal vaccination in all age groups, more prominent on the first group. Before the intervention, infants under two months had a higher risk of getting pertussis in comparison with infants two to six months old (HR 1.15, CI 95%: 1.11–1.19). After the intervention, age under two months is a protective factor compared with two to six months (HR 0.90, CI 95%: 0.82–0.98). The pertussis incidence reduced in all age groups and all Brazil's Regions.     

Cost–benefit of the introduction of new strategies for vaccination against pertussis in Spain: Cocooning and pregnant vaccination strategies

BackgroundPertussis remains a public health problem in countries with high vaccination coverage. Classic vaccination approaches have failed to effectively control the infection. The incidence of pertussis hospitalizations in infants is high, especially in those younger than 3 months who are in high risk of a severe disease and death. Additional strategies are recommended for short-term protection of this vulnerable population. In this study, we estimated the impact of 2 strategies for pertussis prevention in infants younger than 1 year of age—a cocoon vaccination strategy and the vaccination of pregnant women (VPW)—and the cost–benefit of these approaches relative to the current vaccination policy in Spain.MethodsA cost–benefit analysis was conducted from the perspective of the publically-funded Spanish healthcare system, based on the yearly number of hospitalizations during the period of 2009 to 2011. We calculated the absolute risk reduction, the number of parents that would need to be vaccinated to prevent 1 hospitalization or death in infants <1 year, and the net benefit-to-cost ratio of each strategy.ResultsFrom 2009 to 2011, the incidence of pertussis in Spain was 153.44 hospitalizations per 100,000 infants <1 year. The absolute risk reduction for hospitalization would be 42.1/100,000 with cocooning and 75.2/100,000 with VPW. The number of parents needed to vaccinate with the cocoon strategy to prevent 1 pertussis hospitalization would be 4752 and to prevent 1 death, more than 900,000. With VPW, 1331 pregnant women would have to be vaccinated to prevent 1 hospitalization and 200,000 to prevent 1 death. The benefit-to-cost ratio was 0.04 for cocooning and 0.15 for VPW.     

Effect of maternal immunization against pertussis in Medellin and the metropolitan area,Colombia, 2016–2017

BackgroundIn 2013, pertussis immunization (Tdap) for pregnant women was implemented in Colombia to protect newborns in response to increased pertussis incidence.ObjectiveTo assess the effect of Tdap maternal immunization on the concentration of mother/umbilical cord antibodies and the occurrence of pertussis in infants during their first six months of life.MethodsA cohort study in eight randomly selected hospitals in Medellin and metropolitan area of Antioquia, Colombia was conducted in 2015–2016. IgG PT antibody levels in paired maternal and umbilical cord sera were measured from 805 mothers immunized recruited during labor and 200 mothers recruited during the prenatal care before immunization and followed until delivery. Antibodies were analyzed by commercial ELISA kits. 896 infants were followed to detect acute respiratory infections and paroxysms of coughing, inspiratory whoop, apnea, cyanosis or post-tussive vomiting. For laboratory confirmation, B. pertussis- specific real time PCR was performed.ResultsWe observed a high prevalence of titers >100 IU/mL (mother: 18.40% [95% CI 16–21%]; umbilical cord: 23.1% [95% CI 19.2–27.4%]), positive correlation of umbilical cord and maternal antibodies, higher antibody concentration in vaccinated than in non-vaccinated mothers and significant difference in antibody levels before and after vaccination (Wilcoxon test p = 0.000). The trans placental transport ratio was higher if the mother was vaccinated between 26 and 30 weeks of pregnancy and maximum eight weeks before delivery. Two cases of pertussis were confirmed in infants (incidence of 1.99 per 1000).ConclusionThe expected effect of Tdap maternal vaccination against pertussis was observed.     

The epidemiology of pertussis in the Australian Capital Territory, 1999 to 2005--epidemics of testing, disease or false positives?

The increase in pertussis notifications since the 1990s in many countries, including Australia, has been attributed to improved diagnosis. This study aimed to describe the epidemiology of pertussis in the Australian Capital Territory from 1999 to 2005, determine whether the apparent changes could be accounted for by greater recognition and testing, and explore the impact of false positive serology results associated with faulty test kits. The Australian Capital Territory resident notification, laboratory and separation data from 1999 to 2005 were examined and the proportions of positive tests across time periods and age groups compared. Notification rates increased in the years 2000, 2003 and 2005. There was a shift in the age distribution of cases, from children and teenagers in 2000, to teenagers in 2003 and adults in 2005. Testing activity and notification activity were closely related. Comparing the epidemic periods to the preceding inter-epidemic periods, the proportion of positive tests was maintained or increased for all age groups combined and for adults and children (e.g. statistically significant increase from 7.8% to 14.0% in the 2005 epidemic in adults). During each epidemic the proportion of positive tests was statistically significantly higher in the age group with the highest notification activity. Despite similar testing rates in adults in 2003 and 2005, greater disease activity was reported in 2005. Although the numbers were small, polymerase chain reaction and culture positive test results increased in 2003 but not in 2005. The proportion of positive polymerase chain reaction results increased in 2003, providing strong evidence that the apparent epidemic of 2003 was due to a true increase in underlying disease activity. Because of the uncertainty surrounding the timing of the false positive serology results, the study provides weaker support for a true epidemic of pertussis in 2005.     

CpG 1018® adjuvant enhances Tdap immune responses against Bordetella pertussis in mice

Bordetella pertussis is the causative agent of whooping cough (pertussis), a severe respiratory disease that can be fatal, particularly in infants. Despite high vaccine coverage, pertussis remains a problem because the currently used DTaP and Tdap vaccines do not completely prevent infection or transmission. It is well established that the alum adjuvant is a potential weakness of the acellular vaccines because the immunity provided by it is short-term. We aimed to evaluate the potential of CpG 1018® adjuvant to improve antibody responses and enhance protection against B. pertussis challenge in a murine model. A titrated range of Tdap vaccine doses were evaluated in order to best identify the adjuvant capability of CpG 1018. Antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), or the whole bacterium were increased due to the inclusion of CpG 1018. In B. pertussis intranasal challenge studies, we observed improved protection and bacterial clearance from the lower respiratory tract due to adding CpG 1018 to 1/20th the human dose of Tdap. Further, we determined that Tdap and Tdap + CpG 1018 were both capable of facilitating clearance of strains that do not express pertactin (PRN^-), which are rising in prevalence. Functional phenotyping of antibodies revealed that the inclusion of CpG 1018 induced more bacterial opsonization and antibodies of the Th1 phenotype (IgG2a and IgG2b). This study demonstrates the potential of adding CpG 1018 to Tdap to improve immunogenicity and protection against B. pertussis compared to the conventional, alum-only adjuvanted Tdap vaccine.     

Immunogenicity and safety of a tetanus toxoid,reduced diphtheria toxoid and three-component acellular pertussis vaccine in adults 19–64 years of age

Purpose

This study was conducted to assess the immunogenicity and safety of a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine containing three pertussis antigens (Boostrix^®, Tdap3v), currently licensed in the US for use in adolescents 10–18 years of age, in adults 19–64 years of age.

Methods

2284 healthy adults, aged 19–64 years, were randomized to receive a single dose of Tdap vaccine, either Tdap3v or a five-pertussis component Tdap vaccine (Adacel^®, Tdap5v) licensed for adult use in the US. Blood samples were taken before and 1 month after vaccination. Reactogenicity was assessed for 15 days after vaccination.

Results

Tdap3v was comparable to Tdap5v in eliciting seroprotective levels of antibodies to diphtheria and tetanus toxoids, with >98% of subjects having post-vaccination seroprotective antibody levels (≥0.1 IU/mL) against diphtheria or tetanus toxoids. The pertussis components of Tdap3v were shown to be immunogenic in adults, with booster responses to pertussis toxoid (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) observed in 77.2%, 96.9%, and 93.2%, respectively, of Tdap3v recipients, and in 47.1%, 94.0%, and 91.7%, respectively, of Tdap5v recipients. Anti-pertussis antibody GMCs in Tdap3v recipients exceeded those observed in infants following primary DTaP vaccination, in whom efficacy against pertussis disease was subsequently demonstrated. Injection site reactions (pain, redness, and swelling) and fever ≥37.5 °C (99.5 °F) were reported significantly more often (p < 0.05) by Tdap5v recipients than by Tdap3v recipients. Fatigue preventing normal daily activities was reported by a small but significantly greater percentage of Tdap3v recipients (2.5%) than Tdap5v recipients (1.2%, p < 0.05).

Conclusion

In adult recipients, Tdap3v was comparable to an approved Tdap vaccine in providing seroprotection against diphtheria and tetanus, and produced immune responses to pertussis antigens consistent with protection against disease. The overall safety profile of Tdap3v was generally comparable to that of Tdap5v [NCT #106316].     

Trends in Canadian infant pertussis hospitalizations in the pre- and post-acellular vaccine era, 1981–2016

ObjectiveThe acellular pertussis vaccine was introduced into the routine childhood immunization schedule across Canada in 1997–98 and adolescent booster doses were added between 1999 and 2005. We sought to assess the impact of these changes on infant pertussis hospitalizations and admissions to intensive care units (ICU) in Canada.MethodsHospitalizations with a primary diagnosis of pertussis were extracted from the Canadian Discharge Abstract Database (DAD) for cases with hospital discharge dates between 1981 and 2016 using relevant ICD-9 and ICD-10 codes. Only cases with age less than one year at time of admission were included. Disease severity was assessed by admission to ICU. Cases were categorized into two periods: pre-program implementation period (1981–1995) and the post-program implementation period (2006–2016). Incidence rates, risk ratios, and rate differences were calculated for each period and comparisons for the two periods were done using chi-squared and t-tests. Quasi Poisson analysis was used to investigate trends.ResultsWhen comparing the pre- and post-implementation periods, the average annual hospitalization rates for infants less than 1 year declined from 165.1 (95% CI 161.3, 168.9) to 33.6 (95% CI 31.6, 35.6) pertussis-related admissions per 100,000 population, with a corresponding reduction in the risk ratio of 4.9 (95% CI 4.6, 5.2). The risk of admission into an ICU was 1.58 times higher in the pre- versus post-implementation period while the highest reduction in average annual hospitalizations was 263.3 admissions per 100,000 population in infants 2 months of age. In the post-implementation period, infants less than 1 month of age had the highest average annual hospitalization rate at 126.6 (95% CI 113.1, 140.1) hospitalizations per 100,000 infants.ConclusionInfant pertussis hospitalizations have reduced greatly over time. Infants under 2 months of age remain the most at-risk age group for hospitalization and admission to ICU.     

Is pertussis being considered as a cause of persistent cough among adults?

A study was conducted to determine the 1124 French Sentinel network general practitioners ability to consider pertussis as a cause of persistent cough among adults. Pertussis was rarely considered in the differential diagnosis of cough (6%). Factors associated with pertussis being considered included younger age, shorter cough duration, world health organization clinical definition for pertussis, and muscular chest pain.     

The effect of timing of maternal tetanus,diphtheria, and acellular pertussis (Tdap) immunization during pregnancy on newborn pertussis antibody levels – A prospective study

Background

The Centers for Disease Control and Prevention recommend Tdap immunization during pregnancy, preferably at 27–36 weeks.

Aim

To ascertain whether there is a preferential period of maternal Tdap immunization during pregnancy that provides the highest concentration of pertussis-specific antibodies to the newborn.

Methods

This prospective study measured pertussis-specific antibodies in paired maternal-cord sera of women immunized with Tdap after the 20th week of their pregnancy (n = 61).

Results

The geometric mean concentrations (GMCs) of Immunoglobulin G (IgG) to pertussis toxin (PT) were higher in the newborns’ cord sera when women were immunized at 27–30⁺⁶ weeks (n = 21) compared with 31–36 weeks (n = 30) and >36 weeks (n = 7), 46.04 international units/milliliter (IU/mL) (95% CI, 24.29–87.30) vs. 8.69 IU/mL (95% CI, 3.66–20.63) and 21.12 IU/mL (95% CI, 7.93–56.22), p < 0.02, respectively. The umbilical cord GMCs of IgG to filamentous hemagglutinin (FHA) were higher in the newborns’ cord sera when women were immunized at 27–30⁺⁶ weeks compared with 31–36 weeks and >36 weeks, 225.86 IU/mL (95% CI, 182.34–279.76) vs. 178.31 IU/mL (95% CI, 134.59–237.03) and 138.03 IU/mL (95% CI, 97.61–195.16), p < 0.02, respectively.

Conclusions

Immunization of pregnant women with Tdap between 27–30⁺⁶ weeks was associated with the highest umbilical cord GMCs of IgG to PT and FHA compared with immunization beyond 31 weeks gestation. Further research should be conducted to reaffirm these finding in order to promote an optimal pertussis controlling policy.     

The incidence of pertussis hospitalizations among Japanese infants: excess hospitalizations and complications?

We examined pertussis hospitalizations among infants aged <1 year between 2006 and 2008 using the nationwide inpatient database in Japan. A total of 660 infants hospitalized for pertussis were identified. Peak incidence occurred at age 1 month and infants aged 0-2 months (too young for pertussis vaccination) and ≥3 months (eligible for at least one dose of vaccination) accounted for 44·5% and 55·5% of hospitalizations, respectively. Complications related to pertussis were found in 165 (25·0%) cases, including one death; the age at admission did not differ significantly between patients with and those without complications (mean age 4·1 vs. 4·5 months, P=0·12). Seventeen patients required mechanical ventilation. Of the 17 cases, 14 infants were aged <3 months and three infants were aged ≥3 months. Our findings highlight that the vaccination schedule against pertussis may often be delayed in Japan.     

Booster vaccination of toddlers with reduced antigen content diphtheria–tetanus–acellular pertussis vaccine

Immunogenicity and reactogenicity of DTPa and reduced antigen dTpa booster vaccines were compared to a hepatitis A control vaccine in DTPa-primed toddlers aged 18–20 months. Post-booster, all DTPa and dTpa recipients were seroprotected against diphtheria and tetanus, and ≥93.3% had a booster response to pertussis. There were similar reactogenicity rates in the DTPa and dTpa vaccine recipients. Few Grade 3 symptoms were reported. Just over one in four children in the control group had diphtheria antibody at or potentially below the correlate of protection benchmark (0.016 IU/ml). Larger studies should evaluate potential benefits of reduced antigen vaccines and seroprotection in children who do not receive a booster dose of DTPa at this age, including protection against diphtheria until subsequent booster doses are given.