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Lancet (London, England) May 2024Microneedle patches (MNPs) have been ranked as the highest global priority innovation for overcoming immunisation barriers in low-income and middle-income countries.... (Randomized Controlled Trial)
Randomized Controlled 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.
Topics: Humans; Double-Blind Method; Gambia; Female; Male; Rubella Vaccine; Infant; Measles Vaccine; Adult; Adolescent; Rubella; Young Adult; Measles; Needles; Antibodies, Viral
PubMed: 38697170
DOI: 10.1016/S0140-6736(24)00532-4 -
Public Health Reports (Washington, D.C.... 2019The modern era of vaccination was heralded with the licensure of the first 2 measles vaccines in 1963. This new era was distinct from the preceding era of vaccination...
The modern era of vaccination was heralded with the licensure of the first 2 measles vaccines in 1963. This new era was distinct from the preceding era of vaccination for 4 main reasons. First, federal leadership in support of immunization at the local level grew. Second, immunization proponents championed the required vaccination of children as the best means of ensuring a protected population. Third, immunization proponents championed the idea that mass vaccination would not only help manage infectious diseases but also eradicate them. Fourth, the focus of local and federally supported immunization initiatives began to extend to the "mild" and "moderate" diseases of childhood (eg, measles), so-called because they were seen as less severe than previous targets of mass vaccination, such as smallpox, polio, and diphtheria. This article follows the history of measles to explore immunization successes and challenges in this modern era, because measles was the first of the mild and moderate diseases to become the target of a federally supported eradication-through-vaccination campaign, one that relied heavily on the preemptive, required vaccination of children. Its story thus epitomizes the range of political, epidemiological, cultural, and communications challenges to mass immunization in the modern era of vaccination.
Topics: Cultural Characteristics; Disease Eradication; Federal Government; Health Communication; History, 20th Century; Humans; Mass Vaccination; Measles; Measles Vaccine; Politics
PubMed: 30763141
DOI: 10.1177/0033354919826558 -
MMWR. Morbidity and Mortality Weekly... Nov 2021In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan,* with the objective of eliminating measles in five of the six World Health Organization (WHO)...
In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan,* with the objective of eliminating measles in five of the six World Health Organization (WHO) regions by 2020 (1). The Immunization Agenda 2021-2030 (IA2030) uses measles incidence as an indicator of the strength of immunization systems. The Measles-Rubella Strategic Framework 2021-2030 and the Measles Outbreaks Strategic Response Plan 2021-2023** are aligned with the IA2030 and highlight robust measles surveillance systems to document immunity gaps, identify root causes of undervaccination, and develop locally tailored solutions to ensure administration of 2 doses of measles-containing vaccine (MCV) to all children. This report describes progress toward World Health Assembly milestones and measles elimination objectives during 2000-2020 and updates a previous report (2). During 2000-2010, estimated MCV first dose (MCV1) coverage increased globally from 72% to 84%, peaked at 86% in 2019, but declined to 84% in 2020 during the COVID-19 pandemic. All countries conducted measles surveillance, although fewer than one third achieved the sensitivity indicator target of ≥2 discarded cases per 100,000 population in 2020. Annual reported measles incidence decreased 88% during 2000-2016, from 145 to 18 cases per 1 million population, rebounded to 120 in 2019, before falling to 22 in 2020. During 2000-2020, the annual number of estimated measles deaths decreased 94%, from 1,072,800 to 60,700, averting an estimated 31.7 million measles deaths. To achieve regional measles elimination targets, enhanced efforts are needed to reach all children with 2 MCV doses, implement robust surveillance, and identify and close immunity gaps.
Topics: Child; Disease Eradication; Global Health; Humans; Immunization Programs; Incidence; Infant; Measles; Measles Vaccine; World Health Organization
PubMed: 34758014
DOI: 10.15585/mmwr.mm7045a1 -
Vaccine Jan 2020After many decades of vaccination, measles epidemiology varies greatly between and within countries. National immunization programs are therefore encouraged to conduct... (Review)
Review
After many decades of vaccination, measles epidemiology varies greatly between and within countries. National immunization programs are therefore encouraged to conduct regular situation analyses and to leverage models to adapt interventions to local needs. Here, we review applications of models to develop locally tailored interventions to support control and elimination efforts. In general, statistical and semi-mechanistic transmission models can be used to synthesize information from vaccination coverage, measles incidence, demographic, and/or serological data, offering a means to estimate the spatial and age-specific distribution of measles susceptibility. These estimates complete the picture provided by vaccination coverage alone, by accounting for natural immunity. Dynamic transmission models can then be used to evaluate the relative impact of candidate interventions for measles control and elimination and the expected future epidemiology. In most countries, models predict substantial numbers of susceptible individuals outside the age range of routine vaccination, which affects outbreak risk and necessitates additional intervention to achieve elimination. More effective use of models to inform both vaccination program planning and evaluation requires the development of training to enhance broader understanding of models and where feasible, building capacity for modelling in-country, pipelines for rapid evaluation of model predictions using surveillance data, and clear protocols for incorporating model results into decision-making.
Topics: Developing Countries; Disease Eradication; Humans; Immunization Programs; Measles; Measles Vaccine; Models, Theoretical; Vaccination Coverage
PubMed: 31787412
DOI: 10.1016/j.vaccine.2019.11.020 -
PLoS Medicine Mar 2019The PLOS Medicine Editors discuss issues of vaccination uptake in the context of recent and ongoing measles outbreaks.
The PLOS Medicine Editors discuss issues of vaccination uptake in the context of recent and ongoing measles outbreaks.
Topics: Humans; Measles; Measles Vaccine; Patient Acceptance of Health Care; Vaccination
PubMed: 30913211
DOI: 10.1371/journal.pmed.1002770 -
MMWR. Morbidity and Mortality Weekly... Apr 2015In 2005, the Regional Committee for the World Health Organization (WHO) Western Pacific Region (WPR) established a goal to eliminate measles by 2012.The recommended...
In 2005, the Regional Committee for the World Health Organization (WHO) Western Pacific Region (WPR) established a goal to eliminate measles by 2012.The recommended elimination strategies in WPR include 1) ≥95% 2-dose coverage with measles-containing vaccine (MCV) through routine immunization services and supplementary immunization activities (SIAs); 2) high-quality case-based measles surveillance; 3) laboratory surveillance with timely and accurate testing of specimens to confirm or discard suspected cases and detect measles virus genotypes; and 4) measles outbreak preparedness, rapid response, and appropriate case management. In the WPR, the Philippines set a national goal in 1998 to eliminate measles by 2008. This report describes progress toward measles elimination in the Philippines during 1998-2014 and challenges remaining to achieve the goal. WHO-United Nations Children's Fund (UNICEF)-estimated coverage with the routine first dose of MCV (MCV1) increased from 80% in 1998 to 90% in 2013, and coverage with the routine second dose of MCV (MCV2) increased from 10% after nationwide introduction in 2010 to 53% in 2013. After nationwide SIAs in 1998 and 2004, historic lows in the numbers and incidence of reported measles cases occurred in 2006. Despite nationwide SIAs in 2007 and 2011, the number of reported cases and incidence generally increased during 2007-2012, and large measles outbreaks occurred during 2013-2014 that affected infants, young children, older children, and young adults and that were prolonged by delayed and geographically limited outbreak response immunization activities during 2013-2014. For the goal of measles elimination in WPR to be achieved, sustained investments are required in the Philippines to strengthen health systems, implement the recommended elimination strategies, and develop additional strategies to identify and reduce measles susceptibility in specific geographic areas and older age groups.
Topics: Adolescent; Adult; Child; Child, Preschool; Disease Eradication; Genotype; Humans; Immunization Programs; Incidence; Infant; Infant, Newborn; Measles; Measles Vaccine; Measles virus; Philippines; Population Surveillance; Young Adult
PubMed: 25856257
DOI: No ID Found -
MMWR. Morbidity and Mortality Weekly... Sep 2023Worldwide, measles remains a major cause of disease and death; the highest incidence is in the World Health Organization African Region (AFR). In 2011, the 46 AFR member...
Worldwide, measles remains a major cause of disease and death; the highest incidence is in the World Health Organization African Region (AFR). In 2011, the 46 AFR member states established a goal of regional measles elimination by 2020; this report describes progress during 2017-2021. Regional coverage with a first dose of measles-containing vaccine (MCV) decreased from 70% in 2017 to 68% in 2021, and the number of countries with ≥95% coverage decreased from six (13%) to two (4%). The number of countries providing a second MCV dose increased from 27 (57%) to 38 (81%), and second-dose coverage increased from 25% to 41%. Approximately 341 million persons were vaccinated in supplementary immunization activities, and an estimated 4.5 million deaths were averted by vaccination. However, the number of countries meeting measles surveillance performance indicators declined from 26 (62%) to nine (22%). Measles incidence increased from 69.2 per 1 million population in 2017 to 81.9 in 2021. The number of estimated annual measles cases and deaths increased 22% and 8%, respectively. By December 2021, no country in AFR had received verification of measles elimination. To achieve a renewed regional goal of measles elimination in at least 80% of countries by 2030, intensified efforts are needed to recover and surpass levels of surveillance performance and coverage with 2 MCV doses achieved before the COVID-19 pandemic.
Topics: Humans; Africa; Black People; COVID-19; Disease Eradication; Measles; Measles Vaccine; Pandemics
PubMed: 37676836
DOI: 10.15585/mmwr.mm7236a3 -
Lakartidningen Feb 2018
Topics: Humans; Immunity; Measles; Measles Vaccine
PubMed: 29406554
DOI: No ID Found -
Journal of Clinical Microbiology Oct 2020Along with the implementation of measles case-based surveillance, measles vaccine-associated rash illness (VARI) cases were detected in China. To better understand the...
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.
Topics: China; Disease Outbreaks; Exanthema; Humans; Infant; Measles; Measles Vaccine; Measles virus; Vaccination
PubMed: 32878947
DOI: 10.1128/JCM.01472-20 -
Transactions of the Royal Society of... Jan 2015WHO recommends delaying measles vaccination (MV) until maternal antibody has waned. However, early MV may improve child survival by reducing mortality from conditions... (Review)
Review
WHO recommends delaying measles vaccination (MV) until maternal antibody has waned. However, early MV may improve child survival by reducing mortality from conditions other than measles infection. We tested whether early MV improves child survival compared with later MV. We found 43 studies comparing measles-vaccinated and measles-unvaccinated children; however, only 16 studies had specific information that MV had been provided at 4-13 months of age, many before 9 months of age. In the 10 best studies (4 randomized trials and 6 observational studies) control children did not receive MV during follow-up. In eight of these studies the vaccine efficacy against death (VED) was 60% or more. In four studies with information on MV provided both before and after 12 months of age, the all-cause mortality reduction was significantly larger for children vaccinated in infancy (VED=74%; 95% CI 51-86%) than for children vaccinated after 12 months of age (VED=29%; CI 8-46%). Prevention of measles explained little of the reduction in mortality. In five studies with information on measles infection, VED was 67% (51-78%) and when measles deaths were excluded, VED was only reduced to 65% (47-77%). One natural experiment compared MV at 4-8 months versus MV at 9-11 months of age and found significantly lower all-cause mortality with early vaccination, the difference being 39% (8-60%). Child mortality may be reduced if MV is given earlier than currently recommended by international organizations.
Topics: Antibodies, Viral; Child, Preschool; Humans; Immunity, Maternally-Acquired; Immunization Schedule; Immunization, Secondary; Infant; Measles; Measles Vaccine; Survival Analysis; Vaccination
PubMed: 25573106
DOI: 10.1093/trstmh/tru174