Epidemiology Of Pertussis Research Articles

Effect of change in vaccine schedule on pertussis epidemiology in France: a modelling and serological study

In April-May, 2013, France modified its pertussis vaccination schedule, which uses the acellular pertussis vaccine, from three primary doses at 2, 3, and 4 months of age and a first booster at 16-18 months of age (former schedule) to two primary doses at 2 and 4 months of age and a first booster at 11 months of age (new schedule). We aimed to assess the subsequent effect of the vaccine schedule change on pertussis epidemiology in France. In this modelling study, using data collected between Jan 1, 2012, and Dec 31, 2019, from French national surveillance sources, we analysed the PCR test results of nasopharyngeal swabs collected from symptomatic outpatients aged 2-20 years with suspected pertussis. We developed a negative binomial regression model for the number of confirmed pertussis cases by year and age to assess the relative risks of pertussis depending on vaccine schedule. The linear predictor included the year, the age group, the population size, and a proxy of waning immunity. We tested different models in which waning immunity could vary with vaccine schedule and type of primary vaccine. The models were fitted to the 2012-18 data via Bayesian Markov chain Monte Carlo sampling, and the 2019 data were left out for external model validation. We also compared the anti-pertussis toxin (PT) antibody concentrations in leftover sera from children not tested for pertussis or recent respiratory tract infection aged 2-5 years born before and after the vaccine schedule change. We collected data on 7493 confirmed cases of pertussis. The model that best fitted the 2012-18 epidemiological data supported a faster waning of immunity following vaccination with the new vaccine schedule. 3 years after vaccination, the risk of developing pertussis was 1·7 (95% CI 1·4-2·0) times higher for children vaccinated according to the new schedule than those vaccinated according to the former schedule. The model correctly predicted the age distribution of cases in 2019. Geometric mean concentrations (GMC) of anti-PT IgG were 50% lower in children aged 2 years vaccinated with the new schedule (GMC=5·85 IU/mL [95% CI 4·08-8·39]) than in children of the same age vaccinated with the former schedule (GMC=11·62 IU/mL [95% CI 9·05-14·92]; p=0·0016), and 43% lower in children aged 3 years vaccinated with the new schedule (GMC=3·88 IU/mL [95% CI 2·82-5·34]) than those with the former schedule (GMC=6·80 IU/mL [95% CI 4·77-9·70]; p=0·026). A shorter-lived protection induced by the new vaccine schedule recommended in France since 2013 is associated with an increase of pertussis cases in children aged 2-5 years. If similar findings are observed in other countries and clinical trials, these findings should be considered in future pertussis vaccination policies. INCEPTION, Labex-IBEID, Institut Pasteur, and Santé Publique France.

Bordetella pertussis in School-Age Children, Adolescents and Adults: A Systematic Review of Epidemiology and Mortality in Europe.

Pertussis (whooping cough) epidemics persist globally despite high vaccine coverage among infants and young children. The resurgence of pertussis in high-income countries is partly due to waning vaccine immunity, resulting in a pool of unprotected adolescents and adults. However, pertussis is generally less severe in adolescents and adults, and this difference in presentation means it can often be unrecognised by healthcare professionals, meaning that it is largely under-diagnosed in older populations. A systematic search of MEDLINE, EMBASE and BIOSIS was undertaken to identify studies published between 1 January 1990 and 17 June 2019, with information on pertussis epidemiology and mortality in school-aged children, adolescents and adults in Europe. A formal statistical comparison (e.g. using meta-analyses) was not possible because of the mix of methodologies reported. There were 69 epidemiological studies and 19 mortality studies identified for review. Over the past decade, the reported incidence of notified pertussis cases varied widely between European countries, which is likely associated with differences in surveillance systems, diagnostic techniques and reporting regulations. However, several studies show that pertussis is circulating among adolescents and adults in Europe, and although pertussis-related morbidity and mortality are highest in infants, there is evidence that adults aged > 50 years are at increased risk. For example, in a hospital-based surveillance study in Portugal, between 2000 and 2015, 94% of hospitalised pertussis cases were infants aged < 1 year, with a case fatality rate (CFR) of 0.8%; however, among hospitalised adult cases of pertussis, the CFRs were 11.5% (aged 18–64 years) and 17.4% (aged > 65 years). Very few European countries currently include pertussis boosters for adults in the national immunisation strategy. In addition to increasing pertussis vaccination coverage in adolescents and adults, mitigation strategies in European countries should include improved diagnosis and treatment in these populations.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00520-9.

Asymptomatic Bordetella pertussis infections in a longitudinal cohort of young African infants and their mothers.

Recent pertussis resurgence in numerous countries may be driven by asymptomatic infections. Most pertussis surveillance studies are cross-sectional and cannot distinguish asymptomatic from pre-symptomatic infections. Longitudinal surveillance could overcome this barrier, providing more information about the true burden of pertussis at the population level. Here we analyze 17,442 nasopharyngeal samples from a longitudinal cohort of 1320 Zambian mother/infant pairs. Our analysis has two elements. First, we demonstrate that the full range of IS481 qPCR CT values provides insight into pertussis epidemiology, showing concordance of low and high CT results over time, within mother/infant pairs, and in relation to symptomatology. Second, we exploit these full-range qPCR data to demonstrate a high incidence of asymptomatic pertussis, including among infants. Our results demonstrate a wider burden of pertussis infection than we anticipated in this population, and expose key limitations of threshold-based interpretation of qPCR results in infectious disease surveillance.

Bordetella pertussis in School-Age Children, Adolescents, and Adults: A Systematic Review of Epidemiology, Burden, and Mortality in Asia.

Cyclic epidemics of pertussis (whooping cough) have been observed globally over the past twenty years despite high infant vaccine coverage. The resurgence of pertussis in high-income countries is partly due to waning vaccine immunity in older children and adults, as well as better surveillance and diagnostics. Moreover, in adolescents and adults, pertussis symptoms are mild and similar to common cough syndromes, meaning that it is under-diagnosed in older populations. A systematic search of MEDLINE, EMBASE, and BIOSIS was undertaken to identify studies published between 1 January 1990 and 17 June 2019, with information on pertussis epidemiology, burden of illness, and mortality in school-aged children, adolescents, and adults in Asia. Studies identified for inclusion were reviewed narratively because a statistical comparison was not possible due to the mix of methodologies used. The results showed that in East Asia, including Japan, South Korea, China, and Taiwan, pertussis is circulating in older children and adults. Diphtheria–tetanus–pertussis (DTP4) coverage is high in East Asia, yet outbreaks observed in Japan and South Korea suggest that vaccine-acquired immunity had waned in adolescents and adults. Several school outbreaks in China show that pertussis is circulating in young children, with continued circulation in adolescents and adults. There was a lack of information from Southeast/South Asian countries, although pan-Asian serosurveys showed that recent pertussis infection was common in adolescents and in adults with persistent cough. To conclude, the circulation of pertussis in Asian countries with high DTP4 coverage supports the expansion of routine vaccination to include booster doses for children at school entry and adolescents. However, surveillance is weak or absent in many countries, meaning that the true burden of pertussis, particularly among older populations, is unknown.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00439-1.

Bordetella pertussis in School-Age Children, Adolescents, and Adults: A Systematic Review of Epidemiology, Burden, and Mortality in the Middle East.

Despite modern diphtheria-tetanus-pertussis (DTP) vaccines and high vaccine coverage, a resurgence of pertussis (whooping cough) has been observed globally. In North America and Europe, high vaccine coverage in children has led to a shift in the age-specific peak incidence of infection away from infants and towards older children and adolescents. However, much less is known about the prevalence of pertussis in older children and adults in the Middle East. A systematic search of MEDLINE, EMBASE, and BIOSIS was undertaken to identify studies published between 1 January 1990 and 17 June 2019, with information on pertussis epidemiology, burden of illness, and mortality in school-aged children, adolescents, and adults in the Middle East. Studies identified for inclusion were reviewed narratively because a statistical comparison was not possible because of the mix of methodologies used. The results showed that surveillance data are weak or missing in most Middle Eastern countries, and among 24 epidemiological studies identified, most were from Iran (14), Israel (4), and Turkey (3), with single studies from the United Arab Emirates and Iraq. Despite various surveillance periods, clinical definitions, and antibody cut-off values used across the studies, the reported seroprevalence of pertussis antibodies suggested that adolescents and adults are commonly exposed to pertussis in the community and that vaccine-acquired immunity from childhood wanes. Few countries in the Middle East include a diphtheria-tetanus-acellular pertussis (Tdap) booster for adolescents on the national schedule. Israel was the only country with epidemiological data in a population that received Tdap, and the study showed that after the introduction of the adolescent booster dose, there was decrease in pertussis among children aged 5–14 years. To conclude, results from the Middle East suggest that in common with other regions, pertussis is widely circulating and that it might be shifting towards older age groups.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00440-8.

Bordetella pertussis in School-Age Children, Adolescents, and Adults: A Systematic Review of Epidemiology, Burden, and Mortality in Africa.

The Global Pertussis Initiative recommends diphtheria–tetanus–pertussis (DTP3) vaccination of infants aged < 1 year for all African countries, and recommends the vaccination of pregnant women as a primary prevention strategy. However, the role of older children and adults in the transmission of pertussis in Africa is not clear. A systematic search of MEDLINE, EMBASE, and BIOSIS was undertaken to identify studies published between 1 January 1990 and 17 June 2019, with information on pertussis epidemiology, burden of illness, and mortality in school-aged children, adolescents, and adults in Africa. Studies identified for inclusion were reviewed narratively because a statistical comparison was not possible because of the mix of methodologies used.Studies from North Africa (Morocco, Tunisia, and Algeria) reported that although DTP4 vaccine coverage is high, severe pertussis-related complications persist in young children, vaccine-acquired immunity wanes in adolescents, and household contacts are important transmitters of infection. A serosurvey in Gambia showed that 6% of the general population had pertussis antibody levels suggesting recent infection, and studies from Senegal showed that pertussis infection was endemic despite high DTP3 coverage. During a pertussis outbreak in Ethiopia, the case fatality rate was 3.7% overall, and 6.3% among children aged 5–9 years. In a case-surveillance study in South Africa, the incidence of pertussis among hospitalized children was 526/100,000, and infection rates were higher in HIV-exposed and -infected children compared with uninfected children. In conclusion, the highest burden of pertussis in Africa is among infants, and surveillance is lacking in many African countries meaning that the burden of pertussis among infants and infection rates among older children and adults are not well reported, and likely underestimated.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-021-00442-6) contains supplementary material, which is available to authorized users.

Pertussis among patients with clinically compatible illness in the Amhara Regional State, Ethiopia

BackgroundPertussis is an acute respiratory tract disease caused by Bordetella pertussis. In 2014, 24.1 million pertussis cases, resulting in 160,700 deaths, were estimated to have occurred worldwide. This study aimed to determine the epidemiology of pertussis among patients with clinically compatible illness who visited selected hospitals in the Amhara Regional State of Ethiopia. MethodsA cross-sectional study design was used to review pertussis patients with clinically compatible illness. Nasopharyngeal swabs were collected from 515 patients from July 2018 through February 2019. DNA was extracted from all nasopharyngeal swabs and samples were analyzed using real-time (RT-) PCR. Crude and adjusted odds ratios with corresponding 95% confidence intervals were estimated using bivariable and multivariable logistic regression analysis, respectively. ResultsThe overall prevalence of Bordetella species among the study participants was 156 of 515 (30.3%) [95% CI = 26.4–34.6] as determined by Bordetella RT-PCR, including: 65 (41.7%) B. pertussis, 89 (57.1%) indeterminate B. pertussis, one (0.6%) Bordetella holmesii and one (0.6%) Bordetella parapertussis. ConclusionsThis study found that pertussis is potentially endemic and a common health problem among patients visiting health institutions in the Amhara Regional State of Ethiopia. More data regarding pertussis in Ethiopia could inform development of effective prevention strategies.

Epidemiology of Pertussis in Individuals of All Ages Hospitalized With Respiratory Illness in South Africa, January 2013-December 2018.

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. 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. 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. 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.

Impact of Vaccine Schedule Change on Pertussis Epidemiology in France: A Modelling and Serological Study

Background: In 2013, France modified its pertussis vaccination schedule to remove one dose at 3 months of age and change the age of the booster dose from 16 to 11 months. We aimed to assess the subsequent impact on pertussis epidemiology in France. Methods: We analysed the PCR test results of nasopharyngeal swabs (N=7493) collected from symptomatic outpatients aged 2-20 years old between 2012 and 2019 in France. We developed a Poisson regression model in which the number of positive cases by year and age depended on the year, age group, population size of each age group and a proxy of waning immunity that could vary with vaccine schedule. We also compared the anti-pertussis toxin (PT) antibody levels of 315 children born before and after the vaccine schedule change. Findings: The model that best fitted the 2012-2018 epidemiological data supported a faster waning of immunity following vaccination with the new vaccine schedule. Four years after vaccination, the risk of developing pertussis was 2.1 (95% CI, 1.7-2.2) times higher for children vaccinated according to the new schedule than those vaccinated according to the previous schedule. The model correctly predicted the age distribution of cases in 2019. Anti-PT IgG levels were significantly lower in children born after implementation of the new schedule, compared to children born before. Interpretation: A shorter-lived protection induced by the 2/4+11 vaccine schedule recommended in France since 2013 is associated with an increase of pertussis cases in 2-5-year olds. Funding Statement: This project was funded by the INCEPTION interdisciplinary project at Institut Pasteur, “Understanding whooping cough resurgence in Europe by combining genomic, epidemiological and sociological approaches” (French Government Investissements d’Avenir grant ANR-16-CONV-0005). This work received financial support from the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant n_ANR-10-LABX-62-IBEID). Institutional support was provided by Institut Pasteur and Sante publique France. Declaration of Interests: None to declare. Ethics Approval Statement: The data collection received approval by French supervisory ethics authority (CNIL, n°1474593), and was approved by the local Institutional Review board (N° 2020 1028160733). All data processing and storage comply with the General Data Protection Regulation (GDPR) and ethical standards of the National Research Committee. This study was conducted in accordance with the Helsinki Declaration, with informed consent obtained from each patient’s guardians.

1422. Burden of Pertussis in South Korea: Implications for adults

BackgroundThere are a limited number of published studies on pertussis disease burden and epidemiology in South Korea, particularly those evaluating the impact in adults.MethodsWe conducted a systematic literature review on pertussis epidemiology and burden of disease in South Korea. The objective was to highlight evidence gaps which could help improve awareness about pertussis disease in adults in South Korea.ResultsOf 940 articles published between January 2000 to December 2019, 19 articles provided data for pertussis epidemiology and 9 provided data in adults. Laboratory confirmation rates in adults varied according to methodology, likely influenced by study/sampling variations. Three studies reported serological evidence of infection in adolescents and adults (33-57%). Among cases, the average cough duration was 16.5 days (range 7-30 days) and over 85% of cases presented with paroxysmal cough, while only 25% of cases or less presented with a characteristic whoop or post-tussive vomiting. Importantly, in 4 studies reporting vaccination status, almost all adult cases had no history of pertussis vaccination since childhood.ConclusionPrimary childhood vaccination rates in South Korea are among the highest globally, while adult pertussis vaccine uptake appears to be quite low. Our literature review suggests that pertussis is underreported in adults, as evidenced by serology data demonstrating that tetanus antibody levels are low while pertussis toxin antibody levels are relatively high, suggesting continued circulation of community pertussis. These findings highlight the need for strategies such as maternal immunization and decennial revaccination of adults to address the changing epidemiology and waning immunity. Active pertussis testing/reporting and better utilization of adult vaccine registries is required to help provide robust data for vaccine decision-making at the national level. In the current COVID-19 environment, strategies that can reduce clinic or hospital visits will have substantial benefits to authorities managing rapid increases in health care resource utilization, and vaccine preventable diseases provide an easy and immediate target for achieving that goal.DisclosuresBruce Mungall, PhD, the GSK group of companies (Employee, Shareholder) Hyungwoo Kim, MD, MPH, the GSK group of companies (Employee) Kyu-Bin Oh, MD, the GSK group of companies (Employee, Shareholder)

1481. Incidence of Pertussis in Older Adults in England and the United Kingdom: A Large, Retrospective Database Analysis

BackgroundPertussis affects people of all ages and can lead to severe complications in adults, including hospitalization. Pertussis immunity, whether vaccine-induced or from natural infection, wanes over time. Therefore, despite extensive pediatric vaccination against pertussis, adults remain susceptible to the disease. Here we present the reported incidence of pertussis in people ≥ 50 years old (≥ 50yo) in England and the United Kingdom (UK).MethodsWe performed an observational, retrospective database analysis using the UK Clinical Practice Research Datalink GOLD and Aurum primary care databases, and Hospital Episode Statistics database when available for English subjects (HES-Eng), 2009-2018. Occurrence of pertussis was identified by diagnostic codes recorded in primary care only for the UK subset, and primary care and/or secondary care for HES-Eng.ResultsIn the ≥ 50yo UK population, a total of 47.1 million (m) person-years of follow-up (PYFU) including 28.5m PYFU for HES-Eng, were included. In the UK, the pertussis Incidence Rate (IR) across all years was 5.44 per 100,000 PYFU. Yearly IRs ranged from 0.79 – 11.40 per 100,000 PYFU and reflected the cyclic epidemiology of pertussis. A peak of IR was observed in 2012, known to be an outbreak year, and observed IRs were higher in 2013-2018 (4.75 – 9.73 per 100,000 PYFU) than 2009-2011 (0.79 – 1.48 per 100,000 PYFU). In the HES-Eng population, overall IR was 5.76 per 100,000 PYFU. IRs were highest in the younger age groups (HES-Eng: 8.88 in 50-54 yo; 1.42 in ≥ 85 yo) (see table 1 and 2).Table 1 Table 2 ConclusionThe observed reported IR of pertussis was similar in the UK and HES-Eng populations, noting the inclusion of secondary care diagnoses in the latter. The dynamics of IRs across years are consistent with estimated IRs from Public Health England data. Considering the burden of pertussis established elsewhere in older adults, and their non-negligible contribution to the whole population incidence, strategies for the prevention of pertussis should include this age group.DisclosuresEmmanuel Aris, PhD, the GSK group of companies (Employee, Shareholder) Esse Ifebi Akpo, n/a, the GSK group of companies (Employee, Shareholder) Amit Bhavsar, MBBS, MHA, the GSK group of companies (Employee) Lauriane Harrington, n/a, the GSK group of companies (Employee) Evie Merinopoulou, MSc, Evidera Ltd (Employee)the GSK group of companies (Consultant) Nicola Sawalhi-Leckenby, MSc, Evidera Ltd (Employee)the GSK group of companies (Consultant) Elisa Turriani, PhD, the GSK group of companies (Employee) Kinga Meszaros, MBA, the GSK group of companies (Employee, Shareholder) Dimitra Lambrelli, PhD, MPharm, Evidera Ltd (Employee)the GSK group of companies (Consultant) Piyali Mukherjee, MBBS, MPH, the GSK group of companies (Employee, Shareholder)

Comparative genomics of clinical Bordetella pertussis strains against vaccine reference strains of India reveals genomic structural heterogeneity

Background: Pertussis, also known as whooping cough, caused by Bordetella pertussis, is a highly contagious, vaccine-preventable respiratory disease causing neonatal morbidity and mortality worldwide. Pertussis continues to be a serious public health problem in India. Data on incidence of pertussis and molecular epidemiology is scarce in India. The present study investigated the diversity of clinical B. pertussis strains against vaccine reference strains of India at genome structural level. Methods and materials: B. pertussis strains, BPD1 and BPD2 isolated from nasopharyngeal swabs of pediatric patients were included in the study. Swabs were plated in charcoal blood agar and incubated at 37 °C with CO2 for 48 h. Isolates were confirmed by standard biochemical tests and real-time PCR for the targets IS481 and ptxS1 genes. Genomic DNA was extracted and whole genome sequencing was performed using hybrid assembly approach with Ion torrent and MinION reads. Annotation was done using PATRIC and NCBI pipeline. MLST was analyzed through CGE database. Results: Genome comparison of clinical B. pertussis against 5 whole-cell pertussis vaccine reference strains of India and 1 global reference strains, showed novel insertion of repeat region (∼150 kb) flanked by IS481 in one strain and insertion of known ∼128 kb repeat region in another strain. The clinical strains has shown to undergone genome reduction due to insertion or deletion of IS481 repeat regions comparable to vaccine strains. These isolates harboured multiple virulence traits and ptxS toxin subunits. In addition, the isolates harboured pertactin adhesion (prn) gene, dermonecrotic, hemolysin and cytolysin toxins, and genes involved in type II toxin-antitoxin systems. Other virulence genes identified include virB2, B3, B6, B7, B8, B9, B10 and B11. Both these isolates belonged to sequence type, ST2. Conclusion: The comparative analysis showed genome re-arrangement due to insertions, deletions, and inversions in B. pertussis strains resulting in genome structural diversity. The significance of these genome re-arrangement among clinical strains in response to vaccination needs to be studied. Continues monitoring of changes in vaccine strains at genome level is essential. Further, comprehensive studies on whole genomes are required to understand the genome evolution of B. pertussis.

Revisiting the epidemiology of pertussis in Canada, 1924\u20132015: a literature review, evidence synthesis, and modeling study

BackgroundDisease surveillance is central to the public health understanding of pertussis epidemiology. In Canada, public reporting practices have significantly changed over time, creating challenges in accurately characterizing pertussis epidemiology. Debate has emerged over whether pertussis resurged after the introduction of adsorbed pertussis vaccines (1981–1985), and if the incidence fell to its pre-1985 after the introduction of acellular pertussis vaccines (1997–1998). Here, we aim to assemble a unified picture of pertussis disease incidence in Canada.MethodsUsing publicly available pertussis surveillance reports, we collected, analyzed and presented Canadian pertussis data for the period (1924–2015), encompassing the pre-vaccine era, introduction of vaccine, changes to vaccine technology, and the introduction of booster doses. Information on age began to be reported since 1952, but age reporting practices (full, partial or no ages) have evolved over time, and varied across provinces/territories. For those cases reported without age each year, we impute an age distribution by assuming it follows that of the age-reported cases.ResultsBelow the age of 20 years, the adjusted age-specific incidence from 1969 to 1988 is substantially higher than existing estimates. In children < 1 year, the incidence in some years was comparable to that during the 1988–1999 resurgence.ConclusionsThe results presented here suggest that the surge in the average yearly incidence of pertussis that began in 1988 was weaker than previously inferred, and in contrary to the past findings, below age 5, the average yearly incidence of pertussis from 1999 to 2015 (when the incidence dropped again) has been lower than it was from 1969 to 1988.

Epidemiological Prognosis of Pertussis Incidence in Bulgaria.

Epidemiological forecasting facilitates scientifically sound solutions to upcoming theoretical and practical issues, in the development of public health management, in particular of infectious diseases. To critically analyze the most recent scientific advances in the biosocial nature and methodology of epidemiological forecasting to present a real-life example of pertussis, a disease with shifting epidemiology. For the prediction of pertussis morbidity the autoregressive integrated moving average (ARIMA) the model was established by utilizing the method of time series analysis to construct a model of overall morbidity using Time series modeller in SPSS v.25. To model pertussis morbidity we obtained official data from the Ministry of Health and the National Center for Infectious and Parasitic Diseases, since the beginning of disease registration from 1903 until 2018. We also analyzed the shifting epidemiology of pertussis. The proper identification procedures we applied indicated ARIMA (3,0,0) model to best fit our original time series of the annual whooping cough morbidity for the 1921-2018 period. The model predicts better morbidity in a one-step forecast. The incidence rate is expected to be stable at about 1.35 per 100,000 in the next three years, which is close to the 2016 level and lower than those in 2017-2018. The ARIMA (3,0,0) model in our study is an adequate tool for presenting the pertussis morbidity trend and is suitable to forecast near-future disease dynamics, with acceptable error tolerance.

A computational framework for modeling and studying pertussis epidemiology and vaccination

BackgroundEmerging and re-emerging infectious diseases such as Zika, SARS, ncovid19 and Pertussis, pose a compelling challenge for epidemiologists due to their significant impact on global public health. In this context, computational models and computer simulations are one of the available research tools that epidemiologists can exploit to better understand the spreading characteristics of these diseases and to decide on vaccination policies, human interaction controls, and other social measures to counter, mitigate or simply delay the spread of the infectious diseases. Nevertheless, the construction of mathematical models for these diseases and their solutions remain a challenging tasks due to the fact that little effort has been devoted to the definition of a general framework easily accessible even by researchers without advanced modelling and mathematical skills.ResultsIn this paper we describe a new general modeling framework to study epidemiological systems, whose novelties and strengths are: (1) the use of a graphical formalism to simplify the model creation phase; (2) the implementation of an R package providing a friendly interface to access the analysis techniques implemented in the framework; (3) a high level of portability and reproducibility granted by the containerization of all analysis techniques implemented in the framework; (4) a well-defined schema and related infrastructure to allow users to easily integrate their own analysis workflow in the framework. Then, the effectiveness of this framework is showed through a case of study in which we investigate the pertussis epidemiology in Italy.ConclusionsWe propose a new general modeling framework for the analysis of epidemiological systems, which exploits Petri Net graphical formalism, R environment, and Docker containerization to derive a tool easily accessible by any researcher even without advanced mathematical and computational skills. Moreover, the framework was implemented following the guidelines defined by Reproducible Bioinformatics Project so it guarantees reproducible analysis and makes simple the developed of new user-defined workflows.

The burden of laboratory-confirmed pertussis in low- and middle-income countries since the inception of the Expanded Programme on Immunisation (EPI) in 1974: a systematic review and meta-analysis

BackgroundAn effective vaccine against Bordetella pertussis was introduced into the Expanded Programme on Immunisation (EPI) by WHO in 1974, leading to a substantial global reduction in pertussis morbidity and mortality. In low- and middle-income countries (LMICs), however, the epidemiology of pertussis remains largely unknown. This impacts negatively on pertussis control strategies in these countries. This study aimed to systematically and comprehensively review published literature on the burden of laboratory-confirmed pertussis in LMICs over the 45 years of EPI.MethodsElectronic databases were searched for relevant literature (1974 to December 2018) using common and MeSH terms for pertussis. Studies using PCR, culture or paired serology to confirm Bordetella pertussis and parapertussis in symptomatic individuals were included if they had clearly defined numerators and denominators to determine prevalence and mortality rates.ResultsEighty-two studies (49,167 participants) made the inclusion criteria. All six WHO regions were represented with most of the studies published after 2010 and involving mainly upper middle-income countries (n = 63; 77%). PCR was the main diagnostic test after the year 2000.The overall median point prevalence of PCR-confirmed Bordetella pertussis was 11% (interquartile range (IQR), 5–27%), while culture-confirmed was 3% (IQR 1–9%) and paired serology a median of 17% (IQR 3–23%) over the period. On average, culture underestimated prevalence by 85% (RR = 0.15, 95% CI, 0.10–0.22) compared to PCR in the same studies.Risk of pertussis increased with HIV exposure [RR, 1.4 (95% CI, 1.0–2.0)] and infection [RR, 2.4 (95% CI, 1.1–5.1)]. HIV infection and exposure were also related to higher pertussis incidences, higher rates of hospitalisation and pertussis-related deaths.Pertussis mortality and case fatality rates were 0.8% (95% CI, 0.4–1.4%) and 6.5% (95% CI, 4.0–9.5%), respectively. Most deaths occurred in infants less than 6 months of age.ConclusionsDespite the widespread use of pertussis vaccines, the prevalence of pertussis remains high in LMIC over the last three decades. There is a need to increase access to PCR-based diagnostic confirmation in order to improve surveillance. Disease control measures in LMICs must take into account the persistent significant infant mortality and increased disease burden associated with HIV infection and exposure.

Pertussis Infections Among Pregnant Women in the United States, 2012-2017.

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. 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. 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). 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.

Use of a Neonatal-Mouse Model to Characterize Vaccines and Strategies for Overcoming the High Susceptibility and Severity of Pertussis in Early Life.

Newborns and unvaccinated infants, compared to other age groups, are more susceptible to pertussis infection, manifesting severe symptoms leading to a higher mortality. The recent increase in pertussis cases demands more effective strategies to overcome this major health problem. In parallel with maternal-immunization, neonatal-immunization (NI) is a strategy needing revision. Here, using the intranasal-challenge-mouse-model we evaluated the protective capacity of NI in both naïve-mice and those with maternally acquired immunity. We tested our acellular-vaccine-candidate based on outer-membrane-vesicles derived from Bordetella pertussis (OMVP) that induces Th2-profile but also the recommended Th-profile for protection: Th1/Th17-profile and CD4 T-memory-cells that reside in the lungs. Commercial acellular-vaccine (aP) and whole cell-vaccine (wP) inducing mainly Th2-profile and Th1-profile, respectively, were also tested. Analyzing the induced immunity and protection capability of NI included in 1- or 2-dose schedules with the same or different types of vaccine, we detected that the aP-vaccine administered in either single- or 2-dose schedules protected against sublethal B. pertussis infection. Schedules consisting of doses of aP neonatally and of OMVP or wP vaccine during infancy greatly reduced bacterial lung colonization while inducing the highest levels of high-avidity anti-pertussis toxin (PTx) IgG. That OMVP or wP neonatal dose did not interfere with the protection of transferred maternal immunity was especially encouraging. Moreover, OMVP- or wP used as a neonatal dose enhanced the quality of the humoral immune response in immunized pups. Antibodies generated by OMVP-or wP-vaccinated mice born to aP-immunized mothers were of higher avidity than those from mice that harbored only maternal immunity; but when mothers and neonates were immunized with the same aP-vaccine, the humoral response in the neonates was partially suppressed through the blunting of the level of anti-PTx IgG induced by the neonatal aP dose. These results demonstrated that neonatal immunization is a possible strategy to be considered to improve the current pertussis epidemiology. For neonates without maternal-immunity, mixed-vaccination schedules that include the aP- and OMVP-vaccines appear to be the most appropriate to induce protection in the pups. For offspring from immune mothers, to avoid blunting-effect, NI should be carried out with vaccines other than those applied during pregnancy.

Pertussis epidemiology and effect of vaccination among diagnosed children at Vietnam, 2015-2018.

To evaluate effect and costs of pertussis vaccination at Vietnam National Children's Hospital. Pertussis cases were defined by positive laboratory tests of children under 5years January 2015-June 2018, and data on patient characteristics, clinical data and hospitalisation costs were collected through patient records. Of 909 inpatients, 400 (44%) were <2months, the age for first DPT vaccination, and mechanical ventilation was more common than in children >2months (9% vs 4%, OR=2.3, CI 1.3-3.9), as well as persistent cough (99%), violent cough (87%) and pneumonia (91%). Comparing non-vaccinated (172 cases, 19%) and DPT vaccinated patients >2months of age hospitalisation was 106-fold higher (149.6 vs 1.39 per 100000 population), and proportion of severe patients, length of hospital stay and hospitalisation costs were significantly greater (23.9% vs 12.8%; 13 vs 10days; 826 USD vs 582 USD, CI 23-423, P=.03). Incidence and proportion of complications among under 2-month infants were higher than in older patients. DPT vaccination protects children from pertussis infection, and in case of pertussis infection decreases severity. Results indicate that the Ministry of Health should consider adding a booster vaccine for pregnant women in an extended vaccination programme.

Emergence of pertactin-deficient pertussis strains in Australia can be explained by models of vaccine escape

A number of developed countries including Australia have experienced significant pertussis outbreaks in recent years despite consistent high levels of vaccine coverage. Evolutionary changes in Bordetella pertussis carrying variants of the gene encoding pertactin, and the emergence of pertactin-deficient strains (PRN−) in the recent epidemics suggest a possible role of vaccine-driven evolution.In this study, we considered a deterministic 2-strain compartmental model to characterize the relative fitness of PRN− strains and vaccine efficacy against PRN− infection in comparison to the wild-type pertactin-expressing (PRN+) strains. We first showed that the model’s equilibrium behavior allows for replacement and co-existence, depending on key parameters related to transmission, vaccine efficacy and durations of immunity. We then fitted the model to epidemiological and pathogen PRN data from the state of New South Wales, Australia.Fitted model parameters showed that the changes in pertussis epidemiology have been governed by a vaccine-escape B. pertussis strain (PRN−) having a basic reproduction number ∼ 1/2 of the wild-type strain which was in circulation prior to April 2009, against which the vaccine was estimated to have substantially reduced efficacy. While not causal, our results suggest that selective pressure from acellular pertussis vaccination is consistent with the changing epidemiology observed in Australia over the analysis period.