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.

Incidence and severity of pertussis hospitalisations in infants aged less than 1 year in 37 hospitals of six EU/EEA countries, results of PERTINENT sentinel pilot surveillance system, December 2015 to December 2018

Introduction PERTINENT is a pilot active surveillance system of infants hospitalised with pertussis in six European Union/European Economic Area countries (37 hospitals, seven sites). Aim This observational study aimed to estimate annual pertussis incidence per site from 2016 to 2018 and respective trends between 2017 and 2018. Pertussis cases were described, including their severity. Methods We developed a generic protocol and laboratory guidelines to harmonise practices across sites. Cases were hospitalised infants testing positive for Bordetella pertussis by PCR or culture. Sites collected demographic, clinical, laboratory data, vaccination status, and risk/protective factors. We estimated sites’ annual incidences by dividing case numbers by the catchment populations. Results From December 2015 to December 2018, we identified 469 cases (247 males; 53%). The median age, birthweight and gestational age were 2.5 months (range: 0–11.6; interquartile range (IQR): 2.5), 3,280 g (range: 700–4,925; IQR: 720) and 39 weeks (range: 25–42; IQR: 2), respectively. Thirty cases (6%) had atypical presentation either with cough or cyanosis only or with absence of pertussis-like symptoms. Of 330 cases with information, 83 (25%) were admitted to intensive care units including five deceased infants too young to be vaccinated. Incidence rate ratios between 2018 and 2017 were 1.43 in Czech Republic (p = 0.468), 0.25 in Catalonia (p = 0.002), 0.71 in France (p = 0.034), 0.14 in Ireland (p = 0.002), 0.63 in Italy (p = 0.053), 0.21 in Navarra (p = 0.148) and zero in Norway. Conclusions Incidence appeared to decrease between 2017 and 2018 in all but one site. Enhanced surveillance of hospitalised pertussis in Europe is essential to monitor pertussis epidemiology and disease burden.

Revisiting the epidemiology of pertussis in Canada, 1924–2015: a literature review, evidence synthesis, and modeling study

Background Disease 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. Methods Using 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. Results Below 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. Conclusions The 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.

Asymptomatic Bordetella pertussis infections in young African infants and their mothers identified within a longitudinal cohort

ABSTRACTDespite long-standing vaccination programs, pertussis incidence has increased in numerous countries; transmission by asymptomatic individuals is a suspected driver of this resurgence. However, unequivocal evidence documenting asymptomatic infections in adults and children is lacking due, in part, to the cross-sectional nature of most pertussis surveillance studies. In addition, modern pertussis surveillance relies on quantitative PCR (qPCR) using fixed diagnostic thresholds to identify cases.To address this gap, we present a longitudinal analysis of 17,442 nasopharyngeal samples collected from a cohort of 1,320 Zambian mother/infant pairs. Using full-range cycle threshold (CT) values from IS481 qPCR assays, we document widespread asymptomatic infections among mothers and also, surprisingly, among young infants. From an initial group of eight symptomatic infants who tested positive by qPCR, we identify frequent contemporaneous subclinical infections in mothers. Within the full cohort, we observe strong temporal correlation between low- and high-intensity qPCR signals. We compute a single time-averaged score for each individual summarizing the evidence for pertussis infection (EFI), and show that EFI strongly clusters within mother/infant pairs, and is strongly associated with clinical symptomatology and antibiotic use.Overall, the burden of pertussis here is substantially underestimated when restricting diagnostic criteria to IS481 CT≤35. Rather, we find that full-range CT values provide valuable insights into pertussis epidemiology in this population, and illuminate the infection arc within individuals. These findings have significant implications for quantifying asymptomatic pertussis prevalence and its contribution to overall transmission. Our results also expose limitations of threshold-based interpretations of qPCR assays in infectious disease surveillance.IMPORTANCE STATEMENTCurrent pertussis epidemiology rests largely on cross-sectional surveys that use diagnostic thresholds to interpret qPCR results as positive or negative, and thus fail to capture arcs of infection within individuals or populations. By longitudinally monitoring a cohort of African mother/infant pairs and using full-range qPCR results, we quantify the otherwise-hidden evidence for pertussis infection (EFI) in individuals. We demonstrate strong clustering of EFI within mother/infant pairs and quantify the association between EFI and both pertussis symptoms and antibiotic use. Critically, we find strong evidence that asymptomatic pertussis is common in both infants and mothers, indicating that the burden of pertussis has been significantly underestimated in this population. Our results also inform qPCR-based monitoring of other pathogens, such as SARS-CoV-2.

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

Background There are a limited number of published studies on pertussis disease burden and epidemiology in South Korea, particularly those evaluating the impact in adults. Methods We 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. Results Of 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. Conclusion Primary 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. Disclosures Bruce 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)

A computational framework for modeling and studying pertussis epidemiology and vaccination

Background Emerging 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. Results In 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. Conclusions We 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.

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

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 &gt; .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.