Incidence of symptomatic Lyme borreliosis in nine European countries.

OBJECTIVES: To better understand the Lyme borreliosis (LB) burden in Europe, we aimed to estimate the incidence of symptomatic Borrelia burgdorferi sensu lato (Bbsl) infections after adjusting public health LB surveillance data for under-detection of symptomatic Bbsl infections. METHODS: Data from seroprevalence studies and estimates of the symptomatic proportion and duration of antibody detection in Bbsl-infected individuals, derived from reviews of the published literature, were used to adjust public health LB surveillance data to estimate the incidence of symptomatic Bbsl infection in nine European countries from 2018-2022. RESULTS: The prevalence of anti-Bbsl antibodies ranged from 2.3% in Romania to 9.4% in Germany. Under-detection multipliers varied across surveillance systems; using 10-year duration of antibody detection, multipliers were 2.4-10.5 in countries reporting all LB cases and 54.6-722.2 in countries reporting only Lyme neuroborreliosis cases. The incidence of symptomatic Bbsl infection adjusted for under-detection was highest in Finland, Germany, Norway, Poland, and Switzerland, intermediate in the Czech Republic and Denmark, and lowest in Ireland and Romania. CONCLUSIONS: Adjustment of LB surveillance for under-detection found a high incidence of symptomatic Bbsl infection in several European countries. Differences in LB surveillance systems should be considered when comparing surveillance data between countries and when estimating LB disease burden.

Incidence of symptomatic Borrelia burgdorferi sensu lato infection in Romania, 2018-2023.

BACKGROUND: Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl), is the most common tick-borne disease in Europe. Although public health surveillance for LB has been conducted in Romania since 2007, the extent of under-detection of Bbsl infections by LB surveillance has not been estimated. We therefore estimated the under-detection of symptomatic Bbsl infections by LB surveillance to better understand the LB burden in Romania. METHODS: The number of incident symptomatic Bbsl infections were estimated from a seroprevalence study conducted in six counties (population 2.3 M) and estimates of the symptomatic proportion and duration of persistence of anti-Bbsl immunoglobulin G (IgG) antibodies. The number of incident symptomatic Bbsl infections were compared with the number of surveillance-reported LB cases to derive an under-detection multiplier, and then the under-detection multiplier was applied to LB surveillance data to estimate the incidence of symptomatic Bbsl infection from 2018 to 2023. RESULTS: We estimate that there were 1968 individuals with incident symptomatic Bbsl infection in the six counties where the seroprevalence study was conducted in 2020, compared with the 187 surveillance-reported LB cases, resulting in an under-detection multiplier of 10.5 (i.e., for every surveillance-reported LB case, there were 10.5 symptomatic incident Bbsl infections). The incidence of symptomatic Bbsl infection in the six counties was 86.9/100,000 population in 2023, similar to the incidence in 2018-2020 (86.0) and higher than in 2021-2022 (40.3). CONCLUSIONS: There is a higher incidence of symptomatic Bbsl infection than is reported through public health surveillance for LB in Romania. Additional efforts are needed to strengthen disease prevention and address the important public health problem of LB.

Publicly available surveillance data on tick-borne encephalitis in Europe, 2023.

The European Centre for Disease Prevention and Control (ECDC) defines a case of tick-borne encephalitis (TBE) as an infection by the TBE virus (TBEV) with clinical manifestations of central nervous system inflammation (e.g., meningitis, encephalitis). To better understand the TBE surveillance landscape, online searches were conducted to determine if cases of TBE, TBEV infection, acute meningitis or encephalitis, or viral meningitis or encephalitis were subject to statutory reporting in European countries in 2023. In countries with statutory reporting, notification responsibility and available information on surveillance-reported cases were determined. The number of TBE cases reported to ECDC were compared with the number of cases recorded in national surveillance reports. Of 44 countries of the Europe Region of the United Nations, 37 (84 %) mandated statutory reporting of cases of TBE, TBEV infection, or acute/viral meningitis/encephalitis. Twenty-six (87 %) of 30 countries with identified surveillance reports recorded TBE cases in 2020-2023. Of these countries, 17 (65 %) required TBE reporting by clinicians and laboratories, 5 (19 %) by clinicians only, and 4 (15 %) by laboratories only. Twenty-four countries reported on TBE cases to ECDC in 2020; however, surveillance for TBE in Europe is heterogeneous. Standardization of TBE surveillance would enhance the understanding of TBE disease burden in Europe.

Global Seroprevalence of Tick-Borne Encephalitis Antibodies in Humans, 1956-2022: A Literature Review and Meta-Analysis.

Despite the availability of tick-borne encephalitis (TBE) vaccines, the incidence of TBE is increasing. To understand the historical patterns of infection, we conducted a global meta-analysis of studies before December 2023 reporting human antibody prevalence against TBEV (TBE virus) among general or high-risk population groups stratified by country, collection year, serological method, and vaccination status. Pooled data were compared within groups over time by random-effects modeling. In total, 2403 articles were retrieved; 130 articles published since 1959 were included. Data were extracted from 96 general populations (117,620 participants) and 71 high-risk populations (53,986 participants) across 33 countries. Germany had the most population groups (21), and Poland had the most participants (44,688). Seven serological methods were used; conventional IgG/IgM ELISAs were the most common (44%). Four studies (1.7%) used NS1-ELISA serology. Between 1956-1991 and 1992-2022, anti-TBEV seroprevalence remained at ~2.75% across all population groups from "high-risk" areas (p = 0.458) but decreased within general populations (1.7% to 1%; p = 0.001) and high-risk populations (5.1% to 1.3%; p < 0.001), possibly due to differences in the study methodologies between periods. This global summary explores how serological methods can be used to assess TBE vaccination coverage and potential exposure to TBEV or measure TBE burden and highlights the need for standardized methodology when conducting TBE seroprevalence studies to compare across populations.

Borrelia burgdorferi sensu lato prevalence in Ixodes scapularis from Canada: A thirty-year summary and meta-analysis (1990-2020).

Borrelia burgdorferi sensu lato (Bb) are a complex of bacteria genospecies that can cause Lyme disease (LD) in humans after the bite of an infected Ixodes spp. vector tick. In Canada, incidence of LD is increasing in part due to the rapid geographic expansion of Ixodes scapularis across the southcentral and eastern provinces. To better understand temporal and spatial (provincial) prevalence of Bb infection of I. scapularis and how tick surveillance is utilized in Canada to assess LD risk, a literature review was conducted. Tick surveillance studies published between January 1975 to November 2023, that measured the prevalence of Bb in I. scapularis via "passive surveillance" from the public citizenry or "active surveillance" by drag or flag sampling of host-seeking ticks in Canada were included for review. Meta-analyses were conducted via random effects modeling. Forty-seven articles, yielding 26 passive and 28 active surveillance studies, met inclusion criteria. Mean durations of collection for I. scapularis were 2.1 years in active surveillance studies (1999-2020) and 5.5 years by passive surveillance studies (1990-2020). Collectively, data were extracted on 99,528 I. scapularis nymphs and adults collected between 1990-2020 across nine provinces, including Newfoundland & Labrador (33 ticks) and Alberta (208 ticks). More studies were conducted in Ontario (36) than any other province. Across nine provinces, the prevalence of Bb infection in I. scapularis collected by passive surveillance was 14.6% with the highest prevalence in Nova Scotia at 20.5% (minimum studies >1). Among host-seeking I. scapularis collected via active surveillance, Bb infection prevalence was 10.5% in nymphs, 31.9% in adults, and 23.8% across both life stages. Host-seeking I. scapularis nymphs and adults from Ontario had the highest Bb prevalence at 13.6% and 34.8%, respectively. Between 2007-2019, Bb infection prevalence in host-seeking I. scapularis was positively associated over time (p<0.001) which is concurrent with a ∼25-fold increase in the number of annually reported LD cases in Canada over the same period. The prevalence of Bb-infection in I. scapularis has rapidly increased over three decades as reported by tick surveillance studies in Canada which coincides with increasing human incidence for LD. The wide-ranging distribution and variable prevalence of Bb-infected I. scapularis ticks across provinces demonstrates the growing need for long-term standardized tick surveillance to monitor the changing trends in I. scapularis populations and best define LD risk areas in Canada.

Prospective incidence epidemiology study protocol: conducting active surveillance to assess the burden of Lyme disease (BOLD) in primary care practices in endemic areas of six European countries.

INTRODUCTION: Lyme disease (LD) is the most frequent tick-borne disease in the moderate climates of Europe. This study will inform the phase III efficacy study for Pfizer and Valneva's investigational Lyme disease vaccine, VLA15. VLA15 phase III will be conducted in the USA and Europe due to the vaccine's serotype coverage and public health burden of LD. In Europe, the existence and location of sites that have access to populations with high LD annual incidence is uncertain. This active, prospective surveillance study assesses annual LD incidence at general practice (GP)/primary care sites, allowing for phase III site vetting and better characterisation of LD burden in selected regions for study size calculations. METHODS AND ANALYSIS: This burden of Lyme disease (BOLD) study will assess LD incidence overall and by site at 15 GP/primary care practices in endemic areas of 6 European countries from Spring 2021 to December 2022 and will be summarised with counts (n), percentages (%) and associated 95% CIs. Suspected LD cases identified from site's practice panels are documented on screening logs, where clinical LD manifestations, diagnoses and standard of care diagnostic results are recorded. In the initial 12-month enrolment phase, suspected LD cases are offered enrolment. Participants undergo interview and clinical assessments to establish medical history, final clinical diagnosis, clinical manifestations and quality of life impact. Study-specific procedures include LD serology, skin punch biopsies and Lyme manifestation photographs. For every enrolled participant diagnosed with LD, 6-10 age-matched controls are randomly selected and offered enrolment for an embedded LD risk factor analysis. Persistent symptoms or post-treatment LD will be assessed at follow-up visits up to 2 years after initial diagnosis, while patients remain symptomatic. ETHICS AND DISSEMINATION: This study has been approved by all sites' local ethics committees. The results will be presented at conferences and published in peer-reviewed journals.

A systematic literature review of the effectiveness of tick-borne encephalitis vaccines in Europe.

BACKGROUND: Tick-borne encephalitis (TBE) is an infectious disease caused by the tick-borne encephalitis virus (TBEV) in patients with symptoms of central nervous system (CNS) inflammation. More than 25 European countries have one or more TBE-endemic areas. Although two TBE vaccines, FSME-IMMUN® and Encepur®, are commonly used in Europe, there are no published reviews of the real-world effectiveness of TBE vaccines in Europe or elsewhere. METHODS: We searched PubMed for TBE vaccine effectiveness (VE) articles and extracted information on country, study design, study period, study population, number of TBEV-infected cases, number of participants, and VE against TBEV infection and outcomes. RESULTS: We identified 13 studies, conducted in Austria, the Czech Republic, Latvia, Germany, and Switzerland, published in 2003-2023. One study was a cohort investigation of a milk-borne outbreak. In the other studies, 11 (91.7%) used the screening method and two (16.7%) used a case-control design (one study used both). TBE vaccines were highly effective (VE estimates >92%) against TBEV infection in all age groups. Vaccines were also highly protective against mild infections (i.e., infections in patients without symptoms of CNS inflammation), and against infections resulting in TBE and hospitalization. Vaccines were also highly protective against the most serious outcomes such as hospitalization greater than 12 days. Product-specific VE estimates were also high, though limited data were available. Studies in Austria, the Czech Republic, Latvia, and Switzerland estimated that TBE vaccines prevented >1,000 TBE cases a year, avoiding many hospitalizations and deaths, in these countries combined. CONCLUSIONS: Published VE studies demonstrate a high real-world effectiveness of the commercially available TBE vaccines in Europe. Although cases averted have been estimated in only four countries, TBE vaccination prevents thousands of cases in Europe each year. To prevent life-threatening TBE, TBE vaccine uptake and compliance with the vaccination schedule should be increased in residents of, and travelers to, TBE-endemic countries in Europe.

Estimated Incidence of Symptomatic Lyme Borreliosis Cases in Lublin, Poland in 2021.

Lyme borreliosis (LB), the most common tick-borne disease in Europe, is endemic to Poland. Despite public health surveillance with mandatory reporting of LB cases by physicians and laboratories, many symptomatic LB cases are not included in surveillance in Poland. We estimated the extent of the under-ascertainment of symptomatic LB cases via surveillance in the Polish province of Lublin to better understand Poland's LB burden. The number of incident symptomatic LB cases in Lublin in 2010 was estimated from two seroprevalence studies conducted among adults in Lublin, as well as estimates of the proportion of asymptomatic LB cases and the duration of LB antibody persistence. The estimated number of incident symptomatic LB cases was compared to the number of surveillance-reported cases in Lublin to derive an under-ascertainment multiplier. This multiplier was applied to the number of surveillance-reported cases in 2021 to estimate the number and population-based incidence of symptomatic LB cases in Lublin in 2021. We estimate that there are 5.9 symptomatic LB cases for every surveillance-reported LB case in Lublin. Adjusting for under-ascertainment, the estimated number of symptomatic LB cases in Lublin in 2021 was 6204 (population-based incidence: 467.6/100,000). After adjustment for under-ascertainment, the incidence of symptomatic LB in Lublin, Poland, is high.

Estimated Number of Symptomatic Lyme Borreliosis Cases in Adults in Finland in 2021 Using Seroprevalence Data to Adjust the Number of Surveillance-Reported Cases: A General Framework for Accounting for Underascertainment by Public Health Surveillance.

Background: Finland conducts public health surveillance for Lyme borreliosis (LB) based on clinically diagnosed and laboratory-confirmed cases. We used data from seroprevalence studies to determine the extent to which LB cases were underascertained by public health surveillance. Methods: The numbers of incident symptomatic LB cases in 2011 in six regions in Finland were estimated using (1) data from Borrelia burgdorferi sensu lato seroprevalence studies, (2) estimates of the proportion of LB infections that are asymptomatic, and (3) estimates of the duration of LB antibody detection. The numbers of estimated incident symptomatic LB cases were compared with the numbers of surveillance-reported LB cases to estimate regional underascertainment multipliers. Underascertainment multipliers were applied to the numbers of surveillance-reported LB cases in each region in 2021 and summed to estimate the number of symptomatic LB cases in Finland among adults in 2021. A sensitivity analysis evaluated the impact of different durations of antibody detection. Results: Using an asymptomatic proportion of 50% and a 10-year duration of antibody detection, the estimated regional underascertainment multipliers in Finland ranged from 1.0 to 12.2. Applying the regional underascertainment multipliers to surveillance-reported LB cases in each region and summing nationally, there were 19,653 symptomatic LB cases in Finland among adults in 2021 (526/100,000 per year). With 7,346 surveillance-reported LB cases in Finland among adults in 2021, the estimated number of symptomatic LB cases indicate that there were 2.7 symptomatic LB cases for every surveillance-reported LB case among adults. With a 5- or 20-year duration of antibody detection, there were an estimated 36,824 or 11,609 symptomatic LB cases among adults in 2021, respectively. Discussion: Finland has robust public health surveillance for LB, but cases are underascertained. This framework for estimating LB underascertainment can be used in other countries that conduct LB surveillance and have conducted representative LB seroprevalence studies.

An Observational Retrospective Matched Cohort Study of Healthcare Resource Utilisation and Costs in UK Patients with Moderate to Severe Osteoarthritis Pain.

INTRODUCTION: Using data from patients residing in Salford, UK, we aimed to compare healthcare resource utilisation (HCRU) and direct healthcare costs between patients with moderate to severe (M-S) or severe osteoarthritis (OA) pain and those without OA. METHODS: Patients with a M-S OA pain event within a period of chronic pain were indexed from the Salford Integrated Record (SIR) between 2010 and 2017. Patients with a severe pain event formed an OA subcohort. Patients in each OA pain cohort were independently matched to patients without OA, forming two control cohorts. HCRU, prescribed analgesic drugs, and total direct costs per UK standardised tariffs were calculated for the year post-index. Multivariable models were used to identify drivers of healthcare cost. RESULTS: The M-S OA pain and control cohorts each comprised 3123 patients; the severe OA pain and control cohorts each comprised 1922 patients. Patients in both OA pain cohorts had a significantly higher mean number of general practitioner encounters, inpatient, outpatient, and accident and emergency visits, and were prescribed a broader range of analgesic drugs in the year post-index than respective controls. Mean healthcare costs of all types were significantly higher in the M-S and severe OA pain cohorts vs controls (total: M-S £2519 vs £1379; severe £3389 vs £1397). Paracetamol (M-S: 40% of patients had at least one prescription; severe: 50%) and strong opioids (34% and 59%) were the analgesics most prescribed to patients with OA pain. In all cohorts, multivariable models showed that a higher age at index, the presence of gout, osteoporosis, type 2 diabetes, or coronary artery disease, significantly contributed towards higher healthcare costs. CONCLUSION: In the population of Salford, UK, patients with M-S OA pain had significantly higher annual HCRU and costs compared with matched controls without OA; generally, these were even higher in patients with severe OA pain.

Quantifying the Employer Burden of Persistent Musculoskeletal Pain at a Large Employer in the United Kingdom: A Non-interventional, Retrospective Study of Rolls-Royce Employee Data.

OBJECTIVE: To quantify the burden of work-relevant persistent musculoskeletal (MSK) pain to a large UK employer. METHODS: A retrospective, longitudinal, analytical cohort study using linked Rolls-Royce data systems. Cases were employees with a MSK-related referral to occupational health; controls were age-, sex-, and job role-matched employees without such a referral. Outcomes were compared during 12 months' follow-up. RESULTS: Overall, 2382 matched case-control pairs were identified (mean age: 46 y; 82% male). Cases took 39,200 MSK-related sickness absence days in total (equating to £50 million in sickness absence costs). Cases took significantly more all-cause sickness absence days than controls (82,341 [£106 million] versus 19,628 [£26 million]; P < 0.0001). CONCLUSIONS: Despite access to extensive occupational health services, the burden of work-relevant persistent MSK pain remains high in Rolls-Royce. There is a clear need to better understand how to effectively reduce this burden.

The demographics and geographic distribution of laboratory-confirmed Lyme disease cases in England and Wales (2013-2016): an ecological study.

OBJECTIVE: Lyme disease is a tick-borne disease of increasing incidence and public concern across the Northern Hemisphere. However, the socio-demographics and geographic distribution of the population affected in England and Wales are poorly understood. Therefore, the proposed study was designed to describe the demographics and distribution of laboratory-confirmed cases of Lyme disease from a national testing laboratory. DESIGN: An ecological study of routinely collected laboratory surveillance data. SETTING: Public Health England's national Lyme disease testing laboratory. PARTICIPANTS: 3986 laboratory-confirmed cases of Lyme disease between 2013 and 2016. RESULTS: In England and Wales, the incidence of laboratory-confirmed Lyme disease rose significantly over the study period from 1.62 cases per 100 000 in 2013 to 1.95 cases per 100 000 in 2016. There was a bimodal age distribution (with peaks at 6-10 and 61-65 years age bands) with a predominance of male patients. A significant clustering of areas with high Lyme disease incidence was located in southern England. An association was found between disease incidence and socioeconomic status, based on the patient's resident postcode, with more cases found in less deprived areas. Cases were disproportionately found in rural areas compared with the national population distribution. CONCLUSIONS: These results suggest that Lyme disease patients originate from areas with higher socioeconomic status and disproportionately in rural areas. Identification of the Lyme disease hotspots in southern England, alongside the socio-demographics described, will enable a targeted approach to public health interventions and messages.

Glucocorticoid management of adrenal insufficiency in the United Kingdom: assessment using real-world data.

Background and objectives Glucocorticoids are used to manage adrenal insufficiency (AI). We describe treatments used in the United Kingdom and real-world clinical outcomes for each treatment. Methods We used 2010-2016 primary care data from The Health Improvement Network (THIN). Descriptive analyses were conducted, and differences in variables between patients prescribed immediate-release hydrocortisone (IR HC), prednisolone or modified-release hydrocortisone (MR HC) were assessed using Fisher's exact test. Results Overall, 2648 patients were included: 1912 on IR HC (72%), 691 on prednisolone (26%) and 45 (2%) on MR HC. A total of 1174 (44.3%) had primary and 1150 (43.4%) had secondary AI. Patients on prednisolone were older (P < 0.001) and had a greater history of smoking (292/691, P < 0.001) and CVD (275/691, P < 0.001). Patients on MR HC had more PCOS (3/45, P = 0.001) and diabetes (27/45, P = 0.004). The number of GP visits/patient/year was 6.50 in IR HC, 9.54 in prednisolone and 9.11 in MR HC cohorts. The mean number of A&E visits and inpatient and outpatient hospital admissions ranged from 0.42 to 0.93 visits/patient/year. The mean number of adrenal crises/patient/year was between 0.02 and 0.03 for all cohorts. Conclusion IR HC is most commonly used for the management of AI in the United Kingdom, followed by prednisolone. Few patients receive MR HC. The prednisolone and MR HC cohorts displayed a greater prevalence of vascular risk factors compared with IR HC. The occurrence of AC and primary and secondary resource use were similar between treatment cohorts, and they indicate significant resource utilisation. Improved treatment and management of patients with AI is needed.

The Epidemiology of Q Fever in England and Wales 2000-2015.

Between 2000 and 2015, 904 cases of acute Q fever were reported in England and Wales. The case dataset had a male to female ratio of 2.5:1, and a median age of 45 years. Two outbreaks were recognised during this time period, and the incidence of sporadic cases was highest across the southwest of England, and Wales. There are limitations in the surveillance system for Q fever, including possible geographical differences in reporting and limited epidemiological data collection. The surveillance system needs to be strengthened in order to improve the quality and completeness of the epidemiological dataset. The authors conclude with recommendations on how to achieve this.

Healthy animals, healthy people: zoonosis risk from animal contact in pet shops, a systematic review of the literature.

BACKGROUND: Around 67 million pets are owned by households in the United Kingdom, and an increasing number of these are exotic animals. Approximately a third of pets are purchased through retail outlets or direct from breeders. A wide range of infections can be associated with companion animals. OBJECTIVES: This study uses a systematic literature review to describe the transmission of zoonotic disease in humans associated with a pet shop or other location selling pets (incidents of rabies tracebacks and zoonoses from pet food were excluded). DATA SOURCES: PubMed and EMBASE. RESULTS: Fifty seven separate case reports or incidents were described in the 82 papers that were identified by the systematic review. Summary information on each incident is included in this manuscript. The infections include bacterial, viral and fungal diseases and range in severity from mild to life threatening. Infections associated with birds and rodents were the most commonly reported. Over half of the reports describe incidents in the Americas, and three of these were outbreaks involving more than 50 cases. Many of the incidents identified relate to infections in pet shop employees. LIMITATIONS: This review may have been subject to publication bias, where unusual and unexpected zoonotic infections may be over-represented in peer-reviewed publications. It was also restricted to English-language articles so that pathogens that are more common in non-Western countries, or in more exotic animals not common in Europe and the Americas, may have been under-represented. CONCLUSIONS/IMPLICATIONS: A wide spectrum of zoonotic infections are acquired from pet shops. Salmonellosis and psittacosis were the most commonly documented diseases, however more unusual infections such as tularemia also appeared in the review. Given their potential to spread zoonotic infection, it is important that pet shops act to minimise the risk as far as possible.