IntroductionRespiratory coinfections involving Influenza viruses, including Influenza A viruses (IAV) and bacteria, significantly worsen disease severity and remain a major public health concern, particularly during seasonal and pandemic flu outbreaks. Among bacterial pathogens, Streptococcus pneumoniae (Spn) and Streptococcus suis cause secondary infections in humans and swine respectively following influenza. The immunological mechanisms driving coinfection severity, especially the differences between simultaneous and sequential infections, are incompletely defined.MethodsWe developed an in vitro differentiated bone marrow-derived macrophages (BMDMs) model to examine transcriptional and protein-level responses during IAV-Spn coinfection or sequential infection. BMDMs were infected with IAV and Spn either simultaneously or with a 48-hour delay.ResultsRNA-Seq and OLINK proteomic analyses revealed that simultaneous coinfection elicits a synergistic inflammatory response similar to that caused by Spn alone, with strong activation of NF-κB-dependent genes. In sequential superinfection, responses were shaped by viral priming, with bacterial challenge further amplifying genes linked to inflammation and fibrin clot formation, potentially contributing to disease severity. These effects were consistent across different IAV subtypes when tested in combination with porcine Streptococcus suis serotypes that impose a comparable burden in pigs during influenza coinfection. Additionally, age is a determinant of BMDM responses. This model offers an advantageous tool for studying coinfection dynamics in human and veterinary medicine.

Visceral leishmaniasis (VL) is a severe infectious disease caused by protozoan parasites of the Leishmania donovani complex. Blood cytokine concentrations in VL patients can inform us about underlying immunopathogenesis and may serve as a biomarker for treatment effectiveness. However, cytokine levels have not yet been studied in VL patients from Kenya, where case load is high. This study measured the serum cytokine profile, blood parasite load and clinical and haematological features of VL patients from West Pokot County, Kenya, over the course of treatment with sodium stibogluconate and paromomycin (SSG-PM). VL patients recruited at the hospital presented with splenomegaly and weight loss, and frequently had pancytopenia and anaemia. Median Leishmania parasite load in blood, determined with real-time polymerase chain reaction, was 2.6 × 104 parasite equivalents mL−1. Compared to endemic healthy controls, serum interferon gamma (IFN-γ), interleukin 5 (IL-5), IL-6, IL-10, IL-12p70, IL-17A and IL-27 were significantly elevated in untreated VL patients. Severe VL was associated with higher IL-10 and lower IFN-γ levels. After 17 daily injections with SSG-PM, disease symptoms disappeared, leukocyte and thrombocyte counts significantly increased, and blood parasite load decreased to undetectable levels in all VL patients. There was a significant decrease in IL-10 and IL-6, whereas IL-17A levels increased; the remaining cytokines showed no significant concentration change during treatment. In conclusion, the results suggest that SSG-PM treatment of VL patients from West Pokot was effective. Moreover, both inflammatory and regulatory immune responses appeared to decrease during treatment, although the increase in IL-17A could reflect a partial continuation of immune activation.

BackgroundTo date, it is still not clear why during the COVID-19 pandemic children generally developed no or milder symptoms compared to adults. As innate immune responses are crucial in the early defense against pathogens, we aimed at profiling these responses from both adults and children with a primary SARS-CoV-2 infection.MethodsIn the first months of the pandemic, PBMCs and serum were collected from peripheral blood of adults and children at different time points after testing SARS-CoV-2 PCR positive (PCR+). The levels of SARS-CoV-2 Spike-specific IgG were measured in serum. The cells were cultured for 24 hours in medium only, with heat inactivated SARS-CoV-2 (iSARS-CoV-2) or toll-like receptor (TLR) ligands. The levels of secreted cytokines/chemokines as well as monocyte phenotype were determined.ResultsFew days after testing PCR+, PBMCs from PCR+ children secreted higher levels of cytokines/chemokines compared to PCR+ adults, after these cells were incubated either in medium only or after stimulation with iSARS-CoV-2 or TLR ligands. Furthermore, PBMCs from children stimulated with iSARS-CoV-2 secreted significantly higher levels of IL-10 and GM-CSF compared to PBMCs from control children. In contrast, PBMCs from the PCR+ adults secreted lower levels of IL-8 compared to adult controls. Phenotypic analysis of monocytes indicates a smaller proportion non-classical monocytes for adults compared to children. The distinct cytokine profiles, symptom severity, and the proportion of non-classical monocytes correlated to each other. The levels of Spike-specific IgG overtime did not significantly differ between children and adults.ConclusionsWithin the first week after testing PCR+, children showed a stronger inflammatory innate immune profile and experienced less severe symptoms compared to adults. Our data implies correlations between the secretion of cytokines/chemokines, proportion of non-classical monocytes, and symptoms severity. These findings enhance our understanding of the distinct pediatric and adult innate immune profile after SARS-CoV-2 infection and contributes to the knowledge necessary to improve future prevention strategies.

INTRODUCTION:A role for innate immune memory in protection during COVID-19 infection or vaccination has been recently reported. However, no study so far has shown whether the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can train innate immune cells. The aim of this study was to investigate whether this virus can induce trained immunity in human monocytes. METHODS:Monocytes were exposed to inactivated SARS-CoV-2 (iSARS-CoV-2) for 24 h, followed by a resting period in the medium only and a secondary stimulation on day 6 after which the cytokine/chemokine and transcriptomic profiles were determined. RESULTS:Compared to untrained cells, the iSARS-CoV-2-trained monocytes secreted significantly higher levels of IL-6, TNF-α, CXCL10, CXCL9, and CXCL11 upon restimulation. Transcriptome analysis of iSARS-CoV-2-trained monocytes revealed increased expression of several inflammatory genes. As epigenetic and metabolic modifications are hallmarks of trained immunity, we analyzed the expression of genes related to these processes. Findings indicate that indeed SARS-CoV-2-trained monocytes show changes in the expression of genes involved in metabolic pathways including the tricarboxylic acid cycle, amino acid metabolism, and the expression of several epigenetic regulator genes. Using epigenetic inhibitors that block histone methyl and acetyltransferases, we observed that the capacity of monocytes to be trained by iSARS-CoV-2 was abolished. CONCLUSION:Overall, our findings indicate that iSARS-CoV-2 can induce properties associated with trained immunity in human monocytes. These results contribute to the knowledge required for improving vaccination strategies to prevent infectious diseases.

Pertussis is a respiratory infection caused by the Gram-negative bacterium Bordetella pertussis. Despite high vaccination coverage this disease remains a public health concern worldwide. A better understanding of the protective immune responses to B. pertussis is required for the development of improved vaccines. The aim of this study was to determine the production of reactive oxygen species (ROS) by human neutrophils in response to B. pertussis and to determine the contribution of opsonizing antibodies from convalescent pertussis patients in this response. The serum samples from convalescent patients were taken at <3, 9, 18 and 36 months after diagnosis of pertussis. Also included were sera from healthy age-matched controls. We show that neutrophils produced high levels of ROS in response to opsonized, compared to non-opsonized, B. pertussis and that this effect was independent of the time the convalescent serum samples were taken. This indicates the presence of functional opsonizing antibodies up to 3 years after B. pertussis infection. While opsonization of B. pertussis with serum samples from uninfected controls also induced ROS production, sera from infected individuals induced significantly higher ROS levels. Spearman correlations analysis showed that IgG antibodies targeting fimbriae3 followed by pertactin, and BrkA correlate with ROS production. Additionally, we observed that neutrophils killed opsonized B. pertussis in a ROS-dependent manner. Searching for other antigen-specific antibodies from convalescent pertussis patients involved in ROS production by neutrophils may assist in the identification of novel antigens to improve the current pertussis vaccines.

Pertussis is a severe respiratory tract infection caused by Bordetella pertussis . This bacterium infects the ciliated epithelium of the human airways. We investigated the epithelial cell response to B. pertussis infection in primary human airway epithelium (HAE) differentiated at air–liquid interface. Infection of the HAE cells mimicked several hallmarks of B. pertussis infection such as reduced epithelial barrier integrity and abrogation of mucociliary transport. Our data suggests mild immunological activation of HAE by B. pertussis indicated by secretion of IL-6 and CXCL8 and the enrichment of genes involved in bacterial recognition and innate immune processes. We identified IL-1β and IFNγ, present in conditioned media derived from B. pertussis -infected macrophage and NK cells, as essential immunological factors for inducing robust chemokine secretion by HAE in response to B. pertussis . In transwell migration assays, the chemokine-containing supernatants derived from this HAE induced monocyte migration. Our data suggests that the airway epithelium on its own has a limited immunological response to B. pertussis and that for a broad immune response communication with local innate immune cells is necessary. This highlights the importance of intercellular communication in the defense against B. pertussis infection and may assist in the rational design of improved pertussis vaccines.

Respiratory infections caused by Bordetella pertussis are reemerging despite high pertussis vaccination coverage. Since the introduction of the acellular pertussis vaccine in the late twentieth century, circulating B. pertussis strains increasingly lack expression of the vaccine component pertactin (Prn). In some countries, up to 90% of the circulating B. pertussis strains are deficient in Prn. To better understand the resurgence of pertussis, we investigated the response of human monocyte-derived dendritic cells (moDCs) to naturally circulating Prn-expressing (Prn-Pos) and Prn-deficient (Prn-Neg) B. pertussis strains from 2016 in the Netherlands. Transcriptome analysis of moDC showed enriched IFNα response-associated gene expression after exposure to Prn-Pos B. pertussis strains, whereas the Prn-Neg strains induced enriched expression of interleukin- and TNF-signaling genes, as well as other genes involved in immune activation. Multiplex immune assays confirmed enhanced proinflammatory cytokine secretion by Prn-Neg stimulated moDC. Comparison of the proteomes from the Prn-Pos and Prn-Neg strains revealed, next to the difference in Prn, differential expression of a number of other proteins including several proteins involved in metabolic processes. Our findings indicate that Prn-deficient B. pertussis strains induce a distinct and stronger immune activation of moDCs than the Prn-Pos strains. These findings highlight the role of pathogen adaptation in the resurgence of pertussis as well as the effects that vaccine pressure can have on a bacterial population.

Background: Inhalation exposure to biological particulate matter (BioPM) from livestock farms may provoke exacerbations in subjects suffering from allergy and asthma. The aim of this study was to use a murine model of allergic asthma to determine the effect of BioPM derived from goat farm on airway allergic responses.Methods: Fine (<2.5<mu>m) BioPM was collected from an indoor goat stable. Female BALB/c mice were ovalbumin (OVA) sensitized and challenged with OVA or saline as control. The OVA and saline groups were divided in sub-groups and exposed intranasally to different concentrations (0, 0.9, 3, or 9 mu g) of goat farm BioPM. Bronchoalveolar lavage fluid (BALF), blood and lung tissues were collected.Results: In saline-challenged mice, goat farm BioPM induced 1) a dose-dependent increase in neutrophils in BALF and 2) production of macrophage inflammatory protein-3a. In OVA-challenged mice, BioPM induced 1) inflammatory cells in BALF, 2) OVA-specific Immunoglobulin (Ig)G1, 3) airway mucus secretion-specific gene expression. RNAseq analysis of lungs indicates that neutrophil chemotaxis and oxidation-reduction processes were the representative genomic pathways in saline and OVA-challenged mice, respectively.Conclusions: A single exposure to goat farm BioPM enhanced airway inflammation in both saline and OVA-challenged allergic mice, with neutrophilic response as Th17 disorder and eosinophilic response as Th2 disorder indicative of the severity of allergic responses. Identification of the mode of action by which farm PM interacts with airway allergic pathways will be useful to design potential therapeutic approaches.

Effects of airborne biological particulate matter (BioPM; from livestock farms) on the pulmonary airways are not well studied. The aim of the present study was to investigate whether fine (<2.5 μm) BioPM derived from indoor animal stables (two chicken and two pig farms) could modify airway allergic responses by using a mouse model of allergic airway disease (allergic asthma). After intraperitoneal ovalbumin (OVA) sensitization mice were either intranasally challenged with OVA (allergic mice) or saline (non-allergic controls). Mice were also intranasally treated with farm-derived BioPM. Bronchoalveolar lavage fluid (BALF), blood and lung tissues were collected one day after intranasal exposure. BioPM from all the farms caused an acute neutrophilic inflammatory response in non-allergic mice. In allergic mice, BioPM derived from pig farm 2 induced a larger cellular inflammatory response than other farm-derived BioPM. All farm BioPM elicited Th17 cytokine (Interleukin (IL)-23) production except chicken farm 2, whereas Th2 cytokine (IL-5) increase was only induced by BioPM collected from chicken farm 2. These results indicate the exposure of BioPM from chicken and pig farms may cause the enhancement of airway allergic response in mice following exposure to OVA. More variation in the responses between farms was observed in allergic than non-allergic mice. Understanding the source and doses of BioPM that may affect the airway allergic response could help susceptible individuals to avoid worsening their respiratory diseases.

Tolerogenic dendritic cells (tolDCs) are central players in the maintenance of immune tolerance and thereby have been identified as the most favourable candidates for cell therapy of autoimmune diseases. We have recently shown that excretory-secretory products (ES L1) released by Trichinella spiralis larvae induce stable human tolDCs in vitro via Toll-like receptor 2 (TLR2) and TLR4. However, engagement of these receptors did not fully explain the tolerogenic profile of DCs. Here, we observed for the first time that dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) interacts with highly glycosylated ES L1 and contributes to the generation of ES L1-induced tolDCs. Blocking DC-SIGN interfered with the ES L1-induced higher expression of CD40 and CCR7 and the production of IL-10 and TGF-β by DCs. The cooperation of TLR2, TLR4 and DC-SIGN receptors is of importance for the capacity of DCs to prime T cell response toward Th2 and to induce expansion of CD4+CD25+Foxp3+ T cells, as well as for the production of IL-10 and TGF-β by these cells. Overall, these results indicate that induction of tolDCs by ES L1 involves engagement of multiple pattern recognition receptors namely, TLR2, TLR4 and DC-SIGN.

Abstract Background Asthma patients suffer from periodic acute worsening of symptoms (i.e. loss of asthma control or exacerbations), triggered by a variety of exogenous stimuli. With the growing awareness that air pollutants impact respiratory diseases, we investigated whether particulate matter (PM) derived from various livestock farms (BioPM) differentially affected innate and oxidative stress responses in asthma and health. Methods Peripheral blood mononuclear cells (PBMCs), collected from patients sequentially before and during loss of asthma control and from healthy individuals, were exposed to BioPM collected from chicken, goat and pig farms (1 and 5 μg/ml), with or without pre-treatment with antioxidants. Cytokine release and oxidative stress were assessed. Results PBMCs produced IFNγ, IL-1β, IL-10 and TNFα upon stimulation with BioPM, with that from pig farms inducing the highest cytokine levels. Overall, cytokine production was irrespective of the presence or state of disease. However, PBMCs from stable asthma patients upon exposure to the three BioPM showed more extreme TNFα responses than those from healthy subjects. Furthermore, PBMCs obtained during loss of asthma control that were exposed to BioPM from pig farms showed enhanced IFNγ release as well as decreased oxidative stress levels upon pre-treatment with N-acetylcysteine (NAC) compared to stable disease. NAC, but not superoxide dismutase and catalase, also counteracted BioPM-induced cytokine release, indicating the importance of intracellular reactive oxygen species in the production of cytokines. Conclusions BioPM triggered enhanced pro-inflammatory responses by PBMCs from both healthy subjects and asthma patients, with those from patients during loss of asthma control showing increased susceptibility to BioPM from pig farms in particular.

Africa is the second most populous continent and has perennial health challenges. Of the estimated 181 million school aged children in sub-Saharan Africa (SSA), nearly half suffer from ascariasis, trichuriasis, or a combination of these infections. Coupled with these is the problem of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection, which is a leading cause of death in the region. Compared to the effect of the human immunodeficiency virus on the development of TB, the effect of chronic helminth infections is a neglected area of research, yet helminth infections are as ubiquitous as they are varied and may potentially have profound effects upon host immunity, particularly as it relates to TB infection, diagnosis, and vaccination. Protection against active TB is known to require a clearly delineated T-helper type 1 (Th1) response, while helminths induce a strong opposing Th2 and immune-regulatory host response. This Review highlights the potential challenges of helminth-TB co-infection in Africa and the need for further research.

Patients with respiratory diseases in rural areas have been reported to have enhanced responsiveness to ambient particulate matter (PM). In addition to the physical and chemical components, ambient PM can contain microorganisms or parts thereof, referred here as BioPM, that can also contribute to the adverse health effects. This study aimed to characterize the microbial composition of BioPM originating from livestock, and to investigate whether these BioPM can trigger the activation of innate receptors and cells. Coarse (PM2.5–10 μm) and fine (PM<2.5 μm) BioPM samples were collected from indoor chicken, pig and goat farms using the versatile aerosol concentration enrichment system (VACES) connected to a Biosampler. The fungal and bacterial communities were assessed with an amplicon based approach using Next Generation Sequencing (NGS). In parallel, HEK-Blue cells expressing different pattern recognition receptors (Toll like receptors (TLR) 2, 3, 4, 5, 7, 8, 9 and NOD 1, 2) and a human monocytic cell line (MM6) were exposed to BioPM samples from these sites. Distinct airborne microbiota profiles associated with the corresponding animal farm were observed. Moreover, the various BioPM contained mainly ligands for TLR2 and TLR4 resulting in a concentration-dependent increase of pro-inflammatory cytokine secreted by MM6 cells. In addition, we show for the first time that only the pig-derived BioPM induced TLR5 activation. These findings suggest that animal farm specific BioPM trigger distinct inflammatory responses, which may contribute to airway diseases in humans.

Pertussis is a highly contagious respiratory infection caused by the bacterium Bordetella pertussis. Humans are the only known natural reservoir of B. pertussis. In mice, macrophages and NK cells have a key role in confining B. pertussis to the respiratory tract. However, the mechanisms underlying this process, particularly during human infections, remain unclear. Here we characterized the activation of human macrophages and NK cells in response to B. pertussis and unraveled the role of inflammasomes in this process. NLRP3 inflammasome activation by B. pertussis in human macrophage-like THP-1 cells and primary monocyte-derived macrophages (mo-MΦ) was shown by the visualization of ASC-speck formation, pyroptosis, and the secretion of caspase-mediated IL-1β and IL-18. In contrast to macrophages, stimulation of human CD56+CD3- NK cells by B. pertussis alone did not result in activation of these cells. However, co-culture of B. pertussis-stimulated mo-MΦ and autologous NK cells resulted in high amounts of IFNγ secretion and an increased frequency of IL-2Rα+ and HLA-DR+ NK cells, indicating NK cell activation. This activation was significantly reduced upon inhibition of inflammasome activity or blocking of IL-18 in the mo-MΦ/NK cell co-culture. Furthermore, we observed increased secretion of proinflammatory cytokines in the B. pertussis-stimulated mo-MΦ/NK co-culture compared to the mo-MΦ single culture. Our results demonstrate that B. pertussis induces inflammasome activation in human macrophages and that the IL-18 produced by these cells is required for the activation of human NK cells, which in turn enhances the pro-inflammatory response to this pathogen. Our data provides a better understanding of the underlying mechanisms involved in the induction of innate immune responses against B. pertussis. These findings contribute to the knowledge required for the development of improved intervention strategies to control this highly contagious disease.

Whooping cough, caused by Bordetella pertussis, has resurged and presents a global health burden worldwide. B. pertussis strains unable to produce the acellular pertussis vaccine component pertactin (Prn), have been emerging and in some countries represent up to 95% of recent clinical isolates. Knowledge on the effect that Prn deficiency has on infection and immunity to B. pertussis is crucial for the development of new strategies to control this disease. Here, we characterized the effect of Prn production by B. pertussis on human and murine dendritic cell (DC) maturation as well as in a murine model for pertussis infection. We incubated human monocyte-derived DCs (moDCs) with multiple isogenic Prn knockout (Prn-KO) and corresponding parental B. pertussis strains constructed either in laboratory reference strains with a Tohama I background or in a recently circulating clinical isolate. Results indicate that, compared to the parental strains, Prn-KO strains induced an increased production of pro-inflammatory cytokines by moDCs. This pro-inflammatory phenotype was also observed upon stimulation of murine bone marrow-derived DCs. Moreover, RNA sequencing analysis of lungs from mice infected with B. pertussis Prn-KO revealed increased expression of genes involved in cell death. These in vitro and in vivo findings indicate that B. pertussis strains which do not produce Prn induce a stronger pro-inflammatory response and increased cell death upon infection, suggesting immunomodulatory properties for Prn.

Trichinella spiralis, as well as its muscle larvae excretory–secretory products (ES L1), given either alone or via dendritic cells (DCs), induce a tolerogenic immune microenvironment in inbred rodents and successfully ameliorate experimental autoimmune encephalomyelitis. ES L1 directs the immunological balance away from T helper (Th)1, toward Th2 and regulatory responses by modulating DCs phenotype. The ultimate goal of our work is to find out if it is possible to translate knowledge obtained in animal model to humans and to generate human tolerogenic DCs suitable for therapy of autoimmune diseases through stimulation with ES L1. Here, the impact of ES L1 on the activation of human monocyte-derived DCs is explored for the first time. Under the influence of ES L1, DCs acquired tolerogenic (semi-matured) phenotype, characterized by low expression of HLA-DR, CD83, and CD86 as well as moderate expression of CD40, along with the unchanged production of interleukin (IL)-12 and elevated production of IL-10 and transforming growth factor (TGF)-β, compared to controls. The interaction with DCs involved toll-like receptors (TLR) 2 and 4, and this interaction was mainly responsible for the phenotypic and functional properties of ES L1-treated DCs. Importantly, ES L1 potentiated Th2 polarizing capacity of DCs, and impaired their allo-stimulatory and Th1/Th17 polarizing properties. Moreover, ES L1-treated DCs promoted the expansion of IL-10- and TGF-β- producing CD4+CD25hiFoxp3hi T cells in indolamine 2, 3 dioxygenase (IDO)-1-dependent manner and increased the suppressive potential of the primed T cell population. ES L1-treated DCs retained the tolerogenic properties, even after the challenge with different pro-inflammatory stimuli, including those acting via TLR3 and, especially TLR4. These results suggest that the induction of tolerogenic properties of DCs through stimulation with ES L1 could represent an innovative approach for the preparation of tolerogenic DC for treatment of inflammatory and autoimmune disorders.

Bordetella pertussis is a Gram-negative bacterium and the causative agent of whooping cough. Whooping cough is currently re-emerging worldwide and therefore still poses a continuous global health threat. B. pertussis expresses several virulence factors that play a role in evading the human immune response. One of these virulence factors is Virulence associated gene 8 (Vag8). Vag8 is a complement evasion molecule that mediates its effects by binding to the complement regulator C1 inhibitor (C1-INH). This regulatory protein is a fluid phase serine protease that controls proenzyme activation and enzyme activity of not only the complement system but also the contact system. Activation of the contact system results in the generation of bradykinin, a pro-inflammatory peptide. Here, the activation of the contact system by B. pertussis was explored. We demonstrate that recombinant as well as endogenous Vag8 enhanced contact system activity by binding C1-INH and attenuating its inhibitory function. Moreover, we show that B. pertussis itself is able to activate the contact system. This activation was dependent on Vag8 production as a Vag8 knock-out B. pertussis strain was unable to activate the contact system. These findings show a previously overlooked interaction between the contact system and the respiratory pathogen B. pertussis. Activation of the contact system by B. pertussis may contribute to its pathogenicity and virulence.

Correlates of protection (CoPs) against the highly contagious respiratory disease whooping cough, caused by Bordetella pertussis, remain elusive. Characterizing the antibody response to this pathogen is essential towards identifying potential CoPs. Here, we evaluate levels, avidity and functionality of B. pertussis-specific-antibodies from paired plasma samples derived from symptomatic and recovered pertussis patients, as well as controls. Natural infection is expected to induce protective immunity. IgG levels and avidity to nine B. pertussis antigens were determined using a novel multiplex panel. Furthermore, opsonophagocytosis of a B. pertussis clinical isolate by neutrophils was measured. Findings indicate that following infection, B. pertussis-specific antibody levels of (ex-) pertussis patients waned, while the avidity of antibodies directed against the majority of studied antigens increased. Opsonophagocytosis indices decreased upon recovery, but remained higher than controls. Random forest analysis of all the data revealed that 28% of the opsonophagocytosis index variances could be explained by filamentous hemagglutinin-followed by pertussis toxin-specific antibodies. We propose to further explore which other B. pertussis-specific antibodies can better predict opsonophagocytosis. Moreover, other B. pertussis-specific antibody functions as well as the possible integration of these functions in combination with other immune cell properties should be evaluated towards the identification of CoPs against pertussis.

In 2017, about 760,000 children aged 0 to 19 years received a total of 2,140,000 vaccinations within the National Immunisation Programme (NIP). Participation in the NIP was high among children under 10 years of age, despite the drop by around 2-3% for most vaccinations since 2014. An exception in the high participation is the number of girls who was vaccinated against human papillomavirus (HPV), which has declined by 15% since 2016. The number of reports (1,383) of possible adverse events following immunisation in 2017 was lower than the number of reports in 2016 (1,483). NIP target diseases There is an ongoing increase in the number of cases with meningococcal serogroup W (MenW) disease with 80 cases reported in 2017 and 78 up to August 2018. Because of this increase, since May 2018, the MenC vaccination given at 14 months of age has been replaced by a quadrivalent MenACWY vaccination. The case fatality of MenW disease (17%) was substantially higher than for other serogroups. In 2017, the number of measles cases was low (16 reported cases) but higher than in the previous two years. The number of pertussis reports in 2017 was comparable with 2016 (28.7 compared with 32.6 per 10,000). Three people died from pertussis, one infant and two elderly. The number of reports of acute hepatitis B infections stayed stable (0.7 per 100,000 population). Also, the incidence of vaccine type invasive pneumococcal disease (IPD) remained very low in 2017/2018. Once again, the number of reported cases were in 2017 low for mumps (46), Haemophilus influenzae type b (Hib; 46), meningococcal serogroep C (MenC; 9), diphtheria (4), tetanus (1), rubella (0) and polio (0). The inhabitants of Bonaire, St. Eustatius and Saba are predominantly well protected against NIP diseases. However, protection against measles and diphtheria is suboptimal for some age groups. Awareness is needed to prevent these diseases from spreading from neighboring countries, where outbreaks currently are observed. New advice and decisions In July 2018, the Ministry of Health, Welfare and Sports decided to expand the MenACWY vaccination outbreak programme to 13-14 year olds. In 2019, there will be a catch up campaign for all 15-18 year olds. Furthermore, it was decided that vaccination against disease caused by rotavirus will be included in the NIP for risk groups, and that maternal pertussis vaccination in the NIP will be organised by youth health care organisations. The Dutch Health Council advises to offer vaccination against pneumococcal disease to the people 60 years and older. (aut. ref.)