Immunogenicity and safety of concomitant administration of a measles, mumps and rubella vaccine (M-M-RvaxPro) and a varicella vaccine (VARIVAX) by intramuscular or subcutaneous routes at separate injection sites: a randomised clinical trial.
ABSTRACT: When this trial was initiated, the combined measles, mumps and rubella (MMR) vaccine was licensed for subcutaneous administration in all European countries and for intramuscular administration in some countries, whereas varicella vaccine was licensed only for subcutaneous administration. This study evaluated the intramuscular administration of an MMR vaccine (M-M-RvaxPro) and a varicella vaccine (VARIVAX) compared with the subcutaneous route.An open-label randomised trial was performed in France and Germany. Healthy children, aged 12 to 18 months, received single injections of M-M-RvaxPro and VARIVAX concomitantly at separate injection sites. Both vaccines were administered either intramuscularly (IM group, n = 374) or subcutaneously (SC group, n = 378). Immunogenicity was assessed before vaccination and 42 days after vaccination. Injection-site erythema, swelling and pain were recorded from days 0 to 4 after vaccination. Body temperature was monitored daily between 0 and 42 days after vaccination. Other adverse events were recorded up to 42 days after vaccination and serious adverse events until the second study visit.Antibody response rates at day 42 in the per-protocol set of children initially seronegative to measles, mumps, rubella or varicella were similar between the IM and SC groups for all four antigens. Response rates were 94 to 96% for measles, 98% for both mumps and rubella and 86 to 88% for varicella. For children initially seronegative to varicella, 99% achieved the seroconversion threshold (antibody concentrations of >or= 1.25 gpELISA units/ml). Erythema and swelling were the most frequently reported injection-site reactions for both vaccines. Most injection-site reactions were of mild intensity or small size (
Project description:This randomized trial conducted in France compared intramuscular (IM) and subcutaneous (SC) administration of two doses of a measles, mumps, rubella, and varicella (MMRV) combination vaccine (ProQuad®) administered one month apart to 405 children 12-18 months of age (NCT00402831). The 2-dose regimen of MMRV administered IM was shown to be as immunogenic as the 2-dose regimen administered SC for all antigens 6 weeks post-vaccination for the subjects who were initially seronegative for measles, mumps, rubella, or varicella (lower bounds of the two-sided 95% CIs for the difference in response rates for all antigens greater than -10% [range -2.1 for varicella to -3.0 for mumps]). The antibody response rates for all vaccine antigens 6 weeks after the second dose of MMRV were > 99% in both the IM and SC groups. Fewer subjects in the IM group experienced injection-site AEs compared with the SC group (17.8% and 28.6% post-dose 1, and 20.4% and 29.5% post-dose 2, respectively). From Day 0 to Day 4 post-dose 2, fewer subjects reported erythema and swelling in the IM group than in the SC group (15.4% and 27.0%, and 6.0% and 12.5%, respectively). In both groups, most injection-site AEs started during the first four days after vaccination; their intensity was mainly mild or ?2.5 cm. The rates of fever were comparable between the two groups after each dose of MMRV. In conclusion, two doses of the MMRV vaccine were highly immunogenic and well tolerated when administered either SC or IM. ClinicalTrials.gov Identifier: NCT00402831.
Project description:Varicella is a common viral disease affecting almost the entire birth cohort. Although usually self-limiting, some cases of varicella can be serious, with 2 to 6% of cases attending a general practice resulting in complications. The hospitalisation rate for varicella in Europe ranges from 1.3 to 4.5 per 100,000 population/year and up to 10.1% of hospitalised patients report permanent or possible permanent sequelae (for example, scarring or ataxia). However, in many countries the epidemiology of varicella remains largely unknown or incomplete. In countries where routine childhood vaccination against varicella has been implemented, it has had a positive effect on disease prevention and control. Furthermore, mathematical models indicate that this intervention strategy may provide economic benefits for the individual and society. Despite this evidence and recommendations for varicella vaccination by official bodies such as the World Health Organization, and scientific experts in the field, the majority of European countries (with the exception of Germany and Greece) have delayed decisions on implementation of routine childhood varicella vaccination, choosing instead to vaccinate high-risk groups or not to vaccinate at all. In this paper, members of the Working Against Varicella in Europe group consider the practicalities of introducing routine childhood varicella vaccination in Europe, discussing the benefits and challenges of different vaccination options (vaccination vs. no vaccination, routine vaccination of infants vs. vaccination of susceptible adolescents or adults, two doses vs. one dose of varicella vaccine, monovalent varicella vaccines vs. tetravalent measles, mumps, rubella and varicella vaccines, as well as the optimal interval between two doses of measles, mumps, rubella and varicella vaccines). Assessment of the epidemiology of varicella in Europe and evidence for the effectiveness of varicella vaccination provides support for routine childhood programmes in Europe. Although European countries are faced with challenges or uncertainties that may have delayed implementation of a childhood vaccination programme, many of these concerns remain hypothetical and with new opportunities offered by combined measles, mumps, rubella and varicella vaccines, reassessment may be timely.
Project description:A number of live-attenuated varicella vaccines are produced globally that provide protection against the varicella zoster virus. In Mexico, varicella vaccination is not included in the national immunization program and is recommended for use only in high-risk subgroups. We developed a budget impact model to estimate the impact of universal childhood immunization against varicella on the national payer system in Mexico. A scenario of no varicella vaccination was compared to scenarios with vaccination with a single dose at 13 months of age, in alignment with the existing program of immunization with the measles-mumps-rubella vaccine. Nine different vaccination scenarios were envisioned, differing by vaccine type and by coverage. Varicella cases and treatment costs of each scenario were computed in a dynamic transmission model of varicella epidemiology, calibrated to the population of Mexico. Unit costs were based on Mexico sources or were from the literature. The results indicated that each of the three vaccine types increased vaccine acquisition and administration expenditures but produced overall cost savings in each of the first 10 years of the program, due to fewer cases and reduced varicella treatment costs. A highly effective vaccine at 95% coverage produced the greatest cost savings.
Project description:Immunity to measles, mumps, rubella, and varicella-zoster viruses (VZV; MMRV) is a common condition of employment for health care workers (HCWs) to ensure compliance with national standards and state laws. When documentation of complete vaccination or laboratory-confirmed infection is not available, Advisory Committee on Immunization Practices (ACIP) criteria are used to guide vaccination or anti-MMRV IgG testing. We assessed the performance of the BioPlex 2200 MMRV IgG multiplex flow immunoassay (MFI; Bio-Rad Laboratories, Hercules, CA) and matched immunofluorescence assays (IFAs; MBL Bion, Des Plaines, IL) in 220 HCWs categorized by ACIP criteria for presumptive immunity to MMRV. Among HCWs presumptively immune to measles, mumps, rubella, and VZV, the Bio-Rad MFI was positive in 77.3, 85.4, 84.3, and 91.1% of HCWs, respectively. Comparatively, the Bion IFA was positive in 92.9, 91.1, and 93.5% of HCWs presumptively immune to measles, mumps, and VZV (a rubella IFA was unavailable). Among HCWs fully vaccinated against measles, mumps, and VZV, Bio-Rad MFI/Bion IFA positivity rates were 77.4%/93%, 84.8%/90.7%, and 54.5%/90.9%, respectively. The Bio-Rad MFI was positive in 83.7% of HCWs fully vaccinated against rubella. For HCWs whose last vaccination event occurred within 15?years of enrollment, 83.3, 93.3, and 74.2% were positive by the Bio-Rad measles, mumps, and rubella IgG MFIs, respectively. We show significantly decreased Bio-Rad MFI sensitivity for detection of anti-measles and anti-mumps IgG-class antibodies in presumptively immune or fully vaccinated HCWs. Although negative results typically prompt revaccination, failure to recognize presumptive immunity in individuals unable to receive live, attenuated vaccines may have employment implications.
Project description:We report the case of a child presenting with nonfebrile seizures 6 and 13 days after the first vaccination with a measles, mumps, rubella, and varicella (MMRV) combination vaccine. Measles virus RNA was detected in the patient's serum, throat, and urine. Genotyping revealed the Schwarz vaccine virus strain.
Project description:BACKGROUND:Denmark has no general recommendations for vaccination of healthcare workers (HCWs). We explored the self-reported immunity to varicella, measles, mumps, and rubella, reasons for receiving the influenza vaccine or not, and opinions on vaccination of HCWs against varicella, MMR, pertussis, diphtheria, and influenza among staff from departments with a high risk of exposure to infectious agents. METHODS:From May 2019 to August 2019, a structured questionnaire was distributed to clinical and non-clinical HCWs at a tertiary and a general paediatric department in Denmark. Self-reported immunity was defined as either previous infection or vaccination against the disease. RESULTS:Of 619 employed HCWs, 555 (90%) were included. A large proportion were unsure of or denied previous vaccination or infection with measles (20.1%), mumps (30.2%), rubella (21.4%), varicella (12.1%), pertussis (44.1%), and diphtheria (32.1%). Non-clinical personnel and employees born in 1974-1983 had the lowest level of self-reported immunity. Mandatory vaccination of non-immune HCWs was approved by 54-68.9% of participants, and any kind of vaccination (mandatory or as an offer at hospitals) was approved of up to 95.3% of all participants depending on the disease. During the season 2018/19, 214 (38.6%) HCWs received the influenza vaccine, including 20.3% of non-clinical staff, 34.8% of nurses and 56.5% of doctors (P?<?0.001). Reasons for lack of vaccine uptake were mainly employees considering themselves rarely sick, the vaccine was not regarded as necessary, forgetfulness or lack of time. Only 37.8% was in favour of mandatory influenza vaccination. CONCLUSIONS:A large proportion of paediatric HCWs were not aware of their immune status against important vaccine-preventable diseases. >90% supported vaccination of HCWs, with two out of three supporting mandatory MMR, pertussis and diphtheria vaccination. Better information and an official immunisation policy of non-immune HCWs in Denmark is warranted.
Project description:The impact of alternate routes of vaccine administration, subcutaneous (SC) or intramuscular (IM), on the safety and immunogenicity of herpes zoster subunit candidate vaccine (HZ/su) was assessed in Japanese adults aged ? 50 y. During this phase III open-label study, 60 subjects were randomized (1:1) to receive HZ/su through SC or IM routes in a 0, 2 month schedule. Vaccine response rates (VRRs) and geometric mean concentrations (GMCs) of varicella zoster virus glycoprotein E (gE)-specific antibodies were determined by ELISA. Solicited and unsolicited symptoms were recorded for 7 and 30 d after each vaccination and graded 1-3 in severity. Serious adverse events (SAEs) were recorded throughout the study. At one month post-dose 2, VRRs were 100% (95% Confidence Interval (CI): 88.1-100) in both groups; anti-gE antibody GMCs were 44126.1 mIU/ml (95% CI: 36326.1-53601.0) and 45521.5 mIU/ml (95% CI; 37549.5-55185.9) in the SC and IM groups, respectively. Injection site reactions (pain, swelling and redness) were common, and observed more frequently following SC administration. Grade 3 redness and swelling were more frequently observed after SC administration. Fatigue and headache were the most frequently reported general symptoms for both routes of administration. Ten and 7 unsolicited AEs were reported in the SC and IM group, respectively. Two unsolicited AEs (1 in SC; 1 in IM) were considered related to vaccination by the investigator. Three non-fatal SAEs considered unrelated to vaccination were reported during the study. Administration of the HZ/su vaccine candidate resulted in a substantial immune response that was comparable between SC and IM subjects, but local reactogenicity may be greater for SC.
Project description:In Hong Kong, universal varicella vaccination was introduced in July 2014 with a two-dose schedule but the vaccines had been available in the private market since 1996. With data from varicella notification and surveys on immunization coverage, we used the screening method to estimate dose-specific varicella vaccine effectiveness (VE) among preschool children in Hong Kong before universal vaccination. We estimated the VE of one- and two-dose varicella vaccination against all notified varicella as 69.4% (95% confidence interval (95% CI) 69.5-71.2) and 93.4% (95% CI 91.7-94.7), respectively. We found that VE did not decrease with time since receipt. Varicella vaccine was more effective against complications (85.4% [95% CI 48.8-95.8] for one dose and 100% [95% CI -Inf to 100] for two doses) and against hospital admission (75.2% [95% CI 53.4-86.8] for one dose and 93.1% [95% CI 47.1-99.1] for two doses). Lower protection of one-dose varicella vaccine resulted in breakthrough varicella. Under universal vaccination, second-dose varicella vaccine (given as combined measles, mumps, rubella and varicella vaccine) was first scheduled for children when they reach primary one (about 6 years of age) and was recently advanced to 18 months of age. Shortening the interval between the first dose and second dose of varicella vaccination should reduce breakthrough varicella and outbreaks in preschool.
Project description:BACKGROUND:Healthcare personnel (HCP) are at risk of being exposed to or transmitting infections in hospitals, and vaccination against vaccine-preventable diseases (VPDs) is a well-known preventive strategy. Vaccination against influenza, hepatitis B virus, measles-mumps-rubella, varicella, and pertussis is recommended for HCP. However, there is no information on the current status of hospitals' vaccination policies for HCP in Korea. METHODS:We conducted a nationwide survey on hospital vaccination policies and barriers to implementing recommended vaccination programs in 2018. The online survey questionnaire was distributed to 652 hospitals, and 200 of them responded. RESULTS:Of the 200 surveyed hospitals, 151 (75.5%) conducted a pre-employment screening program for at least one VPD, and 196 (98%) had vaccination programs that included at least one vaccine. Influenza vaccine was most commonly included in their programs (97.5%, n = 195), followed by hepatitis B vaccines (69%, n = 138). However, < 25% of the hospitals included other vaccines in their policies (measles-mumps-rubella, 24.5%; varicella, 18.5%; pertussis, 11%). Only 13 hospitals (6.5%) included the five recommended vaccines for HCP in their policies. Influenza vaccination coverage had a mean of 89.9% and was significantly higher in hospitals fully funding the vaccination cost (91.8% vs. 80.4%, P < 0.001). Among hospitals funding influenza vaccines, the coverage was lower in hospitals with ? 700 beds (-6.5%, P = 0.003). Hospitals' financial burden was the most important barrier to implementing vaccination polices as recommended (78.6%, 121/154), followed by lack of awareness (21%) or campaign (21%) and lack of leadership (17%). CONCLUSION:Despite the recommendations on vaccination for HCP, the vaccination policies for HCP differ in hospitals and appear to be insufficient to protect HCP and prevent nosocomial transmission. Strong leadership of each hospital to protect HCP and financial support from the government are required to implement appropriate vaccination policies in hospitals.
Project description:Patients receiving immunosuppressive agents are at risk of life-threatening infections. However, live vaccines are generally contraindicated in them. We conducted a prospective study regarding live attenuated vaccines for them. Patients elder than one year of age with immunosuppressive agents who showed negative or borderline antibody titers (virus-specific IgG levels < 4.0) against one or more of measles, rubella, varicella, and mumps and fulfilled the criteria (CD4 cell counts ? 500/mm3, stimulation index of lymphocyte blast transformation by PHA ? 101.6, serum IgG level ? 300 mg/dl, no steroid use or prednisolone < 1 mg/kg/day or < 2 mg/kg/2 days, trough levels of tacrolimus or cyclosporine were < 10 ng/ml or < 100 ng/ml and under good control of primary disease) were enrolled. Sixty-four vaccinations were administered to 32 patients. The seroconversion rates for measles, rubella, varicella, and mumps were 80.0%, 100.0%, 59.1%, and 69.2%, respectively. No life-threatening adverse events were observed, although one patient suffered from vaccine-strain varicella who showed cellular and humoral immunodeficiency (CD4 cell counts = 511/mm3, stimulation index of lymphocyte blast transformation by PHA = 91.1, serum IgG level = 208 mg/dl). This girl was immunized before we established the criteria for vaccination. Immunization with live attenuated vaccines for patients receiving immunosuppressive agents might be effective and safe if their cellular and humoral immunological parameters are within normal levels. However, determining the criteria for vaccination by immunological parameters should be established to guarantee the safety of live vaccines in the future. Clinical Trial Registration: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000007710. The date of registration: 2012/4/13.