Measles Infection Dose Responses: Insights from Mathematical Modeling.

How viral infections develop can change based on the number of viruses initially entering the body. The understanding of the impacts of infection doses remains incomplete, in part due to challenging constraints, and a lack of research. Gaining more insights is crucial regarding the measles virus (MV). The higher the MV infection dose, the earlier the peak of acute viremia, but the magnitude of the peak viremia remains almost constant. Measles is highly contagious, causes immunosuppression such as lymphopenia, and contributes substantially to childhood morbidity and mortality. This work investigated mechanisms underlying the observed wild-type measles infection dose responses in cynomolgus monkeys. We fitted longitudinal data on viremia using maximum likelihood estimation, and used the Akaike Information Criterion (AIC) to evaluate relevant biological hypotheses and their respective model parameterizations. The lowest AIC indicates a linear relationship between the infection dose, the initial viral load, and the initial number of activated MV-specific T cells. Early peak viremia is associated with high initial number of activated MV-specific T cells. Thus, when MV infection dose increases, the initial viremia and associated immune cell stimulation increase, and reduce the time it takes for T cell killing to be sufficient, thereby allowing dose-independent peaks for viremia, MV-specific T cells, and lymphocyte depletion. Together, these results suggest that the development of measles depends on virus-host interactions at the start and the efficiency of viral control by cellular immunity. These relationships are additional motivations for prevention, vaccination, and early treatment for measles.

Shedding of measles vaccine RNA in children after receiving measles, mumps and rubella vaccination.

BACKGROUND: Measles, mumps, and rubella(MMR) vaccination is critical to measles outbreak responses. However, vaccine reactions and detection of measles vaccine RNA in recently immunized persons may complicate case classification especially in those presenting with another respiratory viral illness. We aim to characterize cases of measles vaccine shedding in recently vaccinated children presenting with respiratory viral symptoms. METHODS: Children who were tested with a multiplex respiratory panel <30 days after receiving MMR were identified. Remnant nasopharyngeal(NP) samples were tested for measles vaccine by PCR. Medical records were reviewed for demographics, presenting symptoms, and test results. RESULTS: From January 2022 to March 2023, 127 NP from children who received MMR were tested. Ninety-six NP were collected after the first dose, of which 33(34.4 %) were positive for vaccine RNA. The median interval between MMR and detection was 11.0 days. Thirty-one NP were collected after the second MMR and 1(3.2 %) was positive; time between the vaccination and detection was 18.9 days. Median cycle threshold(Ct) value of the measles PCR for vaccine shedding was significantly higher than median Ct in children with wild-type infection. CONCLUSION: Shedding of measles vaccine RNA is not uncommon and vaccine RNA can be detected up to 29 days post MMR; the amount of vaccine RNA shedding is low indicated by high Ct values. Clinicians and public health officials should consider performing measles vaccine testing on those testing positive for measles within one month of MMR vaccination, especially if the Ct value is high and definitive epidemiological links are absent.

Measles Vaccine Coverage and Disease Outbreaks: A Systematic Review of the Early Impact of COVID-19 in Low and Lower-Middle Income Countries.

Objectives: We aimed to evaluate changes to measles-containing vaccine (MCV) provision and subsequent measles disease cases in low- and lower-middle income countries (LICs, LMICs) in relation to the COVID-19 pandemic. Methods: A systematic search was conducted of MEDLINE, OVID EMBASE and PubMed records. Primary quantitative and qualitative research studies published from January 2020 were included if they reported on COVID-19 impact on MCV provision and/or measles outbreak rates within LICs and LMICs. Results: 45 studies were included. The change in MCV1 vaccination coverage in national and international regions ranged -13% to +44.4% from pre-COVID time periods. In local regions, the median MCV1 and overall EPI rate changed by -23.3% and -28.5% respectively. Median MCV2 rate was disproportionally impacted in local areas during COVID-interruption time-periods (-48.2%) with ongoing disruption in early-recovery time-periods (-17.7%). 8.9% of studies reported on vaccination status of confirmed measles cases; from these, 71%-91% had received no MCV dose. Conclusion: MCV vaccination coverage experienced ongoing disruption during the recovery periods after initial COVID-19 disruption. Vaccination in local area datasets notably experienced longer-term disruption compared to nationally reported figures.

How did the introduction of the measles-containing vaccine second dose (MCV2) affect measles vaccine uptake? - evidence from Nigeria.

Nigeria has the highest burden of measles worldwide, as measles vaccine uptake remains low. Recently, the second dose of the measles-containing vaccine (MCV2) was introduced as part of the routine immunization (RI) program, and this study examined how it changed the uptake of the measles vaccine and the factors associated with vaccination behavior. The Nigeria Multiple Indicator Cluster Survey (MICS) 2021 was used to compare measles vaccination uptake as well as factors associated with vaccination uptake between children before MCV2 introduction (cohort 1) and after the introduction (cohort 2). The overall rate of measles vaccine uptake was higher among cohort 1 (64%-95%) than among cohort 2 (56%-92%) in all zones because of younger age among cohort 2. The dropout from the first to second measles vaccines was similar between the cohorts (around 24%). Higher maternal education levels and higher household wealth levels were both correlated with the vaccine uptake or both cohorts but a positive correlation between the dropout and mother's education level was observed only among cohort 2, especially in the North West and South West zones. The positive correlation between the dropout and mother's education level among cohort 2 indicates that the introduction of MCV2 as part of RI might have helped to narrow the disparity in measles vaccine uptake in North West and South West zones. Further study is required to investigate strategies employed to reduce the disparity in these zones to apply nationwide.

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.

Adapting response to a measles outbreak in a context of high vaccination and breakthrough cases: an example from Vaud, Switzerland, January to March 2024.

A measles outbreak with 51 cases occurred in the canton of Vaud, Switzerland, between January and March 2024. The outbreak was triggered by an imported case, and 37 (72.5%) subsequent cases were previously vaccinated individuals. Epidemiological investigations showed that vaccinated measles cases were symptomatic and infectious. In a highly vaccinated population, it is important to raise awareness among healthcare professionals to suspect and test for measles virus when an outbreak is declared, irrespective of the vaccination status of the patients.

Measles second dose vaccine uptake and its associated factors among children aged 24-35 months in Northwest Ethiopia, 2022.

Measles is a major public health problem in under-five children, leading to lifelong complications. Therefore, the study aimed to assess the magnitude of measles second-dose vaccine uptake and its determinants among children aged 24-35 months in Northwest Ethiopia. A community-based cross-sectional study was conducted among 418 children aged 24-35 months in Northwest Ethiopia between January 2022 and February 2022. A simple random sampling technique was used to access study subjects. A binary logistic regression model was employed. An adjusted odd ratio with a 95% confidence interval (CI) and a p-value < 0.05 was used to declare significant predictors of measles second dose vaccine uptake. The magnitude of the measles second dose vaccine uptake among children aged 24-35 months was 41.39%. Postnatal care visits (AOR: 4.78, CI 1.49, 15.34), child vaccination status of other scheduled vaccines (AOR: 3.88, CI 2.23, 6.73), awareness of the measles second dose vaccine and its schedule (AOR: 8.924, CI 5.27, 15.09), and distance from the vaccination center (AOR: 0.21, CI 0.06, 0.77) were significantly associated with measles second dose vaccine uptake. The uptake of measles second dose vaccine in the study area was low. Therefore, health workers and other partners should initiate awareness creation programs for mothers/caretaker to improve the uptake of measles second dose vaccine.

Exploring landscape of measles vaccination coverage: A step towards measles elimination goal in India.

INTRODUCTION: Measles remains a critical public health concern causing significant morbidity and mortality globally. Despite the success of measles vaccination programs, challenges persist, particularly in India. This study investigates dose-wise measles vaccination coverage and explores gaps in immunization focusing on zero-dose, one-dose, and two-dose coverage among children aged 24-35 months. DATA SOURCES AND METHODOLOGY: The National Family Health Survey 2019-21 (NFHS-5) served as the data source and the study analyzed information from 43,864 children aged 24-35 months. Sociodemographic variables such as birth order, wealth quintile, gender, social group, religion, residence, mother education, delivery-related factors, and media exposure were considered. Statistical analysis involved weighted estimates, chi-square tests, and multivariate multinomial logistic regression. RESULTS: The study revealed that challenges persist in achieving optimal measles vaccination coverage. Analysis by sociodemographic factors highlighted disparities in coverage, with variations in zero dose prevalence across states and districts. The percentage of zero-dose children was significantly higher, with 11.5% of children in India remaining to receive any measles vaccination. Factors influencing vaccine coverage include birth order, age, wealth quintile, social group, religion, residence, maternal education, place of delivery, media exposure, and mode of delivery. The findings from the spatial analysis show the clustering of zero-dose children is high in the northeastern states of India. DISCUSSION: Measles zero-dose children pose a significant obstacle to achieving elimination goals. Spatial analysis identifies clusters of unvaccinated populations guiding targeted interventions. The study aligns with global initiatives such as the Immunization Agenda 2030 emphasizing equitable vaccine access and discusses how India can tailor its strategies to achieve the goal. Lessons from polio eradication efforts inform strategies for measles elimination, stressing the importance of high-quality data and surveillance. The study underscores the urgency of addressing last-mile measles vaccination gaps in India. Spatially targeted interventions informed by sociodemographic factors can enhance immunization coverage. Achieving measles elimination requires sustained efforts and leveraging lessons from successful vaccination campaigns. The study findings have the potential to contribute to informed decision-making, supporting India's roadmap for the measles and rubella elimination goal.

Coverage and determinants of second-dose measles vaccination among under-five children in East Africa countries: a systematic review and meta-analysis.

Background: One of the biggest breakthroughs of contemporary medicine is measles vaccination. It is essential for the total elimination of measles. Understanding the magnitude and determinants of effective second-dose measles vaccination coverage is a critical task. Accordingly, we set out to check the best available evidence of the pooled second-dose measles vaccination coverage among under-five children in East Africa. Method: We searched electronic databases such as PubMed, Google Scholar, Cochrane, and others. Two reviewers separately carried out the search of the Joanna Briggs Institute, selection of studies, critical appraisal, and data extraction. A third party was involved in resolving the disagreement among the reviewers. Seven studies included in this study, four from Ethiopia, two from Kenya, and one from Tanzania were cross-sectional and published in English language, with publication dates before 29 November 2023. Articles lacking full-text, the intended outcome, and that are not qualitative studies were excluded from the analysis. The Microsoft Excel checklist was used to extract the data and then exported to STATA 11. In addition, I2, Funnel plots, and Egger's test were employed to measure heterogeneity and detect publication bias, respectively. A random effect model was used. Result: The meta-analysis includes a total sample size of 4,962 children from seven articles. The pooled prevalence of second-dose measles vaccination among under-five children in East Africa was found to be 32.22% [95% CI; (18.82, 45.63)], and the significant factors were as follows: birth order (1.72; OR = 95% CI: 1.32, 2.23), information about measles-containing second-dose vaccine (MCV 2) (7.39; OR = 95% CI: 5.21, 10.50), mother's marital status (1.47; OR = 95% CI: 1.05, 2.07), complete immunization for other vaccines (2.17; OR = 95% CI: 1.49, 3.17), and distance of vaccination site (3.31; OR = 95% CI: 2.42, 4.53). Conclusion: The current study found that pooled prevalence of second-dose measles vaccination coverage among under-five children was still very low. It was also observed that birth order, distance of the vaccination site, complete immunization for other vaccines, mother's marital status, and information about MCV were factors associated with second-dose measles vaccination. These factors imply that there is a need for countries and their partners to act urgently to secure political commitment, expand primary health service and health education, and increase vaccination coverage.

Setup of Aerosol Delivery System to Prevent Measles Virus Infection in Nonhuman Primate Model.

Measles virus is one of the most contagious airborne human viruses which keeps causing outbreaks in numerous countries over the world despite the existence of an efficient vaccine. Fusion inhibitory lipopeptides were shown to inhibit viral entry into target cells, and their adequate administration into the respiratory tract may provide a novel preventive approach against airborne infections. Aerosol delivery presents the best administration route to deliver such preventive compounds to the upper and lower respiratory tract. This approach offers a conceptually new strategy to protect the population at risk against infection by respiratory viruses, including measles. It is a noninvasive needle-free approach, which may be used when antiviral protection is required, without any medical assistance. In this chapter, we describe the nebulization approach of lipopeptide compounds in nonhuman primates and the subsequent measles virus challenge.

Measles outbreak investigation in Berhet District, North Shewa, Ethiopia.

Introduction: Measles, though usually self-limiting, can have severe consequences influenced by factors such as vaccination and nutrition, notably vitamin A deficiency and malnutrition. Despite progress, contextual changes and implementation issues have hampered efforts, resulting in increased outbreaks and cases of measles. This study seeks to pinpoint outbreak features, risk factors, and strategies for preventing and controlling measles. Methods: A descriptive cross-sectional study and a 1:2 unmatched case-control study design were employed. All 101 suspected measles cases listed on the line-list were included in the descriptive research, with 60 measles patients and 120 controls included in the case-control investigation. Line-list data were cleaned and analyzed using a pivot table in Microsoft Excel 2016. Subsequently, the data were cleaned, entered into Epi Info 7.2, and exported to SPSS 26 for analysis. Results: Twenty cases occurred per 10,000 individuals. Men accounted for 67.3% of cases, with ages ranging from 5 months to 45 years and mean and standard deviations of 9.6 and 7.6, respectively. Age group of 5-14 years comprised 57.4% of cases, followed by 1-4 years with 24.8%. Being unvaccinated against measles showed an adjusted odds ratio (AOR) of 12.06 (95% CI: 3.12-46.52). Travel history to regions with active cases had an AOR of 5.73 (95% CI: 1.78-18.38). Contact with a measles patient showed an AOR of 10.3 (95% CI: 3.48-30.5). Understanding the measles transmission mechanism had an AOR of 0.164 (95% CI: 0.049-0.55), and awareness of the disease's preventability had an AOR of 0.233 (95% CI: 0.67-0.811). All factors were independently associated with the illness. Conclusion: This outbreak affected a broader age range with a high attack rate, mainly in the age group of 5-14-years. Over 35% of cases lacked measles vaccination, indicating low administrative vaccine coverage. Factors contributing to the outbreak include lack of measles vaccination, travel to areas with active disease, contact with cases, and insufficient knowledge of measles transmission and prevention strategies among mothers and caregivers.

Second dose of measles-containing vaccine coverage and associated factors among children aged 24-36 months in Gondar city, Central Gondar, Northwest Ethiopia, 2023.

Background: Measles caused 207,000 deaths worldwide in 2019. Ethiopia ranks among the top 10 countries in the world with the highest number of measles cases. However, the coverage of the second dose of measles-containing vaccine (MCV2) remains low. To increase coverage, the government of Ethiopia launched a nationwide measles vaccination campaign. Despite this intervention, the coverage is still below target, and there is scarce information in the study area. Therefore, this study aimed to assess MCV2 coverage and associated factors among children aged 24-36 months in Gondar city, Central Gondar, Northwest Ethiopia, 2023. Methods: A community-based cross-sectional study was conducted among 621 children aged 24-36 months using a systematic random sampling technique from 25 April to 25 May. A pre-tested, interviewer-administered, and structured questionnaire was used and collected using Kobo Toolbox and then transferred to Stata version 17 for further analysis. The binary logistic regression model was used to identify factors, and the presence of an association was declared using a p-value of <0.05. Similarly, an adjusted odds ratio with a 95% confidence interval was used to interpret the direction and strength of an association. Results: A total of 621 children, with a response rate of 98.1%, participated in the study. The coverage of the second dose of MCV was 75.68% (95% CI: 72.1-78.9). The following factors were significantly associated with measles-containing vaccine second dose (MCV2) coverage: father as the household head (AOR: 3.06, 95% CI: 1.43-6.44), first birth order (AOR: 4.45, 95% CI: 1.21-16.3), four and above antenatal care (ANC) follow-ups (AOR: 5.18, 95% CI:1.62-16.5), postnatal care (PNC) service utilization (AOR: 2.57, 95% CI:1.27-5.15), at least two doses of vitamin A uptake (AOR: 6.39, 95% CI: 2.67-15.2), mothers having high awareness (AOR: 1.97, 95% CI:1.15-3.4), and good perception (AOR: 3.6, 95% CI: 2-6.47) about measles vaccination. Conclusion and recommendations: The coverage of MCV2 in the study area is lower than the national and global target of above 95%. Head of household, birth order, ANC follow-up, PNC service utilization, vitamin A uptake, awareness, and perception of mothers about measles vaccination were significant factors for MCV2 coverage. Creating awareness, increasing the perception of mothers about measles vaccination, and strengthening the ANC and PNC services will increase the coverage.

[Effects of the vaccination campaign on hospitalization and mortality linked to measles in Brazil in the last decade]. / Efeitos da campanha de vacinação nas internações e mortalidade relacionados ao sarampo no Brasil na última década.

Measles is one of the main causes of morbidity and mortality in the pediatric population and it can be prevented with 100% effectiveness by vaccination. However, the disease remains active in throughout Brazil. The scope of this article is to evaluate the population's adherence to vaccination and the potential connection with hospitalizations and mortality in relation to measles in Brazil. This is an ecological study based on secondary data on mortality and hospitalizations due to measles and vaccination coverage against the disease in Brazil from 2013 to 2022. The peak of adherence to the measles vaccination schedule occurred in the 3 years that preceded the eradication of the disease in the country, which occurred in 2016. In this interval, there are the lowest hospitalization rates, with zero mortality from 2014 to 2017. On the other hand, there has been a marked drop in vaccination rates since 2019, when the disease resurfaced in Brazil. Concomitantly, hospitalization and mortality rates reach the highest recorded values. Population adherence to the complete measles vaccination schedule, which is essential to control the disease and related deaths, is insufficient, which is reflected in hospitalization and mortality rates.

O sarampo é uma das principais causas de morbidade e mortalidade na população pediátrica e pode ser prevenido com 100% de eficácia pela vacinação. No entanto, a doença permanece ativa no território brasileiro. O objetivo do artigo é avaliar a adesão da população à vacinação e a possível relação com hospitalização e mortalidade em relação ao sarampo no Brasil. Trata-se de um estudo ecológico realizado a partir de dados secundários de mortalidade e internações acerca do sarampo e da cobertura vacinal contra a doença no Brasil nos anos de 2013 a 2022. O ápice de adesão ao calendário vacinal contra o sarampo se deu nos três anos que precederam a erradicação da doença no país, ocorrida em 2016. Nesse intervalo, tem-se as menores taxas de internação, com a mortalidade zerada de 2014 a 2017. Em contrapartida, verifica-se, desde então, queda na taxas de vacinação, acentuadas a partir de 2019, quando a doença reaparece no Brasil. Concomitantemente, as taxas de internação e mortalidade atingem os valores mais altos registrados. A adesão populacional ao calendário vacinal completo contra o sarampo, essencial ao controle da doença e dos óbitos relacionados, está insuficiente, o que se reflete nas taxas de internações e mortalidade.

Measles outbreak investigation in Tocha district, southwestern Ethiopia: an unmatched case-control study.

Background: Measles continues to be a public health challenge in Ethiopia. Rumors of suspected measles were notified on April 8, 2023 from Tocha district. We conducted an assessment to describe measles outbreak and determine risk factors for measles infection in the Tocha district of the Dawuro zone, Southwest Ethiopia. Methods: We conducted a 1:2 unmatched case-control studies from April to May 2023. We took all 147 cases registered on line list for descriptive analyses. We used a total of 74 randomly selected cases and 147 controls for case-control part. Any person in Tocha district with laboratory-confirmed measles IgM antibody; or any suspected person epidemiologically linked to confirmed measles cases from March 23 to April 26 2023, were included in the case. Neighborhood who did not fulfill this standard case definition were included in controls. Data were collected using standardized questionnaires deployed on Kobo Collect. Descriptive analyses were conducted using Epi info version 7.2.5.0. The analyses were performed using Statistical Package for Social Science (SPSS) version 26. Binary logistic regression analyses were utilized to select candidate variables. We conducted multiple logistic regression analysis to identify determinants of measles infection at a p value ≤0.05 with 95% confidence interval. Results: The overall attack rate of 22.64/10,000 for general population and 104.59/10,000 among under-five children were attributed to the outbreak with a case fatality rate of 2.72%. Vaccine coverage in the last year and this year were 73.52 and 53.88%, respectively, while vaccine effectiveness in the district was 79%. Poor house ventilation (AOR = 3.540, 95% CI: 1.663-7.535) and having contact history with the case (AOR = 2.528, 95% CI: 1.180-4.557) were positively related to measles infection while being previously vaccinated for measles (AOR = 0.209, 95% CI: 0.180-4.577) reduce risk of measles infections. Conclusion: The highest attack rate was observed among children under 5 years of age, with a case fatality rate of 2.72%. Vaccination coverage was less than what expected to develop herd immunity. Strategies to increase vaccination coverage and strengthening surveillance systems for rumor identification and early responses to prevent person to person transmission are recommended.