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Background In 2020, the Council of State and Territorial Epidemiologists (CSTE) pertussis case definition was modified; the main change was classifying polymerase chain reaction (PCR)-positive cases as confirmed, regardless of cough duration. Pertussis data reported through Enhanced Pertussis Surveillance (EPS) in 7 sites and the National Notifiable Diseases Surveillance System (NNDSS) were used to evaluate the impact of the new case definition. Methods We compared the number of EPS cases with cough onset in 2020 to the number that would have been reported based on the prior (2014) CSTE case definition. To assess the impact of the change nationally, the proportion of EPS cases newly reportable under the 2020 CSTE case definition was applied to 2020 NNDSS data to estimate how many additional cases were captured nationally. Results Among 442 confirmed and probable cases reported to EPS states in 2020, 42 (9.5%) were newly reportable according to the 2020 case definition. Applying this proportion to the 6124 confirmed and probable cases reported nationally in 2020, we estimated that the new definition added 582 cases. Had the case definition not changed, reported cases in 2020 would have decreased by 70% from 2019; the observed decrease was 67%. Conclusions Despite a substantial decrease in reported pertussis cases in the setting of coronavirus disease 2019 (COVID-19), our data show that the 2020 pertussis case definition change resulted in additional case reporting compared with the previous case definition, providing greater opportunities for public health interventions such as prophylaxis of close contacts. [ABSTRACT FROM AUTHOR]

Many respiratory infections are selectively injurious to infants, yet the etiology of age-associated susceptibility is unknown. One such bacterial pathogen is Bordetella pertussis. In adult mice, innate interferon γ (IFN-γ) is produced by natural killer (NK) cells and restricts infection to the respiratory tract. In contrast, infant pertussis resembles disease in NK cell– and IFN-γ–deficient adult mice that experience disseminated lethal infection. We hypothesized that infants exhibit age-associated deficits in NK cell frequency, maturation, and responsiveness to B. pertussis , associated with low IFN-γ levels. To delineate mechanisms behind age-dependent susceptibility, we compared infant and adult mouse models of infection. Infection in infant mice resulted in impaired upregulation of IFN-γ and substantial bacterial dissemination. B. pertussis –infected infant mice displayed fewer pulmonary NK cells than adult mice. Furthermore, the NK cells in the infant mouse lungs had an immature phenotype, and the infant lung showed no upregulation of the IFN-γ–inducing cytokine IL-12p70. Adoptive transfer of adult NK cells into infants, or treatment with exogenous IFN-γ, significantly reduced bacterial dissemination. These data indicate that the lack of NK cell–produced IFN-γ significantly contributes to infant fulminant pertussis and could be the basis for other pathogen-induced, age-dependent respiratory diseases. [ABSTRACT FROM AUTHOR]

Background An increased pertussis burden has been demonstrated among Hispanic or Latino and American Indian or Alaska Native (AI/AN) infants. However, data on potential disparities among other age and racial groups are limited. Methods We analyzed pertussis cases reported through Enhanced Pertussis Surveillance from 2010 to 2017. Pertussis and severe pertussis incidence were calculated by race (White, Black or African American, AI/AN, and Asian or Pacific Islanders), ethnicity (Hispanic or Latino and non-Hispanic or non-Latino), and age. Results Compared with White persons, overall incidence was lower among Black or African American (incidence rate ratio [IRR],.57; 95% confidence interval [CI],.53-.61), AI/AN (IRR, 0.65; 95% CI,.58-.72), and Asian or Pacific Islander persons (IRR, 0.39; 95% CI,.35-.43). Overall incidence of pertussis was higher (1.5-fold; 95% CI, 1.37-1.60) among Hispanic or Latino compared with non-Hispanic or non-Latino adults, potentially related to household size or lower pertussis vaccine uptake among adult Hispanic or Latino cases. Severe pertussis incidence was similar among Black or African American and AI/AN persons compared with White persons. Among infants, severe pertussis incidence was 1.4-fold higher (95% CI, 1.03-1.82) among Black or African American infants than among White infants, and 2.1-fold higher (95% CI, 1.67-2.57) among Hispanic or Latino infants than non-Hispanic or non-Latino infants. Conclusions The contrast between lower reported incidence but similar or higher severe pertussis incidence among Black or African American and AI/AN persons compared with White persons warrants further investigation and may reflect underdiagnosis or underreporting of mild disease. [ABSTRACT FROM AUTHOR]

Background The United States has experienced a resurgence of pertussis following the introduction of acellular pertussis (aP) vaccines. This is likely due to the failure of aP vaccines to induce durable immunity and prevent infection, carriage, and transmission. Methods To evaluate the impact of aP vaccination on the immune response to infection and test the ability of infection to reprogram aP-imprinted immune responses, we challenged unvaccinated and aP-vaccinated baboons with Bordetella pertussis multiple times and accessed the immune responses and outcomes of infections after each exposure. Results Multiple infections were required to elicit T-helper 17 responses and protection in aP-vaccinated animals comparable to responses seen in unvaccinated animals after a single challenge. Even after 3 challenges, T-helper 1 responses were not observed in aP-vaccinated animals. Immunoglobulin G responses to vaccine and nonvaccine antigens were not negatively affected in aP-vaccinated animals. Conclusions Our results indicate that it is possible to retrain aP-primed immune responses, but it will likely require an optimal booster and multiple doses. Our results in the baboon model suggest that circulation of B. pertussis in aP-vaccinated populations is concentrated in the younger age bands of the population, providing information that can guide improved modeling of B. pertussis epidemiology in aP-vaccinated populations. [ABSTRACT FROM AUTHOR]

Background Pertussis is a contagious respiratory disease. Maternal tetanus–diphtheria–acellular pertussis vaccination during pregnancy has been recommended by the United States Centres for Disease Control (US CDC) Advisory Committee on Immunization Practices (ACIP) for unvaccinated pregnant women since October 2011 to prevent infection among infants; in 2012, ACIP extended this recommendation to every pregnancy, regardless of previous vaccination status. The population-level effect of these recommendations on infant pertussis is unknown. This study aimed to examine the impact of the 2011/2012 ACIP pertussis recommendation on pertussis incidence and mortality among US infants. Methods We used monthly data on pertussis deaths among infants aged <1 year between January 2005 and December 2017 in the CDC Death Data and yearly infant pertussis incidence data from the CDC National Notifiable Disease Surveillance System to perform an interrupted time series analysis, accounting for the passage of the Affordable Care Act. Results This study included 156 months of data. A potential decline in trend in infant pertussis incidence was noted during the post-recommendations period. No appreciable differences in trend were found in population-level infant pertussis mortality after the guideline changes in both adjusted and unadjusted models. Results were similar for all mortality sensitivity analyses. Conclusions The 2011/2012 ACIP maternal pertussis vaccination recommendations were not associated with a population-level change in the trend in mortality, but were potentially associated with a decrease in incidence in the USA between 2005 and 2017. [ABSTRACT FROM AUTHOR]

Background Pregnant women and their babies face significant risks from three vaccine-preventable diseases: COVID-19, influenza and pertussis. However, despite these vaccines' proven safety and effectiveness, uptake during pregnancy remains low. Methods We conducted a systematic review (PROSPERO CRD42023399488; January 2012–December 2022 following PRISMA guidelines) of interventions to increase COVID-19/influenza/pertussis vaccination in pregnancy. We searched nine databases, including grey literature. Two independent investigators extracted data; discrepancies were resolved by consensus. Meta-analyses were conducted using random-effects models to estimate pooled effect sizes. Heterogeneity was assessed using the I2 statistics. Results From 2681 articles, we identified 39 relevant studies (n  = 168 262 participants) across nine countries. Fifteen studies (39%) were randomized controlled trials (RCTs); the remainder were observational cohort, quality-improvement or cross-sectional studies. The quality of 18% (7/39) was strong. Pooled results of interventions to increase influenza vaccine uptake (18 effect estimates from 12 RCTs) showed the interventions were effective but had a small effect (risk ratio = 1.07, 95% CI 1.03, 1.13). However, pooled results of interventions to increase pertussis vaccine uptake (10 effect estimates from six RCTs) showed no clear benefit (risk ratio = 0.98, 95% CI 0.94, 1.03). There were no relevant RCTs for COVID-19. Interventions addressed the 'three Ps': patient-, provider- and policy-level strategies. At the patient level, clear recommendations from healthcare professionals backed by text reminders/written information were strongly associated with increased vaccine uptake, especially tailored face-to-face interventions, which addressed women's concerns, dispelled myths and highlighted benefits. Provider-level interventions included educating healthcare professionals about vaccines' safety and effectiveness and reminders to offer vaccinations routinely. Policy-level interventions included financial incentives, mandatory vaccination data fields in electronic health records and ensuring easy availability of vaccinations. Conclusions Interventions had a small effect on increasing influenza vaccination. Training healthcare providers to promote vaccinations during pregnancy is crucial and could be enhanced by utilizing mobile health technologies. [ABSTRACT FROM AUTHOR]

Until recently, members of the classical Bordetella species comprised only pathogenic bacteria that were thought to live exclusively in warm-blooded animals. The close phylogenetic relationship of Bordetella with Achromobacter and Alcaligenes , which include primarily environmental bacteria, suggests that the ancestral Bordetellae were probably free-living. Eventually, the Bordetella species evolved to infect and live within warm-blooded animals. The modern history of pathogens related to the genus Bordetella started towards the end of the 19th century when it was discovered in the infected respiratory epithelium of mammals, including humans. The first identified member was Bordetella pertussis, which causes whooping cough, a fatal disease in young children. In due course, B. bronchiseptica was recovered from the trachea and bronchi of dogs with distemper. Later, a second closely related human pathogen, B. parapertussis , was described as causing milder whooping cough. The classical Bordetella e are strictly host-associated pathogens transmitted via the host-to-host aerosol route. Recently, the B. bronchiseptica strain HT200 has been reported from a thermal spring exhibiting unique genomic features that were not previously observed in clinical strains. Therefore, it advocates that members of classical Bordetella species have evolved from environmental sources. This organism can be transmitted via environmental reservoirs as it can survive nutrient-limiting conditions and possesses a motile flagellum. This study aims to review the molecular basis of origin and virulence properties of obligate host-restricted and environmental strains of classical Bordetella. [ABSTRACT FROM AUTHOR]

Background Despite widespread vaccination, pertussis has re-emerged as a serious public health concern worldwide. Since 2017, Peru has experienced an increase in pertussis cases exhibiting a higher risk of severity and death in young infants. Thus, a dose of the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended for pregnant women in the third trimester. Although evidence suggests the maternal Tdap vaccine is safe and effective, its association with a reduced risk of pertussis in developing countries remains poorly investigated. Methods We conducted a case-control study to evaluate the association between Tdap vaccination during pregnancy and reduction in the risk of pertussis among infants aged <2 months in Peru. Pertussis cases and controls treated in healthcare facilities nationwide between 2019 and 2021 and confirmed by real-time polymerase chain reaction were included. The controls were randomly selected from test-negative patients. Odds ratios (ORs) and vaccine effectiveness (VE) were calculated using a multiple logistic regression model and 1 − (OR) × 100%, respectively. Results Fifty cases and 150 controls were included in the analysis. The mothers of 4% of cases and 16.7% of controls received Tdap vaccination during pregnancy, resulting in an OR of 0.19 (95% confidence interval [CI],.04–.86) and VE of 81% (95% CI, 14%–96%) for preventing pertussis in infants. Conclusions Peruvian infants <2 months old whose mothers received the Tdap vaccine in the third trimester of pregnancy had a significantly lower risk of pertussis. The Tdap vaccination is thus an effective intervention to reduce the burden of pertussis in at-risk populations. [ABSTRACT FROM AUTHOR]

Background Despite high vaccination rates, the United States has experienced a resurgence in reported cases of pertussis after switching to the acellular pertussis vaccine, indicating a need for improved vaccines that enhance infection control. Methods Bordetella pertussis antigens recognized by convalescent-baboon serum and nasopharyngeal wash were identified by immunoproteomics and their subcellular localization predicted. Genes essential or important for persistence in the baboon airway were identified by transposon-directed insertion-site sequencing (TraDIS) analysis. Results In total, 314 B. pertussis antigens were identified by convalescent baboon serum and 748 by nasopharyngeal wash. Thirteen antigens were identified as immunogenic in baboons, essential for persistence in the airway by TraDIS, and membrane-localized: BP0840 (OmpP), Pal, OmpA2, BP1485, BamA, Pcp, MlaA, YfgL, BP2197, BP1569, MlaD, ComL, and BP0183. Conclusions The B. pertussis antigens identified as immunogenic, essential for persistence in the airway, and membrane-localized warrant further investigation for inclusion in vaccines designed to reduce or prevent carriage of bacteria in the airway of vaccinated individuals. [ABSTRACT FROM AUTHOR]

Background Previous Australian studies have shown that delayed vaccination with each of the three primary doses of diphtheria-tetanus-pertussis-containing vaccines (DTP) is up to 50 % in certain subpopulations. We estimated the excess burden of pertussis that might have been prevented if (i) all primary doses and (ii) each dose was given on time. Methods Perinatal, immunization, pertussis notification and death data were probabilistically linked for 1 412 984 infants born in two Australian states in 2000–12. A DTP dose administered >15 days after the recommended age was considered delayed. We used Poisson regression models to compare pertussis notification rates to 1-year of age in infants with ≥1 dose delayed (Aim 1) or any individual dose delayed (Aim 2) versus a propensity weighted counterfactual on-time cohort. Results Of all infants, 42% had ≥1 delayed DTP dose. We estimated that between 39 to 365 days of age, 85 (95% CI: 61–109) cases per 100 000 infants, could have been prevented if all infants with ≥1 delayed dose had received their three doses within the on-time window. Risk of pertussis was higher in the delayed versus the on-time cohort, so crude rates overestimated the excess burden (110 cases per 100 000 infants (95% CI: 95–125)). The estimated dose-specific excess burden per 100 000 infants was 132 for DTP1, 50 for DTP2 and 19 for DTP3. Conclusions We provide robust evidence that improved DTP vaccine timeliness, especially for the first dose, substantially reduces the burden of infant pertussis. Our methodology, using a potential outcomes framework, is applicable to other settings. [ABSTRACT FROM AUTHOR]

Background England's third-trimester maternal pertussis vaccination, introduced in October 2012, was extended to the second trimester in 2016. Maternal vaccination provides high protection against infant disease, but routine second-trimester vaccination has not previously been assessed. Methods National laboratory-confirmed pertussis case surveillance determined vaccination history, maternal vaccination history and hospitalization. Pertussis hospital admissions between 2012 and 2019 were extracted from the Hospital Episode Statistics data set. Vaccine effectiveness (VE) was calculated for pertussis case patients born between October 2012 and September 2018 using the screening method and matching with a nationally representative data set. Results Higher coverage was observed after earlier maternal vaccination with approximately 40% of pregnant women vaccinated ≥13 weeks before delivery. Cases and hospitalizations stabilized at low levels in younger infants but remained elevated in older infants, children, and adults. No deaths occurred in infants with vaccinated mothers after 2016. Of 1162 laboratory-confirmed pertussis cases in the study, 599 (52%) were in infants aged <93 days: 463 (77%) with unvaccinated and 136 (23%) with vaccinated mothers. The VE was equivalent in infants with mothers vaccinated at different gestational periods except in those with mothers vaccinated between 7 days before and 41 days after delivery. Children whose mothers were unvaccinated but with vaccination in a previous pregnancy had a VE against disease of 44% (95% confidence interval, 19%–75%). There was no increased disease risk after primary vaccination in children with mothers vaccinated at least 7 days before delivery. Conclusions National policy recommending vaccination in the second trimester increased earlier maternal vaccine uptake with sustained high VE and impact against early infant disease. [ABSTRACT FROM AUTHOR]

Background Acellular pertussis (aP) vaccines replaced whole-cell pertussis (wP) vaccines for the US childhood primary series in 1997. As women primed with aP vaccines enter childbearing age, protection of infants through tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination during pregnancy may be impacted. Methods Term infants born to women vaccinated with Tdap during pregnancy were included. Geometric mean concentrations (GMCs) of pertussis-specific immunoglobulin G antibodies (international units per milliliter) in cord blood of infants born to women born after 1997 (aP-primed) were compared with those born to women born before 1992 (wP-primed). Results 253 and 506 infants born to aP- and wP-primed women, respectively, were included. Compared with wP-primed women, aP-primed women were younger, more likely to be Hispanic or non-Hispanic Black, and had lower-birthweight infants (P <.01 for all). Antibodies against pertussis toxin (PT) and filamentous hemagglutinin (FHA) were lower among infants born to aP-primed vs wP-primed women (PT, 17.3 vs 36.4; GMC ratio,.475; 95% confidence interval [CI],.408–.552 and FHA, 104.6 vs 121.4; GMC ratio, 0.861; 95% CI,.776–.958). No differences were observed for anti-fimbriae or anti-pertactin antibodies. Conclusions Transplacental anti-pertussis antibody concentrations in infants of women vaccinated with Tdap during pregnancy differed by type of childhood vaccine the women received. Notably, anti-PT antibody levels, considered most important in preventing severe infant disease, were lower in infants born to aP-primed vs wP-primed women. Maternal Tdap vaccination may confer less protection against pertussis in infants born to aP-primed vs those born to wP-primed women. [ABSTRACT FROM AUTHOR]

Background: The emergence of macrolide resistance in Bordetella pertussis, the causative agent of pertussis, due to mutations in the 23S rRNA gene has been recently recognized. However, resistance mechanisms to macrolides in Bordetella parapertussis and Bordetella holmesii remain unknown.Objectives: This study investigated genomic changes induced by in vitro exposure to erythromycin in these three main pathogens responsible for pertussis-like disease.Methods: A set of 10 clinical and reference strains of B. pertussis, B. parapertussis and B. holmesii was exposed to erythromycin for 15 weeks or 30 subculture passages. Antibiotic pressure was achieved by growth on the selective media with erythromycin Etest strips or impregnated discs. Genome polymorphisms and transcriptomic profiles were examined by short- and long-read sequencing of passaged isolates.Results: B. parapertussis and B. holmesii isolates developed significant in vitro resistance to erythromycin (MIC >256 mg/L) within 2 to 7 weeks and at 5 to 12 weeks, respectively. B. pertussis remained phenotypically susceptible to the antibiotic following 15 weeks of exposure, with the MIC between 0.032 to 0.38 mg/L. Genomic analysis revealed that B. holmesii developed resistance due to mutations in the 23S rRNA gene. The resistance mechanism in B. parapertussis was hypothesized as being due to upregulation of an efflux pump mechanism.Conclusions: These findings indicate that both B. holmesii and B. parapertussis can be more prone to induced resistance following exposure to treatment with erythromycin than B. pertussis. The surveillance of macrolide resistance in Bordetella isolates recovered from patients with pertussis, especially persistent disease, is warranted. [ABSTRACT FROM AUTHOR]

The unprovoked aggression of Russian military forces on Ukraine in February 2022 has caused a high influx of refugees, including children, to neighboring countries, particularly Poland. This caused additional pressures on the healthcare system and the need to meet challenges for public health, such as those related to infectious diseases. Here, we discuss the potential epidemiological risks associated with the war-induced influx of refugees (coronavirus disease 2019, measles, pertussis, tetanus, and poliomyelitis) and highlight the need for their swift management through institutional support, educational campaigns, counteracting antiscience misinformation, and pursuing vaccinations of refugees but also improving or maintaining good levels of immunization in populations of countries welcoming them. These are necessary actions to avoid overlapping of war and infectious diseases and associated public health challenges. [ABSTRACT FROM AUTHOR]

Understanding the role of vaccine hesitancy in undervaccination or nonvaccination of childhood vaccines is important for increasing vaccine confidence and uptake. We used data from April to June interviews in the 2018 and 2019 National Immunization Survey–Flu (n  = 78,725, United States), a nationally representative cross-sectional household cellular telephone survey. We determined the adjusted population attributable fraction (PAF) for each recommended childhood vaccine to assess the contribution of vaccine hesitancy to the observed nonvaccination level. Hesitancy is defined as being somewhat or very hesitant toward childhood vaccines. Furthermore, we assessed the PAF of nonvaccination for influenza according to sociodemographic characteristics, Department of Health and Human Services region, and state. The proportion of nonvaccination attributed to parental vaccine hesitancy was lowest for hepatitis B birth dose vaccine (6.5%) and highest for ≥3-dose diphtheria and tetanus toxoids and acellular pertussis vaccine (31.3%). The PAF of influenza nonvaccination was highest for non-Hispanic Black populations (15.4%), households with high educational (17.7%) and income (16.5%) levels, and urban areas (16.1%). Among states, PAF ranged from 25.4% (New Hampshire) to 7.5% (Louisiana). Implementing strategies to increase vaccination confidence and uptake are important, particularly during the coronavirus disease 2019 pandemic. [ABSTRACT FROM AUTHOR]

Introduction Maternal antibody interference of the infant's humoral immune responses raises some concern to the strategy of maternal Tdap (tetanus, diphtheria, acellular pertussis [aP]) vaccination. This study assessed the impact of maternal Tdap antibodies on the infant's pertussis-specific T lymphocyte responses following infant vaccination with an aP containing vaccine, in a term and preterm born cohort. Methods Heparin samples (±0.5 mL) were conveniently drawn from infants of a Belgian prospective cohort study (N = 79, NCT02511327), including Tdap vaccinated (Boostrix®) and nonvaccinated women (no Tdap vaccine in the last 5 years) that delivered at term or prematurely. Sampling was performed before and 1 month after primary (8-12-16 weeks) and booster vaccination (13 or 15 months) with DTaP-IPV-HB-PRP~T vaccine (Hexyon®). Pertussis toxin (PT)-specific CD3+, CD3+ CD4+ and CD3+ CD8+ lymphoblasts and their cytokine secretions were measured using a flow cytometric assay on whole blood (FASCIA) and multiplex technology (Meso Scale Discovery), respectively. Results In total, 57% of all infants were considered PT-specific CD3+ CD4+ lymphoblasts responders after primary and booster vaccination, whereas 17% were CD3+ CD8+ lymphoblast responders. Interferon (IFN)-γ, interleukin (IL)-13, IL-17A, and IL-5 cytokine secretions after primary and booster vaccination were indicative of a mixed T helper (Th) 1/Th2/Th17 cell profile. Lymphoblast and cytokine levels were comparable between term and preterm infants. Nonresponders for IL-13 after booster vaccination had higher maternal PT immunoglobulin G (IgG) levels at birth when compared to responders. Conclusions Term and preterm born infants are capable of inducing Th1, Th2, and Th17 responses after aP vaccination, yet maternal vaccination modulate these responses. Evaluation of this effect in larger trials is needed. [ABSTRACT FROM AUTHOR]

Background: Infant respiratory syncytial virus infection (RSV) has been associated with asthma later in life. We explored the risk of recurrent wheeze or asthma in children with infant RSV-associated hospitalization compared to other respiratory infections.Methods: We performed a retrospective cohort study using Danish national hospital discharge registers. Infants younger than 6 months, born between January 1995 and October 2018, and with a RSV hospital admission were compared to infants hospitalized for injuries, non-RSV acute upper respiratory tract infection (AURTI), pneumonia and other respiratory pathogens, nonpathogen-coded lower respiratory tract infections (LRTI), pertussis, or nonspecific respiratory infections. Infants were followed until recurrent wheeze or asthma diagnosis, death, migration, age 10 years, or study end. We estimated cumulative incidence rate ratios (CIRR) and hazard ratios (HR) adjusted for sex, age at inclusion, hospital length of stay (LOS), maternal smoking, 5-minute APGAR score (APGAR5), prematurity, and congenital risk factors (CRF).Results: We included 68 130 infants, of whom 20 920 (30.7%) had RSV hospitalization. The cumulative incidence rate of recurrent wheeze or asthma was 16.6 per 1000 person-years after RSV hospitalization, higher than after injury (CIRR, 2.69; 95% confidence interval [CI], 2.48-2.92), AURTI (CIRR, 1.48; 95% CI, 1.34-1.58), or pertussis (CIRR, 2.32; 95% CI, 1.85-2.91), similar to pneumonia and other respiratory pathogens (CIRR, 1.15; 95% CI, .99-1.34) and LRTI (CIRR, 0.79; 95% CI, .60-1.04), but lower than nonspecific respiratory infections (CIRR, 0.79; 95% CI, .73-.87). Adjusted HRs for recurrent wheeze or asthma after RSV hospitalization compared to injuries decreased from 2.37 (95% CI, 2.08-2.70) for 0 to <1 year to 1.23 (95% CI, .88-1.73) for 6 to <10 years for term-born children, and from 1.48 (95% CI, 1.09-2.00) to 0.60 (95% CI, .25-1.43) for preterm-born children. Sex, maternal smoking, LOS, CRF, and APGAR5 were independent risk factors.Conclusions: Infant RSV hospitalization is associated with recurrent wheeze and asthma hospitalization, predominantly at preschool age. If causal, RSV prophylaxis, including vaccines, may significantly reduce disease burden of wheeze and asthma. [ABSTRACT FROM AUTHOR]

We previously demonstrated that Bordetella pertussis, the etiologic agent of whooping cough, is able to survive inside human macrophages. The aim of this study was to examine the influence of macrophage polarization in the development of B. pertussis intracellular infections. To this end, primary human monocytes were differentiated into M1, M2a, or M2c macrophages and further infected with B. pertussis. Infected M1 macrophages showed a proinflammatory response evidenced by the production of TNF‐α, IL‐12p70, and IL‐6. Conversely, infection of M2a and M2c macrophages did not induce TNF‐α, IL‐12p70, nor IL‐6 at any time postinfection but showed a significant increase of M2 markers, such as CD206, CD163, and CD209. Interestingly, anti‐inflammatory cytokines, like IL‐10 and TGF‐β, were induced after infection in the 3 macrophage phenotypes. B. pertussis phagocytosis by M1 macrophages was lower than by M2 phenotypes, which may be ascribed to differences in the expression level of B. pertussis docking molecules on the surface of the different phenotypes. Intracellular bactericidal activity was found to be significantly higher in M1 than in M2a or M2c cells, but live bacteria were still detected within the 3 phenotypes at the late time points after infection. In summary, this study shows that intracellular B. pertussis is able to survive regardless of the macrophage activation program, but its intracellular survival proved higher in M2 compared with the M1 macrophages, being M2c the best candidate to develop into a niche of persistence for B. pertussis. [ABSTRACT FROM AUTHOR]

Background: Changes to pertussis vaccination programmes can have impacts on disease burden that should be estimated independently from factors such as age- and period-related trends. We used age-period-cohort (APC) models to explore pertussis incidence in Manitoba over a 25-year period (1992-2017).Methods: We identified all laboratory-confirmed cases of pertussis from Manitoba's Communicable Diseases Database and calculated age-standardized incidence rates. We used APC models to investigate trends in pertussis incidence.Results: During the study period, 2479 cases were reported. Age-standardized rates were highest during a large outbreak in 1994 (55 cases/100 000 person-years), with much lower peaks in 1998, 2012 and 2016. We saw strong age and cohort effects in the APC models, with a steady decrease in incidence with increasing age and increased risk in the cohort born between 1980 and 1995.Conclusions: The highest risk for pertussis was consistently in young children, regardless of birth cohort or time period. The 1981 programme change to an adsorbed whole-cell pertussis vaccine with low effectiveness resulted in reduced protection in the 1981-95 birth cohort and contributed to the largest outbreak of disease during the 25-year study period. [ABSTRACT FROM AUTHOR]

Background: Whooping cough is caused by infection of the airways with Bordetella pertussis (Bp). As interferon gamma (IFN-γ) is essential for protective immunity against Bp, we investigated how IFN-γ is induced by Bp or the virulence antigens filamentous hemagglutinin adhesin, pertactin, or pertussis toxin, and how IFN-γ contributes to local immune responses in humans.Methods: Peripheral blood mononuclear cells (PBMCs) from healthy donors and/or respiratory epithelial cells were stimulated with soluble antigens or inactivated intact Bp and the presence or absence of blocking antibodies or chemokines. Supernatants and cells were analyzed for IFN-γ and chemokine production, and lymphocyte migration was tested using epithelial supernatants.Results: The soluble antigens failed to induce IFN-γ production, whereas inactivated Bp induced IFN-γ production. Natural killer (NK) cells were the main source of IFN-γ production, which was enhanced by interleukin 15. Epithelial-PBMC co-cultures showed robust IFN-γ-dependent CXCL9 and CXCL10 production by the epithelial cells following stimulation with IFN-γ and Bp. The epithelial-derived chemokines resulted in CXCR3-dependent recruitment of NK and T cells.Conclusions: Inactivated Bp, but not antigens, induced potent IFN-γ production by NK cells, resulting in chemoattraction of lymphocytes toward the respiratory epithelium. These data provide insight into the requirements for IFN-γ production and how IFN-γ enhances local immune responses to prevent Bp-mediated disease. [ABSTRACT FROM AUTHOR]

Pertussis, diphtheria, and tetanus (DTP)-containing vaccines combined with polio vaccines are recommended by the World Health Organization as part of routine immunization programs. The decline of immunity after vaccination has been considered as a possible reason for the reemergence of vaccine-preventable diseases worldwide. In this study, we evaluated the potential duration of protective immunity of pertussis, diphtheria, tetanus, and polio through a systematic review and meta-analysis. We examined data on immunological and clinical outcomes. We observed evidence of waning postvaccination immunity for pertussis and diphtheria, whereas tetanus and polio vaccines provided sustained protection. Further research on the risk factors of waning immunity after vaccination and the optimal timing of booster doses for pertussis and diphtheria is needed. [ABSTRACT FROM AUTHOR]

Background Limited data exist on the impact of maternal tetanus, diphtheria, acellular pertussis (Tdap) vaccination for preterm born infants. We report its effect at birth and on antibody-mediated immune responses to a DTaP-IPV-HB-PRP~T vaccine in preterm compared with term infants. Methods Women delivering at term or prematurely were either vaccinated with a Tdap vaccine (Boostrix; GSK) during pregnancy or not vaccinated in the last 5 years. Cord and maternal blood were collected at delivery. Infants were vaccinated with DTaP-IPV-HB-PRP~T vaccine (Hexyon; Sanofi Pasteur) and blood collected before and 1 month after primary (8-12-16 weeks) and before and 1 month after booster vaccination (13 or 15 months for preterm and term, respectively). Immunoglobulin G antibodies against all antigens included in DTaP-IPV-HB-PRP~T vaccine were measured (NCT02511327). Results Cord blood geometric mean concentrations (GMCs) in preterm infants from Tdap-vaccinated women were significantly higher than in term and preterm infants from unvaccinated women. A longer time interval between maternal vaccination and delivery resulted in higher cord blood GMCs in preterm infants. Equal GMCs in term and preterm infants from Tdap-vaccinated women were observed after primary vaccination. After boosting, significantly lower GMCs were seen for pertussis toxin, filamentous hemagglutinin, and tetanus toxoid in preterm compared with term infants from Tdap-vaccinated women, yet still comparable to GMCs in both term and preterm infants from unvaccinated women. Conclusions Preterm infants profit from maternal Tdap vaccination. Prematurity did not influence primary immune responses in the presence of maternal antibodies but was associated with a lower booster immune response. [ABSTRACT FROM AUTHOR]

Gram-negative pathogenic bacteria constitutively shed outer membrane vesicles (OMVs) which play a significant role in the host–pathogen interaction, eventually determining the outcome of the infection. We previously found that Bordetella pertussis , the etiological agent of whooping cough, survives the innate interaction with human macrophages remaining alive inside these immune cells. Adenylate cyclase (CyaA), one of the main toxins of this pathogen, was found involved in the modulation of the macrophage defense response, eventually promoting bacterial survival within the cells. We here investigated whether B. pertussis OMVs, loaded with most of the bacterial toxins and CyaA among them, modulate the macrophage response to the bacterial infection. We observed that the pre-incubation of macrophages with OMVs led to a decreased macrophage defense response to the encounter with the bacteria, in a CyaA dependent way. Our results suggest that CyaA delivered by B. pertussis OMVs dampens macrophages protective function by decreasing phagocytosis and the bactericidal capability of these host cells. By increasing the chances of bacterial survival to the innate encounter with the macrophages, B. pertussis OMVs might play a relevant role in the course of infection, promoting bacterial persistence within the host and eventually, shaping the whole infection process. [ABSTRACT FROM AUTHOR]

Background Little is known about pertussis among pregnant women, a population at increased risk for severe morbidity from respiratory infections such as influenza. We used the Centers for Disease Control and Prevention's Enhanced Pertussis Surveillance (EPS) system to describe pertussis epidemiology among pregnant and nonpregnant women of childbearing age. Methods Pertussis cases in women aged 18–44 years with cough onset between 1 January 2012 and 31 December 2017 were identified in 7 EPS states. Surveillance data were collected through patient and provider interviews and immunization registries. Bridged-race, intercensal population data and live birth estimates were used as denominators. Results We identified 1582 pertussis cases among women aged 18–44 years; 5.1% (76/1499) of patients with a known pregnancy status were pregnant at cough onset. Of the pregnant patients with complete information, 81.7% (49/60) reported onset during the second or third trimester. The median ages of pregnant and nonpregnant patients were 29.0 and 33.0 years, respectively. Most pregnant and nonpregnant patients were White (78.3% vs. 86.4%, respectively; P =.09) and non-Hispanic (72.6% vs. 77.3%, respectively; P =.35). The average annual incidence of pertussis was 7.7/100000 among pregnancy women and 7/3/100000 among nonpregnant women. Compared to nonpregnant patients, more pregnant patients reported whoop (41.9% vs. 31.3%, respectively), posttussive vomiting (58.1% vs. 47.9%, respectively), and apnea (37.3% vs. 29.0%, respectively); however, these differences were not statistically significant (P values >.05 for all). A similar proportion of pregnant and nonpregnant patients reported ever having received Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine; 31.6% vs. 32.7%, respectively; P =.84). Conclusions Our analysis suggests that incidence of pertussis and clinical characteristics of disease are similar among pregnant and nonpregnant women. Continued monitoring is important to further define pertussis epidemiology in pregnant women. [ABSTRACT FROM AUTHOR]

Infants are more likely to develop severe pertussis. We report a malignant pertussis case in a 2-month-old boy with respiratory failure, severe pneumonia, septic shock, and encephalopathy. Bordetella pertussis was detected from nasopharyngeal secretions by polymerase chain reaction, as well as both blood and cerebrospinal fluid samples via metagenomics next-generation sequencing. [ABSTRACT FROM AUTHOR]

Nationally, immunization delivery has decreased significantly during the coronavirus disease 2019 (COVID-19) pandemic. Internationally, >60 national vaccine programs have been disrupted or suspended. As a result of these immunization declines, the global community is at risk for a resurgence in vaccine-preventable infections including measles, pertussis, and polio—all highly contagious diseases that result in significant morbidity and mortality in children. Measles outbreaks have already occurred in many countries that suspended their vaccination programs. Outbreaks in the United States are likely to occur when social distancing stops and children return to school. Healthcare providers have acted quickly to institute multiple risk mitigation strategies to restore vaccine administration. However, childhood immunization rates remain below pre–COVID-19 levels. Partnerships between healthcare providers, community leaders, and local, state, regional, and national public health departments are needed to reassure families that vaccine delivery during COVID-19 is safe and to identify and catch up those children who are underimmunized. [ABSTRACT FROM AUTHOR]

Background Child care employee vaccination policies can protect children and adults from vaccine-preventable diseases (VPDs) in child care programs. We aimed to understand the prevalence and characteristics of employee immunization policies at child care facilities and support among child care administrators for statewide employee vaccination regulations. Methods A postal mail survey was distributed to a cross-sectional sample of 300 center-based and 300 home-based child care programs in Colorado. Programs were asked to report whether they had any type of policy requiring employee immunizations and if they would support statewide regulations mandating employee immunizations for influenza, pertussis, and measles. Results The response rate was 48% (288/600). About 55% of child care programs reported having an employee immunization policy. Child care centers (73%) were more likely than home-based child care programs (30%, P <.001) to report having a policy. Overall, 62% of respondents reported that they would support one or more statewide regulations requiring child care employees to be vaccinated. Home-based programs (71%) were more likely than center-based programs (53%, P =.001) to support one or more statewide child care employee immunization regulations. Conclusions Our findings demonstrate the variability of employee immunization policies at child care programs across Colorado. These results may be used to inform strategies to increase employee immunization uptake and reduce the incidence of VPDs, including developing comprehensive employee immunization policies at the facility and state level. Future research is needed to understand vaccination knowledge, attitudes, and behaviors among child care employees including their perspectives on employee vaccination policies and regulations. [ABSTRACT FROM AUTHOR]

Background In October 2012, a maternal pertussis vaccination program was introduced in England for women between 28 and 32 weeks of pregnancy. In April 2016, the recommended optimal window was extended to 20–32 weeks to improve vaccine coverage and protect preterm infants. This study assesses the impact of offering maternal pertussis vaccination earlier in pregnancy on hospitalized infant pertussis cases. Methods Hospitalized pertussis cases ≤60 days old in England were extracted from Hospital Episode Statistics pre- and post-policy change. Data were linked to laboratory-confirmed cases, and clinical records were reviewed where cases were not matched. Maternal vaccine status of identified cases was established. Median hospital duration was calculated, and a competing risk survival analysis was undertaken to assess multiple factors. Results A total of 201 cases were included in the analysis. Of the 151 cases with reported gestational age, the number of hospitalizations among full-term infants was 60 cases pre-policy and 62 cases post-policy, respectively, while preterm cases declined from 20 to 9 (P =.06). Length of hospital stay did not differ significantly after the policy change. Significantly longer hospital stays were seen in cases aged 0–4 weeks (median of 3 more days than infants aged 5–8 weeks), premature infants (median of 4 more days than term infants), and cases with coinfections (median of 1 more day than those without coinfection). Conclusions The number of preterm infants hospitalized with pertussis in England was halved after the policy change and preterm infants were no longer overrepresented among hospitalized cases. [ABSTRACT FROM AUTHOR]

Pertussis (whooping cough) is a respiratory infection caused by Bordetella pertussis. All ages are susceptible. In the prevaccine era, almost all children became infected. Pertussis is particularly dangerous in young infants, who account for practically all hospitalizations and deaths, but clinical disease is burdensome at any age. Widespread use of pertussis vaccines dramatically reduced cases, but concern over adverse reactions led to the replacement of standard whole-cell by acellular pertussis vaccines that contain only a few selected pertussis antigens and are far less reactogenic. Routine administration of acellular pertussis vaccines combined with diphtheria and tetanus toxoids is recommended in infancy with toddler and preschool boosters, at age 11, and during pregnancy. Boosting in the second half of every pregancy is critical to protection of the newborn. Waning of vaccine immunity over time has become an increasing concern, and several new pertussis vaccines are being evaluated to address this problem. [ABSTRACT FROM AUTHOR]

Background Policy recommendations on pertussis vaccination need to be guided by data, which are limited from low- and middle-income countries. We aimed to describe the epidemiology of pertussis in South Africa, a country with high human immunodeficiency virus (HIV) prevalence and routine pertussis vaccination for 6 decades including the acellular vaccine since 2009. Methods Hospitalized patients of all ages were enrolled at 5 sentinel sites as part of a pneumonia surveillance program from January 2013 through December 2018. Nasopharyngeal specimens and induced sputum were tested by polymerase chain reaction (PCR) for Bordetella pertussis. In addition, demographic and clinical information were collected. Incidence rates were calculated for 2013–2016, and multivariable logistic regression performed to identify factors associated with pertussis. Results Over the 6-year period 19 429 individuals were enrolled, of which 239 (1.2%) tested positive for B. pertussis. Detection rate was highest in infants aged <6 months (2.8%, 155/5524). Mean annual incidence was 17 cases per 100 000 population, with the highest incidence in children <1 year of age (228 per 100 000). Age-adjusted incidence was 65.9 per 100 000 in HIV-infected individuals compared to 8.5 per 100 000 in HIV-uninfected individuals (risk ratio 30.4, 95% confidence interval: 23.0–40.2). Ten individuals (4.2%) with pertussis died; of which 7 were infants aged <6 months and 3 were immunocompromised adults. Conclusions Pertussis continues to be a significant cause of illness and hospitalization in South Africa, despite routine vaccination. The highest burden of disease and death occurred in infants; however, HIV-infected adults were also identified as an important group at risk of B. pertussis infection. [ABSTRACT FROM AUTHOR]

Background: Adult vaccinations may reduce risk for dementia. However, it has not been established whether tetanus, diphtheria, pertussis (Tdap) vaccination is associated with incident dementia.Methods: Hypotheses were tested in a Veterans Health Affairs (VHA) cohort and replicated in a MarketScan medical claims cohort. Patients were at least 65 years of age and free of dementia for 2 years prior to index date. Patients either had or did not have a Tdap vaccination by the start of either of the 2 index periods (2011 or 2012). Follow-up continued through 2018. Controls had no Tdap vaccination for the duration of follow-up. Confounding was controlled using entropy balancing. Competing risk (VHA) and Cox proportional hazard (MarketScan) models estimated the association between Tdap vaccination and incident dementia in all patients and age subgroups (65-69, 70-74, and ≥75 years).Results: VHA patients were, on average, 75.6 (SD ± 7.5) years of age, 4% female, and 91.2% were White. MarketScan patients were 69.8 (SD ± 5.6) years of age, on average and 65.4% were female. After controlling for confounding, patients with, compared to without, Tdap vaccination had a significantly lower risk for dementia in both cohorts (VHA: hazard ratio [HR] = 0.58; 95% confidence interval [CI]:0.54-0.63 and MarketScan: HR = 0.58; 95% CI:0.48-0.70).Conclusions: Tdap vaccination was associated with a 42% lower dementia risk in 2 cohorts with different clinical and sociodemographic characteristics. Several vaccine types are linked to decreased dementia risk, suggesting that these associations are due to nonspecific effects on inflammation rather than vaccine-induced pathogen-specific protective effects. [ABSTRACT FROM AUTHOR]

Background Vaccine effectiveness (VE) studies provide essential evidence on waning vaccine-derived immunity, a major threat to pertussis control. We evaluated how study design affects estimates by comparing 2 case-control studies conducted in Ontario, Canada. Methods We compared results from a test-negative design (TND) with a frequency-matched design (FMD) case-control study using pertussis cases from 2005–2015. In the first study, we identified test-negative controls from the public health laboratory that diagnosed cases and, in the second, randomly selected controls from patients attending the same physicians that reported cases, frequency matched on age and year. We compared characteristics of cases and controls using standardized differences. Results In both designs, VE estimates for the early years postimmunization were consistent with clinical trials (TND, 84%; FMD, 89% at 1–3 years postvaccination) but diverged as time since last vaccination increased (TND, 41%; FMD, 74% by 8 years postvaccination). Overall, we observed lower VE and faster waning in the TND than the FMD. In the TND but not FMD, controls differed from cases in important confounders, being younger, having more comorbidities, and higher healthcare use. Differences between the controls of each design were greater than differences between cases. TND controls were more likely to be unvaccinated or incompletely vaccinated than FMD controls (P  < .001). Conclusions The FMD adjusted better for healthcare-seeking behavior than the TND. Duration of protection from pertussis vaccines is unclear because estimates vary by study design. Caution should be exercised by experts, researchers, and decision makers when evaluating evidence on optimal timing of boosters. [ABSTRACT FROM AUTHOR]

Background Due to delays in vaccinations, diphtheria-tetanus-whole-cell-pertussis (DTP) is often given with or after measles vaccine (MV)—out of sequence. We reanalyzed data from Matlab, Bangladesh, to examine how administration of MV and DTP out-of-sequence was associated with child survival. Methods In sum, 36 650 children born between 1986 and 1999 were followed with registration of vaccinations and survival. Controlling for background factors using Cox proportional hazards models, survival was analyzed between 9 and 24 months of age. We measured the mortality rate ratio (MRR) to compare vaccination groups. Oral polio vaccine (OPV) campaigns, which started in 1995, reduced the mortality rate and reduced the difference between vaccination groups. In the main analysis, we therefore censored for OPV campaigns; there were 151 nonaccident deaths before the OPV campaigns. Results Compared with MV administered alone (MV-only), DTP administered with or after MV had MRR 2.20 (1.31–3.70), and DTP-only had MRR 1.78 (1.01–3.11). Compared with MV-only, DTP administered with MV had a female-male MRR 0.56 (0.13–2.38), significantly different to DTP administered after MV, which had MRR 14.83 (1.88–117.1), test of interaction P  = .011. Compared with having DTP (no MV) as most recent vaccination, MV-only had a nonaccident MRR of 0.56 (0.32–0.99). Conclusion The negative effects of non-live DTP with or after live MV are not explained merely by selection bias. These observations support a live-vaccine-last policy where DTP should not be given with or after MV. [ABSTRACT FROM AUTHOR]

Fifteen Oregon schools excluded undervaccinated students when struck by pertussis outbreaks during the 2017–2018 school year. Of 243 under- or unvaccinated, exposed, students in these schools, 134 (55%) accepted vaccination, and 87 (36%) were excluded and missed a total of 975½ school days. No excluded students were subsequently reported as cases. [ABSTRACT FROM AUTHOR]

To commemorate the 100th anniversary of the Nobel prize being awarded to Jules Bordet, the discoverer of Bordetella pertussis , the 12th International Bordetella Symposium was held from 9 to 12 April 2019 at the Université Libre de Bruxelles, where Jules Bordet studied and was Professor of Microbiology. The symposium attracted more than 300 Bordetella experts from 34 countries. They discussed the latest epidemiologic data and clinical aspects of pertussis, Bordetella biology and pathogenesis, immunology and vaccine development, and genomics and evolution. Advanced technological and methodological tools provided novel insights into the genomic diversity of Bordetella and a better understanding of pertussis disease and vaccine performance. New molecular approaches revealed previously unrecognized complexity of virulence gene regulation. Innovative insights into the immune responses to infection by Bordetella resulted in the development of new vaccine candidates. Such discoveries will aid in the design of more effective approaches to control pertussis and other Bordetella -related diseases. [ABSTRACT FROM AUTHOR]

In October 2012, a maternal pertussis vaccination program was implemented in England following an increased incidence and mortality in infants. We evaluated the cost-effectiveness of the program by comparing pertussis-related infant hospitalizations and deaths in 2012–2017 with nonvaccination scenarios. Despite considerable uncertainties, findings support the cost-effectiveness of the program. [ABSTRACT FROM AUTHOR]

Background Adolescents make decisions about their own vaccinations and will be the childhood vaccine decision makers of tomorrow. It is therefore essential to educate adolescents about the risks of vaccine-preventable diseases and immunization safety. This study evaluated the impact of an interactive education initiative among adolescents at a high school in North Bay Ontario. Methods An anonymized questionnaire to assess students' knowledge, attitudes and beliefs about immunization and vaccine-preventable diseases was administered before and after delivering an interactive session. Chi-squared and Kruskal-Wallis tests were performed to test for differences between pre and post responses. Results The intervention increased the students' awareness that measles is a disease that affects their generation (P  < 0.05). Improvements were also noted in the perceived risk of pertussis (P  < 0.05) and tetanus (0.05). After the session, respondents were also more willing to participate with their parents in decisions affecting their healthcare (P  < 0.05). Students' perception of vaccine safety also improved (P  < 0.001). Conclusions Post survey results suggest that the interactive educational intervention had a positive effect on the adolescents' perceptions and attitudes towards immunization. Further research is required to determine the impact of this type of intervention on adolescents' future decision-making with respect to immunization. [ABSTRACT FROM AUTHOR]

Background Bordetella pertussis is among the leading causes of vaccine-preventable deaths and morbidity globally. Human asymptomatic carriage as a reservoir for community transmission of infections might be a target of future vaccine strategies, but has not been demonstrated. Our objective was to demonstrate that asymptomatic nasopharyngeal carriage of Bordetella pertussis is inducible in humans and to define the microbiological and immunological features of presymptomatic infection. Methods Healthy subjects aged 18–45 years with an antipertussis toxin immunoglobin G (IgG) concentration of <20 international units/ml were inoculated intranasally with nonattenuated, wild-type Bordetella pertussis strain B1917. Safety, colonization, and shedding were monitored over 17 days in an inpatient facility. Colonization was assessed by culture and quantitative polymerase chain reaction. Azithromycin was administered from Day 14. The inoculum dose was escalated, aiming to colonize at least 70% of participants. Immunological responses were measured. Results There were 34 participants challenged, in groups of 4 or 5. The dose was gradually escalated from 103 colony-forming units (0% colonized) to 105 colony-forming units (80% colonized). Minor symptoms were reported in a minority of participants. Azithromycin eradicated colonization in 48 hours in 88% of colonized individuals. Antipertussis toxin IgG seroconversion occurred in 9 out of 19 colonized participants and in none of the participants who were not colonized. Nasal wash was a more sensitive method to detect colonization than pernasal swabs. No shedding of Bordetella pertussis was detected in systematically collected environmental samples. Conclusions Bordetella pertussis colonization can be deliberately induced and leads to a systemic immune response without causing pertussis symptoms. Clinical Trials Registration NCT03751514. [ABSTRACT FROM AUTHOR]

Background Despite recommendations that older adults receive acellular pertussis vaccines, data on direct effectiveness in adults aged over 50 years are sparse. Methods A case-control study nested within an adult cohort. Cases were identified from linked pertussis notifications and each matched to 3 controls on age, sex, and cohort recruitment date. Cases and controls were invited to complete a questionnaire, with verification of vaccination status by their primary care provider. Vaccine effectiveness (VE) was estimated by conditional logistic regression, with adjustment for reported contact with children and area of residence. Results Of 1112 notified cases in the cohort, we had complete data for 333 cases and 506 controls. Among 172 PCR-diagnosed cases (mean age, 61 years), 11.2% versus 19.5% of controls had provider-verified pertussis vaccination, on average, 3.2 years earlier. Adjusted VE against PCR-diagnosed pertussis was 52% (95% CI, 15–73%), nonsignificantly higher if vaccinated within 2 years (63%; −5–87%). Adjusted VE was similar in adults born before 1950, presumed primed by natural infection (51%; −8–77%) versus those born 1950 or later who may have received whole-cell pertussis vaccine (53%; −11–80%) (P -heterogeneity = 0.9). Among 156 cases identified by single-point serology, adjusted VE was −55% (−177–13%). Conclusions We found modest protection against PCR-confirmed pertussis among older adults (mean age, 61 years; range, 46–81 years) within 5 years after acellular vaccine. The most likely explanation for the markedly divergent VE estimate from cases identified by single-titer serology is misclassification arising from limited diagnostic specificity in our setting. [ABSTRACT FROM AUTHOR]

Background Recent increases in pertussis morbidity and mortality rates among young infants have led to a recommendation in some countries for vaccination against pertussis during pregnancy. Having data on the burden of pediatric pertussis in a large population over time is important for establishing the true burden of disease in the acellular pertussis (aP) vaccine era. Here, we describe age-specific epidemiology and morbidity and mortality rates in children hospitalized with pertussis over 17 years across Canada in the aP vaccine era. Methods Patients aged ≤16 years who were admitted to 1 of 12 pediatric tertiary-care hospitals across Canada between 1999 and 2015 with confirmed (laboratory-confirmed or epidemiologically linked) or probable (clinically diagnosed) pertussis were included. Results Overall, 1402 patients with pertussis were included. Infants aged <2 months had the highest mean annual incidences of pertussis hospitalization and intensive care unit (ICU) admission (116.40 [95% confidence interval (CI), 85.32–147.49] and 33.48 [95% CI, 26.35–40.62] per 100 000 population, respectively). The overall proportion of children who required ICU admission was 25.46%, and the proportion was highest in infants aged <2 months (37.90%). Over the span of this study, 21 deaths occurred. Age of <16 weeks, prematurity, encephalopathy, and a confirmed pertussis diagnosis were independent risk factors for ICU admission. Age of <4 weeks, prematurity, and female sex were independent risk factors for death. Conclusions In the aP vaccine era, endemic pertussis still contributes considerably to childhood morbidity and death, particularly in infants aged <2 months. Vaccination against pertussis during pregnancy has the potential to reduce this disease burden. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background In England, acellular pertussis (aP) vaccines replaced whole-cell pertussis (wP) vaccine in the primary immunization course in October 2004. Despite sustained high vaccine coverage, 10 454 cases were confirmed in England in 2011–2012, including 1648 (16%) in those aged 10–19 years. These individuals had been primed with either 3-component (aP3) or 5-component (aP5) aP vaccines or wP vaccine due to temporary supply shortages. We aimed to compare protection provided by different pertussis vaccines. Methods We conducted a case-control study. Individuals born between 1997 and 2005, fully vaccinated in England, were included. Cases were laboratory confirmed between January 2011 and December 2012. Controls were identified from population vaccination registers, representing 20% of the population. We compared the odds of receiving different types of vaccines in cases and controls, adjusting for year of birth and time since last vaccine received. Odds ratios (ORs) were calculated with 95% confidence intervals (CIs). Results We analyzed 403 cases and 581 971 controls with 4 pertussis vaccines recorded. Compared to those who received 3 doses of wP for the primary course, cases had higher odds of receiving 3 doses of aP3 (OR, 3.86 [95% CI, 2.56–5.82]) but no significant association with receipt of 3 doses of aP5 (OR, 0.89 [95% CI,.29–2.73]). Conclusions Previous studies have suggested that aP3 and aP5 vaccines provide shorter duration of protection than wP vaccine. Our findings suggest that a primary course with aP3 is associated with increased risk of confirmed pertussis compared with wP. Although follow-up was shorter for aP5 cohorts, their risk did not seem to differ from wP. [ABSTRACT FROM AUTHOR]

We conducted a systematic review to describe the frequency of mild, atypical, and asymptomatic infection among household contacts of pertussis cases and to explore the published literature for evidence of asymptomatic transmission. We included studies that obtained and tested laboratory specimens from household contacts regardless of symptom presentation and reported the proportion of cases with typical, mild/atypical, or asymptomatic infection. After screening 6789 articles, we included 26 studies. Fourteen studies reported household contacts with mild/atypical pertussis. These comprised up to 46.2% of all contacts tested. Twenty-four studies reported asymptomatic contacts with laboratory-confirmed pertussis, comprising up to 55.6% of those tested. Seven studies presented evidence consistent with asymptomatic pertussis transmission between household contacts. Our results demonstrate a high prevalence of subclinical infection in household contacts of pertussis cases, which may play a substantial role in the ongoing transmission of disease. Our review reveals a gap in our understanding of pertussis transmission. [ABSTRACT FROM AUTHOR]

Background The Lao People's Democratic Republic continues to sustain a considerable burden of vaccine-preventable diseases because of incomplete vaccine coverage and weak vaccine responses. We have assessed seroconversion after routine vaccination with the pentavalent vaccine to capture weaknesses of vaccine management at the different levels of the healthcare system. Methods A total of 1151 children (aged 8–28 months) with 3 documented doses of the pentavalent vaccine delivered at central hospitals in Vientiane and the provincial hospital, 3 district hospitals, and 10 health centers in Bolikhamxay province were enrolled. Sociodemographic information was collected with a standardized questionnaire. Serum samples were analyzed for antibodies against vaccine components, and bivariate and multivariable analyses were performed to identify risk factors for low vaccine responses. Results Seroprotection rates at the provincial, district, and health center level were as high as in central hospitals, but seroprotection rates in areas covered by remote health centers were significantly lower. Protective levels also rapidly decreased with age at sampling. Seroprotection rates in Bolikhamxay against the different components reached 70%–77% and were up to 20% higher than in previous studies in the same region; 18.8% more children received the hepatitis B vaccine birth dose and the hepatitis B virus infection rate was 4 times lower. Conclusions Vaccine immunogenicity has dramatically improved in a central province, likely due to training and investment in the cold chain. Nevertheless, there remains a need to focus on the "last mile" in remote areas were most children are vaccinated through outreach activities. [ABSTRACT FROM AUTHOR]

The article explores Pertussis (also known as "whooping cough") disease is caused mainly by Bordetella pertussis and is severe in young infants and those who are born premature. In order to protect these young infants from whooping cough disease during early life, immunization against pertussis during pregnancy has been recommended in an increasing number of countries over the last decade.

Effective diphtheria, tetanus toxoids, whole-cell pertussis (DTwP) vaccines became available in the 1930s, and they were put into routine use in the United States in the 1940s. Their use reduced the average rate of reported pertussis cases from 157 in 100 000 in the prevaccine era to <1 in 100 000 in the 1970s. Because of alleged reactions (encephalopathy and death), several countries discontinued (Sweden) or markedly decreased (United Kingdom, Germany, Japan) use of the vaccine. During the 20th century, Bordetella pertussis was studied extensively in animal model systems, and many "toxins" and protective antigens were described. A leader in B pertussis research was Margaret Pittman of the National Institutes of Health/US Food and Drug Administration. She published 2 articles suggesting that pertussis was a pertussis toxin (PT)-mediated disease. Dr Pittman's views led to the idea that less-reactogenic acellular vaccines could be produced. The first diphtheria, tetanus, pertussis (DTaP) vaccines were developed in Japan and put into routine use there. Afterward, DTaP vaccines were developed in the Western world, and definitive efficacy trials were carried out in the 1990s. These vaccines were all less reactogenic than DTwP vaccines, and despite the fact that their efficacy was less than that of DTwP vaccines, they were approved in the United States and many other countries. DTaP vaccines replaced DTwP vaccines in the United States in 1997. In the last 13 years, major pertussis epidemics have occurred in the United States, and numerous studies have shown the deficiencies of DTaP vaccines, including the small number of antigens that the vaccines contain and the type of cellular immune response that they elicit. The type of cellular response a predominantly, T2 response results in less efficacy and shorter duration of protection. Because of the small number of antigens (3–5 in DTaP vaccines vs >3000 in DTwP vaccines), linked-epitope suppression occurs. Because of linked-epitope suppression, all children who were primed by DTaP vaccines will be more susceptible to pertussis throughout their lifetimes, and there is no easy way to decrease this increased lifetime susceptibility. [ABSTRACT FROM AUTHOR]

Background The incidence of pertussis in the United States has increased in recent years. While characteristics of severe pertussis infection have been described in infants, fewer data are available in older children and adults. In this analysis, we characterize pertussis infections in hospitalized patients of all ages. Methods Cases of pertussis with cough onset from 1 January 2011 through 31 December 2015 from 7 US Emerging Infections Program Network states were reviewed. Additional information on hospitalized patients was obtained through abstraction of the inpatient medical record. Descriptive and multivariable analyses were conducted to characterize severe pertussis infection and identify potential risk factors. Results Among 15942 cases of pertussis reported, 515 (3.2%) were hospitalized. Three hospitalized patients died. Infants aged <2 months accounted for 1.6% of all pertussis cases but 29.3% of hospitalizations. Infants aged 2–11 months and adults aged ≥65 years also had high rates of hospitalization. Infants aged <2 months whose mothers received acellular pertussis during the third trimester and children aged 2 months to 11 years who were up to date on pertussis-containing vaccines had a 43%–66% reduced risk of hospitalization. Among adolescents aged 12–20 years, 43.5% had a history of asthma, and among adults aged ≥65 years, 26.8% had a history of chronic obstructive pulmonary disease. Conclusions Individuals at the extreme ends of life may be the most vulnerable to severe pertussis infections, though hospitalization was reported across all age groups. Continued monitoring of severe pertussis infections will be important to help guide prevention, control, and treatment options. [ABSTRACT FROM AUTHOR]

Background Despite successful vaccination programs, pertussis remains endemic in the United States, and increasing incidence has been reported. We used national surveillance data to describe pertussis epidemiology, including patient demographic characteristics, geographic distribution, and temporal trends. Methods We included cases reported through the National Notifiable Diseases Surveillance System between 1 January 2000 and 31 December 2016. Differences in case characteristics were compared using Pearson χ2. Average annual incidence (cases per 100 000 population) was calculated overall and by age (<1 year, 1–6 years, 7–10 years, 11–18 years, 19–39 years, 30–64 years, and ≥65 years) and geographic subgroup. Annual percent change was estimated using negative bionomial regression. Results During 2000–2016, 339 420 pertussis cases were reported. The majority were in white (88.2%) and non-Hispanic (81.3%) persons, 9.9% were hospitalized, and 0.1% were fatal; however, differences existed by age. Infants had the highest incidence (75.3/100 000 population), accounting for 88.8% of deaths. Incidence increased significantly over time (P =.0019), increases were observed for all groups except persons aged <1 year and 19–64 years. Elevated case counts among persons aged 7–10 and 11–18 years coincided with the aging of acellular-primed cohorts. Incidence varied by geographic region, with some similarities in disease cyclicity. Conclusions Increasing baseline incidence and changing age distribution of pertussis suggest a central role of the transition to acellular vaccines in the US disease resurgence. Continued monitoring of national data is important to evaluate and optimize pertussis prevention and control strategies. [ABSTRACT FROM AUTHOR]

Background Protection induced by acellular pertussis (aP) vaccines is partial and short-lived, especially in teenagers, calling for novel immunization strategies. Methods We conducted an investigator-driven proof-of-concept randomized controlled trial in aP-primed adolescents in Geneva to assess the immunogenicity and reactogenicity of a novel recombinant aP (r-aP) vaccine including recombinant pertussis toxin (PT) and filamentous hemagglutinin (FHA) coadministered with tetanus-diphtheria toxoids (Td), compared to a licensed tetanus-diphtheria-aP vaccine containing chemically detoxified PT (cd/Tdap). The primary immunological endpoints were day 28/365 geometric mean concentrations (GMCs) of total and neutralizing anti-PT antibodies. Memory B cells were assessed. Results Sixty-two aP-primed adolescents were randomized and vaccinated with r-aP + Td or cd/Tdap. Reactogenicity, adverse events, and baseline GMCs were similar between the groups. Day 28 PT-neutralizing GMCs were low after cd/Tdap (73.91 [95% confidence interval {CI}, 49.88–109.52] IU/mL) and approximately 2-fold higher after r-aP + Td (127.68 [95% CI, 96.73–168.53] IU/mL; P =.0162). Anti-PT GMCs were also low after cd/Tdap (52.43 [95% CI, 36.41–75.50] IU/mL) and 2-fold higher after r-aP + Td (113.74 [95% CI, 88.31–146.50] IU/mL; P =.0006). Day 28 anti-FHA GMCs were similar in both groups. Day 365 anti-PT (but not PT-neutralizing) GMCs remained higher in r-aP + Td vaccinees. PT-specific memory B cells increased significantly after r-aP + Td but not cd/Tdap boosting. Conclusions Boosting aP-primed adolescents with r-aP induced higher anti-PT and PT-neutralizing responses than cd/Tdap and increased PT-specific memory B cells. Despite this superior immunogenicity, r-aP may have to be given repeatedly, earlier, and/or with novel adjuvants to exert an optimal influence in aP-primed subjects. Clinical Trials Registration NCT02946190. [ABSTRACT FROM AUTHOR]