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Incidence rates of Lyme borreliosis, a tickborne disease attributed to infection by Borrelia species, are increasing, and limitations to existing treatments potentiate the possibility of severe outcomes. Nevertheless, there are no licensed vaccines for Lyme borreliosis prevention in humans. This study investigated the immunogenicity and safety of a booster dose of VLA15, an investigational outer surface protein A (OspA)-based Lyme borreliosis vaccine that has previously shown safety and immunogenicity when administered as a primary vaccination series, following a primary VLA15 vaccination series. We report the results of the booster phase of a randomised, observer-blinded, placebo-controlled, multicentre, phase 2 study that enrolled healthy adults aged 18–65 years from five US clinical study centres to receive 135 μg or 180 μg VLA15 or placebo at months 0, 2, and 6 in the main study phase. Participants who received 180 μg VLA15 in the main study phase and did not have relevant protocol deviations were eligible for the booster phase (months 18–30). Participants were randomly reassigned (2:1) to receive an intramuscular injection of a VLA15 booster or placebo 1 year after the completion of primary vaccination (month 18) via a randomisation list generated by an unmasked statistician with a block size of six. Individuals involved in data safety monitoring, rerandomisation, vaccine handling, and vaccine accountability were unmasked; the study sponsor and statisticians were only unmasked after analysis of data up to 1 month after booster administration. All other individuals remained masked throughout the booster phase. The outcomes for the booster phase were the immunogenicity (evaluated in the booster per-protocol population) and safety (evaluated for all participants who received the booster) of the booster dose up to month 30. The study is registered at ClinicalTrials.gov (NCT03970733) and is completed. Between Feb 4 and March 23, 2021, 58 participants (28 men and 30 women) were screened, randomly assigned, and received VLA15 (n=39) or placebo (n=19). One participant in the placebo group was lost to follow-up. The IgG geometric mean titres for each OspA serotype (serotypes 1–6) in the VLA15 group peaked at 1 month after the booster dose (1277·0 U/mL [95% CI 861·8–1892·3] to 2194·5 U/mL [1566·8–3073·7] vs 23·6 U/mL [18·1–30·8] to 36·8 U/mL [26·4–51·3] in the placebo group [p<0·0001 for all serotypes]), remained elevated at month 24 (137·4 U/mL [95·8–196·9] to 265·8 U/mL [202·9–348·2] vs 22·3 U/mL [17·7–28·0] to 29·1 U/mL [20·8–40·6] in the placebo group; p<0·0001 for all serotypes), and declined by month 30 (54·1 U/mL [38·6–75·7] to 101·6 U/mL [77·6–133·1] vs 21·9 U/mL [18·0–26·6] to 24·9 U/mL [19·0–32·6] in the placebo group; p<0·0001 for all serotypes except serotype 1 [p=0·0006]). Solicited local adverse events were reported more frequently in the VLA15 group (35 [92%, 95% CI 79–97] of 38 participants) than the placebo group (six [32%, 15–54] of 19 participants; p<0·0001) after booster vaccination. There was no significant difference in the frequency of solicited systemic adverse events between groups (20 [59%, 42–74] of 34 participants in the VLA15 group vs six [38%, 18–61] of 16 participants in the placebo group). Related unsolicited adverse events (none severe) were reported by two (5%, 1–17) of 39 participants in the VLA15 group and none (0%, 0–17) of 19 participants in the placebo group. There were no severe solicited local or systemic adverse events or deaths during the study. A booster dose of VLA15 is safe and induces substantial anamnestic immune responses against all six OspA serotypes. As with previously investigated OspA-based Lyme borreliosis vaccines, waning immune responses were observed with VLA15, and annual boosters might therefore be required. Valneva.

Increasing incidence rates, insufficient effectiveness of exposure prevention strategies, and the potential for serious outcomes despite antibiotic treatment highlight the need for a preventive vaccine against Lyme borreliosis. VLA15, an investigational Lyme borreliosis vaccine based on outer surface protein A (OspA) variants from clinically relevant Borrelia burgdorferi sensu lato genospecies in North America and Europe, has shown safety and immunogenicity in adults when administered with various three-dose schedules. We aimed to investigate the safety and immunogenicity of two-dose and three-dose schedules of VLA15 within a broader population, including children and adolescents, who are among those at increased risk of Lyme borreliosis. This randomised, observer-blind, placebo-controlled phase 2 trial is taking place at 14 clinical study centres in Lyme borreliosis-endemic areas in the USA. Healthy, eligible participants aged 5–65 years were enrolled in a 2:1:1 ratio to age cohorts of 18–65 years, 12–17 years, and 5–11 years through a staggered age-descending enrolment process. Within each age cohort, participants were randomly assigned with an electronic data capture system in a 1:1:1 ratio to receive intramuscular injections of 180 μg VLA15 at months 0, 2, and 6 (VLA15 M0-2-6 group); 180 μg VLA15 at months 0 and 6, and placebo at month 2 (VLA15 M0-6 group); or placebo at months 0, 2, and 6. Unmasked individuals included site staff and clinical research associates involved in randomisation and handling the investigational product, as well as specific individuals, both internal and external to the sponsor, who regularly reviewed trial safety data (including statisticians preparing relevant tables). All other individuals were masked; unmasking after the database snapshot for month 7 analyses for each age cohort was limited to the trial sponsor, collaboration partner, and statisticians. The primary immunogenicity endpoint was OspA serotype (ST)-specific IgG geometric mean titres (GMTs) assessed by ELISAs at month 7 (ie, 1 month after the third vaccination) and was evaluated in the per-protocol analysis set. The primary safety endpoint was the frequency of solicited local and systemic adverse events occurring within 7 days after each and any vaccination and were assessed in the safety analysis set (ie, all individuals who received at least one vaccination). This report includes safety and immunogenicity data through to month 12. This trial is ongoing but no longer recruiting participants, and is registered with Clinicaltrials.gov (NCT04801420). Between March 15, 2021, and Feb 24, 2022, 625 participants (321 [51%] female, 304 [49%] male) received one or more vaccinations and were included in the safety analysis set. Of these, 190 participants were included in the VLA15 M0-2-6 group, 187 were included in the VLA15 M0-6 group, and 208 were included in the placebo group; 40 additional VLA15 recipients could not be allocated to either VLA15 group because their vaccination schedules were non-compliant with both VLA15 groups due to missed or incorrect vaccinations; however, these individuals were included in safety analyses. OspA-specific ELISA IgG GMTs at month 7 in the overall population (aged 5–65 years) were significantly higher in the VLA15 M0-2-6 group (333·2 [95% CI 275·2–403·4; ST1] to 656·0 [560·2–768·2; ST2] units per mL) and VLA15 M0-6 group (197·3 [156·2–249·3; ST1] to 460·3 [370·6–571·8; ST2] units per mL) compared with the placebo group (21·9 [20·2–23·7; ST2] to 24·3 [22·1–26·7; ST6] units per mL; p<0·0001 for all comparisons); GMTs were also significantly higher in the VLA15 M0-2-6 group than in the VLA15 M0-6 group (all p<0·0001 except for ST2 [p=0·0010] and ST3 [p=0·011]). Among VLA15 recipients, GMTs were highest in children followed by adolescents and then adults. Solicited local adverse events after any vaccination occurred more frequently among VLA15 recipients (M0-2-6, 178 [94%; 95% CI 89–96] of 190; M0-6, 176 [94%; 90–97] of 187) than placebo recipients (71 [34%; 28–41] of 208; p<0·0001 for both comparisons); the same was true for solicited systemic adverse events (M0-2-6, 128 [67%; 95% CI 60–74] of 190, p=0·0015 vs placebo; M0-6, 128 [68%; 61–75] of 187, p=0·0007 vs placebo; placebo, 107 [51%; 45–58] of 208). Most solicited adverse events were mild or moderate in severity; none was grade 4. There were no significant differences in the frequencies of unsolicited adverse events, related unsolicited adverse events, unsolicited serious adverse events (serious adverse events), and adverse events of special interest across groups in the overall population. None of the severe unsolicited adverse events, serious adverse events, or adverse events of special interest were considered related to vaccination and no deaths occurred through to month 12 of the trial. These findings confirm previously observed safety and immunogenicity profiles of VLA15 in adults and extend them to children aged 5 years and older and adolescents. The greater immunogenicity of VLA15 among children and adolescents might translate to increased flexibility in the real-world clinical setting. Pfizer and Valneva.

Tickborne diseases (TBDs) such as Lyme disease result in ≈500,000 diagnoses annually in the United States. Various methods can reduce the abundance of ticks at small spatial scales, but whether these methods lower incidence of TBDs is poorly understood. We conducted a randomized, replicated, fully crossed, placebo-controlled, masked experiment to test whether 2 environmentally safe interventions, the Tick Control System (TCS) and Met52 fungal spray, used separately or together, affected risk for and incidence of TBDs in humans and pets in 24 residential neighborhoods. All participating properties in a neighborhood received the same treatment. TCS was associated with fewer questing ticks and fewer ticks feeding on rodents. The interventions did not result in a significant difference in incidence of human TBDs but did significantly reduce incidence in pets. Our study is consistent with previous evidence suggesting that reducing tick abundance in residential areas might not reduce incidence of TBDs in humans.

Rising Lyme borreliosis incidence rates, potential for severe outcomes, and limitations in accurate and timely diagnosis for treatment initiation suggest the need for a preventive vaccine; however, no vaccine is currently available for human use. We performed two studies in adults to optimise the dose level and vaccination schedule for VLA15, an investigational Lyme borreliosis vaccine targeting outer surface protein A (OspA) serotypes 1–6, which are associated with the most common pathogenic Borrelia species in Europe and North America. Both randomised, observer-blind, placebo-controlled, multicentre phase 2 studies included participants aged 18–65 years without recent history of Lyme borreliosis or tick bites. Study one was conducted at nine clinical research and study centre sites in the USA (n=6), Germany (n=2), and Belgium (n=1); study two was conducted at five of the study one US sites. Based on a randomisation list created by an unmasked statistician for each study, participants were randomly assigned via an electronic case report form randomisation module to receive 90 μg (study one only), 135 μg, or 180 μg VLA15 or placebo by intramuscular injection at months 0, 1, and 2 (study one) or 0, 2, and 6 (study two). Study one began with a run-in phase to confirm safety, after which the Data Safety Monitoring Board recommended the removal of the 90 μg group and continuation of the study. In the study one run-in phase, randomisation was stratified by study site, whereas in the study one main phase and in study two, randomisation was stratified by study site, age group, and baseline B burgdorferi (sensu lato) serostatus. All individuals were masked, other than staff involved in randomisation, vaccine preparation or administration, or safety data monitoring. The primary endpoint for both studies was OspA-specific IgG geometric mean titres (GMTs) at 1 month after the third vaccination and was evaluated in the per-protocol population. Safety endpoints were evaluated in the safety population: all participants who received at least one vaccination. Both studies are registered at ClinicalTrials.gov (study one NCT03769194 and study two NCT03970733) and are completed. For study one, 573 participants were screened and randomly assigned to treatment groups between Dec 21, 2018, and Sept, 26, 2019. For study two, 248 participants were screened and randomly assigned between June 26 and Sept 3, 2019. In study one, 29 participants were assigned to receive 90 μg VLA15, 215 to 135 μg, 205 to 180 μg, and 124 to placebo. In study two, 97 participants were assigned to receive 135 μg VLA15, 100 to 180 μg, and 51 to placebo. At 1 month after the third vaccination (ie, month 3), OspA-specific IgG GMTs in study one ranged from 74·3 (serotype 1; 95% CI 46·4–119·0) to 267·4 units per mL (serotype 3; 194·8–367·1) for 90 μg VLA15, 101·9 (serotype 1; 87·1–119·4) to 283·2 units per mL (serotype 3; 248·2–323·1) for 135 μg, and 115·8 (serotype 1; 98·8–135·7) to 308·6 units per mL (serotype 3; 266·8–356·8) for 180 μg. In study two, ranges at 1 month after the third vaccination (ie, month 7) were 278·5 (serotype 1; 214·9–361·0) to 545·2 units per mL (serotype 2; 431·8–688·4) for 135 μg VLA15 and 274·7 (serotype 1; 209·4–360·4) to 596·8 units per mL (serotype 3; 471·9–754·8) for 180 μg. Relative to placebo, the VLA15 groups had more frequent reports of solicited local adverse events (study one: 94%, 95% CI 91–96 vs 26%, 19–34; study two: 96%, 93–98 vs 35%, 24–49 after any vaccination) and solicited systemic adverse events (study one: 69%, 65–73 vs 43%, 34–52; study two: 74%, 67–80 vs 51%, 38–64); most were mild or moderate. In study one, unsolicited adverse events were reported by 52% (48–57) of participants in the VLA15 groups and 52% (43–60) of those in the placebo groups; for study two these were 65% (58–71) and 69% (55–80), respectively. Percentages of participants reporting serious unsolicited adverse events (study one: 2%, 1–4; study two: 4%, 2–7) and adverse events of special interest (study one: 1%, 0–2; study two: 1%, 0–3) were low across all groups. A single severe, possibly related unsolicited adverse event was reported (worsening of pre-existing ventricular extrasystoles, which resolved after change of relevant concomitant medication); no related serious adverse events or deaths were reported. VLA15 was safe, well tolerated, and elicited robust antibody responses to all six OspA serotypes. These findings support further clinical development of VLA15 using the 180 μg dose and 0-2-6-month schedule, which was associated with the greatest immune responses. Valneva.

This large trial shows the efficacy of a single, prophylactic dose of doxycycline to prevent Lyme disease. Lyme disease is transmitted by the bite of an Ixodes scapularis tick and is the most common vector-borne disease in the United States. 1 This infection may be prevented by vaccination. 2 , 3 However, the vaccine's general acceptance is likely to be limited by its cost (a cost to the pharmacist of $61.25 per dose) and the need for multiple doses to achieve and maintain protection. 2 , 3 In addition, the vaccine is less than 100 percent effective and is currently approved only for persons 15 to 70 years of age. 3 Antimicrobial prophylaxis for persons with I. scapularis tick bites may be a . . .

As the prevalence of Lyme disease increases across Canada, it is imperative that the educational needs of at-risk groups be identified. The current study compared the level of knowledge and the knowledge needs about Lyme disease among individuals that spend time outdoors for work and for recreational purposes. Between December 2018 and February 2019, a survey was distributed to outdoor organizations across New Brunswick, Canada. Within the current sample of 137 individuals, 36% spent time outdoors for their occupation and 64% for recreational activities. Results showed no significant difference between these groups with regard to their level of knowledge, perceived efficacy and performance of various methods of prevention, and educational needs. Overall, the entire sample reported a low level of knowledge about Lyme disease. Participants perceived each prevention behavior to be at least somewhat effective, and behaviors perceived to be more effective were more likely to be carried out, but the performance of the behaviors varied. The most frequently performed behaviors included wearing long pants and protective footwear. Participants identified several aspects of Lyme disease about which they would like to have more information. The findings call attention to the specific needs of at-risk groups that must be considered when developing educational interventions.

Lyme borreliosis develops in 1–5% of individuals bitten by ticks, but with a diagnostic gap affecting up to 30% of patients, a broadly applicable pharmacological prevention strategy is needed. Topical azithromycin effectively eradicated Borrelia burgdorferi sensu lato from the skin in preclinical studies. We assessed its efficacy in human beings. In this randomised, double-blind, placebo-controlled, multicentre trial done in 28 study sites in Germany and Austria, adults were equally assigned to receive topical 10% azithromycin or placebo twice daily for 3 consecutive days, within 72 h of a tick bite being confirmed. Randomisation numbers, which were stratified by study site, were accessed in study centres via an interactive voice-response system, by pharmacists not involved in the study. The primary outcome was the number of treatment failures, defined as erythema migrans, seroconversion, or both, in participants who were seronegative at baseline, had no further tick bites during the study, and had serology results available at 8 weeks (intention-to-treat [ITT] population). This study is registered with EudraCT, number 2011-000117-39. Between July 7, 2011, and Dec 3, 2012, 1371 participants were randomly assigned to treatment, of whom 995 were included in the ITT population. The trial was stopped early because an improvement in the primary endpoint in the group receiving azithromycin was not reached. At 8 weeks, 11 (2%) of 505 in the azithromycin group and 11 (2%) of 490 in the placebo group had treatment failure (odds ratio 0·97, 95% CI 0·42–2·26, p=0·47). Topical azithromycin was well tolerated. Similar numbers of patients had adverse events in the two groups (175 [26%] of 505 vs 177 [26%] of 490, p=0·87), and most adverse events were mild. Topical azithromycin was well tolerated and had a good safety profile. Inclusion of asymptomatic seroconversion into the primary efficacy analysis led to no prevention effect with topical azithromycin. Adequately powered studies assessing only erythema migrans should be considered. A subgroup analysis in this study suggested that topical azithromycin reduces erythema migrans after bites of infected ticks. Ixodes AG.

Because risk perceptions can affect protective behavior and protective behavior can affect risk perceptions, the relations between these 2 constructs are complex and incorrect tests often lead to invalid conclusions. To discuss and carry out appropriate tests of 3 easily confused hypotheses: (a). the behavior motivation hypothesis (perceptions of personal risk cause people to take protective action), (b). the risk reappraisal hypothesis (when people take actions thought to be effective, they lower their risk perceptions), and (c). the accuracy hypothesis (risk perceptions accurately reflect risk behavior). Longitudinal study with an initial interview just after the Lyme disease vaccine was made publicly available and a follow-up interview 18 months later. Random sample of adult homeowners (N = 745) in 3 northeastern U.S. counties with high Lyme disease incidence. Lyme disease vaccination behavior and risk perception were assessed. All 3 hypotheses were supported. Participants with higher initial risk perceptions were much more likely than those with lower risk perceptions to get vaccinated against Lyme disease (OR = 5.81, 95% CI 2.63-12.82, p <.001). Being vaccinated led to a reduction in risk perceptions, chi2(1, N = 745) = 30.90, p <.001, and people vaccinated correctly believed that their risk of future infection was lower than that of people not vaccinated (OR =.44, 95% CI.21-.91, p <.05). The behavior motivation hypothesis was supported in this longitudinal study, but the opposite conclusion (i.e., that higher risk led to less protective behavior) would have been drawn from an incorrect test based only on cross-sectional data. Health researchers should take care in formulating and testing risk-perception-behavior hypotheses.

Background Zoonoses are a growing international threat interacting at the human-animal-environment interface and call for transdisciplinary and multi-sectoral approaches in order to achieve effective disease management. The recent emergence of Lyme disease in Quebec, Canada is a good example of a complex health issue for which the public health sector must find protective interventions. Traditional preventive and control interventions can have important environmental, social and economic impacts and as a result, decision-making requires a systems approach capable of integrating these multiple aspects of interventions. This paper presents the results from a study of a multi-criteria decision analysis (MCDA) approach for the management of Lyme disease in Quebec, Canada. MCDA methods allow a comparison of interventions or alternatives based on multiple criteria. Methods MCDA models were developed to assess various prevention and control decision criteria pertinent to a comprehensive management of Lyme disease: a first model was developed for surveillance interventions and a second was developed for control interventions. Multi-criteria analyses were conducted under two epidemiological scenarios: a disease emergence scenario and an epidemic scenario. Results In general, we observed a good level of agreement between stakeholders. For the surveillance model, the three preferred interventions were: active surveillance of vectors by flagging or dragging, active surveillance of vectors by trapping of small rodents and passive surveillance of vectors of human origin. For the control interventions model, basic preventive communications, human vaccination and small scale landscaping were the three preferred interventions. Scenarios were found to only have a small effect on the group ranking of interventions in the control model. Conclusions MCDA was used to structure key decision criteria and capture the complexity of Lyme disease management. This facilitated the identification of gaps in the scientific literature and enabled a clear identification of complementary interventions that could be used to improve the relevance and acceptability of proposed prevention and control strategy. Overall, MCDA presents itself as an interesting systematic approach for public health planning and zoonoses management with a “One Health” perspective.

Tick-borne diseases are a growing threat to public health in the United States, especially among outdoor workers who experience high occupational exposure to ticks. Long-lasting permethrin-impregnated clothing has demonstrated high initial protection against bites from blacklegged ticks, Ixodes scapularis Say (Acari: Ixodidae), in laboratory settings, and sustained protection against bites from the lone star tick, Amblyomma americanum (L.) (Acari: Ixodidae), in field tests. However, long-lasting permethrin impregnation of clothing has not been field tested among outdoor workers who are frequently exposed to blacklegged ticks. We conducted a 2-yr randomized, placebo-controlled, double-blinded trial among 82 outdoor workers in Rhode Island and southern Massachusetts. Participants in the treatment arm wore factory-impregnated permethrin clothing, and the control group wore sham-treated clothing. Outdoor working hours, tick encounters, and bites were recorded weekly to assess protective effectiveness of long-lasting permethrin-impregnated garments. Factory-impregnated clothing significantly reduced tick bites by 65% in the first study year and by 50% in the second year for a 2-yr protective effect of 58%. No significant difference in other tick bite prevention method utilization occurred between treatment and control groups, and no treatment-related adverse outcomes were reported. Factory permethrin impregnation of clothing is safe and effective for the prevention of tick bites among outdoor workers whose primary exposure is to blacklegged ticks in the northeastern United States.