A Case of a Serum Sickness-Like Reaction After Postexposure Rabies Prophylaxis.

BACKGROUND: Serum sickness secondary to rabies postexposure prophylaxis is not well documented in the medical literature. Our case describes serum sickness after exposure to human-derived rabies immunoglobulin (HRIG) and three human diploid rabies vaccines (HDCV) in a young adult male. CASE REPORT: A 30-year-old previously healthy male patient presented to the Emergency Department with complaints of fever, rash, and jaundice, and had a hospital course complicated by biliary stenosis likely secondary to reactive periportal lymphadenopathy. His initial laboratory values demonstrated obstructive jaundice and slightly elevated complement component 4 levels. These symptoms likely are due to the course of HRIG and HDCV vaccines the patient completed after being exposed to a rabies-positive bat in his home. The patient was hospitalized for 8 days, during which he underwent an endoscopic retrograde cholangiopancreatography with sphincterotomy and biliary stenting. He had one repeat hospitalization for acute blood loss anemia attributed to sphincterotomy, which did not require transfusion or further intervention. Liver biopsy showed cholestatic hepatitis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Medical literature describing serum sickness or a serum sickness-like reaction occurring from exposure to HRIG or HDCV is sparse despite the commonality of postexposure rabies prophylaxis in health care. It is important to educate practitioners on this potential complication and highlight next potential consultations and treatments.

Comparing recombinant human rabies monoclonal antibody (ormutivimab) with human rabies immunoglobulin (HRIG) for postexposure prophylaxis: A phase III, randomized, double-blind, non-inferiority trial.

OBJECTIVES: To evaluate the immunogenicity and safety of an anti-rabies monoclonal antibody (mAb), ormutivimab, compared with human rabies immunoglobulin (HRIG). METHODS: This phase III trial was designed as a randomized, double-blind, non-inferiority clinical trial in patients aged ≥18 years with suspected World Health Organization category Ⅲ rabies exposure. The participants were randomized 1:1 to ormutivimab and HRIG groups. After thorough wound washing and injection of ormutivimab/HRIG on day 0, the vaccination was administered on days 0, 3, 7, 14, and 28. The primary endpoint was the adjusted geometric mean concentration (GMC) of rabies virus-neutralizing activity (RVNA) on day 7. The endpoint of safety included the occurrence of adverse reactions and serious adverse events. RESULTS: A total of 720 participants were recruited. The adjusted-GMC of RVNA (0.41 IU/ml) on day 7 in ormutivimab group was not inferior to that in the HRIG group (0.41 IU/ml), with ratio of adjusted-GMC of 1.01 (95% confidence interval: 0.91, 1.14). The seroconversion rate of the ormutivimab group was higher than that of the HRIG group on days 7, 14, and 42. Most local injection sites and systemic adverse reactions reported from both groups were mild to moderate in severity. CONCLUSION: ormutivimab + vaccine can protect victims aged ≥18 years with category Ⅲ suspected rabies exposure as a component of postexposure prophylaxis. ormutivimab has a weaker influence on the immunity response of rabies vaccines. CLINICAL TRIALS REGISTRATION: ChiCTR1900021478 (the Chinese Clinical Trial Registry of World Health Organization).

Safety of purified Vero cell rabies vaccine manufactured in Pakistan: a comparative analysis of intradermal and intramuscular routes.

BACKGROUND: Rabies vaccines are conventionally given via the intramuscular (IM) route; however, switching the route of administration from IM to intradermal (ID) without affecting efficacy can be advantageous in terms of cost, dosing, and time. Hence, it is indispensable to evaluate its safety along different routes. This study was carried out to ascertain the frequency of adverse drug events (ADEs) and associated factors, as well as to compare safety based on the IM and ID routes. METHODS: A prospective observational study was carried out on 184 individuals with rabies exposure. The vaccination schedules for post-exposure prophylaxis (PEP) included 0.2 milliliter (mL) of purified Vero cell rabies vaccine (PVRV) administered ID at two different sites with 0.1 mL each on days 0, 3, and 7 in first group (3-dose regimen ID) and 0.5 mL administered IM on days 0, 3, 7, 14, and 28 in the second group (5-dose regimen IM). The safety of the vaccines was determined by reviewing ADEs during physical examinations and follow-up. ADEs were characterized by local and systemic effects. RESULTS: Of the total, 99 (53.80%) patients reported ADEs. Those who reported local and systemic ADEs were 80 (43.48%) and 59 (32.06%), respectively, while simultaneous occurrence was reported in 40 (40.40%) patients. The most frequent local ADE (76; 41.30%) reported was pain, followed by erythema (18; 9.78%). Additionally, fever had the highest proportion (25; 13.59%) for systemic effects, followed by headache (15; 8.15%). The patients reported with ADEs by the IM and ID routes were comparable (p >.05). Similarly, both local and systemic effects were also comparable (p >.05). CONCLUSION: Half of the study participants reported ADEs. Almost similar proportions of local and systemic effects were observed. Likewise, the ADEs recorded were comparable for both routes. PVRV carries very low safety concerns with either route for administration.

Serum Sickness like Reaction Postequine Rabies Immunoglobulins.

A 30-year-old, previously healthy adult male received equine rabies immunoglobulins (Ig) (ERIG) along with anti-rabies vaccinations as per protocol for postexposure prophylaxis after an unprovoked rabid dog bite of grade three wound over the shin of the left lower limb. On the 8th day, he developed urticarial rashes beginning from the site of the wound, which gradually became a widespread maculopapular rash. Development of the rash was followed by low-grade fever, nonspecific arthralgias and soreness in the throat. A diagnosis of serum sickness-like illness was made based on history, temporal correlation of administration of ERIG and development of symptoms. He responded well to antihistaminic and a short course of injectable steroids. The purpose of this article is to increase awareness regarding the clinical presentation and management of this rare yet potentially curable adverse event if identified timely.

Rabies Virus Neutralizing Activity, Safety, and Immunogenicity of Recombinant Human Rabies Antibody Compared with Human Rabies Immunoglobulin in Healthy Adults.

Objective: Preliminary assessment of rabies virus neutralizing activity, safety and immunogenicity of a recombinant human rabies antibody (NM57) compared with human rabies immunoglobulin (HRIG) in Chinese healthy adults. Methods: Subjects were randomly (1:1:1) allocated to Groups A (20 IU/kg NM57), B (40 IU/kg NM57), or C (20 IU/kg HRIG). One injection was given on the day of enrollment. Blood samples were collected on days -7 to 0 (pre-injection), 3, 7, 14, 28, and 42. Adverse events (AEs) and serious AEs (SAEs) were recorded over a period of 42 days after injection. Results: All 60 subjects developed detectable rabies virus neutralizing antibodies (RVNAs) (> 0.05 IU/mL) on days 3, 7, 14, 28, and 42. The RVNA levels peaked on day 3 in all three groups, with a geometric mean concentration (GMC) of 0.2139 IU/mL in Group A, 0.3660 IU/mL in Group B, and 0.1994 IU/mL in Group C. At each follow-up point, the GMC in Group B was significantly higher than that in Groups A and C. The areas under the antibody concentration curve over 0-14 days and 0-42 days in Group B were significantly larger than those in Groups A and C. Fifteen AEs were reported. Except for one grade 2 myalgia in Group C, the other 14 were all grade 1. No SAEs were observed. Conclusion: The rabies virus neutralizing activity of 40 IU/kg NM57 was superior to that of 20 IU/kg NM57 and 20 IU/kg HRIG, and the rabies virus neutralizing activity of 20 IU/kg NM57 and 20 IU/kg HRIG were similar. Safety was comparable between NM57 and HRIG.

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.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: In this study, ChAdOx2 RabG showed an acceptable safety and tolerability profile and encouraging immunogenicity, supporting further clinical evaluation. FUNDING: UK Medical Research Council and Engineering and Physical Sciences Research Council.

Safety and immunogenicity of a serum-free purified Vero rabies vaccine in healthy adults: A randomised phase II pre-exposure prophylaxis study.

A serum-free, highly purified Vero cell rabies vaccine (PVRV-NG) is under development. We previously demonstrated that pre-exposure prophylaxis (PrEP) with PVRV-NG had a satisfactory safety profile and was immunogenically non-inferior to the licensed purified Vero cell rabies vaccine in adults. Here, we evaluated the safety and immunogenic non-inferiority of PrEP with PVRV-NG compared to the licensed human diploid cell vaccine (HDCV) in healthy adults (NCT01784874). Participants received three vaccinations (days 0, 7, and 28) as PrEP with or without a booster injection after 12 months. Rabies virus neutralising antibodies (RVNA) were evaluated on days 0, 28 (subgroup only), and 42, and Months 6, 12, and 12 + 14 days (booster group only). Non-inferiority (first primary objective) was based on the proportion of participants with RVNA titres ≥ 0.5 IU/mL (World Health Organization criteria for seroconversion) on day 42, expected to be ≥ 99% (second primary objective). Safety was evaluated after each dose and monitored throughout the study. At day 42, PVRV-NG was non-inferior to HDCV and the first primary objective was met; seroconversion was observed for 98.3% of PVRV-NG recipients and 99.1% of HDCV recipients. As < 99% of participants in the PVRV-NG group had RVNA titres ≥ 0.5 IU/mL, the second primary objective was not met. Booster vaccination produced a strong increase in RVNA titres for all groups, primed with PVRV-NG or HDCV. RVNA geometric mean titres tended to be higher for HDCV than PVRV-NG primary vaccine recipients. In a complementary evaluation using alternative criteria for seroconversion (complete virus neutralization at 1:5 serum dilution), 99.6% and 100% of participants in the PVRV-NG and HDCV groups, respectively, achieved seroconversion across the vaccine groups. No major safety concerns were observed during the study. PVRV-NG was well tolerated, with a similar safety profile to HDCV in terms of incidence, duration, and severity of adverse events after primary and booster vaccinations. ClinicalTrials.gov number: NCT01784874.

Safety and immunogenicity of human rabies vaccine for the Chinese population after PEP: A systematic review and meta-analysis.

AIM: To evaluate the safety and immunogenicity of rabies vaccine for human use after post-exposure in China. METHODS: A systematic search was performed from PubMed, EMBASE, CNKI and Cochrane Library database, supplemented by manual retrieval. According to the inclusion and exclusion criteria, a meta-analysis was performed using Stata 16.0 software after independent literature screening, data extraction and quality assessment by two evaluators. RESULTS: A total of 32 studies were included. It was found that rabies vaccination after PEP could induce the body to produce sufficient RVNA. Both Essen and Zagreb regimens showed good immunogenicity, with no significant difference in systemic events and local events after PEP, but a relatively high incidence of local and systemic events after PEP under the Zagreb regimen. CONCLUSION: For the Chinese population, rabies vaccination after PEP has shown relatively a good immune efficacy and acceptable safety for preventing human rabies. The survey also found that the Zagreb regimen was comparable to the Essen regimen in terms of rabies prophylaxis with an acceptable safety profile.

Case Report: Rabies Vaccine-Induced Thrombotic Thrombocytopenic Purpura in a Patient With Systemic Lupus Erythematosus.

For patients with autoimmune diseases, vaccination is controversial. The use of vaccination in patients with autoimmune diseases is controversial. There are many reports of secondary thrombotic thrombocytopenic purpura cases after various vaccinations. Thrombotic thrombocytopenic purpura is a rare thrombotic microangiopathy characterized by microvascular pathological hemolytic anemia, severe thrombocytopenia, and ischemic organ damage with a very high fatality rate. We report a case of thrombotic thrombocytopenic purpura in a patient with systemic lupus erythematosus after rabies vaccination. She developed gastrointestinal bleeding nearly a month after the vaccination. Laboratory tests confirmed a severe deficiency of ADAMTS13 and the presence of ADAMTS13 autoantibodies. Through early identification of thrombotic thrombocytopenic purpura, immunosuppressive therapy, and plasma exchange treatment, the patient was saved from danger. This case suggests that attenuated vaccines may also have unexpected adverse effects in patients with long-term use of immunosuppressive drugs and autoimmune diseases. To our knowledge, this is the first case report of thrombotic thrombocytopenic purpura in a patient with systemic lupus erythematosus secondary to rabies vaccination.

Commentary on the implications of safety and efficacy studies in pediatric patients with administration of human rabies immune globulin (HRIG)?

The FDA strongly encourages rigorous safety and efficacy studies in all age groups for which vaccines and treatments for pervasive and severe diseases are intended. Until recently, there had been no safety and efficacy studies conducted in children for human rabies immune globulins. The publication," Safety, and efficacy of rabies immunoglobulin in pediatric patients with suspected exposure", Human Vaccines & Immunotherapeutics, 17:7, 2090-2096, was the first study that prospectively reviewed the use of KEDRAB® 150 IU/ml in 30 pediatric patients ages 0.5-14.9 years old. The results showed that 93.3% achieved RVNA titer >/ = 5 IU/ml, on day 14. Also, no participants reported a serious adverse event (SAE), or an adverse event (AE) leading to study discontinuation, and there were no deaths. The most common treatment emergent adverse events (TEAE) were injection-site pain. Currently there are 3 HRIG products on the US market, KEDRAB®, HyperRab® and Imogam® Rabies HT, but only KEDRAB® has published safety and efficacy data in a pediatric population. While it is common practice to prescribe medications for pediatric patients "off-label" there now exists one product with safety data in children. It is worth considering if this creates a higher medical liability for the prescriber and institution.

Safety and Immunogenicity of a novel three-dose recombinant nanoparticle rabies G protein vaccine administered as simulated post exposure immunization: A randomized, comparator controlled, multicenter, phase III clinical study.

BACKGROUND: Rabies vaccines are lifesaving in human post animal exposure. However, the compliance to the complete course of vaccine is found to be only 60%. Hence, there is a need for safe and immunogenic, shorter course vaccine that can enhance the compliance and effectively prevent the disease. OBJECTIVES: To establish a noninferiority of a novel three-dose recombinant rabies G protein vaccine to be administered as simulated postexposure prophylaxis when compared to five-dose WHO prequalified vaccine for better safety and immunogenicity. METHODS: A multi-centric, open label, assessor blind, center-specific block randomized, parallel design, phase III clinical study was conducted among 800 subjects. The eligible subjects were randomized in 2:1 ratio for recombinant rabies G protein vaccine and the reference vaccine. Subjects in recombinant rabies G protein vaccine arm received three doses of vaccine on days 0, 3, and 7, while subjects in reference vaccine arm received five doses of WHO prequalified vaccine on days 0, 3, 7, 14, and 28. RESULTS: The socio-demographic characteristics of the two arms were comparable. About 9.9% subjects in recombinant rabies G protein vaccine arm and 17.2% subjects in reference arm reported adverse events. The sero-protection on day 14 was found to be 99.24% and 97.72% in recombinant rabies G protein vaccine arm and reference vaccine arm respectively and the difference was statistically nonsignificant. CONCLUSION: The novel three-dose recombinant rabies G protein vaccine administered as simulated postexposure prophylaxis was noninferior to five dose WHO prequalified vaccine in terms of safety and immunogenicity.

Anaphylaxis after rabies vaccination for dogs in Japan.

Severe adverse reactions after rabies vaccination in dogs were examined from 317 cases reported to the Ministry of Agriculture, Forestry and Fisheries (MAFF) in Japan during 15-year period from April 2004 to March 2019. We found that 109 of the 317 dogs showed anaphylaxis (0.15/100,000 vaccinated dogs), and 71 of the 109 cases of anaphylaxis resulted in death (0.10/100,000 vaccinated dogs). We measured bovine serum albumin (BSA) in four commercially available rabies vaccines and found the levels ranged from 0.1 to 16.6 µg/dose. Our survey showed that the rate of anaphylaxis to rabies vaccines in dogs is rare, although some cases of anaphylaxis resulted in death. Veterinarians should be well prepared to deal with vaccine-associated anaphylaxis.

Safety, immunogenicity of lyophilized purified vero cell cultured rabies vaccine administered in Zagreb and Essen regimen in post-exposure subjects: A post-marketing, parallel control clinical trial.

To compare the safety and immunogenicity of lyophilized PVRV under Zagreb and Essen regimen.A post-marketing parallel control clinical trial was conducted. Totally 240 subjects were assigned to two groups randomly, immunized with lyophilized PVRV under Zagreb and Essen schedule. Solicited adverse events were observed after each dose and unsolicited adverse events were collected. Serum samples were collected on days 0, 7, 14, 42, 180 and 365 to be used to determine immunogenicity level. No severe adverse events (SAE) were observed. The incidence of adverse events under Zagreb and Essen were similar and there was no significant difference between the two groups and within all age groups. Fever and pain were the most frequently reported systemic and local adverse events (AEs) respectively. There were no differences in the GMT and the positive seroconversion rate between these two groups. All participants in the Zagreb group obtained protective effect on day 14, while 99.16% of the subjects obtained in the Essen group. Both groups showed similar enduring immunity. Immunizations under Zagreb and Essen regimens showed similar safety and immunogenicity. For lyophilized PVRV, Zagreb was non-inferior to Essen to patients of all age groups.

Safety and immunogenicity of rabies vaccine as 4 - dose Essen Intramuscular regimen for post exposure prophylaxis: A non - randomized, comparative controlled study.

Introduction: World Health Organization has recommended that in healthy persons with category III exposures, who receive wound care and rabies immunoglobulin infiltration, a vaccine regimen consisting of 4 doses administered intramuscularly on days 0, 3, 7, and 14 can be used as an alternative to the 5-dose intramuscular regimen.Objective: To assess the clinical safety and immunogenicity of rabies vaccine administered as 4-dose Essen intramuscular regimen for post-exposure prophylaxis.Methods: A non-randomized, comparative, controlled study was conducted at the anti-rabies clinic, KIMS Hospital and Research Center, Bangalore, India. The study subjects were divided into study group i.e., 4-dose intramuscular regimen, and control group i.e., 5-dose intramuscular regimen, and were given post-exposure prophylaxis. All subjects were followed for any adverse drug events. Rabies virus neutralizing antibodies was determined on day 14, 90 & 180 at the WHO collaborating center, NIMHANS, Bangalore, India to assess the immunogenicity.Results: The present study included 70 adult animal bite victims, 35 each in study group and control group. The incidence of ADEs was 7.8% in 4-dose Essen group and 7.0% in 5-dose Essen group;the difference between them was not significant (P > .05). Similarly, all the subjects in both the groups had protective antibody titers of ≥ 0.5 IU/mL (100% seroprotective) from day 14 till day 180; the difference between two groups was also not significant (P > .05).Conclusion: The 4-dose intramuscular Essen post-exposure prophylaxis regimen was found to be clinically safe and immunogenic.

Safety and efficacy of rabies immunoglobulin in pediatric patients with suspected exposure.

Rabies is a deadly viral zoonosis with global disease burden. Following exposure to a rabid animal, post-exposure prophylaxis (PEP) is the standard of care for unvaccinated persons. Despite the large proportion of pediatric cases, limited safety and efficacy data exist for use in pediatric patients. We report the safety, efficacy, and immunogenicity of a phase 4, prospective, 2-center, open-label, single-arm clinical trial evaluating human rabies immunoglobulin (HRIG150; KEDRAB 150 IU/mL) as part of PEP in patients (aged <17) with suspected or confirmed rabies exposure, where PEP was indicated. Thirty participants received 20 IU/kg HRIG150 infiltrated into the detectable wound site(s), with any remainder injected intramuscularly, concomitantly with the first of a 4-dose series (days 0, 3, 7, and 14) of rabies vaccine. Rabies virus neutralizing antibody (RVNA) titers and tolerability were assessed on day 14 following administration. Participant safety was monitored for 84 days. No serious adverse events, rabies infections, or deaths were recorded. Twenty-one participants (70.0%) experienced a total of 57 treatment-emergent adverse events (TEAEs) within 14 days following administration. Twelve participants (40.0%) experienced a total of 13 adverse events deemed treatment related. All TEAEs were mild in severity. On day 14, 28 participants (93.3%) had RVNA levels of ≥0.5 IU/mL (mean±standard deviation: 18.89 ± 31.61). These results demonstrate that HRIG150 is well tolerated and effective in pediatric patients as a component of PEP. To the authors' knowledge, this study is the first to establish pediatric safety and efficacy of HRIG in the US.

Parsonage-Turner posterior a vacunación antirrábica por mordedura de murciélago: comunicación de un caso / Parsonage-Turner after rabies vaccination due to bat bite: case report

Introducción:Paciente adulto masculino que consulta por mordedura de murciélago. Se realiza aplicación de vacuna antirrábica y toxoide tetánico, tras lo cual presenta alteraciones motoras, sensitivas y dolor de difícil manejo en el miembro superior derecho. Siendo un reto diagnóstico de manera inicial, posterior a estudios electrofisiológicos se consideró un síndrome de Parsonage-Turner. Este caso es relevante por la asociación de vacuna antirrábica no descrita en antecedentes de inmunización en revisiones previas.Caso clínico:Se le realizaron varias pruebas diagnósticas e imágenes como ecografías, resonancia magnética y estudios electrofisiológicos los cuales confirmaron el diagnóstico de neuritis braquial (síndrome de Parsonage-Turner). El paciente recibió intervenciones quirúrgicas con fascitomías y neurólisis, además de múltiples manejos farmacológicos para dolor, incluyendo opioides fuertes, neuromoduladores, antidepresivos y medicamentos por bomba intratecal, con disminución solo del 50 % de los síntomas de dolor y afectación a su calidad de vida.Conclusión:El caso nos muestra cómo el síndrome de Parsonage-Turner, una enfermedad neurológica con etiología desconocida, se puede cronificar en un síndrome doloroso al no tener un diagnóstico temprano o someter al paciente procedimientos no indicados. Este síndrome debe considerarse en la atención de urgencias y consulta externa por sus consecuencias a largo plazo y el difícil manejo de los síntomas crónicos. Hay una relación causal reportada en la literatura con el toxoide tetánico, pero este se aplicó previo a los síntomas; no hay referencias de inicio de síntomas posterior a la vacuna antirrábica, lo cual puede generar a futuro, una relación causal si se encontraran nuevos casos.(AU)

Introduction:Adult male patient who suffers a bat bite, after which rabies vaccine and tetanus toxoid are administered; later, he presents on the right upper limb severe motor, sensory and pain disorders. Initially a diagnostic challenge, after electrophysiological studies, Parsonage-Turner syndrome was considered. This case is relevant since the association between rabies vaccine and this syndrome has not been described.Clinical case:Several diagnostic tests and images were performed, including ultrasound, magnetic resonance and electrophysiological studies, which confirmed the diagnosis of brachial neuritis (Parsonage-Turner syndrome). Even though the patient received surgical interventions with fasciotomies and neurolysis as well as multiple pharmacological pain management with strong opioids, neuromodulators, antidepressants and intrathecal pump medications, there was a 50 % decrease in pain symptoms and an impairment of their quality of life.Conclusion:The case shows a Parsonage-Turner syndrome, a neurological disease with unknown etiology, with difficult diagnosis which can lead to chronic pain syndrome or unnecessary surgical procedures. This syndrome should be considered in emergency care and outpatient care due to its long-term consequences and the difficult management of chronic symptoms. There is a causal relationship reported in the literature with tetanus toxoid, but it was applied prior to symptoms; there are no reports of onset of symptoms after the rabies vaccine, which may generate a causal relationship in the future if new cases are found.(AU)

Anaphylaxis to simultaneous administration of inactivated tissue culture hepatitis A vaccine and purified chick embryo cell rabies vaccine after multiple doses.

Both the inactivated hepatitis A vaccine (Aimmugen) and purified chick embryo cell rabies vaccine (PCECV, Rabipur) are well tolerated. Anaphylaxis has rarely been reported as an adverse reaction of these vaccines. There have been no reports or published case reports of anaphylaxis due to Aimmugen. According to the Japanese Ministry of Health, Labour and Welfare Aimmugen adverse reaction report, no cases of anaphylaxis have been reported from April 2013 to August 2016. Twenty cases of anaphylaxis due to PCECV (RabAvert) have been reported from 1997 to 2005 in USA, whereas 2 cases have been reported from 2006 to 2016. We report a case of anaphylaxis after multiple vaccinations in a 24-year-old man with ulcerative colitis, previous medical history of tonsillectomy for IgA nephropathy and no history of allergies.

Immunogenicity and safety of purified vero cell-cultured rabies vaccine under Zagreb 2-1-1 or 5-dose Essen regimen in the healthy Chinese subjects: a randomized, double-blind, positive controlled phase 3 clinical trial.

Aim: The aims of the study were to evaluate the non-inferiority of the safety and immunogenicity of a new trial purified vero cell-cultured rabies vaccine (trial vaccine) in healthy subjects comparing with the control purified vero cell-cultured rabies vaccine (control vaccine) following Essen regimen and to evaluate the non-inferiority of the safety and immunogenicity of the trial vaccine following two intramuscular regimens, between Zagreb and Essen regimen. Methods: Serum samples were collected before vaccination and on d 7, 14, 35/42 post vaccination. Adverse events (AEs) were recorded for 30 d following each vaccination. This study was registered in the Chinese Clinical Trial Registry (ChiCTR-PPR-15007057). Results: There was no significant difference in the incidence of AEs, local and systemic reactions, among Zagreb group, Essen group, and control group. But the incidence of solicited AEs was a significant difference among the three groups (p = 0.0498). The incidence of solicited AEs was higher in Essen group than that in control group and Zagreb group (p = 0.0278, p = 0.0248). In the subjects whose antibodies were seronegative before vaccination, the seroconversion rates of antibodies among three groups were all 100.0% on d 14 and d 35/42. The Essen group was not inferior to the control group, and the Zagreb group was not inferior to the Essen group on d 14. On d 14 and d 35/42, the geometric mean concentration of the three groups was much higher than the immune protection level of 0.5 IU/ml. Conclusions: The trial vaccine had good safety and immunogenicity, and the trial vaccine is not inferior to the control vaccine. Abbreviations: PVRV: purified vero cell-cultured rabies vaccine; AE: adverse event; CI: confidence interval; GMC: geometric mean concentration; IM: intramuscular; NIFDC: National Institutes for Food and Drug Control; PPS: per-protocol set; SS: safety set; REFIT: Rapid Fluorescent Focus Inhibition Test; RVNA: rabies virus neutralizing antibody; WHO: World Health Organization.