Vaccine Associated Measles Complicated by Suspected Measles Inclusion Body Encephalitis in a Pediatric Leukemia Patient and Stem Cell Transplant Recipient: A Focus on Clinical Evolution and Management.

BACKGROUND: Immunocompromised individuals are at increased risk for severe disease and complications from viral infections, highlighting the importance of vaccination. However, in extremely rare situations, vaccine associated viral infections can be associated with disseminated disease and complications in immunocompromised hosts. CASE: Herein, we present a case of a 1-year-old child diagnosed with acute myeloid leukemia less than 2 weeks after receiving live viral vaccines who developed acute vaccine-strain measles virus disease, later complicated by central nervous system involvement following hematopoietic stem cell transplantation. A brain biopsy specimen was positive for vaccine-strain measles virus detected by reverse transcriptase polymerase chain reaction. MANAGEMENT AND OUTCOME: She was treated with intravenous ribavirin, inosine pranobex, intrathecal interferon-alpha and donor lymphocyte infusion following measles-mumps-rubella vaccine boost. Despite these measures, the patient suffered neurologic decline and dysautonomia, expiring after compassionate extubation. Management and ideal risk mitigation strategies are discussed within the context of existing literature for this rare complication.

A prospective randomized controlled study of Mycobacterium Indicus Pranii vaccine, Measles Mumps Rubella vaccine and Vitamin D3 in extragenital cutaneous warts.

DESIGN: Interventional, prospective, four arm randomized control. SETTING: Outpatient department, Department of Dermatology, Venereology and Leprology, AIIMS Jodhpur (Rajasthan), India. PARTICIPANTS: Two hundred patients. METHODS: The intervention administered in the groups were normal saline (A), vitamin D3 (B), MIP (C), and MMR (D). The injections were given into the largest wart at 2-weekly intervals until complete clearance or for a maximum of seven sittings. Post-treatment clearance of the injected wart and the distant wart was compared on the basis of change in wart number, percentage clearance, and mean time to complete clearance. Side effects were recorded. RESULTS: A total of 197 patients were recruited. The mean percentage improvement in the injected and non-injected warts was 68.4% and 66.8%, respectively. Intention to treat analysis (ITT) showed that complete clearance of lesions in injected wart occurred in placebo, vit D3 , MMR, and MIP arms in 64%, 66%, 58%, and 55% patients, respectively (p > 0.05), while in the non-injected warts in 62%, 64%, 52%, and 53%, respectively (p > 0.05). The mean time to achieve complete clearance of wart was fastest in MIP at 7.1 weeks followed by MMR at 7.2 weeks, VIT D3 at 7.4 weeks and in placebo group 7.8 weeks (p > 0.05). Side effects noted were fever, pain, erythema, and swelling which was highest in VIT D3 group (p < 0.05). CONCLUSION: The efficacy of immunotherapies was comparable to placebo with minimal side effects.

Case report: Persistent shedding of a live vaccine-derived rubella virus in a young man with severe combined immunodeficiency and cutaneous granuloma.

A young man with X-linked severe combined immunodeficiency developed a persistent vaccine-derived rubella virus (VDRV) infection, with the emergence of cutaneous granulomas more than fifteen years after receipt of two doses of measles-mumps-rubella (MMR) vaccine. Following nasopharyngeal swab (NP) collection, VDRV was detected by real-time polymerase chain reaction (RT-qPCR) and sequencing, and live, replication-competent VDRV was isolated in cell culture. To assess duration and intensity of viral shedding, sequential respiratory samples, one cerebrospinal fluid sample, and two urine samples were collected over 15 months, and VDRV RNA was detected in all samples by RT-qPCR. Live VDRV was cultured from nine of the eleven respiratory specimens and from one urine specimen. To our knowledge, this was the first reported instance of VDRV cultured from respiratory specimens or from urine. To assess potential transmission to close contacts, NP specimens and sera were collected from all household contacts, all of whom were immunocompetent and previously vaccinated with MMR. VDRV RNA was not detected in any NP swabs from the contacts, nor did serologic investigations suggest VDRV transmission to any contacts. This report highlights the need to understand the prevalence and duration of VDRV shedding in granuloma patients and to estimate the risk of VDRV transmission to immune and non-immune contacts.

A comparative evaluation of therapeutic response in warts to intralesional vitamin D3 versus intralesional measles, mumps, and rubella vaccine.

The infection of keratinocytes by human papilloma virus (HPV) causes warts. These are of different types based on morphological and anatomical grounds. This has led to the development of strategies involved in the treatment of warts by induction of delayed hypersensitivity reactions. The current study aims to compare the therapeutic response and side effect profile of intralesional vitamin D3 and measles, mumps, and rubella (MMR). The aim of this study is to study the therapeutic response of two intralesional immunotherapies in warts and compare their efficacies and side effects. A single-blind randomized control trial was conducted over 12 months on 100 patients using the purposive sampling technique. Randomly, half of the participants received one of the two immunotherapies. The clinical response was evaluated on the basis of decrease in wart size, wart number, wart distribution, and photographic comparison. The mean size of the largest wart in the vitamin D3 group was found to be 0.70 cm, and in the MMR group, it was 0.79 cm in breadth. The mean onset of first response was 3.55 weeks in the vitamin D3 group and 3.85 weeks in the MMR group. Complete response was seen in 54% and 62% of study participants in the vitamin D3 and MMR groups respectively. The study recommends that both intralesional vitamin D3 and MMR are efficacious in treating cutaneous warts, with MMR agents being moderately better compared to vitamin D3 in terms of warts clearance and side effects profile.

Intralesional Measles-Mumps-Rubella Vaccine for Genital Warts: Report of two cases with a review of literature.

Genital warts are caused by several strains of Human Papilloma Viruses. Although asymptomatic in most cases, they can be psychologically and physically distressing for patients. Recently, intralesional immunotherapy using different antigens-such as Bacille Calmette-Guerin vaccine, candida antigen and measles, mumps, and rubella (MMR) vaccine-have shown promising efficacy in the treatment of genital warts. We report two cases in Omani males who presented to the Dermatology Department at Barka Polyclinic with recalcitrant genital warts that resolved completely with intralesional injection of the MMR vaccine.

Efficacy, immunogenicity, and safety of available vaccines in children on biologics: A systematic review and meta-analysis.

Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known. OBJECTIVE: A systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics. METHODS: The protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics. RESULTS: We retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found. EFFICACY: limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration. SAFETY: vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014). CONCLUSIONS: More evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population.

Linear IGA bullous dermatosis potentially triggered by vaccination.

Linear IgA bullous dermatosis (LABD) is a mucocutaneous autoimmune blistering disease affecting both adults and children. It is caused by IgA antibodies targeting multiple antigens along the basement membrane zone, leading to disruption of dermoepidermal junction and development of bullous lesions which often presents in characteristic arrangement. Although most LABD cases have been reported to be idiopathic, different triggers have been described, including several drugs and infection. However, the occurrence of vaccine-induced cases of LABD is not widely known and accepted due to the few reports available. We present two cases of LABD occurred following different triggers, rising the suspicion for a possible pathogenetic role of vaccines.

Anaphylaxis rates associated with COVID-19 vaccines are comparable to those of other vaccines.

We retrieved data on 8940 anaphylaxis cases post-COVID-19 vaccination from the US Vaccine Adverse Event Reporting System and the European EudraVigilance from week 52/2020 through week 31/2021 and compared them with those of other vaccines. Overall, 837,830,000 COVID-19 vaccine doses were delivered in the US and Europe during the study period, for which the vaccine name was known. The mean anaphylaxis rate was estimated at 10.67 cases per 106 doses of COVID-19 vaccines (range: 7.99-19.39 cases per 106 doses depending on the vaccine). COVID-19 vaccines ranked fifth in reported anaphylaxis rates, behind rabies, tick-borne encephalitis, measles-mumps-rubella-varicella, and human papillomavirus vaccines (70.77, 20, 19.8, and 13.65 cases per 106 vaccine doses, respectively). COVID-19 vaccines are within the range of anaphylaxis rates reported across several common vaccines in these two passive reporting systems. These data should be communicated to reassure the general population about the safety profile of COVID-19 vaccines.

Vaccines for measles, mumps, rubella, and varicella in children.

BACKGROUND: Measles, mumps, rubella, and varicella (chickenpox) are serious diseases that can lead to serious complications, disability, and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness. This is an update of a review published in 2005 and updated in 2012. OBJECTIVES: To assess the effectiveness, safety, and long- and short-term adverse effects associated with the trivalent vaccine, containing measles, rubella, mumps strains (MMR), or concurrent administration of MMR vaccine and varicella vaccine (MMR+V), or tetravalent vaccine containing measles, rubella, mumps, and varicella strains (MMRV), given to children aged up to 15 years. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2019, Issue 5), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to 2 May 2019), Embase (1974 to 2 May 2019), the WHO International Clinical Trials Registry Platform (2 May 2019), and ClinicalTrials.gov (2 May 2019). SELECTION CRITERIA: We included randomised controlled trials (RCTs), controlled clinical trials (CCTs), prospective and retrospective cohort studies (PCS/RCS), case-control studies (CCS), interrupted time-series (ITS) studies, case cross-over (CCO) studies, case-only ecological method (COEM) studies, self-controlled case series (SCCS) studies, person-time cohort (PTC) studies, and case-coverage design/screening methods (CCD/SM) studies, assessing any combined MMR or MMRV / MMR+V vaccine given in any dose, preparation or time schedule compared with no intervention or placebo, on healthy children up to 15 years of age. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the methodological quality of the included studies. We grouped studies for quantitative analysis according to study design, vaccine type (MMR, MMRV, MMR+V), virus strain, and study settings. Outcomes of interest were cases of measles, mumps, rubella, and varicella, and harms. Certainty of evidence of was rated using GRADE. MAIN RESULTS: We included 138 studies (23,480,668 participants). Fifty-one studies (10,248,159 children) assessed vaccine effectiveness and 87 studies (13,232,509 children) assessed the association between vaccines and a variety of harms. We included 74 new studies to this 2019 version of the review. Effectiveness Vaccine effectiveness in preventing measles was 95% after one dose (relative risk (RR) 0.05, 95% CI 0.02 to 0.13; 7 cohort studies; 12,039 children; moderate certainty evidence) and 96% after two doses (RR 0.04, 95% CI 0.01 to 0.28; 5 cohort studies; 21,604 children; moderate certainty evidence). The effectiveness in preventing cases among household contacts or preventing transmission to others the children were in contact with after one dose was 81% (RR 0.19, 95% CI 0.04 to 0.89; 3 cohort studies; 151 children; low certainty evidence), after two doses 85% (RR 0.15, 95% CI 0.03 to 0.75; 3 cohort studies; 378 children; low certainty evidence), and after three doses was 96% (RR 0.04, 95% CI 0.01 to 0.23; 2 cohort studies; 151 children; low certainty evidence). The effectiveness (at least one dose) in preventing measles after exposure (post-exposure prophylaxis) was 74% (RR 0.26, 95% CI 0.14 to 0.50; 2 cohort studies; 283 children; low certainty evidence). The effectiveness of Jeryl Lynn containing MMR vaccine in preventing mumps was 72% after one dose (RR 0.24, 95% CI 0.08 to 0.76; 6 cohort studies; 9915 children; moderate certainty evidence), 86% after two doses (RR 0.12, 95% CI 0.04 to 0.35; 5 cohort studies; 7792 children; moderate certainty evidence). Effectiveness in preventing cases among household contacts was 74% (RR 0.26, 95% CI 0.13 to 0.49; 3 cohort studies; 1036 children; moderate certainty evidence).  Vaccine effectiveness against rubella, using a vaccine with the BRD2 strain which is only used in China, is 89% (RR 0.11, 95% CI 0.03 to 0.42; 1 cohort study; 1621 children; moderate certainty evidence).  Vaccine effectiveness against varicella (any severity) after two doses in children aged 11 to 22 months is 95% in a 10 years follow-up (rate ratio (rr) 0.05, 95% CI 0.03 to 0.08; 1 RCT; 2279 children; high certainty evidence). Safety There is evidence supporting an association between aseptic meningitis and MMR vaccines containing Urabe and Leningrad-Zagreb mumps strains, but no evidence supporting this association for MMR vaccines containing Jeryl Lynn mumps strains (rr 1.30, 95% CI 0.66 to 2.56; low certainty evidence). The analyses provide evidence supporting an association between MMR/MMR+V/MMRV vaccines (Jeryl Lynn strain) and febrile seizures. Febrile seizures normally occur in 2% to 4% of healthy children at least once before the age of 5. The attributable risk febrile seizures vaccine-induced is estimated to be from 1 per 1700 to 1 per 1150 administered doses. The analyses provide evidence supporting an association between MMR vaccination and idiopathic thrombocytopaenic purpura (ITP). However, the risk of ITP after vaccination is smaller than after natural infection with these viruses. Natural infection of ITP occur in 5 cases per 100,000 (1 case per 20,000) per year. The attributable risk is estimated about 1 case of ITP per 40,000 administered MMR doses. There is no evidence of an association between MMR immunisation and encephalitis or encephalopathy (rate ratio 0.90, 95% CI 0.50 to 1.61; 2 observational studies; 1,071,088 children; low certainty evidence), and autistic spectrum disorders (rate ratio 0.93, 95% CI 0.85 to 1.01; 2 observational studies; 1,194,764 children; moderate certainty). There is insufficient evidence to determine the association between MMR immunisation and inflammatory bowel disease (odds ratio 1.42, 95% CI 0.93 to 2.16; 3 observational studies; 409 cases and 1416 controls; moderate certainty evidence). Additionally, there is no evidence supporting an association between MMR immunisation and cognitive delay, type 1 diabetes, asthma, dermatitis/eczema, hay fever, leukaemia, multiple sclerosis, gait disturbance, and bacterial or viral infections.  AUTHORS' CONCLUSIONS: Existing evidence on the safety and effectiveness of MMR/MMRV vaccines support their use for mass immunisation. Campaigns aimed at global eradication should assess epidemiological and socioeconomic situations of the countries as well as the capacity to achieve high vaccination coverage. More evidence is needed to assess whether the protective effect of MMR/MMRV could wane with time since immunisation.

Neurologic Safety Monitoring of COVID-19 Vaccines: Lessons From the Past to Inform the Present.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global effort to rapidly develop and deploy effective and safe coronavirus disease 2019 (COVID-19) vaccinations. Vaccination has been one of the most effective medical interventions in human history, although potential safety risks of novel vaccines must be monitored, identified, and quantified. Adverse events must be carefully assessed to define whether they are causally associated with vaccination or coincidence. Neurologic adverse events following immunizations are overall rare but with significant morbidity and mortality when they occur. Here, we review neurologic conditions seen in the context of prior vaccinations and the current data to date on select COVID-19 vaccines including mRNA vaccines and the adenovirus-vector COVID-19 vaccines, ChAdOx1 nCOV-19 (AstraZeneca) and Ad26.COV2.S Johnson & Johnson (Janssen/J&J).

Granulomatous dermatitis following measles, mumps, and rubella vaccination.

Granulomatous dermatitis following the administration of various vaccines has previously been reported. However, cases of cutaneous granulomatosis following the measles, mumps, and rubella (MMR) vaccine have not yet been reported. We report the case of a 3-year-old boy with a granuloma annulare-like reaction following MMR vaccination.

Safety of vaccines used for routine immunization in the United States: An updated systematic review and meta-analysis.

BACKGROUND: Understanding the safety of vaccines is critical to inform decisions about vaccination. Our objective was to conduct a systematic review of the safety of vaccines recommended for children, adults, and pregnant women in the United States. METHODS: We searched the literature in November 2020 to update a 2014 Agency for Healthcare Research and Quality review by integrating newly available data. Studies of vaccines that used a comparator and reported the presence or absence of key adverse events were eligible. Adhering to Evidence-based Practice Center methodology, we assessed the strength of evidence (SoE) for all evidence statements. The systematic review is registered in PROSPERO (CRD42020180089). RESULTS: Of 56,603 reviewed citations, 338 studies reported in 518 publications met inclusion criteria. For children, SoE was high for no increased risk of autism following measles, mumps, and rubella (MMR) vaccine. SoE was high for increased risk of febrile seizures with MMR. There was no evidence of increased risk of  intussusception with rotavirus vaccine at the latest follow-up (moderate SoE), nor of diabetes (high SoE). There was no evidence of increased risk or insufficient evidence for key adverse events for newer vaccines such as 9-valent human papillomavirus and meningococcal B vaccines. For adults, there was no evidence of increased risk (varied SoE) or insufficient evidence for key adverse events for the new adjuvanted inactivated influenza vaccine and recombinant adjuvanted zoster vaccine. We found no evidence of increased risk (varied SoE) for key adverse events among pregnant women following tetanus, diphtheria, and acellular pertussis vaccine, including stillbirth (moderate SoE). CONCLUSIONS: Across a large body of research we found few associations of vaccines and serious key adverse events; however, rare events are challenging to study. Any adverse events should be weighed against the protective benefits that vaccines provide.

Post Vaccine Rubella During a Measles Outbreak: Clinical Case.

Rubella is a vaccine preventable infection, and congenital rubella the most feared complication of this disease. Although young adult women are at greatest risk of post-vaccine rubella, this is also the group who potentially benefits the most from vaccine protection. Since post-vaccine disease has a mild and self-limited course, the benefit clearly exceeds the risk. During a measles outbreak in the north of Portugal, a 38-year-old woman presented with cervical posterior lymphadenopathies, fever and a maculo-papular rash one week after the administration of the measles, mumps and rubella vaccine. Measles was discarded and rubella viremia was demonstrated. Symptoms of rubella are non-specific and laboratory confirmation is essential. This is particularly relevant during a measles outbreak.

A rubéola é uma infeção prevenível por vacina, sendo a rubéola congénita a apresentação mais grave da doença. Apesar de serem o grupo que mais beneficia dela, as mulheres em idade fértil são também o grupo com maior risco de doença associada à vacina. Uma vez que as manifestações clínicas são ligeiras e transitórias, o benefício compensa largamente o risco. Durante o surto de sarampo que ocorreu no Porto em 2018, uma mulher de 38 anos recebeu a primeira dose da vacina contra o sarampo, rubéola e papeira. Uma semana depois, recorreu ao Serviço de Urgência por febre, exantema maculo-papular e adenopatias cervicais posteriores. Foi excluído sarampo e demonstrada viremia pelo vírus da rubéola. Os sintomas da rubéola são inespecíficos pelo que a confirmação laboratorial é essencial. Isto é ainda mais relevante em contexto de surto de sarampo.

Meningitis aséptica por virus parotídeo asociada a la vacuna

Resumen Comunicamos el caso de un lactante mayor previamente sano, que luego de tres semanas de recibir la vacuna SPR (sarampión, parotiditis, rubeola) presentó fiebre, aumento de volumen parotídeo y compromiso de conciencia. Se diagnosticó una meningitis aséptica, con pleocitosis en el LCR de predominio mononuclear, detectándose virus parotídeo en LCR por biología molecular. En el Instituto de Salud Pública de Chile se realizó serología (IgM e IgG) que resultó positiva. La muestra de saliva confirmó la etiología por virus parotídeo con genotipo N. La evolución fue favorable, sin secuelas al seguimiento a seis meses. Ante esta situación clínica, se revisó la información respecto a la asociación y causalidad de esta entidad clínica y vacuna SPR, focalizado en diferentes cepas del virus parotiditis.

Abstract We report the case of an older infant with no prior morbidity that approximately 3 weeks after receiving MMR vaccination (measles, mumps, rubella) was hospitalized for feverish symptoms, increased parotid volume and compromised consciousness. Aseptic meningitis was diagnosed, detecting pleocytosis in the CSF, predominantly mononuclear, and confirming by molecular biology, presence of parotid virus in CSF. A study was carried out by the Institute of Public Health of Chile, where serology (IgM and IgG) was positive. Saliva sample confirmed the etiology of parotid virus with genotype N. The evolution was favorable and at 6-month follow-up, there were no sequelae. Given this clinical situation, information regarding the association and causality of this clinical entity and the MMR vaccine, focused on different strains of the mumps virus, was reviewed.

A comparative study of the efficacy and safety of intralesional measles, mumps, and rubella vaccine versus intralesional vitamin D3 for the treatment of warts in children.

BACKGROUND: Intralesional vitamin D3 has recently emerged as a new treatment for cutaneous warts. The use of the measles, mumps, and rubella (MMR) vaccine for this purpose is an established modality. However, relevant data on the efficacy of either the MMR vaccine or vitamin D3 as immunotherapy for cutaneous warts in the pediatric population are limited. OBJECTIVES: To compare the efficacy and safety of intralesional injections of MMR vaccine to intralesional injections of vitamin D3 in children aged 8-16 years with multiple warts. METHODS: A total of 74 children were randomly allocated into two groups. Group A patients received intralesional MMR vaccine into the largest wart, and group B received intralesional vitamin D3 into the largest wart. The injections were repeated every 4 weeks until clearance or for a maximum of three treatments. After the last injection, children were followed up every 2 weeks for 3 months, and at the sixth month, a final clinical assessment was conducted. RESULTS: Of 74 children, 60 completed the study, with 30 children in each group. Complete clearance of the injected wart was observed in 26 (86.67%) patients in the MMR group (group A) and 23 (76.7%) patients in the vitamin D3 group (group B). Distant warts cleared in 23 (76.7%) patients in group A compared to 20 (66.6%) patients in group B. There was no significant difference between groups. No recurrence was seen in group A, whereas two (6.6%) children in group B exhibited recurrence in the ensuing 6-month follow-up. The most common adverse events were injection site pain and swelling. CONCLUSION: Both intralesional MMR and vitamin D3 are safe, generally well-tolerated, and equally effective in children for the treatment of cutaneous warts.

Vaccines for measles, mumps, rubella, and varicella in children.

BACKGROUND: Measles, mumps, rubella, and varicella (chickenpox) are serious diseases that can lead to serious complications, disability, and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness. This is an update of a review published in 2005 and updated in 2012. OBJECTIVES: To assess the effectiveness, safety, and long- and short-term adverse effects associated with the trivalent vaccine, containing measles, rubella, mumps strains (MMR), or concurrent administration of MMR vaccine and varicella vaccine (MMR+V), or tetravalent vaccine containing measles, rubella, mumps, and varicella strains (MMRV), given to children aged up to 15 years. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2019, Issue 5), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to 2 May 2019), Embase (1974 to 2 May 2019), the WHO International Clinical Trials Registry Platform (2 May 2019), and ClinicalTrials.gov (2 May 2019). SELECTION CRITERIA: We included randomised controlled trials (RCTs), controlled clinical trials (CCTs), prospective and retrospective cohort studies (PCS/RCS), case-control studies (CCS), interrupted time-series (ITS) studies, case cross-over (CCO) studies, case-only ecological method (COEM) studies, self-controlled case series (SCCS) studies, person-time cohort (PTC) studies, and case-coverage design/screening methods (CCD/SM) studies, assessing any combined MMR or MMRV / MMR+V vaccine given in any dose, preparation or time schedule compared with no intervention or placebo, on healthy children up to 15 years of age. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the methodological quality of the included studies. We grouped studies for quantitative analysis according to study design, vaccine type (MMR, MMRV, MMR+V), virus strain, and study settings. Outcomes of interest were cases of measles, mumps, rubella, and varicella, and harms. Certainty of evidence of was rated using GRADE. MAIN RESULTS: We included 138 studies (23,480,668 participants). Fifty-one studies (10,248,159 children) assessed vaccine effectiveness and 87 studies (13,232,509 children) assessed the association between vaccines and a variety of harms. We included 74 new studies to this 2019 version of the review. Effectiveness Vaccine effectiveness in preventing measles was 95% after one dose (relative risk (RR) 0.05, 95% CI 0.02 to 0.13; 7 cohort studies; 12,039 children; moderate certainty evidence) and 96% after two doses (RR 0.04, 95% CI 0.01 to 0.28; 5 cohort studies; 21,604 children; moderate certainty evidence). The effectiveness in preventing cases among household contacts or preventing transmission to others the children were in contact with after one dose was 81% (RR 0.19, 95% CI 0.04 to 0.89; 3 cohort studies; 151 children; low certainty evidence), after two doses 85% (RR 0.15, 95% CI 0.03 to 0.75; 3 cohort studies; 378 children; low certainty evidence), and after three doses was 96% (RR 0.04, 95% CI 0.01 to 0.23; 2 cohort studies; 151 children; low certainty evidence). The effectiveness (at least one dose) in preventing measles after exposure (post-exposure prophylaxis) was 74% (RR 0.26, 95% CI 0.14 to 0.50; 2 cohort studies; 283 children; low certainty evidence). The effectiveness of Jeryl Lynn containing MMR vaccine in preventing mumps was 72% after one dose (RR 0.24, 95% CI 0.08 to 0.76; 6 cohort studies; 9915 children; moderate certainty evidence), 86% after two doses (RR 0.12, 95% CI 0.04 to 0.35; 5 cohort studies; 7792 children; moderate certainty evidence). Effectiveness in preventing cases among household contacts was 74% (RR 0.26, 95% CI 0.13 to 0.49; 3 cohort studies; 1036 children; moderate certainty evidence). Vaccine effectiveness against rubella is 89% (RR 0.11, 95% CI 0.03 to 0.42; 1 cohort study; 1621 children; moderate certainty evidence). Vaccine effectiveness against varicella (any severity) after two doses in children aged 11 to 22 months is 95% in a 10 years follow-up (rate ratio (rr) 0.05, 95% CI 0.03 to 0.08; 1 RCT; 2279 children; high certainty evidence). Safety There is evidence supporting an association between aseptic meningitis and MMR vaccines containing Urabe and Leningrad-Zagreb mumps strains, but no evidence supporting this association for MMR vaccines containing Jeryl Lynn mumps strains (rr 1.30, 95% CI 0.66 to 2.56; low certainty evidence). The analyses provide evidence supporting an association between MMR/MMR+V/MMRV vaccines (Jeryl Lynn strain) and febrile seizures. Febrile seizures normally occur in 2% to 4% of healthy children at least once before the age of 5. The attributable risk febrile seizures vaccine-induced is estimated to be from 1 per 1700 to 1 per 1150 administered doses. The analyses provide evidence supporting an association between MMR vaccination and idiopathic thrombocytopaenic purpura (ITP). However, the risk of ITP after vaccination is smaller than after natural infection with these viruses. Natural infection of ITP occur in 5 cases per 100,000 (1 case per 20,000) per year. The attributable risk is estimated about 1 case of ITP per 40,000 administered MMR doses. There is no evidence of an association between MMR immunisation and encephalitis or encephalopathy (rate ratio 0.90, 95% CI 0.50 to 1.61; 2 observational studies; 1,071,088 children; low certainty evidence), and autistic spectrum disorders (rate ratio 0.93, 95% CI 0.85 to 1.01; 2 observational studies; 1,194,764 children; moderate certainty). There is insufficient evidence to determine the association between MMR immunisation and inflammatory bowel disease (odds ratio 1.42, 95% CI 0.93 to 2.16; 3 observational studies; 409 cases and 1416 controls; moderate certainty evidence). Additionally, there is no evidence supporting an association between MMR immunisation and cognitive delay, type 1 diabetes, asthma, dermatitis/eczema, hay fever, leukaemia, multiple sclerosis, gait disturbance, and bacterial or viral infections. AUTHORS' CONCLUSIONS: Existing evidence on the safety and effectiveness of MMR/MMRV vaccines support their use for mass immunisation. Campaigns aimed at global eradication should assess epidemiological and socioeconomic situations of the countries as well as the capacity to achieve high vaccination coverage. More evidence is needed to assess whether the protective effect of MMR/MMRV could wane with time since immunisation.

Infectious vaccine-derived rubella viruses emerge, persist, and evolve in cutaneous granulomas of children with primary immunodeficiencies.

Rubella viruses (RV) have been found in an association with granulomas in children with primary immune deficiencies (PID). Here, we report the recovery and characterization of infectious immunodeficiency-related vaccine-derived rubella viruses (iVDRV) from diagnostic skin biopsies of four patients. Sequence evolution within PID hosts was studied by comparison of the complete genomic sequences of the iVDRVs with the genome of the vaccine virus RA27/3. The degree of divergence of each iVDRV correlated with the duration of persistence indicating continuous intrahost evolution. The evolution rates for synonymous and nonsynonymous substitutions were estimated to be 5.7 x 10-3 subs/site/year and 8.9 x 10-4 subs/site/year, respectively. Mutational spectra and signatures indicated a major role for APOBEC cytidine deaminases and a secondary role for ADAR adenosine deaminases in generating diversity of iVDRVs. The distributions of mutations across the genes and 3D hotspots for amino acid substitutions in the E1 glycoprotein identified regions that may be under positive selective pressure. Quasispecies diversity was higher in granulomas than in recovered infectious iVDRVs. Growth properties of iVDRVs were assessed in WI-38 fibroblast cultures. None of the iVDRV isolates showed complete reversion to wild type phenotype but the replicative and persistence characteristics of iVDRVs were different from those of the RA27/3 vaccine strain, making predictions of iVDRV transmissibility and teratogenicity difficult. However, detection of iVDRV RNA in nasopharyngeal specimen and poor neutralization of some iVDRV strains by sera from vaccinated persons suggests possible public health risks associated with iVDRV carriers. Detection of IgM antibody to RV in sera of two out of three patients may be a marker of virus persistence, potentially useful for identifying patients with iVDRV before development of lesions. Studies of the evolutionary dynamics of iVDRV during persistence will contribute to development of infection control strategies and antiviral therapies.

Febrile convulsions during recovery after anesthesia in an infant with history of MMR vaccination: A case report.

RATIONALE: Seizures are rare during the perioperative period; in most cases, there is a previous history of epilepsy or surgery-associated seizures. Febrile convulsions may occur when the body temperature rises above 38°C; this is the most common cause of seizures in children. Febrile convulsions after general anesthesia in the postanesthetic care unit (PACU) without a past or family history are rare. Some reviews suggest that since anesthesia changes immunity, elective surgery should be postponed three weeks after live vaccination. PATIENT: A 12-month-old female with bilateral hearing loss underwent cochlear implantation under general anesthesia. She did not have any history of convulsions or developmental disorders. However, 1 week before surgery, measles-mumps-rubella (MMR) vaccination was given as a regular immunization. DIAGNOSES: Forty minutes after arrival at the PACU, sudden generalized tonic-clonic movement occurred during recovery and the patient's measured body temperature exceeded 38.0°C. INTERVENTIONS: Thiopental sodium was administered intravenously as an anticonvulsant, and the tonic-clonic movement stopped immediately. Endotracheal intubation was performed to secure the airway, and tepid massage and diclofenac ß-dimethylaminoethanol administration were performed to lower the patient's body temperature. OUTCOMES: There was no further fever and no seizures, and no other neurological deficits were observed until discharge. LESSONS: The anesthesiologist should check the recent vaccination history even if the patient has not developed particular symptoms after vaccination. It is important to know that febrile convulsions may occur in patients who have recently received MMR vaccination.