Despite Safe and Effective Vaccine, Measles Cases and Deaths Increased Worldwide From 2021 to 2022.

This Medical News story discusses the latest data on measles cases, deaths, and vaccination coverage worldwide.

Economic impact of vaccine safety incident in Ukraine: The economic case for safety system investment.

BACKGROUND: Vaccine confidence and coverage decreased following a death temporally but not causally related to measles vaccination in Ukraine in 2008. Large measles outbreaks including international exportations followed. Herein we characterize this experience including associated costs. METHODS: Mixed-methods were used to characterize this vaccine safety incident and quantify health and economic costs. Qualitative interviews illuminate the incident, social climate, and corruption that influenced vaccine confidence in Ukraine. A literature review explored attitudes toward vaccines in the USSR and post-independence Ukraine. Infectious disease incidence was examined before and after the vaccine safety incident. An economic analysis estimated associated healthcare costs, including prevention and outbreak control measures, additional vaccination activities due to failure of the 2008 campaign, treatment costs for new cases domestically and foreign exportation, and productivity loss from treatment time and mortality for new cases. FINDINGS: Vaccine hesitancy and distrust in government and public health programs due to corruption existed in Ukraine before the vaccine safety incident. The mishandling of the 2008 incident catalyzed the decline of vaccine confidence and prompted poor procurement decisions, leading to a drop in infant vaccination coverage, increased domestic measles cases, and exportation of measles. The estimated cost of this incident was approximately $140 million from 2008 to 2018. INTERPRETATION: Absent a rapid and credible vaccine safety response, a coincidental death following immunization resulted in major outbreaks of measles with substantial economic costs. Adequate investments in a post-licensure safety system may help avoid similar future incidents.

Study protocol for a phase 1/2, single-centre, double-blind, double-dummy, randomized, active-controlled, age de-escalation trial to assess the safety, tolerability and immunogenicity of a measles and rubella vaccine delivered by a microneedle patch in healthy adults (18 to 40 years), measles and rubella vaccine-primed toddlers (15 to 18 months) and measles and rubella vaccine-naïve infants (9 to 10 months) in The Gambia [Measles and Rubella Vaccine Microneedle Patch Phase 1/2 Age De-escalation Trial].

BACKGROUND: New strategies to increase measles and rubella vaccine coverage, particularly in low- and middle-income countries, are needed if elimination goals are to be achieved. With this regard, measles and rubella vaccine microneedle patches (MRV-MNP), in which the vaccine is embedded in dissolving microneedles, offer several potential advantages over subcutaneous delivery. These include ease of administration, increased thermostability, an absence of sharps waste, reduced overall costs and pain-free administration. This trial will provide the first clinical trial data on MRV-MNP use and the first clinical vaccine trial of MNP technology in children and infants. METHODS: This is a phase 1/2, randomized, active-controlled, double-blind, double-dummy, age de-escalation trial. Based on the defined eligibility criteria for the trial, including screening laboratory investigations, 45 adults [18-40 years] followed by 120 toddlers [15-18 months] and 120 infants [9-10 months] will be enrolled in series. To allow double-blinding, participants will receive either the MRV-MNP and a placebo (0.9% sodium chloride) subcutaneous (SC) injection or a placebo MNP and the MRV by SC injection (MRV-SC). Local and systemic adverse event data will be collected for 14 days following study product administration. Safety laboratories will be repeated on day 7 and, in the adult cohort alone, on day 14. Unsolicited adverse events including serious adverse events will be collected until the final study visit for each participant on day 180. Measles and rubella serum neutralizing antibodies will be measured at baseline, on day 42 and on day 180. Cohort progression will be dependent on review of the unblinded safety data by an independent data monitoring committee. DISCUSSION: This trial will provide the first clinical data on the use of a MNP to deliver the MRV and the first data on the use of MNPs in a paediatric population. It will guide future product development decisions for what may be a key technology for future measles and rubella elimination. TRIAL REGISTRATION: Pan-African Clinical Trials Registry 202008836432905 . CLINICALTRIALS: gov NCT04394689.

Health effects of utilising hospital contacts to provide measles vaccination to children 9-59 months-a randomised controlled trial in Guinea-Bissau.

BACKGROUND: Measles vaccination coverage in Guinea-Bissau is low; fewer than 80% of children are currently measles vaccinated before 12 months of age. The low coverage hampers control of measles. Furthermore, accumulating evidence indicates that measles vaccine has beneficial non-specific effects, strengthening the resistance towards other infections. Thus, even if children are not exposed to measles virus, measles-unvaccinated children may be worse off. To increase vaccination coverage, WHO recommends that contacts with the health system for mild illness are utilised to vaccinate. Currently, in Guinea-Bissau, curative health system contacts are not utilised. METHODS: Bandim Health Project registers out-patient consultations and admissions at the paediatric ward of the National Hospital in Guinea-Bissau. Measles-unvaccinated children aged 9-59 months consulting for milder illness or being discharged from the paediatric ward will be invited to participate in a randomised trial. Among 5400 children, randomised 1:1 to receive standard measles vaccine or a saline placebo, we will test the hypothesis that providing a measles vaccine at discharge lowers the risk of admission/mortality (composite outcome) during the subsequent 6 months by 25%. All enrolled children are followed through the Bandim Health Project registration system and through telephone follow-up. The first 1000 enrolled children are furthermore followed through interviews on days 2, 4, 7 and 14 after enrolment. DISCUSSION: Utilising missed vaccination opportunities can increase vaccination coverage and may improve child health. However, without further evidence for the safety and potential benefits of measles vaccination, these curative contacts are unlikely to be used for vaccination in Guinea-Bissau. TRIAL REGISTRATION: www. CLINICALTRIALS: gov NCT04220671 . Registered on 5 January 2020.

Safety of measles and pertussis-containing vaccines in children with autism spectrum disorders.

OBJECTIVES: To determine whether children aged 4-7 years with a diagnosis of autism spectrum disorders (ASD) were at increased risk of fever, febrile seizures, or emergency department (ED) visits following measles- or pertussis-containing vaccines compared with children without ASD. METHODS: The study included children born between 1995-2012, aged 4-7 years at vaccination, and members of six healthcare delivery systems within Vaccine Safety Datalink. We conducted self-controlled risk interval analyses comparing rates of outcomes in risk and control intervals within each group defined by ASD status, and then compared outcome rates between children with and without ASD, in risk and control intervals, by estimating difference-in-differences using logistic regressions. RESULTS: The study included 14,947 children with ASD and 1,650,041 children without ASD. After measles- or pertussis-containing vaccination, there were no differences in association between children with and without ASD for fever (ratio of rate ratio for measles-containing vaccine = 1.07, 95% CI 0.58-1.96; for pertussis-containing vaccine = 1.16, 95% CI 0.63-2.15) or ED visits (ratio of rate ratio for measles-containing vaccine = 1.11, 95% CI 0.80-1.54; for pertussis-containing vaccine = 0.87, 95% CI 0.59-1.28). Febrile seizures were rare. Pertussis-containing vaccines were associated with small increased risk of febrile seizures in children without ASD. CONCLUSION: Children with ASD were not at increased risk for fever or ED visits compared with children without ASD following measles- or pertussis-containing vaccines. These results may provide further reassurance that these vaccines are safe for all children, including those with ASD.

Measles vaccination of special risk groups.

Measles is an important vaccine preventable disease with significant morbidity and mortality. Although measles vaccine is a safe and effective vaccine available worldwide for more than 50 years, still immunization efforts have not successfully reached the WHO goal of 95% vaccination coverage. Hesitancy is especially increased amongst parents of children with chronic conditions. Contraindications for measles-containing vaccines are well defined and include history of anaphylactic reactions to neomycin, history of severe allergic reaction to previous vaccination, pregnancy, and severe immunosuppression. Concurrently, precautions for measles-containing vaccines include amongst other, history of thrombocytopenia or thrombocytopenic purpura and personal or family history of seizures of any etiology. This article aims to address misconceptions on measles vaccine safety and review data on adverse events among special groups of subjects at increased risk following measles immunization.

Congenital Rubella Syndrome Surveillance After Measles Rubella Vaccination Introduction in Yogyakarta, Indonesia.

BACKGROUND: Congenital rubella syndrome (CRS) is a fatal disease causing severe congenital defects. Indonesia had the highest CRS cases in the world in 2016 with a commitment to achieve elimination of rubella disease by 2020, through the campaign and introduction of measles rubella (MR) national vaccination program in 2017 and 2018. This study aimed to describe the impact of the national vaccination campaign by conducting surveillance of CRS cases and comparing the incidence of new CRS cases before and after the MR vaccination campaign. METHODS: From July 2015 to July 2020, we conducted surveillance of CRS in Yogyakarta. Suspected patients underwent complete clinical examinations. Serology was tested for the presence of IgM and IgG antibodies against rubella. Descriptive analysis was used to characterize the demographic and clinical characteristics of the cases before and after the MR vaccination campaign. RESULTS: The study involved 229 infants who were suspected for CRS. Laboratory-confirmed cases were found in 47 of them (20.86%). Most of the laboratory-confirmed cases (55.3%) were reported among 1-5 months old infants. Common clinical features among laboratory-confirmed cases included structural heart defects in 43 (91.4%). There was a significant decrease (60.9%) of CRS incidence from 0.39 per 1000 live births in the precampaign era to 0.08 in the postcampaign era (P = 0.00). CONCLUSION: There has been a significant declining number of CRS cases based on pre- and post-MR vaccination campaign in Yogyakarta, Indonesia. An effective surveillance system will help monitor the number of CRS cases.

Adverse events following immunization: Findings from 2017/2018 measles vaccination campaign, Nigeria AEFI reporting in 2017/2018 measles vaccination campaign.

INTRODUCTION: An Adverse event following immunization (AEFI) is an untoward medical occurrence following immunization and which may not have a necessary causal relationship with the usage of a vaccine. The World Health Organization categories AEFI into two; serious and non-serious. An AEFI is considered serious if it is life-threatening, requires inpatient hospitalization or results in death. The measles vaccine is safe and effective however because it is a live-attenuated injectable vaccine it is more prone to AEFI as compared to non-injectable vaccines when given in large numbers over a short period as is the nature of measles mass vaccination campaigns (MVC). This article describes Nigeria's experience on AEFI reporting during the 2017/2018 Measles vaccination campaign (MVC). METHODS: We reviewed various materials which included the Open Data Kit (ODK) which is an open source smartphone-based data collecting tool, operations room reports, measles campaign tally sheets, AEFI line listing forms, the post measles campaign coverage survey report and the report of the AEFI national expert committee review of the 2017/2018 Nigeria measles MVC. RESULTS: A total of 6,214 suspected cases of AEFI were line listed from all 36 states and the Federal Capital Territory(FCT) during the 2017/2018 MVC with Fever(38%) and pain at injection site the (30%)most common reports. Overall, 99.7% AEFIs were reported to be non-serious AEFIs, with almost all cases resolved fully with no long-term sequalae.. The national incidence of suspected AEFI per 100,000 population was 16.3 with subnational incidence highest in Kebbi state (101.3/100,000) and lowest in Bayelsa state (0.8/100,000). CONCLUSION: Adequate AEFI reporting, Investigation and management remains important in managing the risk of a disruption of mass campaigns. The deployment of supervisors during campaign may play an important role in improving the identification and reporting of suspected AEFI. Further inquiries about AEFIs during the post campaign coverage evaluation also played a role in improving AEFI reporting and documentation. The real-time, on the spot, follow up by the national operations team helped with decision making and intervention including AEFI investigations and assessments.

Effects of measles-containing vaccination in children with severe underlying neurologic disease.

BACKGROUND: Measles outbreaks pose significant risk for those unvaccinated. PATIENTS AND METHODS: Measles-containing vaccine was offered to unvaccinated children with severe neurologic diseases during a measles outbreak. Vaccination adverse events were reported by parents 30 days following vaccination. Long term effects were evaluated 12 months post vaccination. RESULTS: Twenty-seven children were vaccinated (36 doses given). Half of parents (51.8%) reported no adverse events following immunization. Adverse events included afebrile seizures (6/36), fever alone (5/36) and febrile seizures (5/36). Two children required hospitalization. Quadrivalent measles-containing vaccine combined with varicella was associated with febrile seizures (p = 0.04). No child needed adjustment of the anti-epileptic treatment or exhibited developmental regression. CONCLUSION: Ina series of children with prior severe neurologic disease, the safety-tolerability profile ofvaccines containing a measles vaccine component suggests that vaccination is justified. Main side effect was seizure aggravation in children with known epileptic disease.

Diphtheria-Tetanus-Pertussis (DTP) Vaccine Is Associated With Increased female-Male Mortality. Studies of DTP administered before and after measles vaccine.

BACKGROUND: The third dose of diphtheria-tetanus-pertussis vaccine (DTP3) is used to monitor immunization programs. DTP has been associated with higher female mortality. METHODS: We updated previous literature searches for DTP studies of mortality by sex. We examined the female/male (F/M) mortality rate ratio (MRR) with increasing number of doses of DTP and for subsequent doses of measles vaccine (MV) after DTP and of DTP after MV. RESULTS: Eight studies had information on both DTP1 and DTP3. The F/M MRR was 1.17 (95% confidence interval [CI], .88-1.57) after DTP1 and increased to 1.66 (95% CI, 1.32-2.09) after DTP3. Following receipt of MV, the F/M MRR declined to 0.63 (95% CI, .42-.96). In 11 studies the F/M MRR increased to 1.73 (95% CI, 1.33-2.27) when DTP-containing vaccine was administered after MV. CONCLUSIONS: F/M MRR increased with increasing doses of DTP. After MV, girls had lower mortality than boys. With DTP after MV, mortality increased again for girls relative to boys. No bias can explain these changes in F/M MRR. DTP does not improve male survival substantially in situations with herd immunity to pertussis and higher F/M MRR after DTP may therefore reflects an absolute increase in female mortality.

Vaccine-associated measles in a patient treated with natalizumab: a case report.

BACKGROUND: Safety of live vaccines in patients treated with immunosuppressive therapies is not well known, resulting in contradictory vaccination recommendations. We describe here the first case of vaccine-associated measles in a patient on natalizumab treatment. CASE PRESENTATION: A young female patient with relapsing-remitting multiple sclerosis on natalizumab treatment received the live attenuated measles, mumps, and rubella vaccine in preparation for a change in her treatment in favour of fingolimod, with established immunosuppressive qualities. Seven days after receiving the vaccine, our patient experienced diffuse muscle pain, fatigue, and thereafter developed a fever and then an erythematous maculopapular rash, compatible with vaccine associated measles. This was later confirmed by a positive measles RT-PCR throat swab. The patient's symptoms resolved without any sequelae. CONCLUSION: In this case report we review the immunosuppressive qualities of natalizumab and the evidence in favour and against live vaccines in patients on this treatment. Our findings reveal the insufficient understanding of the immunosuppressive effects of new immunomodulators, and thus of the safety of live vaccines in patients on such medications. While this case triggers precaution, there is insufficient evidence to conclude that natalizumab treatment could favor the onset of vaccine-associated measles.

Reduction in Short-term Outpatient Consultations After a Campaign With Measles Vaccine in Children Aged 9-59 Months: Substudy Within a Cluster-Randomized Trial.

BACKGROUND: We assessed a measles vaccination campaign's potential short-term adverse events. METHODS: In a cluster-randomized trial assessing a measles vaccination campaign's effect on all-cause mortality and hospital admission among children aged 9-59 months in Guinea-Bissau, children received a measles vaccination (intervention) or a health check-up (control). One month to 2 months later, we visited a subgroup of children to ask mothers/guardians about outpatient consultations since enrollment. In log-binomial models, we estimated the relative risk (RR) of nonaccidental outpatient consultations. RESULTS: Among 8319 children (4437 intervention/3882 control), 652 nonaccidental outpatient consultations occurred (322 intervention/330 control). The measles vaccination campaign tended to reduce nonaccidental outpatient consultations by 16% (RR, 0.84 [95% confidence interval {CI}, .65-1.11]), especially if caused by respiratory symptoms (RR, 0.68 [95% CI, .42-1.11]). The reduction tended to be larger in children who prior to trial enrollment had a pentavalent vaccination (diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae type b) as the most recent vaccination (RR, 0.61 [95% CI, .42-.89]) than in children who prior to trial enrollment had a routine measles vaccination as the most recent vaccination (RR, 0.93 [95% CI, .68-1.26]) (P = .04 for interaction). CONCLUSIONS: In the short term, a measles vaccination campaign seems not to increase nonaccidental outpatient consultations but may reduce them. CLINICAL TRIALS REGISTRATION: NCT03460002.

Measles Vaccine-Associated Rash Illness in China: an Emerging Issue in the Process of Measles Elimination.

Along with the implementation of measles case-based surveillance, measles vaccine-associated rash illness (VARI) cases were detected in China. To better understand the characteristics of VARI, 101 VARI cases confirmed by measles virus genotyping in 2011 to 2018 were analyzed in this study. With the decrease in measles incidence, the detection rate of VARI cases increased among the cases confirmed by genotyping. Compared with genotype H1 wild-type measles, VARI occurred throughout the year, without obvious seasonal distribution. Infants and children of ages 8 to 23 months were the main population of VARI. VARI mainly occurred within 14 days after measles vaccination. The number of VARI cases peaked on the 8th day after measles vaccination, which was later than that of genotype H1 wild-type measles cases with a measles vaccination history. VARI presents clinical symptoms similar to those of measles. The frequencies of the "3Cs" (cough, coryza, and conjunctivitis), Koplik spots, and complications in VARI cases were significantly lower than those in wild-type measles cases. In total, 94.06% of sequences from VARI cases were identical to measles vaccine strain S191 in the C-terminal 450-nucleotide sequence of the nucleoprotein (N-450) gene. A few substitutions were found in N-450 sequences of the VARI cases. The confirmation of VARI has become an emerging issue in the process of measles elimination. Rapid confirmation of VARI is critical for measles surveillance and will help to determine the response measures for measles, especially in measles preelimination and elimination settings. The suspected measles cases with measles-containing vaccine (MCV) vaccination were recommended to be tested by the laboratory to identify wild-type measles or VARI.

Cases of aseptic meningitis after vaccination against mumps in Russia (2009-2019).

OBJECTIVES: Mumps is a highly contagious viral infection prevented by immunization with live attenuated vaccines. Mumps vaccines have proven to be safe and effective; however, rare cases of aseptic meningitis (AM) can occur after vaccination. The range of meningitis occurrence varies by different factors (strain, vaccine producer, and so on). Monovaccines or divaccines (mumps-measles vaccine), prepared from the strain Leningrad-3 (L-3), are used in Russia. Meningitis occurrence after vaccination has been established previously as very low. Nevertheless, with the number of children being vaccinated every year, vaccine-associated AM cases still occur. There is no official statistics on AM incidence after mumps vaccines, and information on AM features as an adverse event of mumps vaccination is limited and mostly devoted to vaccines, prepared from strains other than L-3. STUDY DESIGN: The study included patients with AM who were vaccinated against mumps in the previous 30 days before the present disease onset during 2009-2019. METHODS: Patients admitted to Infectious Clinical Hospital No. 1, Moscow, Russia, with AM were observed by a pediatrician and were screened for etiological agents of meningitis. RESULTS: Seven patients were enrolled, and clinical features and the course of infection are presented. CONCLUSIONS: Detection of only 7 cases of AM associated with mumps vaccination during the 10-year period supports very low occurrence of this adverse event after immunization with the L-3 strain-based mumps vaccines. Nevertheless, the annual number of AM cases that occur after mumps vaccination remains unknown and poorly diagnosed in practice because of the low awareness of physicians of this adverse reaction. Detection and objective coverage of such cases can lead to a weakening of 'antivaccination' moods in a society and to restoration of confidence in the healthcare system.

Is it or is it not? Lessons learned from a case of suspected vaccine strain measles.

OBJECTIVE: Measles continues to be a threat to Australia. While post-eradication risks are low, imported measles cases from overseas travellers who are non-immune can cause small outbreaks. This case report discusses the challenge of identifying wild-type measles in an individual who was recently vaccinated with measles-containing vaccine (MCV). METHODS: A positive polymerase chain reaction (PCR) result for measles for an adult who had recently received a measles-containing vaccine was notified. Investigation revealed no known epidemiological link, recent overseas travel or contact with recent measles cases during the incubation period. RESULTS: The results of the initial sequencing to distinguish between wild-type and vaccine-strain measles were inconclusive. A decision was made to re-run the genotyping, collect additional specimens and quarantine the case until a definitive result was obtained. Sequencing and genotyping revealed that this indeed was a wild-type measles strain. CONCLUSIONS: Changing epidemiology of measles means distinguishing between wild-type and vaccine-strain measles has become a new challenge. Implications for public health: The reflection of the public health management of this case has provided a valuable teaching tool for public health professionals globally, particularly in low incidence measles countries.

Identifying Vaccine-associated Rash Illness Amidst a Large Measles Outbreak: Minnesota, 2017.

Characteristics of vaccine-associated rash illness (VARI) and confirmed measles cases were compared during a measles outbreak. Although some clinical differences were noted, measles exposure and identification of the vaccine strain were helpful for public health decision-making. Rapid, vaccine strain-specific diagnostic assays will more efficiently distinguish VARI from measles.

Emergent measles-containing vaccination recommendation for aged 6-11 months and detection of vaccine-associated measles during a large measles outbreak in Okinawa, Japan, in 2018.

Okinawa Prefecture, Japan, experienced a large measles outbreak from March to May 2018. During this outbreak, there were 99 laboratory-confirmed cases and 14 vaccine-associated measles cases. In addition to the reinforcement of routine immunization, Okinawa prefectural government introduced emergent measles-containing vaccination recommendations for infants aged 6-11 months as part of the outbreak response. Increased concern exists in Okinawa about measles in infants following a previous outbreak from 1998 to 2001, when nine children including four infants died. Of 8062 infants aged 6-11 months who received measles-containing vaccine (MCV), six developed vaccine-associated measles; incidence was 0.74 per 1000 doses (95%CI 0.27-1.62). This was similar to that of first dose routine immunization recipients at one year of age (IR 0.60, 95%CI 0.20-1.78). Among 14 vaccine-associated measles cases, throat swab samples showed the highest positive rate (92.9%) by real-time reverse transcription polymerase chain reaction (RT-qPCR), followed by urine (25.0%) and whole blood (7.7%) samples. Furthermore, one throat swab sample classified as equivocal by RT-qPCR was positive by conventional RT-PCR (RT-PCR). During an outbreak, it is critical to distinguish between cases with measles-like symptoms caused by wild circulating virus and those caused by vaccine-derived virus as accurately and urgently as possible because the public health response will be quite different. No infant deaths were observed during this outbreak, and no severe adverse events following immunization were seen among infants 6-11 months old who were given MCV as a public health response. Thus, we conclude that introduction of emergent MCV was effective and describing the characteristics of vaccine-associated measles cases during a measles outbreak will be helpful for future outbreak response efforts.

Transverse myelitis following measles vaccination in a rhesus macaque (Macaca mulatta).

A 16-year-old rhesus macaque presented with progressive, ascending quadriparesis following measles vaccination. He was diagnosed with transverse myelitis following MRI, gross necropsy, and histopathology. This is the first report of transverse myelitis in a rhesus macaque following measles vaccination.