Rabies Pre-exposure Prophylaxis Research Articles

Understanding the journey towards rabies vaccination for travellers: Results of a cross-sectional survey with patients and providers in the US, Germany, Sweden, and Switzerland

BackgroundAlthough cases of rabies in international travellers are uncommon, they are a fatal risk which can be alleviated through vaccination prior to travel. As international travel recovers post-COVID, it is vital that travellers are made aware of the risk of rabies when travelling to endemic countries and supported to receive the vaccine when eligible. MethodsOnline surveys were conducted in the US, Germany, Sweden and Switzerland between November 2022–January 2023 with both patients and healthcare providers (HCPs). Eligibility criteria for patients included those eligible for rabies pre-exposure prophylaxis (PrEP) due to travel location and activity; HCPs had to be providers of travel vaccinations. In both surveys, questions were asked about discussion of rabies vaccination, decision of whether to administer a rabies vaccine, recommendation to get the rabies vaccine, and final decision to get a vaccine. ResultsThe final patient sample included n = 1557 patients who were eligible for rabies pre-exposure prophylaxis (US n = 504, Germany n = 353, Sweden n = 350, Switzerland n = 350) and n = 219 HCPs (US n = 75, Germany n = 75, Sweden n = 32, Switzerland n = 37). Although all patients in the sample were eligible for rabies vaccination, only 15 % felt they were at risk of getting rabies, and only 18 % received the rabies vaccine before their trip. HCPs reported discussing PrEP and/or PrEP and PEP with 30 % of patients presenting for travel vaccination advice, on average. ConclusionsAwareness and perception of rabies risk, and lack of consistent HCP discussion of the need for rabies PrEP may be major barriers to uptake of the vaccine for patients who are eligible to receive it.

Assessing the immunogenicity of pre-exposure rabies prophylaxis and interchangeability of booster doses in a cohort of high-risk individuals

Assessing the immunogenicity of pre-exposure rabies prophylaxis and interchangeability of booster doses in a cohort of high-risk individuals

Burden of dog bite injuries and wound management practices to prevent rabies among dog owners.

Despite members of dog-owning families being at a higher risk of dog bites owing to their proximity to dogs in their household, there are hardly any studies from India which focus on the burden of dog bites among them and their rabies control and prevention practices. This study aimed to estimate the burden of dog bites among dog owners and their wound management practices to prevent rabies. A cross-sectional study was conducted among pet dog owners in a high-end housing society of National Capital Region of Delhi. A pre-tested and pre-validated schedule was used to collect data by consecutive sampling through community survey. Data were analyzed using R software. The incidence of dog bites and the status of rabies prevention practices adopted by the participants are presented as proportions. Chi-square test was applied to compare proportions. A total of 100 families were studied, which covered 355 family members. The incidence of dog bites in the past 1 year was found to be 44/355, 12.4% (95% confidence interval 9.2-16.3%). Pet dogs were responsible for 31/44 (70.5%) bites. Among 44 dog bite incidents, 30 (68.2%) reported taking any injection after the incident, and 10 (22.7%) reported receiving an anti-rabies vaccine. Only six out of 100 families reported at least one family member covered by rabies pre-exposure prophylaxis. The incidence of dog bites among the dog owners was high. The rabies pre- and post-exposure prophylaxis practices adopted by the participants were found to be inadequate.

Can a single visit rabies pre-exposure prophylaxis eliminate the need for rabies immunoglobulin in last minute travellers?

Highlight Current limited evidence indicate that one-visit intradermal/intramuscular rabies pre-exposure prophylaxis is effective in priming the immune system, followed by two-visit (on days 0 and 3) intramuscular post-exposure prophylaxis to rapidly boost antibodies to adequate levels in the event of potential rabies exposure.

Expert consensus on pre-exposure rabies prophylaxis

Pre-exposure rabies prophylaxis, also known as immunoprophylaxis before exposure to rabies, refers to preventive rabies vaccination for individuals at risk of rabies infection before rabies exposure, which is one of the important strategies for rabies prevention. Pre-exposure rabies prophylaxis can reduce the risk of individual rabies and reduce the cost of post-exposure prophylaxis by establishing an immunologic barrier in advance and the memory immune response after the booster. In view of the current situation that clinicians in China have relatively insufficient knowledge of pre-exposure rabies prophylaxis, the Rabies Prevention and Control Committee of the Chinese Preventive Medicine Association and Animal Injury Treatment Branch of China Association for Disaster and Emergency Rescue Medicine organized domestic experts in relevant fields to write this expert consensus in accordance with the latest guidelines, expert consensus, and the latest clinical evidence. This consensus describes the concept and significance of pre-exposure rabies prophylaxis, immunization procedures and cost-effectiveness respectively, and puts forward recommendations on pre-exposure rabies prophylaxis strategies. It is hoped that this consensus can improve clinicians' understanding of pre-exposure rabies prophylaxis and increase the rate of pre-exposure rabies prophylaxis among people at high risk of exposure in China.

Boostability after single-visit pre-exposure prophylaxis with rabies vaccine: a randomised controlled non-inferiority trial

After rabies pre-exposure prophylaxis (PrEP) vaccination, scarcely available rabies immunoglobulins are not required for post-exposure prophylaxis (PEP). However, PrEP is not sufficiently accessible as it is cost-intensive and time-intensive. This study investigates whether rabies PrEP schedules can be shortened to one visit, removing some of these barriers. In a block-randomised (2:2:2:1) controlled, multicentre non-inferiority trial, healthy adult travellers (aged 18-50 years and >50 years) were randomly assigned to (A) single-visit intramuscular (1·0 mL); (B) single-visit intradermal (0·2 mL); (C) standard two-visit intramuscular (1·0 mL; day 0 and 7) PrEP; or (D) no rabies vaccination. 6 months later, participants received simulated intramuscular rabies PEP (1·0 mL; day 0 and 3). Rabies virus neutralising antibody (RVNA) concentrations were measured repeatedly. The primary outcome was the fold increase in geometric mean RVNA concentrations between day 0 and 7 after simulated PEP for all participants. The two main comparisons of this primary outcome are between the standard two-visit schedule and the one-visit intramuscular schedule, and between the standard two-visit schedule and the one-visit intradermal schedule. The non-inferiority margin was 0·67. This study is registered with EudraCT, 2017-000089-31. Between May 16, 2018, and March 26, 2020, 288 healthy adult travellers were randomly assigned and 214 participants were evaluated for the primary outcome. Single-visit intramuscular rabies PrEP induced an anamnestic antibody response non-inferior compared with the two-visit intramuscular schedule; single-visit intradermal PrEP did not. The fold increases in the single-visit intramuscular and the single-visit intradermal schedule were 2·32 (95% CI [1·43-3·77]) and 1·11 (0·66-1·87) times as high as the fold increase in the standard schedule, respectively. No vaccine-related serious adverse events were observed. Adverse events related to vaccination were mostly mild. Single intramuscular rabies vaccination can effectively prime travellers (aged 18-50 years), and potentially other populations, and could replace current standard two-visit rabies vaccination as PrEP. ZonMW. For the Dutch translation of the abstract see Supplementary Materials section.

Immune response after rabies pre-exposure prophylaxis and a booster dose in Australian bat carers.

Periodic vaccination against rabies is essential for individuals at continuing risk of rabies exposure. There is limited evidence on long-term immunogenicity after a 3-dose intramuscular (3IM) pre-exposure prophylaxis (PrEP) and single IM booster dose, thus current guideline recommendations differ in the interval for serology tests following PrEP and boosters. This study investigated post-PrEP and post-booster persistence of antibodies in Australian bat carers. Bat carers who received 3IM PrEP/booster doses and had post-PrEP/booster serology test results were included. The proportion of antibody-negative (<0.5 EU/mL) individuals after PrEP/booster dose were examined. Three hundred and five participants (65.6% females, median age at PrEP 43.1 years) were included. The proportion who were antibody-negative varied depending on the time between 3IM PrEP and the serology test: 8.0% <1 year, 29.8% 1-2 years, 21.2% 2-3 years and 7.7% >3 years. Ninety-one participants receiving booster doses were further assessed. Only one participant was antibody-negative at >3 years after receiving one IM booster dose. Our findings support that a serology test should be performed 1 year after 3IM PrEP, followed by first booster if required. Rabies antibodies persist for many years after receiving the booster doses. The interval between subsequent serology tests and the first booster dose should be no longer than 3 years. Future studies are required to provide more insight into the most appropriate timing of subsequent boosters.

Immunogenicity and 1-year boostability of a three-dose intramuscular rabies pre-exposure prophylaxis schedule in adults receiving immunosuppressive monotherapy: a prospective single-centre clinical trial.

For immunocompromised patients (ICPs), administration of rabies immunoglobulins (RIG) after exposure is still recommended regardless of prior vaccination, due to a lack of data. We aimed to assess the 1-year boostability of a three-dose rabies pre-exposure prophylaxis (PrEP) schedule in individuals using immunosuppressive monotherapy. In this prospective study, individuals on immunosuppressive monotherapy with a conventional immunomodulator (cIM) or a TNF-alpha inhibitor (TNFi) for a chronic inflammatory disease received a three-dose intramuscular PrEP schedule (days 0,7,21-28) with 1mL Rabipur®, followed by a two-dose simulated post-exposure prophylaxis (PEP) schedule (days 0,3) after 12months. Rabies neutralizing antibodies were assessed at baseline, on day 21-28 (before the third PrEP dose), day 60, month 12 and month 12 + 7days. The primary outcome was 1-year boostability, defined as the proportion of patients with a neutralizing antibody titre of ≥ 0.5IU/mL at month 12 + 7days. Secondary outcomes were geometric mean titres (GMTs) and factors associated with the primary endpoint. We included 56 individuals, of whom 52 completed the study. The 1-year boostability was 90% (47/52) with a GMT of 6.16 (95% CI 3.83-9.91). All participants seroconverted at some point in the study. Early response to PrEP (at day 21-28) was significantly associated with 100% boostability (Odds Ratio 51; 95% confidence interval [5.0-6956], P < 0.01). The vaccination schedule was safe and well tolerated. No vaccine-related serious adverse events occurred. In patients using immunosuppressive monotherapy, a three-dose rabies PrEP schedule followed by a two-dose PEP schedule is immunogenic, with all patients seroconverting at some point in the study. Although boostability 7days after PEP was not 100%, nobody would wrongly be denied RIG when only administered to those who responded early to PrEP while reducing the administration of RIG by 73%.

One-week intramuscular or intradermal pre-exposure prophylaxis with human diploid cell vaccine or Vero cell rabies vaccine, followed by simulated post-exposure prophylaxis at one year: A phase III, open-label, randomized, controlled trial to assess immunogenicity and safety

Shorter rabies pre-exposure prophylaxis (PrEP) regimens may offer improved convenience and feasibility over classic 3-week regimens, for example in regions with poor access to vaccines or for travelers to rabies-endemic regions. In this multicenter, open-label, controlled trial, 570 healthy participants aged 2–64 years were randomized to receive: 1-week PrEP (vaccination days [D]0 and 7; Group 1) or classic 3-week PrEP regimen (D0, D7, and D21; Group 2) with one 1.0 mL intramuscular [IM] dose of human diploid cell culture rabies vaccine (HDCV) at each visit; 1-week PrEP with two 0.1 mL intradermal (ID) HDCV doses at each visit (Group 3); or 1-week PrEP with one 0.5 mL IM dose (Group 4) or two 0.1 mL ID doses (Group 5) of Vero cell rabies vaccine (PVRV) at each visit. Participants received simulated post-exposure prophylactic (PEP) vaccination (two IM or ID doses of HDCV or PVRV three days apart) one year later. Rabies virus neutralizing antibody titers and seroconversion (titers ≥ 0.5 IU/mL) rates were assessed 14 days and up to 1 year post-PrEP, and pre- and post-PEP. Safety was assessed throughout the study. Seroconversion rates were high 14 days post-last PrEP injection (ranging from 96.7 % to 97.2 % across groups 1, 3–5; 1-week PrEP) and reached 100 % in Group 2 (3-week PrEP). Non-inferiority of Group 1 versus Group 2 in terms of seroconversion rates 14 days post-last PrEP injection (primary objective) was not demonstrated. After simulated PEP, all groups showed rapid and robust immune responses, with all but one participant achieving seroconversion (titers ≥ 0.5 IU/mL). There were no safety concerns, and the tolerability profiles of the vaccines were similar across the groups.A 1-week, IM or ID PrEP regimen with HDCV or PVRV provided efficacious priming, enabling rapid robust anamnestic responses to simulated PEP 1 year later across age groups.ClinicalTrials.gov number: NCT03700242.WHO Universal Trial Number (UTN): U1111-1183-5743.

Safety and immunogenicity of a simian-adenovirus-vectored rabies vaccine: an open-label, non-randomised, dose-escalation, first-in-human, single-centre, phase 1 clinical trial

Rabies kills around 60 000 people each year. ChAdOx2 RabG, a simian adenovirus-vectored rabies vaccine candidate, might have potential to provide low-cost single-dose pre-exposure rabies prophylaxis. This first-in-human study aimed to evaluate its safety and immunogenicity in healthy adults. We did a single-centre phase 1 study of ChAdOx2 RabG, administered as a single intramuscular dose, with non-randomised open-label dose escalation at the Centre for Clinical Vaccinology and Tropical Medicine, Oxford, UK. Healthy adults were sequentially allocated to groups receiving low (5 × 109 viral particles), middle (2·5 × 1010 viral particles), and high doses (5 x 1010 viral particles) of ChAdOx2 RabG and were followed up to day 56 after vaccination. The primary objective was to assess safety. The secondary objective was to assess immunogenicity with the internationally standardised rabies virus neutralising antibody assay. In an optional follow-up phase 1 year after enrolment, we measured antibody maintenance then administered a licensed rabies vaccine (to simulate post-exposure prophylaxis) and measured recall responses. The trial is registered with ClinicalTrials.gov, NCT04162600, and is now closed to new participants. Between Jan 2 and Oct 28, 2020, 12 adults received low (n=3), middle (n=3), and high doses (n=6) of ChAdOx2 RabG. Participants reported predominantly mild-to-moderate reactogenicity. There were no serious adverse events. Virus neutralising antibody concentrations exceeded the recognised correlate of protection (0·5 IU/mL) in three middle-dose recipients and six high-dose recipients within 56 days of vaccination (median 18·0 IU/mL). The median peak virus neutralising antibody concentrations within 56 days were 0·7 IU/mL (range 0·0-54·0 IU/mL) for the low-dose group, 18·0 IU/mL (0·7-18·0 IU/mL) for the middle-dose group, and 18·0 IU/mL (6·0-486·0 IU/mL) for the high-dose group. Nine participants returned for the additional follow-up after 1 year. Of these nine participants, virus neutralising antibody titres of more than 0·5 IU/mL were maintained in six of seven who had received middle-dose or high-dose ChAdOx2 RabG. Within 7 days of administration of the first dose of a licensed rabies vaccine, nine participants had virus neutralising antibody titres of more than 0·5 IU/mL. In this study, ChAdOx2 RabG showed an acceptable safety and tolerability profile and encouraging immunogenicity, supporting further clinical evaluation. UK Medical Research Council and Engineering and Physical Sciences Research Council.

Two-year immunogenicity of a pre-exposure rabies vaccination administered as a two-dose schedule.

In a young and healthy population, immunogenicity at two years of a rabies PrEP in a two-dose IM schedule is satisfying. This regimen may be appropriate in people occupationally exposed to RABV, or traveling to highly endemic countries, provided they receive two booster doses in case of exposure.

Long-term persistence of antibodies and boostability after rabies intradermal pre-exposure prophylaxis.

Currently, there is limited data on long-term persistence of antibodies and boostability of intradermal (ID) rabies pre-exposure prophylaxis (PrEP) schedules. This study investigated travellers who received a primary ID PrEP schedule at least 5years previously to determine the persistence of antibodies and subsequent antibody response after one 0.1-ml ID booster dose. Adults (age ≥ 18years) who had previously received ID PrEP at a specialist travel medicine clinic in Brisbane, Australia were included. At Day 0, blood was collected for serology and one dose of 0.1-ml ID rabies vaccine (Verorab®) was administered. At Day 7, serology was repeated. At Day 14, participants were given results and enquired if they experienced adverse events following immunization (AEFIs). Antibodies were measured using Platelia Rabies II ELISA; levels ≥0.5 EU/mL were considered antibody-positive. 158 participants were included [64.6% female, median age at enrolment 56.4years, interquartile range (IQR) 42.4-65.2years], and median time since the primary ID PrEP was 8.5years (IQR 6.9-11.7years). The majority of participants (82.3%) were antibody-positive at Day 0. The proportion of participants who were antibody-positive at Day 0 was higher among those who were younger at primary vaccination (87.0% if aged<50years, 75.8% of aged ≥50years). The proportion of participants who were antibody-positive declined as median time since primary vaccination increased, though the trend was not statistically significant (p-trend = 0.187). All except one participant (99.4%) were antibody-positive after one ID booster dose. AEFIs were reported by 42.4% of participants and were mainly mild. Rabies antibodies persist for many years after ID PrEP and can be rapidly boosted with a single ID dose. Future studies are needed to confirm that ID PrEP primes the immune system sufficiently so that boosters are not routinely needed, and only given in the event of a rabies-prone exposure.

Rabies Exposures in International Travelers: A Review

Up to 2% of international travelers report an animal contact which raises the possibility of rabies exposure. Travelassociated rabies is rare; however, infection is essentially fatal once expressed yet death is preventable by timely postexposure prophylaxis (PEP) -- thorough wound cleansing, local injection of rabies immune globulin (RIG) and a vaccine series. To begin to provide initial guidance if contacted by a patient potentially exposed to rabies while abroad, key questions the clinician should ask in a stepwise fashion are: (1) What animal was involved? (2) What was the actual exposure and in what country did it occur? (3) How many wounds, location (including mucosal surfaces), severity and what wound care performed? (4) Is the traveler immunocompromised? (5) Was either preexposure rabies prophylaxis or PEP previously given? (6) Is rabies PEP clearly indicated and/or is expert advice and guidance needed? (7) Where is the traveler, what level of acceptable care is accessible and how long to access it? And (8) What formulation of rabies immune globulin and vaccine is available and what injection protocol is in-use? Framed here by experience with four travelers, answers to these and additional questions set the stage for the clinician’s initial guidance and action. The goal and clinical relevance of this review is straightforward – to maximize the opportunity for travelers who warrant rabies PEP to promptly receive it.

Rabies Vaccine Disposition: Trends in Vaccination Among Israeli Travelers.

Travelers are a risk-group for rabies; however, few are protected. We describe changes in pre-travel vaccination rates and post-travel referrals after animal contact. We conducted a nationwide, retrospective study for 2014-2018. The ratio of rabies vaccine courses distributed to travelers and the number of Israeli-tourist-entries to endemic countries was calculated, as was the proportion of travelers referred to a post-travel clinic after animal contact. During the study period, the ratio of pre-travel vaccine courses distributed nationally to outgoing tourism to endemic countries was stable at ≈0.7%; 13% of 256,969 pre-travel consultations included recommendation for rabies vaccination. Backpackers were more likely to be immunized (40.2%) than business travelers (4.4%) or travelers planning organized/high-end travel (2.0%). However, rates of rabies vaccination among backpackers showed a decline during the study period. Post-travel referrals after animal contact were stable at 2% of all referrals; most were exposed in Asia (69.5%) and 51% were bitten by dogs. Only 38% received post-exposure prophylaxis abroad. We conclude that only a minority of Israeli travelers, including backpackers, receive rabies pre-exposure prophylaxis. The proportion of travelers with potentially rabid animal contact is not decreasing; however, many exposed travelers do not receive post-exposure prophylaxis during travel. Because rabies control programs have been compromised in endemic countries during the COVID-19 pandemic, the need to provide rabies protection to travelers has become more urgent. After the ACIP's adoption of the World Health Organization's (WHO) 2-dose regimen, a revision of current vaccine guidelines is required to provide a simplified, more inclusive rabies vaccine policy.

Immunogenicity of 2-dose pre-exposure rabies vaccine co-administered with quadrivalent influenza vaccine in children

ObjectivesThe World Health Organization recommends a 2-dose rabies pre-exposure prophylaxis (PrEP) regimen. This study aimed to compare the immunogenicity of rabies PrEP regimens co-administered with inactivated quadrivalent influenza vaccine (IIV4). MethodsChildren aged 3 to 9 years were randomly assigned (2:2:1) to receive 0.25 mL of chromatographically purified Vero cell rabies vaccine intramuscularly: Group A at day 0, 7 with IIV4; Group B at day 0, 28 with IIV4; Group C at day 0, 7. A booster-dose of CPRV was given on day 365. Primary outcome was the proportion of children with protective rabies virus neutralizing antibody (RVNA) ≥ 0.5 IU/mL, on day 42 and 7 days post-booster. ResultsFrom November 2019 to January 2020; 100 children with a median age (IQR) of 5.4 years (4.8-7.3) were enrolled. All participants achieved protective RVNA titers on day 42 and 7-days post booster. Geometric mean titers (GMT) at day 42 were Group A, 8.98(95%CI 7.06-11.42); Group B, 23.89(95%CI 19.33-29.51); Group C, 9.94(95%CI 7.03-14.06). Likewise, RVNA GMT at 7 days post-booster were Group A, 42.53(95%CI 18.41-66.64); Group B, 23.19(95%CI 17.28-29.10); Group C, 57.75 (95%CI 35.86-79.67). ConclusionsThe 2-dose PrEP regimen of rabies vaccine produces adequate immune response either 0,7 or 0, 28 regimens.

Knowledge, attitudes and perceptions about rabies among the people in the community, healthcare professionals and veterinary practitioners in Bangladesh

It is crucial to explore knowledge, attitudes and perceptions (KAP) about rabies among the people in the community, the personnel dealing with animal bite management and suspected rabies patients, including humans and animals, to facilitate intervention in improving rabies elimination strategies. In 2016, we conducted an interactive face-to-face survey in three different districts of Bangladesh to understand the extent of KAP towards rabies in the community peoples (CPs), human healthcare professionals (HCPs) and veterinary practitioners (VPs). A set of prescribed questions was employed to measure what proportion of each group possessed sufficient knowledge, positive attitudes and adequate perceptions about rabies. A total of 1133 CPs, 211 HCPs and 168 VPs were interviewed by using a standard questionnaire comprising both closed and open-ended questions. Of the CPs, 49% identified the disease correctly (i.e. rabies is caused by an animal bite or a scratch). Only 29% of the CPs were aware that a wound should be washed immediately with soap and water after an animal bite or a scratch. However, only 49% of the CPs, 65% of the HCPs and 60% of the VPs felt that it is important to consult a physician and receive post-exposure vaccine as the first line of treatment following an animal exposure. Among the HCPs, 23% of the respondents did not possess sufficient knowledge about animal bites as categorised by the World Health Organization (WHO), and 12% of the respondents did not possess the knowledge on how to manage an animal bite properly. Out of 52% of the VPs who previously treated suspected rabid animals, only 29% had a history of taking rabies pre-exposure prophylaxis (PEP). Lack of formal education and rural subsistence were found to largely contribute to poor rabies KAP level among the CPs (P ≤ 0.01). There has been a high demand for proper training to be provided to HCPs and VPs for the effective management of an animal bite incidence in human and animals, respectively. Multi-sectoral collaboration through integrated One Health initiatives including community education, awareness programmes, facilitation of rabies PEP, and dog vaccination as well as its population control are critical in the way forward to control rabies in Bangladesh.

Systematic Booster after Rabies Pre-Exposure Prophylaxis to Alleviate Rabies Antibody Monitoring in Individuals at Risk of Occupational Exposure.

Pre-exposure rabies prophylaxis (PrEP) is recommended for people at frequent or increased risk of professional exposure to lyssavirus (including rabies virus). PrEP provides protection against unrecognized exposure. After the primary vaccination, one’s immune response against rabies may decline over time. We aimed to evaluate the immune response to rabies in individuals immunized for occupational reasons before and after a booster dose of the rabies vaccine. With this aim, we retrospectively documented factors associated with an inadequate response in individuals vaccinated for occupational purposes. Our findings analyzed data from 498 vaccinated individuals and found that 17.2% of participants had an inadequate antibody titration documented after their primary vaccination without the booster, while inadequate response after an additional booster of the vaccine was evidenced in 0.5% of tested participants. This study showed that a single booster dose of vaccine after PrEP conferred a high and long-term immune response in nearly all individuals except for rare, low responders. A systematic rabies booster after primary vaccination may result in alleviating the monitoring strategy of post-PrEP antibody titers among exposed professionals.

Rabies vaccination strategies in the Netherlands in 2018: a cost evaluation.

BackgroundThe risk of contracting rabies is low for travellers. However, the number of Dutch travellers potentially exposed abroad following an animal-associated injury and needing post-exposure prophylaxis (PEP) has increased, resulting in increased costs.AimHere, we evaluated the costs and the cost-effectiveness of different pre- and post-exposure interventions in the Netherlands, taking into account the 2018 World Health Organization (WHO) recommendations for the prevention of rabies.MethodsA decision tree-based economic model was constructed. We calculated and compared the cost of different WHO pre-exposure prophylaxis (PrEP) recommendations, intramuscular vs intradermal vaccination and PEP subsequent to increased vaccination coverage in risk groups. We estimated cost-effectiveness, expressed as incremental costs per rabies immunoglobulin (RIG) administration averted, using a societal perspective. Statistical uncertainty regarding number of travellers and vaccination coverage was assessed.ResultsTotal costs at the national level were highest using previous WHO recommendations from 2012, estimated at EUR 15.4 million annually. Intradermal vaccinations in combination with the current recommendations led to the lowest costs, estimated at EUR 10.3 million. Higher vaccination uptake resulted in higher overall costs. The incremental costs per RIG administration averted varied from EUR 21,300-46,800.ConclusionsThe change in rabies PrEP and PEP recommendations in 2018 reduced total costs. Strategies with increased pre-travel vaccination uptake led to fewer RIG administrations and fewer vaccinations after exposure but also to higher total costs. Although larger scale intradermal administration of rabies vaccine can reduce total costs of PrEP and can positively influence vaccination uptake, it remains a costly intervention.

Factors influencing the immune response after a single-dose 3-visit pre-exposure rabies intradermal vaccination schedule: A retrospective multivariate analysis

BackgroundThe World Health Organization (WHO) recommends intradermal (ID) rabies vaccination as a safe and immunogenic alternative to intramuscular administration. The aim of this study is to determine which factors influence the levels of rabies virus neutralizing antibodies (RVNA) after a 3-visit ID rabies vaccination. MethodsThis is a retrospective secondary data analysis study based on electronic health record vaccination data of Belgian military subjects who received ID rabies Pre-exposure prophylaxis (PrEP) with a single-dose 3-visit regimen during the period 2014–2017. Logistic regression was performed to identify predictive factors of RVNA level ≥3.0 IU/mL and >10 IU/mL. ResultsThe second analysis performed on the 2025 subjects (100% seroconverted with a RVNA ≥ 0.5 IU/mL) shows a significantly better immune response in subjects younger than 30 years compared to all other age-groups, a gender-difference to predict RVNA ≥ 3.0 IU/mL (OR 2.30 [1.26–4.22] comparing “female” to “male”) and the influence of the vaccination schedule (OR 2.28 [1.15–4.53] comparing “late - very variable” to “correct” schedule) to predict > 10 IU/ml. Multivariate analysis also demonstrates that a postponed serology control significantly influences the Rapid Fluorescent Focus Inhibition Test (RFFIT). ConclusionGender and age significantly influence the response to ID rabies vaccine. Timing of RVNA determination is important to correctly assess the response to vaccination. A single-dose 3-visit ID rabies PrEP schedule is a dose-sparing effective alternative to the double-dose 2-visit ID schedule. When the minimum time interval between doses is respected, RVNA determination is not necessary.

Immunogenicity and safety of two-visit, intradermal pre-exposure rabies prophylaxis simultaneously administrated with chimeric live-attenuated Japanese encephalitis vaccine in children living in rabies and Japanese encephalitis endemic country

BackgroundReducing the number of doses required for pre-exposure prophylaxis (PrEP) would make it more feasible and cost-effective to implement in children at the highest risk of rabies exposure in Asia. We studied immune response of 2-site intradermal (ID) injection of rabies vaccine on days 0 and 28 for rabies PrEP simultaneously administrated with live-attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) for children living in endemic area. Research design and methodsSeronegative children (n = 49) aged 12–16 months were randomized 2:1 into two groups: Group A subjects were vaccinated with 0.1-mL ID injection of purified Vero cell rabies vaccine (PVRV), each at two sites on day (D) 0 and D28; Group B subjects were vaccinated with conventional 0.5-mL intramuscular PVRV on D0, D7 and D28. Both groups received one dose of JE-CV subcutaneously on D0 and D365. Rabies virus neutralizing antibody (RVNA) titers were measured on D0, D42 and D365 after vaccination; Japanese Encephalitis (JE) neutralizing antibody titers were determined on D0, D42, D365 and D379. ResultsAll children had RVNA ≥ 0.5 IU/mL on D42 (geometric mean titers [GMTs] of RVNA 14.35 IU/mL [Group A] and 14.83 IU/mL [Group B], p > 0.05]). On D365, RVNA GMTs of subjects in group A and B were 1.50 IU/mL and 2.00 IU/mL (p > 0.05), respectively. All children had seroprotection following booster dose of JE-CV. There were no vaccine-related SAEs observed. ConclusionThe 2-site ID PrEP with PVRV on days 0 and 28 co-administrated with JE-CV are safe and immunogenic.