RESUMO
BACKGROUND: Genetic variation underly inter-individual variation in host immune responses to infectious diseases, and may affect susceptibility or the course of signs and symptoms. METHODS: We performed genome-wide association studies in a prospective cohort of 1138 patients with physician-confirmed Lyme borreliosis (LB), the most common tick-borne disease in the Northern hemisphere caused by the bacterium Borrelia burgdorferi sensu lato. Genome-wide variants in LB patients-divided into a discovery and validation cohort-were compared to two healthy cohorts. Additionally, ex vivo monocyte-derived cytokine responses of peripheral blood mononuclear cells to several stimuli including Borrelia burgdorferi were performed in both LB patient and healthy control samples, as were stimulation experiments using mechanistic/mammalian target of rapamycin (mTOR) inhibitors. In addition, for LB patients, anti-Borrelia antibody responses were measured. Finally, in a subset of LB patients, gene expression was analysed using RNA-sequencing data from the ex vivo stimulation experiments. RESULTS: We identified a previously unknown genetic variant, rs1061632, that was associated with enhanced LB susceptibility. This polymorphism was an eQTL for KCTD20 and ETV7 genes, and its major risk allele was associated with upregulation of the mTOR pathway and cytokine responses, and lower anti-Borrelia antibody production. In addition, we replicated the recently reported SCGB1D2 locus that was suggested to have a protective effect on B. burgdorferi infection, and associated this locus with higher Borrelia burgdorferi antibody indexes and lower IL-10 responses. CONCLUSIONS: Susceptibility for LB was associated with higher anti-inflammatory responses and reduced anti-Borrelia antibody production, which in turn may negatively impact bacterial clearance. These findings provide important insights into the immunogenetic susceptibility for LB and may guide future studies on development of preventive or therapeutic measures. TRIAL REGISTRATION: The LymeProspect study was registered with the International Clinical Trials Registry Platform (NTR4998, registration date 2015-02-13).
Assuntos
Grupo Borrelia Burgdorferi , Borrelia burgdorferi , Borrelia , Doença de Lyme , Humanos , Estudo de Associação Genômica Ampla , Estudos Prospectivos , Leucócitos Mononucleares , Suscetibilidade a Doenças , Doença de Lyme/genética , Doença de Lyme/diagnóstico , Borrelia burgdorferi/genética , Citocinas/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/uso terapêutico , Grupo Borrelia Burgdorferi/genética , Secretoglobinas/genéticaRESUMO
BACKGROUND: This prospective study assesses symptoms 3 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection compared to test-negative and population controls, and the effect of vaccination prior to infection. METHODS: Participants enrolled after a positive (cases) or negative (test-negative controls) SARS-CoV-2 test, or after invitation from the general population (population controls). After 3 months, participants indicated presence of 41 symptoms and severity of 4 symptoms. Permutation tests were used to select symptoms significantly elevated in cases compared to controls and to compare symptoms between cases that were vaccinated or unvaccinated prior to infection. RESULTS: In total, 9166 cases, 1698 symptomatic but test-negative controls, and 3708 population controls enrolled. At 3 months, 13 symptoms, and severity of fatigue, cognitive impairment, and dyspnea were significantly elevated incases compared to controls. Of cases, 48.5% reported ≥1 significantly elevated symptom compared to 29.8% of test-negative controls and 26.0% of population controls. Effect of vaccination could be determined for cases aged <65 years, and was significantly protective for loss of smell and taste but not for other symptoms. DISCUSSION: Three months after SARS-CoV-2 infection, almost half of cases report symptoms, which was higher than background prevalence and test-negative prevalence. Vaccination prior to infection was protective against loss of smell and taste in cases aged <65 years.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Países Baixos/epidemiologia , COVID-19/epidemiologia , Anosmia , Controle da População , Prevalência , Estudos ProspectivosRESUMO
Laboratory diagnosis of Lyme borreliosis (LB) is mainly based on serology, which has limitations, particularly in the early stages of the disease. In recent years there have been conflicting reports concerning a new diagnostic tool using the cytokine interferon-gamma (IFN-γ). Previous studies have generally found low concentrations of IFN-γ in early LB infection. The goal of this study is to investigate IFN-γ regulation during early LB and provide insights into the host response to B. burgdorferi. We performed in vitro experiments with whole blood assays and peripheral blood mononuclear cells (PBMCs) of LB patients and healthy volunteers exposed to B. burgdorferi and evaluated the IFN-γ response using ELISA and related interindividual variation in IFN-γ production to the presence of single nucleotide polymorphisms. IFN-γ production of B. burgdorferi-exposed PBMCs and whole blood was amplified by the addition of interleukin-12 (IL-12) to the stimulation system. This effect was observed after 24 h of B. burgdorferi stimulation in both healthy individuals and LB patients. The effect was highly variable between individuals, but was significantly higher in LB patients 6 weeks since the start of antibiotic treatment compared to healthy individuals. IL-12 p40 and IL-18 mRNA were upregulated upon exposure to B. burgdorferi, whereas IL-12 p35 and IFN-γ mRNA expression remained relatively unchanged. SNP Rs280520 in the downstream IL-12 pathway, Tyrosine Kinase 2, was associated with increased IFN-γ production. This study shows that IL-12 evokes an IFN-γ response in B. burgdorferi exposed cells, and that LB patients and healthy controls respond differently to this stimulation.
Assuntos
Borrelia burgdorferi , Doença de Lyme , Humanos , Interferon gama , Interleucina-12 , Leucócitos Mononucleares , RNA MensageiroRESUMO
Previous studies have shown that monocytes can be 'trained' or tolerized by certain stimuli to respond stronger or weaker to a secondary stimulation. Rewiring of glucose metabolism was found to be important in inducing this phenotype. As we previously found that Borrelia burgdorferi (B. burgdorferi), the causative agent of Lyme borreliosis (LB), alters glucose metabolism in monocytes, we hypothesized that this may also induce long-term changes in innate immune responses. We found that exposure to B. burgdorferi decreased cytokine production in response to the TLR4-ligand lipopolysaccharide (LPS). In addition, B. burgdorferi exposure decreased baseline levels of glycolysis, as assessed by lactate production. Using GWAS analysis, we identified a gene, microfibril-associated protein 3-like (MFAP3L) as a factor influencing lactate production after B. burgdorferi exposure. Validation experiments proved that MFAP3L affects lactate- and cytokine production following B. burgdorferi stimulation. This is mediated by functions of MFAP3L, which includes activating ERK2 and through activation of platelet degranulation. Moreover, we showed that platelets and platelet-derived factors play important roles in B. burgdorferi-induced cytokine production. Certain platelet-derived factors, such chemokine C-X-C motif ligand 7 (CXCL7) and (C-C motif) ligand 5 (CCL5), were elevated in the circulation of LB patients in comparison to healthy individuals.
Assuntos
Lipopolissacarídeos , Doença de Lyme , Humanos , Ligantes , Receptor 4 Toll-Like , Quimiocinas/metabolismo , Glucose , LactatosRESUMO
During the first wave of the severe acute respiratory syndrome-coronavirus-2 epidemic in the Netherlands, notifications consisted mostly of patients with relatively severe disease. To enable real-time monitoring of the incidence of mild coronavirus disease 2019 (COVID-19) - for which medical consultation might not be required - the Infectieradar web-based syndromic surveillance system was launched in mid-March 2020. Our aim was to quantify associations between Infectieradar participant characteristics and the incidence of self-reported COVID-19-like illness. Recruitment for this cohort study was via a web announcement. After registering, participants completed weekly questionnaires, reporting the occurrence of a set of symptoms. The incidence rate of COVID-19-like illness was estimated and multivariable Poisson regression used to estimate the relative risks associated with sociodemographic variables, lifestyle factors and pre-existing medical conditions. Between 17 March and 24 May 2020, 25 663 active participants were identified, who reported 7060 episodes of COVID-19-like illness over 131 404 person-weeks of follow-up. The incidence rate declined over the analysis period, consistent with the decline in notified cases. Male sex, age 65+ years and higher education were associated with a significantly lower COVID-19-like illness incidence rate (adjusted rate ratios (RRs) of 0.80 (95% CI 0.76-0.84), 0.77 (0.70-0.85), 0.84 (0.80-0.88), respectively) and the baseline characteristics ever-smoker, asthma, allergies, diabetes, chronic lung disease, cardiovascular disease and children in the household were associated with a higher incidence (RRs of 1.11 (1.04-1.19) to 1.69 (1.50-1.90)). Web-based syndromic surveillance has proven useful for monitoring the temporal trends in, and risk factors associated with, the incidence of mild disease. Increased relative risks observed for several patient factors could reflect a combination of exposure risk, susceptibility to infection and propensity to report symptoms.
Assuntos
COVID-19/epidemiologia , SARS-CoV-2 , Autorrelato , Vigilância de Evento Sentinela , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Internet , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: After antibiotic treatment of Lyme borreliosis, a subset of patients report persistent symptoms, also referred to as post-treatment Lyme disease syndrome. The reported prevalence of persistent symptoms varies considerably, and its pathophysiology is under debate. The LymeProspect study has been designed to investigate the prevalence, severity, and a wide range of hypotheses on the etiology of persistent symptoms among patients treated for Lyme borreliosis in the Netherlands. METHODS: LymeProspect is a prospective, observational cohort study among adults with proven or probable Lyme borreliosis, either erythema migrans or disseminated manifestations, included at the start of antibiotic treatment. During one year of follow-up, participants are subjected to questionnaires every three months and blood is collected repeatedly during the first three months. The primary outcome is the prevalence of persistent symptoms after treatment, assessed by questionnaires online focusing on fatigue (CIS, subscale fatigue severity), pain (SF-36, subscale pain) and neurocognitive dysfunction (CFQ). Potential microbiological, immunological, genetic, epidemiological and cognitive-behavioral determinants for persistent symptoms are secondary outcome measures. Control cohorts include patients with long-lasting symptoms and unconfirmed Lyme disease, population controls, and subjects having reported a tick bite not followed by Lyme borreliosis. DISCUSSION: This article describes the background and design of the LymeProspect study protocol. This study is characterized by a prospective, explorative and multifaceted design. The results of this study will provide insights into the prevalence and determinants of persistent symptoms after treatment for Lyme borreliosis, and may provide a rationale for preventive and treatment recommendations. TRIAL REGISTRATION: NTR4998 (Netherlands Trial Register). Date of registration: 13 February 2015.
Assuntos
Doença de Lyme/tratamento farmacológico , Doença de Lyme/epidemiologia , Adulto , Idoso , Animais , Antibacterianos/uso terapêutico , Mordeduras e Picadas/complicações , Protocolos Clínicos , Estudos de Coortes , Eritema Migrans Crônico/tratamento farmacológico , Eritema Migrans Crônico/epidemiologia , Eritema Migrans Crônico/etiologia , Fadiga/etiologia , Humanos , Doença de Lyme/etiologia , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prevalência , Estudos Prospectivos , Inquéritos e Questionários , CarrapatosRESUMO
In January 2017, an increase in reported Salmonellaenterica serotype Bovismorbificans cases in the Netherlands was observed since October 2016. We implemented a case-control study to identify the source, including all cases after December 2016. Adjusted odds ratios were calculated using logistic regression analysis. We traced back the distribution chain of suspected food items and sampled them for microbiological analysis. Human and food isolates were sequenced using whole genome sequencing (WGS). From October 2016 to March 2017, 54 S. Bovismorbificans cases were identified. Sequencing indicated that all were infected with identical strains. Twenty-four cases and 37 controls participated in the study. Cases were more likely to have consumed ham products than controls (aORâ¯=â¯13; 95% CI: 2.0-77) and to have shopped at a supermarket chain (aORâ¯=â¯7; 95% CI: 1.3-38). Trace-back investigations led to a Belgian meat processor: one retail ham sample originating from this processor tested positive for S. Bovismorbificans and matched the outbreak strain by WGS. All ham products related to the same batch were removed from the market to prevent further cases. This investigation illustrates the importance of laboratory surveillance for all Salmonella serotypes and the usefulness of WGS in an outbreak investigation.
Assuntos
Busca de Comunicante/métodos , Carne/microbiologia , Intoxicação Alimentar por Salmonella/epidemiologia , Intoxicação Alimentar por Salmonella/microbiologia , Salmonella/isolamento & purificação , Estudos de Casos e Controles , Surtos de Doenças , Feminino , Humanos , Masculino , Países Baixos/epidemiologia , Salmonella/classificação , Salmonella/genética , Sequenciamento Completo do GenomaRESUMO
Background: Lyme borreliosis (LB) is the most frequently reported tick-borne infection in Europe and North America. The aim of this study was to estimate the cost-of-illness of LB in the Netherlands. We used available incidence estimates from 2010 for tick bite consultations and three symptomatic LB outcomes: erythema migrans (EM), disseminated LB and Lyme-related persisting symptoms. The cost was estimated using these incidences and the average cost per patient as derived from a patient questionnaire. We estimated the cost from a societal perspective, including healthcare cost, patient cost and production loss, using the friction cost method and a 4% annual discount rate. Tick bites and LB in 2010 led to a societal cost of 19.3 million (95% CI 15.6-23.4; 16.6 million population) for the Netherlands. Healthcare cost and production loss each constituted 48% of the total cost (9.3 and 9.2 million/year), and patient cost 4% (0.8 million/year). Of the total cost, 37% was related to disseminated LB, followed by 27% for persisting symptoms, 22% for tick bites and 14% for EM. Per outcome, for an individual case the mean cost of disseminated LB and Lyme-related persisting symptoms was both around 5700; for EM and GP consultations for tick bites this was 122 and 53. As an alternative to the friction cost method, the human capital method resulted in a total cost of 23.5 million/year. LB leads to a substantial societal cost. Further research should therefore focus on additional preventive interventions.
Assuntos
Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde/estatística & dados numéricos , Doença de Lyme/economia , Humanos , Incidência , Doença de Lyme/epidemiologia , Países Baixos/epidemiologia , Inquéritos e Questionários , Picadas de Carrapatos/economia , Picadas de Carrapatos/epidemiologiaRESUMO
Lyme borreliosis (LB) is the most prevalent tick-borne disease in Europe. Erythema migrans (EM), an early, localised skin rash, is its most common presentation. Dissemination of the bacteria can lead to more severe manifestations including skin, neurological, cardiac, musculoskeletal and ocular manifestations. Comparison of LB incidence rates in the European Union (EU)/European Economic Area (EEA) and Balkan countries are difficult in the absence of standardised surveillance and reporting procedures. We explored six surveillance scenarios for LB surveillance in the EU/EEA, based on the following key indicators: (i) erythema migrans, (ii) neuroborreliosis, (iii) all human LB manifestations, (iv) seroprevalence, (v) tick bites, and (vi) infected ticks and reservoir hosts. In our opinion, neuroborreliosis seems most feasible and useful as the standard key indicator, being one of the most frequent severe LB manifestations, with the possibility of a specific case definition. Additional surveillance with erythema migrans as key indicator would add value to the surveillance of neuroborreliosis and lead to a more complete picture of LB epidemiology in the EU/EEA. The other scenarios have less value as a basis for EU-level surveillance, but can be considered periodically and locally, as they could supply complementary insights.
Assuntos
Borrelia burgdorferi/isolamento & purificação , Eritema Migrans Crônico/epidemiologia , Doença de Lyme/epidemiologia , Doenças Transmitidas por Carrapatos/microbiologia , Animais , Mordeduras e Picadas , Monitoramento Epidemiológico , Eritema Migrans Crônico/etiologia , Europa (Continente)/epidemiologia , União Europeia , Feminino , Humanos , Incidência , Doença de Lyme/microbiologia , Masculino , Vigilância da População , Estudos Soroepidemiológicos , Doenças Transmitidas por Carrapatos/epidemiologiaRESUMO
BACKGROUND: Nationwide surveys have shown a threefold increase in general practitioner (GP) consultations for tick bites and early Lyme borreliosis from 1994 to 2009 in the Netherlands. We now report an update on 2014, with identical methods as for the preceding GP surveys. METHODS: To all GPs in the Netherlands, a postal questionnaire was sent inquiring about the number of consultations for tick bites and erythema migrans diagnoses (most common manifestation of early Lyme borreliosis) in 2014, and the size of their practice populations. RESULTS: Contrasting to the previously rising incidence of consultations for tick bites between 1994 and 2009, the incidence decreased in 2014 to 488 consultations for tick bites per 100,000 inhabitants, i.e., 82,000 patients nationwide. This survey revealed a first sign of stabilization of the previously rising trend in GP diagnosed erythema migrans, with 140 diagnoses per 100,000 inhabitants of the Netherlands. This equals about 23,500 annual diagnoses of erythema migrans nationwide in 2014. CONCLUSIONS: In contrast to the constantly rising incidence of GP consultations for tick bites and erythema migrans diagnoses in the Netherlands between 1994 and 2009, the current survey of 2014 showed a first sign of stabilization of erythema migrans diagnoses and a decreased incidence for tick bite consultations.
Assuntos
Clínicos Gerais/estatística & dados numéricos , Doença de Lyme/epidemiologia , Picadas de Carrapatos/epidemiologia , Eritema Migrans Crônico/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologiaRESUMO
BACKGROUND: Lyme borreliosis (LB) is the most commonly reported tick-borne infection in Europe and North America. In the last 15 years a 3-fold increase was observed in general practitioner consultations for LB in the Netherlands. To support prioritization of prevention and control efforts for LB, we estimated its burden expressed in Disability-Adjusted Life Years (DALYs). METHODS: We used available incidence estimates for three LB outcomes: (i) erythema migrans (EM), (ii) disseminated LB and (iii) Lyme-related persisting symptoms. To generate DALYs, disability weights and duration per outcome were derived using a patient questionnaire including health-related quality of life as measured by the EQ-5D. RESULTS: We estimated the total LB burden for the Netherlands in 2010 at 10.55 DALYs per 100,000 population (95% CI: 8.80-12.43); i.e. 0.60 DALYs for EM, 0.86 DALYs for disseminated LB and 9.09 DALYs for Lyme-related persisting symptoms. Per patient this was 0.005 DALYs for EM, 0.113 for disseminated LB and 1.661 DALYs for a patient with Lyme-related persisting symptoms. In a sensitivity analysis the total LB burden ranged from 7.58 to 16.93 DALYs per 100,000 population. CONCLUSIONS: LB causes a substantial disease burden in the Netherlands. The vast majority of this burden is caused by patients with Lyme-related persisting symptoms. EM and disseminated Lyme have a more modest impact. Further research should focus on the mechanisms that trigger development of these persisting symptoms that patients and their physicians attribute to LB.
Assuntos
Pessoas com Deficiência/estatística & dados numéricos , Nível de Saúde , Doença de Lyme/fisiopatologia , Anos de Vida Ajustados por Qualidade de Vida , Efeitos Psicossociais da Doença , Pessoas com Deficiência/psicologia , Feminino , Humanos , Incidência , Masculino , Países Baixos/epidemiologia , Qualidade de Vida , Índice de Gravidade de Doença , Fatores de TempoRESUMO
Objectives: Different SARS-CoV-2 variants can differentially affect the prevalence of Post Covid-19 Condition (PCC). This prospective study assesses prevalence and severity of symptoms three months after an Omicron infection, compared to Delta, test-negative and population controls. This study also assesses symptomology after reinfection and breakthrough infections. Methods: After a positive SARS-CoV-2 test, cases were classified as Omicron or Delta based on ≥ 85% surveillance prevalence. Three months after enrolment, participants indicated point prevalence for 41 symptoms and severity, using validated questionnaires for four symptoms. PCC prevalence was estimated as the difference in prevalence of at least one significantly elevated symptom, identified by permutation test, in cases compared to population controls. Results: At three months follow-up, five symptoms and severe dyspnea were significantly elevated in Omicron cases (n = 4138) compared to test-negative (n = 1672) and population controls (n = 2762). PCC prevalence was 10·4% for Omicron cases and 17·7% for Delta cases (n = 6855). In Omicron cases, severe fatigue and dyspnea were more prevalent in reinfected than primary infected, while severity of symptoms did not significantly differ between cases with a booster or primary vaccination course. Conclusions: Prevalence of PCC is 41% lower after Omicron than Delta at three months. Reinfection seems associated with more severe long-term symptoms compared to first infection.
RESUMO
The incidence of Lyme borreliosis has risen, accompanied by persistent symptoms. The innate immune system and related cytokines are crucial in the host response and symptom development. We characterized cytokine production capacity before and after antibiotic treatment in 1,060 Lyme borreliosis patients. We observed a negative correlation between antibody production and IL-10 responses, as well as increased IL-1Ra responses in patients with disseminated disease. Genome-wide mapping the cytokine production allowed us to identify 34 cytokine quantitative trait loci (cQTLs), with 31 novel ones. We pinpointed the causal variant at the TLR1-6-10 locus and validated the regulation of IL-1Ra responses at transcritpome level using an independent cohort. We found that cQTLs contribute to Lyme borreliosis susceptibility and are relevant to other immune-mediated diseases. Our findings improve the understanding of cytokine responses in Lyme borreliosis and provide a genetic map of immune function as an expanded resource.
Assuntos
Citocinas , Doença de Lyme , Locos de Características Quantitativas , Doença de Lyme/imunologia , Doença de Lyme/genética , Doença de Lyme/microbiologia , Humanos , Citocinas/genética , Citocinas/metabolismo , Masculino , Feminino , Interleucina-10/genética , Adulto , Estudo de Associação Genômica Ampla , Pessoa de Meia-Idade , Proteína Antagonista do Receptor de Interleucina 1/genética , Borrelia burgdorferi/imunologia , Borrelia burgdorferi/genética , Antibacterianos , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença , IdosoRESUMO
Objective: It is unclear how self-reported severe fatigue and difficulty concentrating after SARS-CoV-2 infection relate to objective neuropsychological functioning. The study aimed to compare neuropsychological functioning between individuals with and without these persistent subjective complaints. Method: Individuals with and without persistent severe fatigue (Checklist Individual Strength (CIS) fatigue ≥ 35) and difficulty concentrating (CIS concentration ≥ 18) at least 3 months after SARS-CoV-2 infection were included. Neuropsychological assessment was performed on overall cognitive functioning, attention, processing speed, executive functioning, memory, visuo-construction, and language (18 tests). T-scores -1.5 SD below population normative data (T ≤ 35) were classified as "impaired". Results: 230 participants were included in the study, of whom 22 were excluded from the analysis due to invalid performance. Of the participants included in the analysis, 111 reported persistent complaints of severe fatigue and difficulty concentrating and 97 did not. Median age was 54 years, 59% (n = 126) were female, and participants were assessed a median of 23 months after first infection (IQR: 16-28). With bivariate logistic regression, individuals with persistent complaints had an increased likelihood of slower information processing speed performance on the Stroop word reading (OR = 2.45, 95%CI = 1.02-5.84) compared to those without persistent complaints. Demographic or clinical covariates (e.g. hospitalization) did not influence this association. With linear regression techniques, persistent complaints were associated with lower t-scores on the D2 CP, TMT B, and TMT B|A. There were no differences in performance on the other neuropsychological tests. Conclusions: Individuals with subjective severe fatigue and difficulty concentrating after COVID-19 do not typically demonstrate cognitive impairment on extensive neuropsychological testing.
RESUMO
BACKGROUND: Because there may be substantial hidden mortality caused by common seasonal pathogens, we estimated the number of deaths in elderly persons attributable to viruses and bacteria for which robust weekly laboratory surveillance data were available. METHODS: On weekly time series (1999-2007) we used regression models to associate total death counts in individuals aged 65-74, 75-84, and ≥85 years (a population of 2.5 million) with pathogen circulation-influenza A (season-specific), influenza B, respiratory syncytial virus (RSV), parainfluenza, enterovirus, rotavirus, norovirus, Campylobacter, and Salmonella-adjusted for extreme outdoor temperatures. RESULTS: Influenza A and RSV were significantly (P < .05) associated with mortality in all studied age groups; influenza B and parainfluenza were additionally associated in those aged ≥75 years, and norovirus was additionally associated in those aged ≥85 years. The proportions of deaths attributable to seasonal viruses were 6.8% (≥85 years), 4.4% (75-84 years), and 1.4% (65-74 years), but with great variations between years. Influenza occasionally showed lower impact than some of the other viruses. CONCLUSIONS: The number of different pathogens associated with mortality in the older population increases with increasing age. Besides influenza A and RSV, influenza B, parainfluenza and norovirus may also contribute substantially to elderly mortality.
Assuntos
Infecções por Caliciviridae/mortalidade , Infecções por Campylobacter/mortalidade , Infecções por Enterovirus/mortalidade , Influenza Humana/mortalidade , Infecções por Paramyxoviridae/mortalidade , Infecções por Vírus Respiratório Sincicial/mortalidade , Infecções por Salmonella/mortalidade , Idoso , Idoso de 80 Anos ou mais , Infecções por Caliciviridae/epidemiologia , Infecções por Caliciviridae/virologia , Infecções por Campylobacter/epidemiologia , Infecções por Campylobacter/microbiologia , Infecções por Enterovirus/epidemiologia , Infecções por Enterovirus/virologia , Humanos , Influenza Humana/epidemiologia , Influenza Humana/virologia , Países Baixos/epidemiologia , Infecções por Paramyxoviridae/epidemiologia , Infecções por Paramyxoviridae/virologia , Análise de Regressão , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/virologia , Infecções por Salmonella/epidemiologia , Infecções por Salmonella/microbiologia , Estações do AnoRESUMO
Lyme borreliosis (LB) is not notifiable in many European countries, and accurate data on the incidence are often lacking. This study aimed to determine the seroprevalence of Borrelia burgdorferi sensu lato (s.l.)-specific antibodies in the general population of The Netherlands, and to determine risk factors associated with seropositivity. Sera and questionnaires were obtained from participants (n = 5592, aged 0-88 years) enrolled in a nationwide serosurveillance study. The sera were tested for B. burgdorferi s.l.-specific IgM and IgG antibodies using ELISA and immunoblot. Seroprevalence was estimated controlling for the survey design. Risk factors for seropositivity were analyzed using a generalized linear mixed-effect model. In 2016/2017, the seroprevalence in The Netherlands was 4.4% (95% CI 3.5-5.2). Estimates were higher in men (5.7% [95% CI 4.4-7.2]) than in women (3.1% [95% CI 2.0-4.0]), and increased with age from 2.6% (95% CI 1.4-4.4) in children to 7.7% (95% CI 5.9-7.9) in 60- to 88-year-olds. The seroprevalence for B. burgdorferi s.l. in the general population in The Netherlands was comparable to rates reported in European countries. The main risk factors for seropositivity were increasing age, being male and the tick bite frequency. The dynamics of LB infection are complex and involve variables from various disciplines. This could be further elucidated using infectious disease modelling.
RESUMO
[This corrects the article DOI: 10.1016/j.lanepe.2021.100142.].
RESUMO
BACKGROUND: Patients treated for Lyme borreliosis (LB) frequently report persistent symptoms. Little is known about risk factors and etiology. METHODS: In a prospective observational cohort study with a follow-up of one year, we assessed a range of microbiological, immunological, genetic, clinical, functional, epidemiological, psychosocial and cognitive-behavioral variables as determinants of persistent symptoms after treatment for LB. Between 2015 and 2018 we included 1135 physician-confirmed LB patients at initiation of antibiotic therapy, through clinical LB centers and online self-registration. Two reference cohorts of individuals without LB (n = 4000 and n = 2405) served as a control. Prediction analyses and association studies were used to identify determinants, as collected from online questionnaires (three-monthly) and laboratory tests (twice). FINDINGS: Main predictors of persistent symptoms were baseline poorer physical and social functioning, higher depression and anxiety scores, more negative illness perceptions, comorbidity, as well as fatigue, cognitive impairment, and pain in 295 patients with persistent symptoms. The primary prediction model correctly indicated persistent symptoms in 71.0% of predictions (AUC 0.79). In patients with symptoms at baseline, cognitive-behavioral responses to symptoms predicted symptom persistence. Of various microbiological, immunological and genetic factors, only lower IL-10 concentrations in ex vivo stimulation experiments were associated with persistent symptoms. Clinical LB characteristics did not contribute to the prediction of persistent symptoms. INTERPRETATION: Determinants of persistent symptoms after LB were mainly generic, including baseline functioning, symptoms and cognitive-behavioral responses. A potential role of host immune responses remains to be investigated. FUNDING: Netherlands Organisation for Health Research and Development (ZonMw); the Dutch Ministry of Health, Welfare and Sport (VWS).
Assuntos
Doença de Lyme , Humanos , Estudos Prospectivos , Doença de Lyme/diagnóstico , Doença de Lyme/tratamento farmacológico , Doença de Lyme/epidemiologia , Antibacterianos/uso terapêutico , Países Baixos , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: The risk factors for persistent fatigue and cognitive complaints after infection with SARS-CoV-2 and the underlying pathophysiology are largely unknown. Both clinical factors and cognitive-behavioural factors have been suggested to play a role in the perpetuation of complaints. A neurobiological aetiology, such as neuroinflammation, could be the underlying pathophysiological mechanism for persisting complaints.To unravel factors associated with persisting complaints, VeCosCO will compare individuals with and without persistent fatigue and cognitive complaints >3 months after infection with SARS-CoV-2. The study consists of two work packages. The first work package aims to (1) investigate the relation between persisting complaints and neuropsychological functioning; (2) determine risk factors and at-risk phenotypes for the development of persistent fatigue and cognitive complaints, including the presence of postexertional malaise and (3) describe consequences of persistent complaints on quality of life, healthcare consumption and physical functioning. The second work package aims to (1) determine the presence of neuroinflammation with [18F]DPA-714 whole-body positron emission tomography (PET) scans in patients with persisting complaints and (2) explore the relationship between (neuro)inflammation and brain structure and functioning measured with MRI. METHODS AND ANALYSIS: This is a prospective case-control study in participants with and without persistent fatigue and cognitive complaints, >3 months after laboratory-confirmed SARS-CoV-2 infection. Participants will be mainly included from existing COVID-19 cohorts in the Netherlands covering the full spectrum of COVID-19 acute disease severity. Primary outcomes are neuropsychological functioning, postexertional malaise, neuroinflammation measured using [18F]DPA-714 PET, and brain functioning and structure using (f)MRI. ETHICS AND DISSEMINATION: Work package 1 (NL79575.018.21) and 2 (NL77033.029.21) were approved by the medical ethical review board of the Amsterdam University Medical Centers (The Netherlands). Informed consent is required prior to participation in the study. Results of this study will be submitted for publication in peer-reviewed journals and shared with the key population.
Assuntos
COVID-19 , Humanos , COVID-19/complicações , SARS-CoV-2 , Estudos de Casos e Controles , Qualidade de Vida , Doenças Neuroinflamatórias , Fatores de Risco , Fadiga/etiologiaRESUMO
The emergence of Schmallenberg virus (SBV), a novel orthobunyavirus, in ruminants in Europe triggered a joint veterinary and public health response to address the possible consequences to human health. Use of a risk profiling algorithm enabled the conclusion that the risk for zoonotic transmission of SBV could not be excluded completely. Self-reported health problems were monitored, and a serologic study was initiated among persons living and/or working on SBV-affected farms. In the study set-up, we addressed the vector and direct transmission routes for putative zoonotic transfer. In total, 69 sheep farms, 4 goat farms, and 50 cattle farms were included. No evidence for SBV-neutralizing antibodies was found in serum of 301 participants. The lack of evidence for zoonotic transmission from either syndromic illness monitoring or serologic testing of presumably highly exposed persons suggests that the public health risk for SBV, given the current situation, is absent or extremely low.