Retrospective database analysis for clinical diagnoses commonly associated with pneumococcal diseases in the Malaysian healthcare system over a 3-year period (2013-2015).

BACKGROUND: Pneumococcal disease caused by Streptococcus pneumoniae is an important cause of morbidity and mortality across all ages, particularly in younger children and older adults. Here, we describe pneumococcal disease hospitalizations at Ministry of Health (MoH) facilities in Malaysia between 2013 and 2015. METHODS: This was a retrospective databases analysis. Tabular data from the Malaysian Health Data Warehouse (MyHDW) were used to identify microbiologically confirmed, pneumococcal disease hospitalizations and deaths during hospitalization, using hospital-assigned ICD-10 codes (i.e., classified as meningitis, pneumonia, or non-meningitis non-pneumonia). Case counts, mortality counts, and case fatality rates were reported by patient age group and by Malaysian geographic region. RESULTS: A total of 683 pneumococcal disease hospitalizations were identified from the analysis: 53 pneumococcal meningitis hospitalizations (5 deaths and 48 discharges), 413 pneumococcal pneumonia hospitalizations (24 deaths and 389 discharges), and 205 non-meningitis non-pneumonia pneumococcal disease hospitalizations (58 deaths and 147 discharges). Most hospitalizations occurred in children aged < 2 years. Crude mortality was highest among children aged < 2 years (for all three disease categories), among adults aged ≥ 65 years (for pneumococcal pneumonia), or among adults aged 65-85 years (for non-meningitis non-pneumonia pneumococcal disease). The case fatality rate, all ages included, was 5.8% for pneumococcal pneumonia, 9.1% for pneumococcal meningitis, and 28.3% for non-meningitis non-pneumonia pneumococcal disease. CONCLUSIONS: Our study is the first to document pneumococcal disease hospitalizations and deaths during hospitalization in Malaysia. Although this database analysis likely underestimated case counts, and the true disease burden could be even greater, the study demonstrates a substantial burden of pneumococcal disease. Public health measures, including vaccination, would significantly contribute to the prevention of hospitalizations and deaths associated with pneumococcal disease in Malaysia.

The burden of Clostridioides difficile infections in South-East Asia and the Western Pacific: A narrative review.

BACKGROUND: Clostridioides difficile (formerly Clostridium difficile) is well-documented in Europe and North America to be a common cause of healthcare-associated gastrointestinal tract infections. In contrast, C difficile infection (CDI) is infrequently reported in literature from Asia, which may reflect a lack of clinician awareness. We conducted a narrative review to better understand CDI burden in Asia. METHODS: We searched the PubMed database for English language articles related to C difficile, Asia, epidemiology, and molecular characteristics (eg, ribotype, antimicrobial resistance). RESULTS: Fifty-eight articles that met eligibility criteria were included. C difficile prevalence ranged from 7.1% to 45.1 % of hospitalized patients with diarrhea, and toxigenic strains among all C difficile in these patients ranged from 68.2% to 91.9 % in China and from 39.0% to 60.0 % outside of China. Widespread C difficile ribotypes were RT017, RT014/020, RT012, and RT002. Recurrence in patients with CDI ranged from 3.0% to 17.2 %. Patients with CDI typically had prior antimicrobial use recently. High rates of resistance to ciprofloxacin, clindamycin, and erythromycin were frequently reported. CONCLUSION: The regional CDI burden in Asia is still incompletely documented, seemingly due to low awareness and limited laboratory testing. Despite this apparent under recognition, the current CDI burden highlights the need for broader surveillance and for application of preventative measures against CDI in Asia.

Vaccine-Preventable Disease Incidence Based on Clinically, Radiologically, and Etiologically Confirmed Outcomes: Systematic Literature Review and Re-analysis of Pneumococcal Conjugate Vaccine Efficacy Trials.

BACKGROUND: Vaccine regulatory decision making is based on vaccine efficacy against etiologically confirmed outcomes, which may underestimate the preventable disease burden. To quantify this underestimation, we compared vaccine-preventable disease incidence (VPDI) of clinically defined outcomes with radiologically/etiologically confirmed outcomes. METHODS: We performed a systematic review of efficacy trials for several vaccines (1997-2019) and report results for pneumococcal conjugate vaccines. Data were extracted for outcomes within a clinical syndrome, organized from most sensitive to most specific. VPDI was determined for each outcome, and VPDI ratios were calculated, with a clinically defined outcome (numerator) and a radiologically/etiologically confirmed outcome (denominator). RESULTS: Among 9 studies, we calculated 27 VPDI ratios; 24 had a value >1. Among children, VPDI ratios for clinically defined versus vaccine serotype otitis media were 0.6 (95% CI not calculable), 2.1 (1.5-3.0), and 3.7 (1.0-10.2); the VPDI ratios comparing clinically defined with radiologically confirmed pneumonia ranged from not calculable to 2.7 (1.2-10.4); the VPDI ratio comparing clinically suspected invasive pneumococcal disease (IPD) with laboratory-confirmed IPD was 3.8 (95% CI not calculable). Among adults, the ratio comparing clinically defined with radiologically confirmed pneumonia was 1.9 (-6.0 to 9.1) and with vaccine serotype-confirmed pneumonia was 2.9 (.5-7.8). CONCLUSIONS: While there is substantial uncertainty around individual point estimates, there is a consistent trend in VPDI ratios, most commonly showing under-ascertainment of 1.5- to 4-fold, indicating that use of clinically defined outcomes is likely to provide a more accurate estimate of a pneumococcal conjugate vaccine's public health value.

Systematic Review and Meta-analysis of Lyme Disease Data and Seropositivity for Borrelia burgdorferi, China, 2005‒2020.

Since its initial identification in 1986, Lyme disease has been clinically diagnosed in 29 provinces in China; however, national incidence data are lacking. To summarize Lyme disease seropositivity data among persons across China, we conducted a systematic literature review of Chinese- and English-language journal articles published during 2005‒2020. According to 72 estimates that measured IgG by using a diagnostic enzyme-linked assay (EIA) alone, the seropositivity point prevalence with a fixed-effects model was 9.1%. A more conservative 2-tier testing approach of EIA plus a confirmatory Western immunoblot (16 estimates) yielded seropositivity 1.8%. Seropositivity by EIA for high-risk exposure populations was 10.0% and for low-risk exposure populations was 4.5%; seropositivity was highest in the northeastern and western provinces. Our analysis confirms Lyme disease prevalence, measured by seropositivity, in many Chinese provinces and populations at risk. This information can be used to focus prevention measures in provinces where seropositivity is high.

Mental Health Outcomes of Unaccompanied Refugee Minors: a Rapid Review of Recent Research.

PURPOSE: To examine mental health outcomes of unaccompanied refugee minors during global policy shift. Additionally, to consider mental health service delivery and placement type for this group. METHODS: A rapid systematic search of research published since 2018 which related to mental health outcomes of unaccompanied refugee minors. Data extracted, risk of bias assessed and outcomes reviewed qualitatively. RESEARCH FINDINGS: We found 181 papers, of which 14 met inclusion criteria. This review found consistently high levels of PTSD and PTSS among URMs in various contexts. Exposure to trauma, being unaccompanied (compared to accompanied), being female and being older are associated with poor outcomes. Depression and anxiety were consistently high among URMs and associated with discrimination, limited language attainment and daily hassles. High rates of mental illness and symptoms among unaccompanied refugee minors were consistent across national and settlement contexts but the quality of the evidence is variable with significant heterogeneity of assessment. We relate persistence of poor mental health outcomes with problems accessing mental health services and discuss the role of key post-migration factors influencing outcomes-in particular placement type and the use of detention centres.

Sensitivity to Haptic Sound-Localization Cues at Different Body Locations.

Cochlear implants (CIs) recover hearing in severely to profoundly hearing-impaired people by electrically stimulating the cochlea. While they are extremely effective, spatial hearing is typically severely limited. Recent studies have shown that haptic stimulation can supplement the electrical CI signal (electro-haptic stimulation) and substantially improve sound localization. In haptic sound-localization studies, the signal is extracted from the audio received by behind-the-ear devices and delivered to each wrist. Localization is achieved using tactile intensity differences (TIDs) across the wrists, which match sound intensity differences across the ears (a key sound localization cue). The current study established sensitivity to across-limb TIDs at three candidate locations for a wearable haptic device, namely: the lower tricep and the palmar and dorsal wrist. At all locations, TID sensitivity was similar to the sensitivity to across-ear intensity differences for normal-hearing listeners. This suggests that greater haptic sound-localization accuracy than previously shown can be achieved. The dynamic range was also measured and far exceeded that available through electrical CI stimulation for all of the locations, suggesting that haptic stimulation could provide additional sound-intensity information. These results indicate that an effective haptic aid could be deployed for any of the candidate locations, and could offer a low-cost, non-invasive means of improving outcomes for hearing-impaired listeners.

Public exposure to ultrasound and very high-frequency sound in air.

Recent work showing the presence of a new generation of ultrasound (US) sources in public places has reopened the debate about whether there are adverse effects of US on humans, and has identified weaknesses in standards and exposure guidelines. Systems that rely on very high-frequency sound (VHFS) and US include public-address voice-alarm (PAVA) systems (whose operational status is often monitored using tones at ∼20 kHz) and pest deterrents. In this study, sound pressure levels (SPLs) produced by 16 sources that were either publically available or installed in busy public spaces were measured. These sources were identified through a citizen science project, wherein members of the public were asked to provide smartphone recordings of VHFS/US sources. With measurements made in realistic listening positions, pest deterrents were found that produced levels of up to 100 dB SPL at ∼20 kHz, and a hand dryer was found to produce 84 dB SPL at 40 kHz. PAVA systems were found to emit lower levels of up to 76 dB SPL at ∼20 kHz. Pest deterrents measured breach recommended safe listening limits for public exposure for people who are nearby even for relatively short periods.

Effects of very high-frequency sound and ultrasound on humans. Part II: A double-blind randomized provocation study of inaudible 20-kHz ultrasound.

Some people have reported symptoms such as nausea, dizziness, and headaches that they attribute to ultrasound (US) emitted by devices in public places. The primary aim of the present study was to investigate whether inaudible US can provoke adverse symptoms compared to a sham presentation, under double-blind conditions. A second aim was to investigate whether the expectation of US being present could provoke adverse symptoms (a nocebo response). The US stimulus was a 20 kHz tone presented continuously for 20 min set to at least 15 dB below the participants' detection threshold, giving a typical sound pressure level (SPL) of 84 dB. No evidence that US provoked symptoms was found, but there was evidence of small nocebo effects. A case study on an individual with high self-reported sensitivity to US gave similar results. The present study did not reproduce the severe symptoms reported previously by some members of the public; this may be due to the SPL or duration of the stimulus, or strength of the nocebo stimulus. These findings cannot be used to predict outcomes from exposures to sounds that are audible to the individual in question, or to sounds with higher SPLs, longer durations, or different frequency content.

Effects of very high-frequency sound and ultrasound on humans. Part I: Adverse symptoms after exposure to audible very-high frequency sound.

Various adverse symptoms resulting from exposure to very high-frequency sound (VHFS) and ultrasound (US) have previously been reported. This study aimed to establish whether these symptoms are experienced under controlled laboratory conditions and are specific to VHFS/US. To do this, participants were exposed to VHFS/US (at frequencies between 13.5 and 20 kHz and sound pressure levels between 82 and 92 dB) and to a 1 kHz reference stimulus, both at 25 dB above their hearing threshold. The VHFS/US and reference stimuli were presented 4 times, each time for 3 min, during which participants performed a sustained attention task, rated their symptom severity, and had their galvanic skin response (GSR) measured to assess their level of anxiety. Prior to exposure, participants were assigned either to a symptomatic or an asymptomatic group, based on their prior history of symptoms that they attributed to VHFS/US. In both groups, overall discomfort ratings were higher in the VHFS/US condition than the reference condition. In the symptomatic group only, difficulty concentrating and annoyance were also rated higher in the VHFS/US than the reference condition. No difference between the two stimulus conditions was seen in performance on the attention task or on average GSRs for either group.

Measurements of ultrasonic deterrents and an acoustically branded hairdryer: Ambiguities in guideline compliance.

Acoustic radiation from three commercial pest deterrents and two hair dryers were measured in an anechoic chamber. The deterrents were chosen because the frequency range at which they emit the most energy is either in the very high-frequency sound band (11.2-17.8 kHz) or the ultrasound band (greater than 17.8 kHz). These are sources that may be heard by a subset of the general population, with the young typically having better high frequency sensitivity. A hairdryer reported to increase the frequency of the motor noise above the audible hearing range was compared with a standard hairdryer. The outputs of the deterrents are compared against six international regulations and guidelines for audible and ultrasound exposure. Multiple ambiguities in the application of these guidelines are discussed. These ambiguities could lead to a device being considered as in compliance despite unconventionally high levels. Even if a device measured here meets a guideline, actual exposures can exceed those taken here and may therefore breach guidelines if the listener is closer to the device or reflections increase the exposure level.

Individual differences in regional cortical volumes across the life span are associated with regional optical measures of arterial elasticity.

Aging is often accompanied by changes in brain anatomy and cerebrovascular health. However, the specific relationship between declines in regional cortical volumes and loss of cerebral arterial elasticity is less clear, as only global or very localized estimates of cerebrovascular health have been available. Here we employed a novel tomographic optical method (pulse-DOT) to derive local estimates of cerebral arterial elasticity and compared regional volumetric estimates (obtained with FreeSurfer) with optical arterial elasticity estimates from the same regions in 47 healthy adults (aged 18-75). Between-subject analyses revealed a global correlation between cortical volume and cortical arterial elasticity, which was a significant mediator of the association between age and cortical volume. Crucially, a novel within-subject analysis highlighted the spatial association between regional variability in cortical volumes and arterial elasticity in the same regions. This association strengthened with age. Gains in the predictability of cortical volumes from arterial elasticity data were obtained by sharpening the resolution up to individual cortical regions. These results indicate that some of the variance of sub-clinical age-related brain atrophy is associated with differences in the status of cerebral arteries, and can help explain the unique patterns of brain atrophy found within each individual.

Improved tactile speech perception using audio-to-tactile sensory substitution with formant frequency focusing.

Haptic hearing aids, which provide speech information through tactile stimulation, could substantially improve outcomes for both cochlear implant users and for those unable to access cochlear implants. Recent advances in wide-band haptic actuator technology have made new audio-to-tactile conversion strategies viable for wearable devices. One such strategy filters the audio into eight frequency bands, which are evenly distributed across the speech frequency range. The amplitude envelopes from the eight bands modulate the amplitudes of eight low-frequency tones, which are delivered through vibration to a single site on the wrist. This tactile vocoder strategy effectively transfers some phonemic information, but vowels and obstruent consonants are poorly portrayed. In 20 participants with normal touch perception, we tested (1) whether focusing the audio filters of the tactile vocoder more densely around the first and second formant frequencies improved tactile vowel discrimination, and (2) whether focusing filters at mid-to-high frequencies improved obstruent consonant discrimination. The obstruent-focused approach was found to be ineffective. However, the formant-focused approach improved vowel discrimination by 8%, without changing overall consonant discrimination. The formant-focused tactile vocoder strategy, which can readily be implemented in real time on a compact device, could substantially improve speech perception for haptic hearing aid users.

Improved tactile speech perception and noise robustness using audio-to-tactile sensory substitution with amplitude envelope expansion.

Recent advances in haptic technology could allow haptic hearing aids, which convert audio to tactile stimulation, to become viable for supporting people with hearing loss. A tactile vocoder strategy for audio-to-tactile conversion, which exploits these advances, has recently shown significant promise. In this strategy, the amplitude envelope is extracted from several audio frequency bands and used to modulate the amplitude of a set of vibro-tactile tones. The vocoder strategy allows good consonant discrimination, but vowel discrimination is poor and the strategy is susceptible to background noise. In the current study, we assessed whether multi-band amplitude envelope expansion can effectively enhance critical vowel features, such as formants, and improve speech extraction from noise. In 32 participants with normal touch perception, tactile-only phoneme discrimination with and without envelope expansion was assessed both in quiet and in background noise. Envelope expansion improved performance in quiet by 10.3% for vowels and by 5.9% for consonants. In noise, envelope expansion improved overall phoneme discrimination by 9.6%, with no difference in benefit between consonants and vowels. The tactile vocoder with envelope expansion can be deployed in real-time on a compact device and could substantially improve clinical outcomes for a new generation of haptic hearing aids.

Improved tactile speech robustness to background noise with a dual-path recurrent neural network noise-reduction method.

Many people with hearing loss struggle to understand speech in noisy environments, making noise robustness critical for hearing-assistive devices. Recently developed haptic hearing aids, which convert audio to vibration, can improve speech-in-noise performance for cochlear implant (CI) users and assist those unable to access hearing-assistive devices. They are typically body-worn rather than head-mounted, allowing additional space for batteries and microprocessors, and so can deploy more sophisticated noise-reduction techniques. The current study assessed whether a real-time-feasible dual-path recurrent neural network (DPRNN) can improve tactile speech-in-noise performance. Audio was converted to vibration on the wrist using a vocoder method, either with or without noise reduction. Performance was tested for speech in a multi-talker noise (recorded at a party) with a 2.5-dB signal-to-noise ratio. An objective assessment showed the DPRNN improved the scale-invariant signal-to-distortion ratio by 8.6 dB and substantially outperformed traditional noise-reduction (log-MMSE). A behavioural assessment in 16 participants showed the DPRNN improved tactile-only sentence identification in noise by 8.2%. This suggests that advanced techniques like the DPRNN could substantially improve outcomes with haptic hearing aids. Low-cost haptic devices could soon be an important supplement to hearing-assistive devices such as CIs or offer an alternative for people who cannot access CI technology.

Is overshoot caused by an efferent reduction in cochlear gain?

Under certain conditions, detection of a masked tone is improved by a preceding sound ("precursor"). This phenomenon is referred to as the "temporal effect" or "overshoot". A prevalent model of overshoot, referred to as the "gain reduction model", posits that overshoot is caused by efferent reduction in cochlear gain mediated by the medial olivocochlear (MOC) bundle. The model predicts that reduction in cochlear gain will reduce masking when masking is suppressive or when masking is excitatory and the signal-to-masker ratio is high. This study was aimed at testing the validity of these predictions. It consisted of two experiments. The first experiment investigated the relative contributions of suppressive versus excitatory masking to overshoot. The signal was a short 4-kHz tone pip, and the masker and precursor were limited to contain energy either only within (-on-frequency) or only outside (off-frequency) the cochlear filter around the signal frequency. The on-frequency masker would be expected to cause mainly excitatory masking, whereas masking by the off-frequency masker would be expected to be mainly suppressive. Only the off-frequency masker and precursor yielded -significant overshoot. This suggests that measurable overshoot requires suppressive masking. The second experiment sought to quantify the effect of a precursor on cochlear -suppression more directly by measuring the amount of suppression caused by a 4.75-kHz suppressor on a lower-frequency (4-kHz) suppressee with and without a precursor present. Suppression was measured using a forward-masking paradigm. While we found large suppression and large overshoot, we found no reduction in suppression by the precursor. This is contrary to the gain reduction model. Taken together, our results indicate that measurable overshoot requires off-frequency masking and that off-frequency overshoot must be caused by a mechanism other than MOC-mediated reduction in cochlear suppression.

Improving speech perception for hearing-impaired listeners using audio-to-tactile sensory substitution with multiple frequency channels.

Cochlear implants (CIs) have revolutionised treatment of hearing loss, but large populations globally cannot access them either because of disorders that prevent implantation or because they are expensive and require specialist surgery. Recent technology developments mean that haptic aids, which transmit speech through vibration, could offer a viable low-cost, non-invasive alternative. One important development is that compact haptic actuators can now deliver intense stimulation across multiple frequencies. We explored whether these multiple frequency channels can transfer spectral information to improve tactile phoneme discrimination. To convert audio to vibration, the speech amplitude envelope was extracted from one or more audio frequency bands and used to amplitude modulate one or more vibro-tactile tones delivered to a single-site on the wrist. In 26 participants with normal touch sensitivity, tactile-only phoneme discrimination was assessed with one, four, or eight frequency bands. Compared to one frequency band, performance improved by 5.9% with four frequency bands and by 8.4% with eight frequency bands. The multi-band signal-processing approach can be implemented in real-time on a compact device, and the vibro-tactile tones can be reproduced by the latest compact, low-powered actuators. This approach could therefore readily be implemented in a low-cost haptic hearing aid to deliver real-world benefits.

Systematic Literature Review of the Epidemiological Characteristics of Pneumococcal Disease Caused by the Additional Serotypes Covered by the 20-Valent Pneumococcal Conjugate Vaccine.

Higher valency pneumococcal conjugate vaccines (PCV15 and PCV20) have been developed to address the disease burden of current non-vaccine serotypes. This review describes the epidemiological characteristics of serotypes beyond PCV13 (serotypes 8, 10A, 11A, 12F, 15B/C, 22F, and 33F; PCV20nonPCV13 serotypes). Peer-reviewed studies published between 1 January 2010 (the year PCV13 became available) and 18 August 2020 were systematically reviewed (PROSPERO number: CRD42021212875). Data describing serotype-specific outcomes on disease proportions, incidence, severity, and antimicrobial non-susceptibility were summarized for individual and aggregate PCV20nonPCV13 serotypes by age group and by type and duration of pediatric PCV immunization program. Of 1168 studies, 127 (11%) were included in the analysis. PCV20nonPCV13 serotypes accounted for 28% of invasive pneumococcal disease (IPD), although the most frequent serotypes differed between children (10A, 15B/C) and adults (8, 12F, 22F). In children, serotype 15B/C tended to be more frequently associated with pneumococcal meningitis and acute otitis media; in adults, serotype 8 was more frequently associated with pneumonia and serotype 12F with meningitis. Serotypes 10A and 15B/C in children and 11A and 15B/C in adults were often associated with severe IPD. Serotype 15B/C was also among the most frequently identified penicillin/macrolide non-susceptible PCV20nonPCV13 serotypes. These results could inform decision making about higher valency PCV choice and use.

Seroprevalence of Lyme Borreliosis in Europe: Results from a Systematic Literature Review (2005-2020).

Background: Lyme borreliosis (LB), a tick bite-transmitted infection caused by Borrelia burgdorferi sensu lato (Bbsl) complex spirochetes, is the most common tickborne disease in Europe. Studies in European countries have reported LB seroprevalence (prevalence of antibodies to Bbsl infection) and diagnostic strategies used for testing. We conducted a systematic literature review to summarize contemporary LB seroprevalence in Europe. Methods: PubMed, Embase, and CABI Direct (Global Health) databases were searched from 2005 to 2020 to identify studies reporting LB seroprevalence in European countries. Reported single-tier and two-tier test results were summarized; algorithms (standard or modified) were used to interpret final test results from studies that used two-tier testing. Results: The search yielded 61 articles from 22 European countries. Studies used a range of diagnostic testing methods and strategies (48% single-tier, 46% standard two-tier, and 6% modified two-tier). In 39 population-based studies, of which 14 were nationally representative, seroprevalence estimates ranged from 2.7% (Norway) to 20% (Finland). There was substantial heterogeneity among studies in terms of design, cohort types, periods sampled, sample sizes, and diagnostics, which limited cross-study comparisons. Nevertheless, among studies that reported seroprevalence in persons with greater exposure to ticks, LB seroprevalence was higher among these groups than in the general population (40.6% vs. 3.9%). Furthermore, among studies that used two-tier testing, general population LB seroprevalence was higher in Western Europe (13.6%) and Eastern Europe (11.1%) than in Northern Europe (4.2%) and Southern Europe (3.9%). Conclusion: Despite variations in LB seroprevalence between and within European subregions and countries, high seroprevalence was observed in certain geographic regions and particular risk groups, suggesting significant disease burden and supporting the need for improved, targeted public health interventions such as vaccination. Harmonized approaches to serologic testing and more nationally representative seroprevalence studies are needed to better understand the prevalence of Bbsl infection in Europe.

Incidence of Lyme Borreliosis in Europe from National Surveillance Systems (2005-2020).

Background: Lyme borreliosis (LB) is the most common tick-borne disease in Europe. To inform European intervention strategies, including vaccines under development, we conducted a systematic review for LB incidence. Methods: We searched publicly available surveillance data reporting LB incidence in Europe from 2005 to 2020. Population-based incidence was calculated as the number of reported LB cases per 100,000 population per year (PPY), and high LB risk areas (incidence >10/100,00 PPY for 3 consecutive years) were estimated. Results: Estimates of LB incidence were available for 25 countries. There was marked heterogeneity in surveillance systems (passive vs. mandatory and sentinel sites vs. national), case definitions (clinical, laboratory, or both), and testing methods, limiting comparison across countries. Twenty-one countries (84%) had passive surveillance; four (Belgium, France, Germany, and Switzerland) used sentinel surveillance systems. Only four countries (Bulgaria, France, Poland, and Romania) used standardized case definitions recommended by European public health institutions. Among all surveillance systems and considering any case definition for the most recently available years, national LB incidences were highest in Estonia, Lithuania, Slovenia, and Switzerland (>100 cases/100,000 PPY), followed by France and Poland (40-80/100,000 PPY), and Finland and Latvia (20-40/100,000 PPY). Incidences were lowest in Belgium, Bulgaria, Croatia, England, Hungary, Ireland, Norway, Portugal, Romania, Russia, Scotland, and Serbia (<20/100,000 PPY). At the subnational level, highest LB incidences (>100/100,000 PPY) were observed in areas of Belgium, Czech Republic, France, Germany, and Poland. Overall, on average 128,888 cases are reported annually. An estimated 202/844 million (24%) persons in Europe reside in areas of high LB incidence and 202/469 million (43.2%) persons reside in areas of high LB incidence among countries with surveillance data. Conclusion: Our review showed substantial variability in reported LB incidence across and within European countries, with highest incidences reported from the Eastern, Northern (Baltic states and Nordic countries), and Western Europe surveillance systems. Standardization of surveillance systems, including wider implementation of common case definitions, is urgently needed to interpret the range of differences in LB incidence observed across European countries.

Incidence of Lyme Borreliosis in Europe: A Systematic Review (2005-2020).

Background: Lyme borreliosis (LB) is the most common tick-borne disease in Europe, but the burden of disease is incompletely described. Methods: We conducted a systematic review across PubMed, EMBASE, and CABI Direct (Global Health) databases, from January 1, 2005, to November 20, 2020, of epidemiological studies reporting incidence of LB in Europe (PROSPERO, CRD42021236906). Results: The systematic review yielded 61 unique articles describing LB incidence (national or subnational) in 25 European countries. Substantial heterogeneity in study designs, populations sampled, and case definitions restricted data comparability. The European Union Concerted Action on Lyme Borreliosis (EUCALB)-published standardized LB case definitions were used by only 13 (21%) of the 61 articles. There were 33 studies that provided national-level LB incidence estimates for 20 countries. Subnational LB incidence was available from an additional four countries (Italy, Lithuania, Norway, and Spain). The highest LB incidences (>100 cases per 100,000 population per year [PPY]) were reported in Belgium, Finland, the Netherlands, and Switzerland. Incidences were 20-40/100,000 PPY in the Czech Republic, Germany, Poland, and Scotland and <20/100,000 PPY in Belarus, Croatia, Denmark, France, Ireland, Portugal, Russia, Slovakia, Sweden, and the United Kingdom (England, Northern Ireland, and Wales); markedly higher incidences were observed at the subnational level (up to 464/100,000 PPY in specific local areas). Conclusions: Although countries in Northern (Finland) and Western (Belgium, the Netherlands, and Switzerland) Europe reported the highest LB incidences, high incidences also were reported in some Eastern European countries. There was substantial subnational variation in incidence, including high incidences in some areas of countries with low overall incidence. This review, complemented by the incidence surveillance article, provides a comprehensive view into LB disease burden across Europe that may guide future preventive and therapeutic strategies-including new strategies on the horizon.