A measles and rubella vaccine microneedle patch in The Gambia: a phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial.

BACKGROUND: Microneedle patches (MNPs) have been ranked as the highest global priority innovation for overcoming immunisation barriers in low-income and middle-income countries. This trial aimed to provide the first data on the tolerability, safety, and immunogenicity of a measles and rubella vaccine (MRV)-MNP in children. METHODS: This single-centre, phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial was conducted in The Gambia. To be eligible, all participants had to be healthy according to prespecified criteria, aged 18-40 years for the adult cohort, 15-18 months for toddlers, or 9-10 months for infants, and to be available for visits throughout the follow-up period. The three age cohorts were randomly assigned in a 2:1 ratio (adults) or 1:1 ratio (toddlers and infants) to receive either an MRV-MNP (Micron Biomedical, Atlanta, GA, USA) and a placebo (0·9% sodium chloride) subcutaneous injection, or a placebo-MNP and an MRV subcutaneous injection (MRV-SC; Serum Institute of India, Pune, India). Unmasked staff ransomly assigned the participants using an online application, and they prepared visually identical preparations of the MRV-MNP or placebo-MNP and MRV-SC or placebo-SC, but were not involved in collecting endpoint data. Staff administering the study interventions, participants, parents, and study staff assessing trial endpoints were masked to treatment allocation. The safety population consists of all vaccinated participants, and analysis was conducted according to route of MRV administration, irrespective of subsequent protocol deviations. The immunogenicity population consisted of all vaccinated participants who had a baseline and day 42 visit result available, and who had no protocol deviations considered to substantially affect the immunogenicity endpoints. Solicited local and systemic adverse events were collected for 14 days following vaccination. Unsolicited adverse events were collected to day 180. Age de-escalation between cohorts was based on the review of the safety data to day 14 by an independent data monitoring committee. Serum neutralising antibodies to measles and rubella were measured at baseline, day 42, and day 180. Analysis was descriptive and included safety events, seroprotection and seroconversion rates, and geometric mean antibody concentrations. The trial was registered with the Pan African Clinical Trials Registry PACTR202008836432905, and is complete. FINDINGS: Recruitment took place between May 18, 2021, and May 27, 2022. 45 adults, 120 toddlers, and 120 infants were randomly allocated and vaccinated. There were no safety concerns in the first 14 days following vaccination in either adults or toddlers, and age de-escalation proceeded accordingly. In infants, 93% (52/56; 95% CI 83·0-97·2) seroconverted to measles and 100% (58/58; 93·8-100) seroconverted to rubella following MRV-MNP administration, while 90% (52/58; 79·2-95·2) and 100% (59/59; 93·9-100) seroconverted to measles and rubella respectively, following MRV-SC. Induration at the MRV-MNP application site was the most frequent local reaction occurring in 46 (77%) of 60 toddlers and 39 (65%) of 60 infants. Related unsolicited adverse events, most commonly discolouration at the application site, were reported in 35 (58%) of 60 toddlers and 57 (95%) of 60 infants that had received the MRV-MNP. All local reactions were mild. There were no related severe or serious adverse events. INTERPRETATION: The safety and immunogenicity data support the accelerated development of the MRV-MNP. FUNDING: Bill & Melinda Gates Foundation.

What's going on with measles?

Measles is a highly transmissible systemic viral infection associated with substantial mortality primarily due to secondary infections. Measles induces lifelong immunity to reinfection but loss of immunity to other pathogens. An attenuated live virus vaccine is highly effective, but lapses in delivery have resulted in increasing cases worldwide. Although the primary cause of failure to control measles is failure to vaccinate, waning vaccine-induced immunity and the possible emergence of more virulent virus strains may also contribute.

A measles-vectored vaccine candidate expressing prefusion-stabilized SARS-CoV-2 spike protein brought to phase I/II clinical trials: candidate selection in a preclinical murine model.

In the early COVID-19 pandemic with urgent need for countermeasures, we aimed at developing a replicating viral vaccine using the highly efficacious measles vaccine as vector, a promising technology with prior clinical proof of concept. Building on our successful pre-clinical development of a measles virus (MV)-based vaccine candidate against the related SARS-CoV, we evaluated several recombinant MV expressing codon-optimized SARS-CoV-2 spike glycoprotein. Candidate V591 expressing a prefusion-stabilized spike through introduction of two proline residues in HR1 hinge loop, together with deleted S1/S2 furin cleavage site and additional inactivation of the endoplasmic reticulum retrieval signal, was the most potent in eliciting neutralizing antibodies in mice. After single immunization, V591 induced similar neutralization titers as observed in sera of convalescent patients. The cellular immune response was confirmed to be Th1 skewed. V591 conferred long-lasting protection against SARS-CoV-2 challenge in a murine model with marked decrease in viral RNA load, absence of detectable infectious virus loads, and reduced lesions in the lungs. V591 was furthermore efficacious in an established non-human primate model of disease (see companion article [S. Nambulli, N. Escriou, L. J. Rennick, M. J. Demers, N. L. Tilston-Lunel et al., J Virol 98:e01762-23, 2024, https://doi.org/10.1128/jvi.01762-23]). Thus, V591 was taken forward into phase I/II clinical trials in August 2020. Unexpected low immunogenicity in humans (O. Launay, C. Artaud, M. Lachâtre, M. Ait-Ahmed, J. Klein et al., eBioMedicine 75:103810, 2022, https://doi.org/10.1016/j.ebiom.2021.103810) revealed that the underlying mechanisms for resistance or sensitivity to pre-existing anti-measles immunity are not yet understood. Different hypotheses are discussed here, which will be important to investigate for further development of the measles-vectored vaccine platform.IMPORTANCESARS-CoV-2 emerged at the end of 2019 and rapidly spread worldwide causing the COVID-19 pandemic that urgently called for vaccines. We developed a vaccine candidate using the highly efficacious measles vaccine as vector, a technology which has proved highly promising in clinical trials for other pathogens. We report here and in the companion article by Nambulli et al. (J Virol 98:e01762-23, 2024, https://doi.org/10.1128/jvi.01762-23) the design, selection, and preclinical efficacy of the V591 vaccine candidate that was moved into clinical development in August 2020, 7 months after the identification of SARS-CoV-2 in Wuhan. These unique in-human trials of a measles vector-based COVID-19 vaccine revealed insufficient immunogenicity, which may be the consequence of previous exposure to the pediatric measles vaccine. The three studies together in mice, primates, and humans provide a unique insight into the measles-vectored vaccine platform, raising potential limitations of surrogate preclinical models and calling for further refinement of the platform.

Onward Virus Transmission after Measles Secondary Vaccination Failure.

Measles in persons with secondary vaccination failure (SVF) may be less infectious than cases in unvaccinated persons. Our systematic review aimed to assess transmission risk for measles after SVF. We searched PubMed, Embase, and Web of Science databases from their inception dates. Inclusion criteria were articles describing persons who were exposed to measles-infected persons who had experienced SVF. Across the included 14 studies, >3,030 persons were exposed to measles virus from SVF cases, of whom 180 were susceptible, indicating secondary attack rates of 0%-6.25%. We identified 109 cases of SVF from the studies; 10.09% (n = 11) of case-patients transmitted the virus, resulting in 23 further cases and yielding an effective reproduction number of 0.063 (95% CI 0.0-0.5). These findings suggest a remarkably low attack rate for SVF measles cases, suggesting that, In outbreak situations, public health management of unvaccinated persons could be prioritized over persons with SVF.

Analysis of Suspected Measles Cases with Discrepant Measles-Specific IgM and rRT-PCR Test Results, Japan.

We investigated clinically suspected measles cases that had discrepant real-time reverse transcription PCR (rRT-PCR) and measles-specific IgM test results to determine diagnoses. We performed rRT-PCR and measles-specific IgM testing on samples from 541 suspected measles cases. Of the 24 IgM-positive and rRT-PCR--negative cases, 20 were among children who received a measles-containing vaccine within the previous 6 months; most had low IgG relative avidity indexes (RAIs). The other 4 cases were among adults who had an unknown previous measles history, unknown vaccination status, and high RAIs. We detected viral nucleic acid for viruses other than measles in 15 (62.5%) of the 24 cases with discrepant rRT-PCR and IgM test results. Measles vaccination, measles history, and contact history should be considered in suspected measles cases with discrepant rRT-PCR and IgM test results. If in doubt, measles IgG avidity and PCR testing for other febrile exanthematous viruses can help confirm or refute the diagnosis.

Immunogenicity, safety, and tolerability of a recombinant measles-vectored Lassa fever vaccine: a randomised, placebo-controlled, first-in-human trial.

BACKGROUND: Lassa fever is a substantial health burden in west Africa. We evaluated the safety, tolerability, and immunogenicity of a recombinant, live-attenuated, measles-vectored Lassa fever vaccine candidate (MV-LASV). METHODS: This first-in-human phase 1 trial-consisting of an open-label dose-escalation stage and an observer-blinded, randomised, placebo-controlled treatment stage-was conducted at a single site at the University of Antwerp, Antwerp, Belgium, and involved healthy adults aged 18-55 years. Participants in the dose-escalation stage were sequentially assigned to a low-dose group (two intramuscular doses of MV-LASV at 2 × 104 times the median tissue culture infectious dose) or a high-dose group (two doses at 1 × 105 times the median tissue culture infectious dose). Participants in the double-blinded treatment stage were randomly assigned in a 2:2:1 ratio to receive low dose, high dose, or placebo. The primary endpoint was the rate of solicited and unsolicited adverse events up to study day 56 and was assessed in all participants who received at least one dose of investigational product. The trial is registered with ClinicalTrials.gov, NCT04055454, and the European Union Drug Regulating Authorities Clinical Trials Database, 2018-003647-40, and is complete. FINDINGS: Between Sept 26, 2019, and Jan 20, 2020, 60 participants were enrolled and assigned to receive placebo (n=12) or MV-LASV (n=48). All 60 participants received at least one study treatment. Most adverse events occurred during the treatment phase, and frequencies of total solicited or unsolicited adverse events were similar between treatment groups, with 96% of participants in the low-dose group, 100% of those in the high-dose group, and 92% of those in the placebo group having any solicited adverse event (p=0·6751) and 76% of those in the low-dose group, 70% of those in the high-dose group, and 100% of those in the placebo group having any unsolicited adverse event (p=0·1047). The only significant difference related to local solicited adverse events, with higher frequencies observed in groups receiving MV-LASV (24 [96%] of 25 participants in the low-dose group; all 23 [100%] participants in the high-dose group) than in the placebo group (6 [50%] of 12 participants; p=0·0001, Fisher-Freeman-Halton test). Adverse events were mostly of mild or moderate severity, and no serious adverse events were observed. MV-LASV also induced substantial concentrations of LASV-specific IgG (geometric mean titre 62·9 EU/ml in the low-dose group and 145·9 EU/ml in the high-dose group on day 42). INTERPRETATION: MV-LASV showed an acceptable safety and tolerability profile, and immunogenicity seemed to be unaffected by pre-existing immunity against the vector. MV-LASV is therefore a promising candidate for further development. FUNDING: Coalition for Epidemic Preparedness Innovations.

Vaccine-induced neutralizing antibodies bind to the H protein of a historical measles virus.

Measles is a highly contagious airborne viral disease. It can lead to serious complications and death and is preventable by vaccination. The live-attenuated measles vaccine (LAMV) derived from a measles virus (MV) isolated in 1954 has been in use globally for six decades and protects effectively by providing a durable humoral and cell-mediated immunity. Our study addresses the temporal stability of epitopes on the viral surface glycoprotein hemagglutinin (H) which is the major target of MV-neutralizing antibodies. We investigated the binding of seven vaccine-induced MV-H-specific monoclonal antibodies (mAbs) to cell-free synthesized MV-H proteins derived from the H gene sequences obtained from a lung specimen of a fatal case of measles pneumonia in 1912 and an isolate from a current case. The binding of four out of seven mAbs to the H protein of both MV strains provides evidence of epitopes that are stable for more than 100 years. The binding of the universally neutralizing mAbs RKI-MV-12b and RKI-MV-34c to the H protein of the 1912 MV suggests the long-term stability of highly conserved epitopes on the MV surface.

Measles outbreak in the adult age group: Clinical, laboratory, and epidemiological features of the 11 patients admitted to the hospital.

The measles virus, also known as the morbillivirus, or MV, is a virus that infects humans. The goal of this research is to assess to adult cases of measles. Eleven patients thought to be confirmed cases of measles were enrolled in the investigation. Following the identification of symptoms of tiredness, fever, and rash in one soldier, the results of 10 more troops from the pertinent military group were assessed. The diagnosis was made based on the presence of serum immunoglobulin M (IgM) and positive polymerase chain reaction (PCR) results. When the control IgM, immunoglobulin G, and PCR findings were evaluated a fortnight after hospitalization, a cluster of 11 incidents was found. It is now necessary to address the issue of the cautious stance towards vaccination or the anti-vaccination sentiment that has grown increasingly popular, particularly in light of the COVID-19 pandemic, for both our nation and the entire world.

Global vaccine coverage and childhood survival estimates: 1990-2019.

Objective: To quantify the association between reduction in child mortality and routine immunization across 204 countries and territories from 1990 to 2019. Methods: We used child mortality and vaccine coverage data from the Global Burden of Disease Study. We used a modified child survival framework and applied a mixed-effects regression model to estimate the reduction in deaths in children younger than 5 years associated with eight vaccines. Findings: Between 1990 and 2019, the diphtheria-tetanus-pertussis (DTP), measles, rotavirus and Haemophilus influenzae type b vaccines were significantly associated with an estimated 86.9 (95% confidence interval, CI: 57.2 to 132.4) million fewer deaths in children younger than 5 years worldwide. This decrease represented a 24.2% (95% CI: 19.8 to 28.9) reduction in deaths relative to a scenario without vaccines. The DTP and measles vaccines averted 46.7 (95% CI: 30.0 to 72.7) million and 37.9 (95% CI: 25.4 to 56.8) million deaths, respectively. Of the total reduction in child mortality associated with vaccines, 84.2% (95% CI: 83.0 to 85.1) occurred in 73 countries supported by Gavi, the Vaccine Alliance, with an estimated 45.4 (95% CI: 29.8 to 69.2) million fewer deaths from 2000 to 2019. The largest reductions in deaths associated with these four vaccines were in India, China, Ethiopia, Pakistan and Bangladesh (in order of the size of reduction). Conclusion: Vaccines continue to reduce childhood mortality significantly, especially in Gavi-supported countries, emphasizing the need for increased investment in routine immunization programmes.

Measles Outbreak Associated with a Migrant Shelter - Chicago, Illinois, February-May 2024.

Measles, a highly contagious respiratory virus with the potential to cause severe complications, hospitalization, and death, was declared eliminated from the United States in 2000; however, with ongoing global transmission, infections in the United States still occur. On March 7, 2024, the Chicago Department of Public Health (CDPH) confirmed a case of measles in a male aged 1 year residing in a temporary shelter for migrants in Chicago. Given the congregate nature of the setting, high transmissibility of measles, and low measles vaccination coverage among shelter residents, measles virus had the potential to spread rapidly among approximately 2,100 presumed exposed shelter residents. CDPH immediately instituted outbreak investigation and response activities in collaboration with state and local health departments, health care facilities, city agencies, and shelters. On March 8, CDPH implemented active case-finding and coordinated a mass vaccination campaign at the affected shelter (shelter A), including vaccinating 882 residents and verifying previous vaccination for 784 residents over 3 days. These activities resulted in 93% measles vaccination coverage (defined as receipt of ≥1 recorded measles vaccine dose) by March 11. By May 13, a total of 57 confirmed measles cases associated with residing in or having contact with persons from shelter A had been reported. Most cases (41; 72%) were among persons who did not have documentation of measles vaccination and were considered unvaccinated. In addition, 16 cases of measles occurred among persons who had received ≥1 measles vaccine dose ≥21 days before first known exposure. This outbreak underscores the need to ensure high vaccination coverage among communities residing in congregate settings.

Progress Toward Measles Elimination - World Health Organization Eastern Mediterranean Region, 2019-2022.

In 2015, all 22 World Health Organization Eastern Mediterranean Region (EMR) countries and areas (countries) pledged to achieve measles elimination by 2020. Despite success in several countries, most countries in the region still have not eliminated measles. This report updates a previous report and describes progress toward measles elimination in EMR during 2019-2022. During that period, estimated regional coverage with the first and second doses of a measles-containing vaccine (MCV) was 82%-83% and 76%-78%, respectively. During 2019-2022, approximately 160 million children were vaccinated during national or subnational supplementary immunization activities. Reported confirmed regional measles incidence decreased from 29.8 cases per 1 million population in 2019 to 7.4 in 2020, but then increased 68%, to 50.0 in 2022 because of challenges providing immunization services and conducting surveillance during the COVID-19 pandemic. Surveillance indicators deteriorated in 11 (50%) of the 22 EMR countries. During 2019-2022, four countries in the region were verified as having achieved measles elimination, but other countries reported immunity gaps and increased measles incidence in 2022. To achieve measles elimination in EMR, national immunization programs, especially in those countries with high measles incidence, will need to continue to recover from the COVID-19 pandemic, increase overall vaccination coverage to close immunity gaps, and maintain high-quality disease surveillance.

Guarding the gatekeepers: a comprehensive approach to control nosocomial measles.

PURPOSE: Despite substantial vaccination progress, persistent measles outbreaks challenge global elimination efforts, particularly within healthcare settings. In this paper, we critically review the factors contributing to measles outbreak and effective control measures for nosocomial transmission of measles. METHODS: We systematically searched electronic databases for articles up to 17th May, 2023. This was performed by two independent reviewers, with any disagreements resolved by a third reviewer. We also searched governmental and international health agencies for relevant studies. RESULTS: Forty relevant articles were systematically reviewed, revealing key factors fuelling measles outbreak in healthcare settings, including high transmissibility capability; high intensity exposure; delayed care; failure to use protective equipment and implement control measures; vaccine failure; unclear immunisation history and lack of registries; and lacking recommendation on healthcare workers' (HCWs) measles vaccination. To combat these challenges, successful control strategies were identified which include early notification of outbreak and contact tracing; triaging all cases and setting up dedicated isolation unit; strengthening protective equipment use and physical measures; improving case detection; determining immunity status of HCWs; establishing policy for measles vaccination for HCWs; management of exposed personnel; and developing a pre-incident response plan. CONCLUSION: A coordinated and comprehensive approach is essential to promptly identify and manage measles cases within healthcare settings, necessitating multifactorial strategies tailored to individual settings. These findings provide a valuable foundation for refining strategies to achieve and maintain measles elimination status in healthcare environments.

Epidemiology of measles outbreaks, incidence and associated risk factors in Ethiopia from 2000 to 2023: a systematic review and meta-analysis.

BACKGROUND: Although a universal vaccine is available and Ethiopia is working outstandingly towards measles elimination, a recurrent measles outbreak has occurred each year in different parts of the country. Therefore, understanding the epidemiology of measles cases, the incidence of confirmed measles virus cases and related risk factors is crucial. Here, we conducted a systematic review and meta-analysis to summarize information regarding the epidemiology, measles incidence rate and risk factors for national measles infections occurring in the past two decades, from 2000 to 2023. METHODS: Data from electronic databases, including PubMed, African Journal Online, WHO databases and Google Scholars, were searched to identify studies describing measles outbreaks, incidence rates and associated factors in Ethiopia that occurred between 2000 and 2023. Important basic information was extracted in an Excel spreadsheet and imported into Comprehensive Meta-analysis Software version 3 to evaluate the associations between measles outbreaks and different risk factors. We pooled the odds ratios (ORs) and 95% confidence intervals (CIs) for every included risk factor to evaluate the associations with measles outbreaks. RESULTS: We included 36 studies involving 132,502 patients with confirmed measles cases in Ethiopia. The results of this systematic review and meta-analysis revealed that measles outbreaks were more frequently reported in the Oromia region (73,310 (33.1%)), followed by the Southern Nation Nationalities of Ethiopia region (29,057 (13.4%)). The overall pooled analysis indicated that the prevalence of measles susceptibility was 67.5% (95% CI: 67.3-67.8%), with an I2 of 99.86% and a p value for heterogeneity < 0.0001. The non-vaccinated status of the children, their contact history with measles cases, their travel history, the presence of cases in family or neighbors, and malnourished patients were identified as factors associated with the high prevalence and recurrent measles infections in Ethiopia. CONCLUSION: The results of this systematic review and meta-analysis indicated that the pooled prevalence of measles infection was high, which is a public health concern in Ethiopia. Thus, strengthening healthcare services, regular vaccination campaigns, and the integration of health education activities with other services may decrease the incidence rate.

Hospital-acquired infections and unvaccinated children due to chronic diseases: an investigation of the 2017-2019 measles outbreak in the northern region of Vietnam.

BACKGROUND: Measles remains a major public health burden worldwide. Parents often hesitate to vaccinate children with chronic diseases. We investigated the association between the percentage of vaccination and chronic diseases and explore hospital infections' role in the 2017-2019 measles outbreak across northern Vietnam provinces. METHODS: A total of 2,064 children aged 0-15 years old admitted for measles to the National Children's Hospital during the outbreak were included in the study. Demographic information, clinical characteristics, vaccination statuses and laboratory examination were extracted from electronic medical records, vaccination records, or interviews with parents when other sources were unavailable. RESULTS: The incidence rate that provincial hospitals sent to the National Children's Hospital was proportional to the population density of their provinces of residence. Early nosocomial transmission of measles was observed before community-acquired cases emerged in many provinces. Among patients aged over 18 months, those with chronic diseases had a proportion of vaccination of 9.4%, lower than patients without chronic diseases at 32.4%. Unvaccinated patients had a higher proportion of hospital-acquired infections with aOR = 2.42 (1.65-3.65), p < 0.001 relative to vaccinated patients. The proportion of hospital-acquired infections was higher among children with chronic diseases compared to those without, with aOR = 3.81 (2.90-5.02), p < 0.001. CONCLUSION: Measles spread in healthcare settings prior to community cases that occurred in several provinces. We recommend enhancing hospital infection control by increasing staff training and improving early detection and isolation during non-outbreak periods. Measles patients with chronic diseases exhibited lower proportions of vaccination and faced a higher risk of hospital-acquired infections. It is crucial to establish comprehensive vaccination guidelines and enhance parental awareness regarding the significance and safety of measles vaccination to protect these vulnerable individuals.

Interplay of missed opportunity for vaccination and poor response to the vaccine led to measles outbreak in a slum area of Eastern Mumbai, India.

In the third week of September 2022, an outbreak of measles was reported from a slum in Eastern Mumbai, India. We sought to investigate whether failure to vaccinate or vaccine failure was the cause. We constructed an epidemic curve, drew a spot map, and calculated the attack rate and case-fatality ratio. We calculated vaccine effectiveness (VE) for one and two doses of measles vaccine in an unmatched case-control study and did stratified analysis by sex, availability of vaccination card, and migrant status. We identified 358 cases and four deaths with a 11.3% attack rate and 1.1% case fatality, both being highest among 0-24-month-old boys. The epidemic curve suggested a propagated mode of spread. The VE for two doses was 64% (95% confidence interval (CI): 23-73%) among under-5-year-old children and 70% (95% CI: 28-88%) among 5-15-year-old children. Failure to vaccinate, consequent to the COVID-19 pandemic, and vaccine hesitancy might have led to the accumulation of susceptible children in the community. Additionally, the occurrence of case-patients among vaccinated suggests reduced VE, which needs further investigation into humoral and cell-mediated immunity as well as contributory factors including nutritional status. Outbreak response immunization to complete immunization of missed and dropout children was carried out to control the outbreak.

Assessing measles risk transmission in Iran: a utilization of the World Health Organization's programmatic risk assessment tool,2022.

BACKGROUND: Despite successful efforts to eliminate measles in Iran, imported measles cases continue to be reported. Because measles is endemic in neighboring countries. This research aims to evaluate the risk of measles transmission in different regions of Iran. METHODS: Measles case-based surveillance data of the Expanded Program of Immunization containing 31 provinces and 463 districts from 2019 to 2021 were assessed. The WHO Measles Programmatic Risk Assessment tool was used to evaluate the risk of disease transmission in four domains: population immunity, surveillance quality, program delivery performance, and threat assessment. scores were categorized as low, medium, high, or very high risk. RESULTS: During 2019-2021, the average incidence of measles was 1.9 per 1 million. Chabahar and Mashhad with 76 and ./6per million reported the highest and lowest incidence respectively. All 463 districts were categorized as low risk in risk assessment. Andimeshk, Chabahar, and Bojnurd obtained the highest risk scores with 27, 24, and 25 respectively. All districts were classified as low risk for population immunity. The average coverage of (MMR1) and (MMR2) was 95% or higher. All districts received the minimum points for surveillance quality. CONCLUSION: All regions are placed at a low level of disease transmission risk. However, the tool is not able to assess the risk at the rural or peripheral sectors level. The indicators used in this tool are the same for all countries with different epidemiological features (elimination, endemic). Sensitivity analysis can optimize the use of this tool for countries with different disease conditions.

Incomplete Immunity for Varicella and Measles in Pediatric Organ Transplant Candidates. Real World Experience From an Infectious Diseases Pre-Transplantation Clinic.

BACKGROUND: Vaccinating pediatric solid organ transplant candidates against measles and varicella is crucial due to the risk of severe disease in immunosuppressed recipients and general avoidance of live virus vaccines post-transplantation. The world saw a resurgence of measles starting 2012 prompting the American Society of Transplantation in 2015 to release guidelines on recognition, prevention, and post-exposure prophylaxis of this disease in solid transplant recipients. This study aims to assess the extent of incomplete immunity to these viruses in candidates and the approach to immunity optimization during a period of heightened awareness. METHODS: A cross-sectional study from 2012 to 2016 at Cleveland Clinic Children's included pediatric solid organ transplant candidates. Data on vaccination history, serology, and demographics were collected. Incomplete immunity was defined by incomplete vaccination or seronegativity. RESULTS: Among 91 candidates, 54.9% had complete varicella vaccination. Serological varicella immunity among patients tested varied by age: < 7 years, 50.0% positive in patients with complete schedules, none in the incomplete; ≥ 7 years, 50.0% positive in patients with complete schedules, 65.5% in the incomplete. For measles, 69.2% had complete vaccination, with immunity varying by age among those tested: < 7 years, 84.6% positive in patients with complete schedules, 42.9% in the incomplete; ≥ 7 years, 81.0% with complete, 62.5% with incomplete. Only 31.1% of those who qualified for a varicella additional dose and 28% who qualified for an additional measles dose received it, respectively. CONCLUSIONS: Incomplete immunity to varicella and measles was prevalent in pediatric solid organ transplant candidates at our center during the study period. Despite an increase in global measles activity, our efforts to optimize immunity through additional vaccine doses were only partially successful. Future research should focus on addressing strategies and understanding barriers to ensure timely vaccination for this vulnerable population prior to transplant, especially during periods of increased viral activity.

Steroid use in measles: A retrospective cohort study during the 2017 outbreak in tertiary referral center, Rome and Latina, Italy.

INTRODUCTION: Since early January 2017, a new measles outbreak in Italy has been observed. The aim of the study was to compare features between adults and children measles cases and evaluate the effect of steroid treatment on the above parameters. METHODS: A retrospective multicenter, descriptive study was performed. We analyzed all patients admitted to the Department of Public Health and Infectious Diseases, Sapienza University, Rome and Latina, from January 2017 to December 2017 and discharged with diagnosis of measles. RESULTS: We identified 113 patients discharged with the diagnosis of measles infection cases of which 59 adults and 54 children (≤16 years). In adult population 32 patients (54 %) were males, with a median age of 30.5 years old and all unvaccinated (100 %). Keratoconjunctivitis 30 (50 %) was the most frequent complication. In pediatric population 27 (50 %) patients were males, with a median age of 3 years old. Information on measles vaccination status was available for only 21 (38.8 %) of cases. Keratoconjunctivitis 40 (74 %) was the most frequent complication. Analyzing the differences between adult and pediatric patients we found that children were significantly more likely to have keratoconjunctivitis and diarrhea as complications than adults in which the rate of thrombocytopenia and hepatitis was highest. Thirty-nine adult subjects (66 %) have been treated with systemic corticosteroids. CONCLUSIONS: Pediatric patients differ from adults in complications and liver involvement. Regarding steroids use, although there is no clear indication of steroid use during measles, there is no evidence of a worse outcome in our cases series.

Equity in vaccine coverage in Uganda from 2000 to 2016: revealing the multifaceted nature of inequity.

BACKGROUND: This study analyses vaccine coverage and equity among children under five years of age in Uganda based on the 2016 Uganda Demographic and Health Survey (UDHS) dataset. Understanding equity in vaccine access and the determinants is crucial for the redress of emerging as well as persistent inequities. METHODS: Applied to the UDHS for 2000, 2006, 2011, and 2016, the Vaccine Economics Research for Sustainability and Equity (VERSE) Equity Toolkit provides a multivariate assessment of immunization coverage and equity by (1) ranking the sample population with a composite direct unfairness index, (2) generating quantitative measure of efficiency (coverage) and equity, and (3) decomposing inequity into its contributing factors. The direct unfairness ranking variable is the predicted vaccination coverage from a logistic model based upon fair and unfair sources of variation in vaccination coverage. Our fair source of variation is defined as the child's age - children too young to receive routine immunization are not expected to be vaccinated. Unfair sources of variation are the child's region of residence, and whether they live in an urban or rural area, the mother's education level, the household's socioeconomic status, the child's sex, and their insurance coverage status. For each unfair source of variation, we identify a "more privileged" situation. RESULTS: The coverage and equity of the Diphtheria-Pertussis-Tetanus vaccine, 3rd dose (DPT3) and the Measles-Containing Vaccine, 1st dose (MCV1) - two vaccines indicative of the health system's performance - improved significantly since 2000, from 49.7% to 76.8% and 67.8% to 82.7%, respectively, and there are fewer zero-dose children: from 8.4% to 2.2%. Improvements in retaining children in the program so that they complete the immunization schedule are more modest (from 38.1% to 40.8%). Progress in coverage was pro-poor, with concentration indices (wealth only) moving from 0.127 (DPT3) and 0.123 (MCV1) in 2000 to -0.042 and -0.029 in 2016. Gains in overall equity (composite) were more modest, albeit significant for most vaccines except for MCV1: concentration indices of 0.150 (DPT3) and 0.087 (MCV1) in 2000 and 0.054 and 0.055 in 2016. The influence of the region and settings (urban/rural) of residence significantly decreased since 2000. CONCLUSION: The past two decades have seen significant improvements in vaccine coverage and equity, thanks to the efforts to strengthen routine immunization and ongoing supplemental immunization activities such as the Family Health Days. While maintaining the regular provision of vaccines to all regions, efforts should be made to alleviate the impact of low maternal education and literacy on vaccination uptake.

Health system barriers to the first dose of measles immunization in Ethiopia: a qualitative study.

BACKGROUND: Ethiopia has made considerable progress toward measles elimination. Despite ongoing efforts, the country remains among those with the highest number of children missing their initial dose of measles vaccine, and the disease continues to be a public health emergency. The barriers within the health system that hinder the first dose of measles immunization have not been thoroughly investigated. This study aims to identify these barriers within the Ethiopian context. METHODS: Qualitative research, using purposive expert sampling to select key informants from health organizations in Addis Ababa, Ethiopia was employed. We conducted in-depth face-to-face interviews using a semi-structured interview guide. A thematic analysis based on the World Health Organization's health systems building blocks framework was conducted. RESULTS: The study uncovered substantial health system barriers to the uptake of the first dose of the measles vaccine in Ethiopia. These barriers include; restricted availability of immunization services, vaccine stockouts, shortage of cold chain technologies, data inaccuracy resulting from deliberate data falsification or accidental manipulation of data, as well as data incompleteness. CONCLUSION: Our research highlighted significant health system barriers to MCV1 immunization, contributing to unmet EPI targets in Ethiopia. Our results suggest that to accelerate the country towards measles elimination, there is an urgent need to improve the health systems components such as service delivery, information systems, as well as access to vaccine and cold chain technologies.