IL-17 and IFN-γ-producing respiratory tissue resident memory CD4†T cells persist for decades in adults immunized as children with whole cell pertussis vaccines.

The objective was to determine if antigen-specific tissue resident memory T (TRM) cells persist in respiratory tissues of adults immunized as children with whole cell pertussis (wP) or acellular pertussis (aP) vaccines. Mononuclear cells from tonsil or nasal tissue cells were cultured with Bordetella pertussis antigens and TRM cells quantified by flow cytometry. Adults immunized with wP vaccines as children had significantly more IL-17A and IFN-y-producing TRM cells that respond to B. pertussis antigens in respiratory tissues when compared with aP-primed donors. Our findings demonstrate that wP vaccines induce CD4 TRM cells that can persist in respiratory tissues for decades.

Role of the Putative Histidine Kinase BP1092 in Bordetella pertussis Virulence Regulation and Intracellular Survival.

Bordetella pertussis persists inside host cells, and virulence factors are crucial for intracellular adaptation. The regulation of B. pertussis virulence factor transcription primarily occurs through the modulation of the two-component system (TCS) known as BvgAS. However, additional regulatory systems have emerged as potential contributors to virulence regulation. Here, we investigate the impact of BP1092, a putative TCS histidine kinase that shows increased levels after bacterial internalization by macrophages, on B. pertussis proteome adaptation under nonmodulating (Bvg+) and modulating (Bvg-) conditions. Using mass spectrometry, we compare B. pertussis wild-type (wt), a BP1092-deficient mutant (ΔBP1092), and a ΔBP1092 trans-complemented strain under both conditions. We find an altered abundance of 10 proteins, including five virulence factors. Specifically, under nonmodulating conditions, the mutant strain showed decreased levels of FhaB, FhaS, and Cya compared to the wt. Conversely, under modulating conditions, the mutant strain exhibited reduced levels of BvgA and BvgS compared to those of the wt. Functional assays further revealed that the deletion of BP1092 gene impaired B. pertussis ability to survive within human macrophage THP-1 cells. Taken together, our findings allow us to propose BP1092 as a novel player involved in the intricate regulation of B. pertussis virulence factors and thus in adaptation to the intracellular environment. The data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier PXD041940.

Virus-like particles displaying the mature C-terminal domain of filamentous hemagglutinin are immunogenic and protective against Bordetella pertussis respiratory infection in mice.

Bordetella pertussis, the bacterium responsible for whooping cough, remains a significant public health challenge despite the existing licensed pertussis vaccines. Current acellular pertussis vaccines, though having favorable reactogenicity and efficacy profiles, involve complex and costly production processes. In addition, acellular vaccines have functional challenges such as short-lasting duration of immunity and limited antigen coverage. Filamentous hemagglutinin (FHA) is an adhesin of B. pertussis that is included in all multivalent pertussis vaccine formulations. Antibodies to FHA have been shown to prevent bacterial attachment to respiratory epithelial cells, and T cell responses to FHA facilitate cell-mediated immunity. In this study, FHA's mature C-terminal domain (MCD) was evaluated as a novel vaccine antigen. MCD was conjugated to virus-like particles via SpyTag-SpyCatcher technology. Prime-boost vaccine studies were performed in mice to characterize immunogenicity and protection against the intranasal B. pertussis challenge. MCD-SpyVLP was more immunogenic than SpyTag-MCD antigen alone, and in Tohama I strain challenge studies, improved protection against challenge was observed in the lungs at day 3 and in the trachea and nasal wash at day 7 post-challenge. Furthermore, a B. pertussis strain encoding genetically inactivated pertussis toxin was used to evaluate MCD-SpyVLP vaccine immunity. Mice vaccinated with MCD-SpyVLP had significantly lower respiratory bacterial burden at both days 3 and 7 post-challenge compared to mock-vaccinated animals. Overall, these data support the use of SpyTag-SpyCatcher VLPs as a platform for use in vaccine development against B. pertussis and other pathogens.

Immunization with an mRNA DTP vaccine protects against pertussis in rats.

Bordetella pertussis is a Gram-negative bacterium that is the causative agent of the respiratory disease known as pertussis. Since the switch to the acellular vaccines of DTaP and Tap, pertussis cases in the US have risen and cyclically fallen. We have observed that mRNA pertussis vaccines are immunogenic and protective in mice. Here, we further evaluated the pertussis toxoid mRNA antigen and refined the formulation based on optimal pertussis toxin neutralization in vivo. We next evaluated the mRNA pertussis vaccine in Sprague-Dawley rats using an aerosol B. pertussis challenge model paired with whole-body plethysmography to monitor coughing and respiratory function. Female Sprague-Dawley rats were primed and boosted with either commercially available vaccines (DTaP or wP-DTP), an mRNA-DTP vaccine, or mock-vaccinated. The mRNA-DTP vaccine was immunogenic in rats and induced antigen-specific IgG antibodies comparable to DTaP. Rats were then aerosol challenged with a streptomycin-resistant emerging clinical isolate D420Sm1. Bacterial burden was assessed at days 1 and 9 post-challenge, and the mRNA vaccine reduced burden equal to both DTaP and wP-DTP. Whole-body plethysmography revealed that mRNA-DTP vaccinated rats were well protected against coughing which was comparable to the non-challenged group. These data suggest that an mRNA-DTP vaccine is immunogenic in rats and provides protection against aerosolized B. pertussis challenge in Sprague-Dawley rats.

BECC438b TLR4 agonist supports unique immune response profiles from nasal and muscular DTaP pertussis vaccines in murine challenge models.

The protection afforded by acellular pertussis vaccines wanes over time, and there is a need to develop improved vaccine formulations. Options to improve the vaccines involve the utilization of different adjuvants and administration via different routes. While intramuscular (IM) vaccination provides a robust systemic immune response, intranasal (IN) vaccination theoretically induces a localized immune response within the nasal cavity. In the case of a Bordetella pertussis infection, IN vaccination results in an immune response that is similar to natural infection, which provides the longest duration of protection. Current acellular formulations utilize an alum adjuvant, and antibody levels wane over time. To overcome the current limitations with the acellular vaccine, we incorporated a novel TLR4 agonist, BECC438b, into both IM and IN acellular formulations to determine its ability to protect against infection in a murine airway challenge model. Following immunization and challenge, we observed that DTaP + BECC438b reduced bacterial burden within the lung and trachea for both administration routes when compared with mock-vaccinated and challenged (MVC) mice. Interestingly, IN administration of DTaP + BECC438b induced a Th1-polarized immune response, while IM vaccination polarized toward a Th2 immune response. RNA sequencing analysis of the lung demonstrated that DTaP + BECC438b activates biological pathways similar to natural infection. Additionally, IN administration of DTaP + BECC438b activated the expression of genes involved in a multitude of pathways associated with the immune system. Overall, these data suggest that BECC438b adjuvant and the IN vaccination route can impact efficacy and responses of pertussis vaccines in pre-clinical mouse models.

ER-transiting bacterial toxins amplify STING innate immune responses and elicit ER stress.

The cGAS/STING sensor system drives innate immune responses to intracellular microbial double-stranded DNA (dsDNA) and bacterial cyclic nucleotide second messengers (e.g., c-di-AMP). STING-dependent cell-intrinsic responses can increase resistance to microbial infection and speed pathogen clearance. Correspondingly, STING activation and signaling are known to be targeted for suppression by effectors from several bacterial pathogens. Whether STING responses are also positively regulated through sensing of specific bacterial effectors is less clear. We find that STING activation through dsDNA, by its canonical ligand 2'-3' cGAMP, or the small molecule DMXAA is potentiated following intracellular delivery of the AB5 toxin family member pertussis toxin from Bordetella pertussis or the B subunit of cholera toxin from Vibrio cholerae. Entry of pertussis toxin or cholera toxin B into mouse macrophages triggers markers of endoplasmic reticulum (ER) stress and enhances ligand-dependent STING responses at the level of STING receptor activation in a manner that is independent of toxin enzymatic activity. Our results provide an example in which STING responses integrate information about the presence of relevant ER-transiting bacterial toxins into the innate inflammatory response and may help to explain the in vivo adjuvant effects of catalytically inactive toxins.

Eosinophils as drivers of bacterial immunomodulation and persistence.

Traditionally, eosinophils have been linked to parasitic infections and pathological disease states. However, emerging literature has unveiled a more nuanced and intricate role for these cells, demonstrating their key functions in maintaining mucosal homeostasis. Eosinophils exhibit diverse phenotypes and exert multifaceted effects during infections, ranging from promoting pathogen persistence to triggering allergic reactions. Our investigations primarily focus on Bordetella spp., with particular emphasis on Bordetella bronchiseptica, a natural murine pathogen that induces diseases in mice akin to pertussis in humans. Recent findings from our published work have unveiled a striking interaction between B. bronchiseptica and eosinophils, facilitated by the btrS-mediated mechanism. This interaction serves to enhance pathogen persistence while concurrently delaying adaptive immune responses. Notably, this role of eosinophils is only noted in the absence of a functional btrS signaling pathway, indicating that wild-type B. bronchiseptica, and possibly other Bordetella spp., possess such adeptness in manipulating eosinophils that the true function of these cells remains obscured during infection. In this review, we present the mounting evidence pointing toward eosinophils as targets of bacterial exploitation, facilitating pathogen persistence and fostering chronic infections in diverse mucosal sites, including the lungs, gut, and skin. We underscore the pivotal role of the master regulator of Bordetella pathogenesis, the sigma factor BtrS, in orchestrating eosinophil-dependent immunomodulation within the context of pulmonary infection. These putative convergent strategies of targeting eosinophils offer promising avenues for the development of novel therapeutics targeting respiratory and other mucosal pathogens.

Assessing the Impact of the 2020 Council of State and Territorial Epidemiologists Case Definition for Pertussis on Reported Pertussis Cases.

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.

Population-Based Study of Pertussis Incidence and Risk Factors among Persons >50 Years of Age, Australia.

Despite vaccination programs, pertussis has been poorly controlled, especially among older adults in Australia. This longitudinal, retrospective, observational study aimed to estimate the incidence and risk factors of pertussis among persons ≥50 years of age in Australia in the primary care setting, including those with underlying chronic obstructive pulmonary disease (COPD) or asthma. We used the IQVIA general practitioner electronic medical record database to identify patients ≥50 years of age with a clinical diagnosis of pertussis during 2015-2019. Pertussis incidence rates ranged from 57.6 to 91.4 per 100,000 persons and were higher among women and highest in those 50-64 years of age. Patients with COPD or asthma had higher incidence rates and an increased risk for pertussis compared with the overall population ≥50 years of age. Our findings suggest that persons ≥50 years of age in Australia with COPD or asthma have a higher incidence of and risk for pertussis diagnosis.

Reemergence of Bordetella parapertussis, United States, 2019-2023.

To determine changes in Bordetella pertussis and B. parapertussis detection rates, we analyzed 1.43 million respiratory multiplex PCR test results from US facilities from 2019 through mid-2023. From mid-2022 through mid-2023, Bordetella spp. detection increased 8.5-fold; 95% of detections were B. parapertussis. While B. parapertussis rates increased, B. pertussis rates decreased.

Strengthening Bordetella pertussis genomic surveillance by direct sequencing of residual positive specimens.

Whole-genome sequencing (WGS) of microbial pathogens recovered from patients with infectious disease facilitates high-resolution strain characterization and molecular epidemiology. However, increasing reliance on culture-independent methods to diagnose infectious diseases has resulted in few isolates available for WGS. Here, we report a novel culture-independent approach to genome characterization of Bordetella pertussis, the causative agent of pertussis and a paradigm for insufficient genomic surveillance due to limited culture of clinical isolates. Sequencing libraries constructed directly from residual pertussis-positive diagnostic nasopharyngeal specimens were hybridized with biotinylated RNA "baits" targeting B. pertussis fragments within complex mixtures that contained high concentrations of host and microbial background DNA. Recovery of B. pertussis genome sequence data was evaluated with mock and pooled negative clinical specimens spiked with reducing concentrations of either purified DNA or inactivated cells. Targeted enrichment increased the yield of B. pertussis sequencing reads up to 90% while simultaneously decreasing host reads to less than 10%. Filtered sequencing reads provided sufficient genome coverage to perform characterization via whole-genome single nucleotide polymorphisms and whole-genome multilocus sequencing typing. Moreover, these data were concordant with sequenced isolates recovered from the same specimens such that phylogenetic reconstructions from either consistently clustered the same putatively linked cases. The optimized protocol is suitable for nasopharyngeal specimens with diagnostic IS481 Ct < 35 and >10 ng DNA. Routine implementation of these methods could strengthen surveillance and study of pertussis resurgence by capturing additional cases with genomic characterization.

Use and Waste of Reconstituted Whole Blood Exchange Transfusions: An 11-year National Observational Study.

OBJECTIVES: To identify indications for exchange transfusions, assess the use and waste of exchange transfusion products (ie, reconstituted whole blood exchange transfusions), and determine nationwide distribution and prevalence of these transfuions in the Netherlands. STUDY DESIGN: All nine neonatal intensive care units (NICU) and 15 non-NICU hospitals participated in this retrospective, observational, cohort study. We retrieved data on indications for and use of all exchange transfusion products ordered by participating centers over an 11-year period. RESULTS: A total of 574 patients for whom 1,265 products were ordered were included for analyses. Severe ABO (32.6%) and non-ABO (25.2%) immune hemolysis and subsequent hyperbilirubinemia were the most frequent indications. Rare indications were severe leukocytosis in Bordetella pertussis (2.1%) and severe anemia (1.5%). Approximately half of all ordered products remained unused. In 278 of 574 neonates (48.4%), one or more products were not used, of which 229 (82.7%) were due to the resolving of severe hyperbilirubinemia with further intensification of phototherapy. The overall prevalence of neonates who received an exchange transfusion was 14.6:100,000 liveborn neonates. CONCLUSION: A considerable proportion of products remained unused, and annually a limited number of patients are treated with an exchange transfusion in the Netherlands, highlighting the rarity of the procedure in the Netherlands.

Synthesis of oligosaccharides from terminal B. pertussis LPS pentasaccharide and definition of the minimal epitope recognized by anti-pertussis antibodies.

Pertussis vaccines have been very effective in controlling whooping-cough epidemics but are ineffective in controlling circulation in older children and adults, thus facilitating the onset of future outbreaks. Antibodies against the lipopolysaccharide could reduce the carriage of the bacteria, its circulation, and transmission. The oligosaccharide fragments from the lipopolysaccharide may become a potential complement to existing vaccines in the form of protein glycoconjugates. An important step in the development of this type of vaccine is defining the minimal oligosaccharide epitope recognized by B. pertussis anti-lipopolysaccharide antibodies. This paper describes the complete synthesis of oligosaccharides containing two to five monosaccharide units corresponding to the pentasaccharide at the nonreducing end of the lipooligosaccharide and their recognition by mice and rabbit antibodies elicited against whole-cell B. pertussis. For the first time, we report that the terminal disaccharide, α-D-GlcNAcp-(1 → 4)-(2,3-di-NAc)-D-ManAp acid is the minimal structure recognized by antibodies induced by B. pertussis.

Biological impact of manual blood exchange in malignant Bordetella pertussis infection in infants.

BACKGROUND AND OBJECTIVES: Manual blood exchange (MBE) is a leukoreduction therapy for hyperleukocytosis in Bordetella spp. INFECTION: We describe the impact of BE on clinical and biological parameters in critically ill children with malignant pertussis. MATERIALS AND METHODS: This is a monocentric retrospective review of patients with malignant pertussis infection treated with MBE. It describes the evolution of haemodynamic, ventilatory, haematologic and metabolic characteristics before and after MBE. RESULTS: Between January 2006 and December 2021, nine patients (median age 43 days, range: 13-80 days) had 16 MBE for malignant pertussis. All patients were mechanically ventilated, and 7/9 patients developed pulmonary hypertension during their paediatric intensive care unit (PICU) stay. Overall, 3/9 patients survived, and the mean PICU length of stay was 8.5 days (range: 1-52 days). We found a significant reduction of the leukocyte count (pre-MBE: 61.8 G/L [interquartile range (IQR): 55.8-74.8] vs. post-MBE: 19.4 G/L [IQR: 17.7-24.1]; p ≤ 0.001) and significant oxygenation improvement (pre-MBE SpO2/FiO2: 190 [IQR: 106-200] vs. post-MBE SpO2/FiO2: 242 [IQR: 149-250]; p = 0.03). The main side effects were a significant reduction of thrombocytes (pre-MBE: 411 G/L [IQR: 166.5-563.5] vs. post-MBE: 66 G/L [IQR: 46-82.5]; p = <0.001) and of ionized calcium (iCa) (pre-MBE iCa: 1.3 [IQR: 1.22-1.37] vs. post-MBE iCa: 1.25 [IQR: 1.85-2.24]; p = 0.03). CONCLUSION: MBE efficiently reduces leukocytes and improves oxygenation in severe Bordetella pertussis infection in infants. Careful monitoring of calcium and thrombocytes seems mandatory.

Strain identity of Bordetella pertussis isolates from household members based on whole-genome sequencing.

We evaluated the genetic diversity of Bordetella pertussis, the causative agent of pertussis, within households by whole-genome sequencing. In pairwise comparisons of 23 isolates collected from 11 households, single-nucleotide polymorphism (SNP) analysis revealed extremely low SNP diversity (≤1 SNP) between isolate pairs: no SNPs were detected in 10 households and one SNP was obtained in the remaining household. This SNP was uncommon for B. pertussis and resulted in a nonsynonymous substitution (Ala303Thr) in nicotinate phosphoribosyltransferase. We demonstrated that the same strain is transmitted between household members and that B. pertussis is genomically stable during household transmission.

Current understanding of Bordetella-induced cough.

Typical pathogenic bacteria of the genus Bordetella cause respiratory diseases, many of which are characterized by severe coughing in host animals. In human infections with these bacteria, such as whooping cough, coughing imposes a heavy burden on patients. The pathophysiology of this severe coughing had long been uncharacterized because convenient animal models that reproduce Bordetella-induced cough have not been available. However, rat and mouse models were recently shown as useful for understanding, at least partially, the causative factors and the mechanism of Bordetella-induced cough. Many types of coughs are induced under various physiological conditions, and the neurophysiological pathways of coughing are considered to vary among animal species, including humans. However, the neurophysiological mechanisms of the coughs in different animal species have not been entirely understood, and, accordingly, the current understanding of Bordetella-induced cough is still incomplete. Nevertheless, recent research findings may open the way for the development of prophylaxis and therapeutic measures against Bordetella-induced cough.

Seroconversion and seroprevalence of TORCH infections in a pregnant women cohort study, Mombasa, Kenya, 2017-2019.

Women infected during pregnancy with TORCH (Toxoplasmosis, Other, Rubella, Cytomegalovirus, and Herpes simplex viruses) pathogens have a higher risk of adverse birth outcomes including stillbirth / miscarriage because of mother-to-child transmission. To investigate these risks in pregnant women in Kenya, we analyzed serum specimens from a pregnancy cohort study at three healthcare facilities. A sample of 481 participants was selected for TORCH pathogen antibody testing to determine seroprevalence. A random selection of 285 from the 481 participants was selected to measure seroconversion. These sera were tested using an IgG enzyme-linked immunosorbent assay against 10 TORCH pathogens. We found that the seroprevalence of all but three of the 10 TORCH pathogens at enrollment was >30%, except for Bordetella pertussis (3.8%), Treponema pallidum (11.4%), and varicella zoster virus (0.5%). Conversely, very few participants seroconverted during their pregnancy and were herpes simplex virus type 2 (n = 24, 11.2%), parvovirus B19 (n = 14, 6.2%), and rubella (n = 12, 5.1%). For birth outcomes, 88% of the participant had live births and 12% had stillbirths or miscarriage. Cytomegalovirus positivity at enrolment had a statistically significant positive association with a live birth outcome (p = 0.0394). Of the 10 TORCH pathogens tested, none had an association with adverse pregnancy outcome.

The effectiveness of maternal pertussis vaccination for protecting Aboriginal and Torres Strait Islander infants against infection, 2012-2017: a retrospective cohort study.

OBJECTIVES: To evaluate the effectiveness of maternal pertussis vaccination for preventing pertussis infections in Aboriginal and Torres Strait Islander infants under seven months of age. STUDY DESIGN: Retrospective cohort study; analysis of linked administrative health data. SETTING, PARTICIPANTS: Mother-infant cohort (Links2HealthierBubs) including all pregnant women who gave birth to live infants (gestational age ≥ 20 weeks, birthweight ≥ 400 g) in the Northern Territory, Queensland, and Western Australia during 1 January 2012 - 31 December 2017. MAIN OUTCOME MEASURES: Proportions of women vaccinated against pertussis during pregnancy, rates of pertussis infections among infants under seven months of age, and estimated effectiveness of maternal vaccination for protecting infants against pertussis infection, each by Indigenous status. RESULTS: Of the 19 892 Aboriginal and Torres Strait Islander women who gave birth to live infants during 2012-2017, 7398 (37.2%) received pertussis vaccine doses during their pregnancy, as had 137 034 of 259 526 non-Indigenous women (52.8%; Indigenous v non-Indigenous: adjusted odds ratio, 0.66; 95% confidence interval [CI], 0.62-0.70). The annual incidence of notified pertussis infections in non-Indigenous infants declined from 16.8 (95% CI, 9.9-29) in 2012 to 1.4 (95% CI, 0.3-8.0) cases per 10 000 births in 2017; among Aboriginal and Torres Strait Islander infants, it declined from 47.6 (95% CI, 16.2-139) to 38.6 (95% CI, 10.6-140) cases per 10 000 births. The effectiveness of maternal vaccination for protecting non-Indigenous infants under seven months of age against pertussis infection during 2014-17 was 68.2% (95% CI, 51.8-79.0%); protection of Aboriginal and Torres Strait Islander infants was not statistically significant (36.1%; 95% CI, -41.3% to 71.1%). CONCLUSIONS: During 2015-17, maternal pertussis vaccination did not protect Aboriginal and Torres Strait Islander infants in the NT, Queensland, and WA against infection. Increasing the pertussis vaccination rate among pregnant Aboriginal and Torres Strait Islander women requires culturally appropriate, innovative strategies co-designed in partnership with Indigenous organisations and communities.

Global burden of pertussis in 204 countries and territories, from 1990 to 2019: results from the Global Burden of Disease Study 2019.

OBJECTIVES: This study aimed to examine the impact of pertussis on the global, regional, and national levels between 1990 and 2019. METHODS: Data on pertussis on a global scale from 1990 to 2019 were collected from the 2019 Global Burden of Disease Study. We performed a secondary analysis to report the global epidemiology and disease burden of pertussis. RESULTS: During the period spanning from 1990 to 2019, pertussis exhibited a steady global decline in the age-standardized incidence rate (ASIR), age-standardized disability-adjusted life years rate (ASYR), and age-standardized death rate (ASDR). Nevertheless, upon delving into an in-depth analysis of various regions, it was apparent that ASIR in southern sub-Saharan Africa, ASYR and ASDR in high-income North America, and ASDR in Western Europe and Australasia, were witnessing an upward trajectory. Moreover, a negative correlation was observed between the Socio­demographic Index (SDI) and burden inflicted by pertussis. Notably, the incidence of pertussis was comparatively lower in men than in women, with 0-4-year-olds emerging as the most profoundly affected demographic. CONCLUSION: The global pertussis burden decreased from 1990 to 2019. However, certain regions and countries faced an increasing disease burden. Therefore, urgent measures are required to alleviate the pertussis burden in these areas.

Pertussis seasonal variation in Northern Vietnam: the evidence from a tertiary hospital.

BACKGROUND: Pertussis is a highly contagious and dangerous respiratory disease that threatens children's health in many countries, including Vietnam, despite vaccine coverage. From 2015 to 2018, Vietnam experienced an increasing number of pertussis patients. Therefore, this study aimed to investigate the trend and examine the seasonal variations of pertussis in North Vietnam. METHODS: Data were collected from medical records of all under-5-year-old inpatients admitted to the National Children's Hospital in Hanoi, Vietnam (VNCH) 2015-2018. A descriptive analysis was performed to describe the distribution of incident cases by year and season. Linear multivariable regression was conducted to investigate the association between the incidence of cases and seasonality adjusted by age and vaccination status. RESULTS: We identified 1063 laboratory-confirmed patients during 2015-2018, including 247 (23.2%) severe patients. The number of pertussis patients admitted to VNCH per 1000 hospitalizations was 3.2 in 2015, compared to 1.9, 3.1, and 2.1 in 2016, 2017, and 2018, respectively. Outbreaks occurred biennially; however, there was no significant difference in the number of severe patients over this period. Most cases occurred in the hot season (509 patients, or nearly half of the study population). With the adjustment of the vaccination rate and average age, the risk of pertussis-associated hospitalization in the mild season and the hot season was 21% (95% CI [0.12; 0.3]) and 15% (95% CI [0.05; 0.25]) higher than that in the warm season, respectively. The rate of hospitalizations was high in the mild season (28.9%) and the warm season (30.8%), nearly twice as much as that in the hot season; nevertheless, the death rate was only striking high in the mild season, about 5-6 times as much as those in the other seasons. CONCLUSION: The pertussis incidence in Northern Vietnam varied between seasons, peaking in the hot season (April-July). However, severe patients and deaths increased in the mild season (December-March). Interventions, for example, communication activities on pertussis and vaccination, are of immense importance in lowering the prevalence of pertussis. In addition, early diagnoses and early warnings performed by health professionals should be encouraged.