Case Ascertainment of Measles during a Large Outbreak-Laboratory Compared to Epidemiological Confirmation.

Measles is a highly contagious viral disease, and hence, sufficient herd immunity is obligatory to prevent infection transmission. Measles is still a cause of considerable disease burden globally, mainly in children. During a national measles outbreak in Israel in 2018-2019, the peak incidence rates occurred in the Jerusalem district. Most measles cases in the Jerusalem district (75.5%, 1702) were observed in children younger than 15 years of age, 49.2% (1109) were in children under 5 years of age, and 18.9% (425) were in infants under 1 year of age. The routine measles vaccination schedule includes two doses at 1 and 6 years of age. Most cases (1828, 81.1%) were unvaccinated (zero measles vaccine doses). These cases comprised the 425 affected infants under 1 year of age, who were ineligible for vaccination, along with the 1403 children over 1 year of age, who were otherwise unvaccinated. This study aimed to describe the epidemiologic and laboratory features of this measles outbreak, and to investigate case ascertainment (laboratory confirmed compared to epidemiologically confirmed cases). The study population included 2254 measles cases notified during the period spanning June 2018 to May 2019 in the Jerusalem district (incidence rate 176 per 10,000 population). Of the 2254 cases, 716 (31.8%) were laboratory confirmed, and 1538 (68.2%) were confirmed as epidemiologically linked. Most laboratory confirmed cases (420, 58.7%) underwent real-time PCR tests. Serological tests (measles IgM and IgG) were used in 189 (26.4%) cases, and a combination of RT-PCR and serology was used in 107 (14.9%) cases. In a multivariate model analysis, the variables significantly associated (after adjustment) with higher odds for laboratory confirmation included month of disease onset (late), additional measles cases in the household (single case), place of medical treatment (hospital; either emergency department, or hospitalization) and vaccination status (at least one prior vaccine dose). The measles outbreak described demonstrates the urgency of addressing vaccination gaps with appropriate outbreak prevention programs. The road to measles elimination needs to be paved with robust public health infrastructure, excellent field epidemiology for outbreak surveillance, investigation, and control, and laboratory proficiency.

Detection of measles vaccine virus and measles-specific immunoglobulin M in children vaccinated against measles-mumps-rubella during measles outbreak.

Information regarding the detection perioid of measles vaccine virus (MeVV) RNA in human nasopharyngeal samples and measles-specific antibodies following measles-mumps-rubella (MMR) vaccination is limited. During contact tracing for a measles outbreak at a hospital in Republic of Korea, 4 out of 206 children vaccinated with MMR underwent real-time RT-PCR assay for measles and measles-specific antibodies test. Measles virus RNA was detected in 2 children, all of which was vaccine virus strain RNA (genotype A). In a healthy 27-month-old boy, MeVV RNA was detected 448 days after MMR vaccination. Measles-specific IgM was positive 1097 days following vaccination in a 4-year-old girl. MeVV RNA and measles-specific IgM were detected for a considerable period following primary MMR vaccination. Physicians should exercise caution when interpreting positive RT-PCR results for MeVV or measles-specific IgM from a child with measles-associated symptoms who has been recently vaccinated against measles.

Early B cell transcriptomic markers of measles-specific humoral immunity following a 3rd dose of MMR vaccine.

B cell transcriptomic signatures hold promise for the early prediction of vaccine-induced humoral immunity and vaccine protective efficacy. We performed a longitudinal study in 232 healthy adult participants before/after a 3rd dose of MMR (MMR3) vaccine. We assessed baseline and early transcriptional patterns in purified B cells and their association with measles-specific humoral immunity after MMR vaccination using two analytical methods ("per gene" linear models and joint analysis). Our study identified distinct early transcriptional signatures/genes following MMR3 that were associated with measles-specific neutralizing antibody titer and/or binding antibody titer. The most significant genes included: the interleukin 20 receptor subunit beta/IL20RB gene (a subunit receptor for IL-24, a cytokine involved in the germinal center B cell maturation/response); the phorbol-12-myristate-13-acetate-induced protein 1/PMAIP1, the brain expressed X-linked 2/BEX2 gene and the B cell Fas apoptotic inhibitory molecule/FAIM, involved in the selection of high-affinity B cell clones and apoptosis/regulation of apoptosis; as well as IL16 (encoding the B lymphocyte-derived IL-16 ligand of CD4), involved in the crosstalk between B cells, dendritic cells and helper T cells. Significantly enriched pathways included B cell signaling, apoptosis/regulation of apoptosis, metabolic pathways, cell cycle-related pathways, and pathways associated with viral infections, among others. In conclusion, our study identified genes/pathways linked to antigen-induced B cell proliferation, differentiation, apoptosis, and clonal selection, that are associated with, and impact measles virus-specific humoral immunity after MMR vaccination.

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.

Neutralizing antibody titers against D8 genotype and persistence of measles humoral and cell-mediated immunity eight years after the first dose of measles, mumps, and rubella vaccine in Brazilian children.

OBJECTIVE: Assess the level of measles vaccine-induced neutralizing antibodies against the D8 genotype and the persistence of humoral and cell-mediated immunity in children who received their first dose of the measles, mumps, and rubella vaccine eight years previously. METHODS: Measles-specific IgG and neutralizing antibodies were determined in serum using ELISA and plaque reduction neutralization test, respectively. Cellular response was evaluated from peripheral blood mononuclear cells (PBMC). IFN-γ-secreting cells, memory B and T cells, and immunological mediators were assayed by ELISpot, flow cytometry, and multiplex liquid microarray assay, respectively. RESULTS: Antibody concentrations declined over time; however, the vaccine-induced neutralizing antibodies' effect against D8 and vaccinal genotypes persisted. PBMC stimulated with the vaccine virus exhibited specific IFN- γ-measles-secreting responses in most participants. Participants with high levels of neutralizing antibodies showed a higher proportion of activated B cells compared to participants with low levels of neutralizing antibodies, while proportions of memory CD4+ and CD8+ T cells were similar between these groups. PBMC supernatant cytokine levels showed a significant difference between stimulated and non-stimulated conditions for IL-2, TNF-α, IL-10, and CXCL10. CONCLUSION: Despite the decline in antibody concentrations over time, the participants still demonstrated neutralizing capacity against the measles D8 genotype five to eight years after the second dose of the measles, mumps, and rubella vaccine. Additionally, most of the enrolled children exhibited cell-mediated immunity responses to measles virus stimulation.

In Vitro Sensitivity of Neuroendocrine Neoplasms to an Armed Oncolytic Measles Vaccine Virus.

Neuroendocrine neoplasms represent a heterogenous group of rare tumors whose current therapeutic options show only limited efficacy. Oncolytic viruses exert their mode of action through (onco-)lysis of infected tumor cells and the induction of a systemic antitumoral immune response in a virus-induced inflammatory micromilieu. Here, we investigated the potential of our well-established second-generation suicide-gene armed oncolytic measles vaccine virus (MeV-SCD) in five human NEN cell lines. First, (i) expression of the MeV receptor CD46 and (ii) its correlation with primary infection rates were analyzed. Next, (iii) promising combination partners for MeV-SCD were tested by employing either the prodrug 5-fluorocytosine, which is converted into the chemotherapeutic compound 5-fluorouracil, or the mTOR-inhibitor everolimus. As a result, MeV-SCD was found to kill all NEN tumor cell lines efficiently in a dose-dependent manner. This oncolytic effect was further enhanced by exploiting the prodrug-converting system, which was found to be highly instrumental in overcoming the partial resistance found in a single NEN cell line. Furthermore, viral replication was unaffected by everolimus, which is a basic requirement for combined use in NEN patients. These data suggest that MeV-SCD has profound potential for patients with NEN, thus paving the way for early clinical trials.

Predictors for low coverage of uptake of second dose of measles vaccine among children in sub-Saharan Africa, 2023: a systematic review and meta-analysis.

Background: Measles became a public health important disease in sub-Saharan Africa. World Health Organization recommended measles-containing vaccine dose 2 (MCV2) through routine service delivery. This study aims to determine coverage of second-dose measles vaccination uptake and its predictors among children aged 24-35 months in sub-Saharan Africa. Methods and materials: We conducted an extensive search of literature as indicated in the guideline of reporting systematic review and meta-analysis (PRISMA). The databases used were PubMed, Google Scholar, and HINARI literature. Results: The overall uptake of the second dose of measles vaccine uptake was 41% (95% CI: 28.90-53.47). Caregiver's awareness of the importance of the second dose of measles (2.51, 95% CI 1.77, 3.25), educational status of mothers (1.30, 95% CI 1.16, 1.45), distance from vaccination site (1.22, 95% CI 1.12, 1.32), and attending four and above ANC visit (2.72, 95% CI 2.29, 3.15) were determinants for second dose measles vaccine uptake. Conclusion: Coverage of the second dose of measles uptake in Sub-Saharan Africa was low (41%) which is lower than the recommendation from WHO. Therefore policymakers and stakeholders should increase mother's awareness. Also, special strategies should be developed for those who are far from the vaccination site. Abbreviation and acronyms: ANC: Ante Natal Care; JBI: Joanna Briggs Institute; MCV1: Measles containing vaccine dose 1; MCV2: Measles containing vaccine dose 2; WHO: World Health Organization.

Laboratory response to an infant with suspected measles vaccine associated fever and rash in Sri Lanka.

Background: Measles is a highly contagious illness. Sri Lanka (SL) has eliminated the measles in 2019. The country is at risk of importation of measles and there could be vaccine-associated measles like illnesses. Therefore, it is important to investigate patients with fever, rash to differentiate the wild-type from vaccine-type excluding other suspected pathogens to direct infection prevention and control strategies. The objective is to describe the laboratory investigation procedure in an immunocompetent child, developed fever, rash following measles containing vaccine in post-measles eliminated period, SL. Methods: This laboratory based investigation was carried out in National Measles Laboratory, SL. Blood and throat swab were received from a patient with fever, rash, cough and coryza developed at tenth day of receiving the measles containing live-attenuated vaccine. Samples were tested for measles, rubella, and other relevant pathogens according to the laboratory testing algorithm for an immunocompetent child with fever, rash and flu like symptoms. Results: Measles vaccine type A, Edmonston-strain virus was detected after sequencing in throat swab and measles IgM and IgG were positive at sixth-week of illness-onset. In addition, influenza A RNA was detected in throat swab at day-three with detectable parvoB19 IgM in blood sample received at sixth-week of post-onset symptoms. Conclusions: Measles like illness of this immunocompetent child who received measles containing vaccine could be due to measles vaccine-type A or influenza infection. In a measles eliminated, resource-limited setting in SL, there should be a well-defined, testing algorithm to exclude prevalent possible pathogens according to epidemiological and clinical information.

Pervasive Parental Hesitancy and Resistance towards Measles Rubella Vaccination in Jordan.

Measles remains a highly contagious and potentially severe infectious disease, necessitating high vaccine coverage. However, misinformation and measles vaccine hesitancy/resistance have posed significant challenges to achieving this goal. The COVID-19 pandemic further exacerbated these challenges, leading to a measles outbreak in Jordan in 2023. This study aimed to investigate the acceptance of the measles rubella (MR) vaccine among parents in Jordan and to identify its associated determinants. This cross-sectional questionnaire-based study was conducted using a previously Arabic-validated version of the Parental Attitudes towards Childhood Vaccines (PACV) survey instrument. Data collection took place in October 2023, and the final study sample comprised a total of 391 parents, with mothers representing 69.8% of the participants (n = 273). The majority of participating parents expressed either resistance (n = 169, 43.2%) or hesitancy (n = 168, 43.0%) towards MR vaccination, while only 54 participants (13.8%) expressed MR vaccine acceptance. Multivariate analysis revealed that trust in vaccine safety/efficacy, behavior, and having fewer offspring were significantly associated with MR vaccine acceptance. The current study revealed a concerning level of MR vaccine hesitancy/resistance among parents in Jordan, which could signal a public health alarm in the country. Urgent and targeted interventions are strongly recommended to address this issue, including mass campaigns aimed at building trust in the MR vaccine's safety/efficacy. Additionally, there is an urgent need for effective public health initiatives to ensure sufficient measles vaccine coverage to prevent future outbreaks of this serious disease.

Evaluating effective measles vaccine coverage in the Malaysian population accounting for between-dose correlation and vaccine efficacy.

BACKGROUND: Malaysia introduced the two dose measles-mumps-rubella (MMR) vaccine in 2004 as part of its measles elimination strategy. However, despite high historical coverage of MCV1 and MCV2, Malaysia continues to report high measles incidence. This study suggests a novel indicator for investigating population immunity against measles in the Malaysian population. METHODS: We define effective vaccine coverage (EVC) of measles as the proportion of a population vaccinated with measles-containing vaccine (MCV) and effectively protected against measles infection. A quantitative evaluation of EVC throughout the life course of Malaysian birth cohorts was conducted accounting for both vaccine efficacy (VE) and between-dose correlation (BdC). Measles vaccination coverage was sourced from WHO-UNICEF estimates of Malaysia's routine immunisation coverage and supplementary immunisation activities (SIAs). United Nations World population estimates and projections (UNWPP) provided birth cohort sizes stratified by age and year. A step wise joint Bernoulli distribution was used to proportionate the Malaysian population born between 1982, the first year of Malaysia's measles vaccination programme, and 2021, into individuals who received zero dose, one dose and multiple doses of MCV. VE estimates by age and doses received are then adopted to derive EVC. A sensitivity analysis was conducted using 1000 random combinations of BdC and VE parameters. RESULTS: This study suggests that no birth cohort in the Malaysian population has achieved > 95% population immunity (EVC) conferred through measles vaccination since the measles immunisation programme began in Malaysia. CONCLUSION: The persistence of measles in Malaysia is due to pockets of insufficient vaccination coverage against measles in the population. Monitoring BdC through immunisation surveillance systems may allow for the identification of susceptible subpopulations (primarily zero-dose MCV individuals) and increase the coverage of individuals who are vaccinated with multiple doses of MCV. This study provides a tool for assessment of national-level population immunity of measles conferred through vaccination and does not consider subnational heterogeneity or vaccine waning. This tool can be readily applied to other regions and vaccine-preventable diseases.

Vaccination coverage and predictors of influenza, pneumococcal, herpes zoster, tetanus, measles, and hepatitis B vaccine uptake among adults in Greece.

OBJECTIVES: Insufficient adult vaccination coverage rates remain an international challenge. This nationwide study aimed at exploring vaccination coverage and predictors of influenza, pneumococcal, herpes zoster, tetanus, measles, and hepatitis B vaccine uptake, following the recommendations of the National Immunization Program for adults. STUDY DESIGN: This was a multicenter, mixed-methods study conducted at 23 primary care units in six different regions of Greece. METHODS: A pretested questionnaire was administered to three randomly selected adults who visited each practice daily for 30 consecutive working days. RESULTS: Among the 1571 participants, vaccination coverage for influenza in the high-risk groups was 55%, 36% for pneumococcal disease, 12% for herpes zoster (HZ), 21% for tetanus, 33% for measles, and 11% for hepatitis B. Perception of low susceptibility to disease due to good health status, concerns about side-effects and vaccines' efficacy, and mistrust in pharmaceutical companies were among common factors associated with the vaccines uptake. The strongest factor associated with the participants' vaccination status was their doctor's recommendation (odds ratio [95% confidence interval] influenza: 6.06 [4.52-8.14], pneumococcal disease: 15.73 [10.98-22.52], HZ: 17.01 [9.05-31.96], tetanus: 23.93 [16.20-35.35], measles: 33.47 [16.85-66.47], and hepatitis B: 73.92 [17.47-312.74]). Being well-informed about each vaccine was also a predictor of its uptake. CONCLUSIONS: Vaccination coverage was suboptimal and especially low in tetanus, HZ, and hepatitis B immunization. Person-centered approach, with provision of appropriate information about vaccines' safety and efficacy, responding to each patient's needs, as well as physicians' strong recommendation for vaccination are considered crucial to advocate against the spread of vaccine misinformation and increase vaccination coverage.

Measles vaccine uptake among Italian medical students compared to the pre-COVID-19 era.

The COVID-19 pandemic has severely affected health systems worldwide and raised the issue of vaccine hesitancy. In 2022, the World Health Organization reported an outbreak of measles infection among people over 20 years of age in the European Region. Previous studies found low rates of measles immunization among Italian healthcare workers (HCWs) and medical students. Vaccine hesitancy is a relevant cause of low immunization rate among HCWs and the general population. We aim to evaluate the measles vaccine uptake among medical students of a large teaching hospital, compared to the pre-pandemic period. This is a retrospective observational study, that evaluated the immune status and the vaccine acceptance rate for measles in medical students at the University of Tor Vergata, Rome, who underwent occupational health surveillance from 1 January to 1 December 2022. We also compared the data with the results of a pre-pandemic survey conducted in 2018. Vaccine uptake among unprotected medical students was 59.5%. The data showed no significant difference in vaccine uptake compared with the pre-COVID-19 period. Conversely, the rate of serologically immune subjects to measles increased from 89.66% in 2018 to 97.45% in 2022 as a result of the recent mandatory vaccination policy. Despite efforts to tackle vaccine hesitancy during the COVID-19 pandemic, measles vaccine uptake is still low among young adults starting their medical training, and their compliance with free workplace vaccination offers is suboptimal. Occupational health services should raise awareness among workers and work together to implement strategies to achieve comprehensive measles vaccination coverage among occupational health workers.

The third dose of measles-containing vaccine induces robust immune responses against measles in young seronegative healthcare workers who had previous two-dose measles vaccination.

BACKGROUND: Despite the low measles antibody positivity rate among young healthcare workers (HCWs) who have previously received two doses of a measles-containing vaccine (MCV), whether an additional dose of MCV acts as a booster remains unknown. Thus, we aimed to evaluate the immune responses to a third dose of MCV in young HCWs. METHODS: Hospital-wide measles seroprevalence was assessed using enzyme-linked immunosorbent assay (ELISA). The immunogenicity of a third dose of MCV was determined in young seronegative HCWs (born between 1986 and 1997) who had previously received a two-dose measles vaccination. RESULTS: A total of 3033 (92.6%) HCWs had anti-measles immunoglobulin G. The lowest seropositivity rate was observed in HCWs aged 20-24 years (87.7%). In this group, HCWs who received a third dose of MCV had higher seropositivity than those who received a second dose (89.5% vs. 75.4%). A third dose of MCV was administered to 18 HCWs who did not have anti-measles IgG despite two doses. Neutralizing antibody titers increased significantly 4 weeks after the third vaccination. Although neutralizing antibody titers decreased 1 year post vaccination, 17 (94.4%) HCWs had medium (121-900 mIU/mL) or high (>900 mIU/mL) levels. Furthermore, the third dose of MCV increased the measles virus-specific T-cell effector function. CONCLUSIONS: The third dose of MCV induced a strong immune response against measles in young seronegative HCWs who had previously received a two-dose measles vaccination.

Serological Response to COVID-19 and Its Association With Measles-Rubella (MR)-Containing Vaccines.

BACKGROUND AND OBJECTIVES:  Epidemiological studies suggest that coronavirus disease 2019 (COVID-19) has a less severe disease course and a more favorable prognosis among children. Childhood vaccines and heterologous immunity have been suggested as reasons for this. Additionally, the structural similarity between the measles, rubella, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus particles may affect immune responses. The objective of this study was to compare COVID-19 antibody titers and disease severity between measles-rubella (MR) vaccinated and unvaccinated children. Additionally, we aimed to evaluate and compare the antibody response in recipients of a single dose and two doses of the MR vaccine. METHODS:  The study was prospective and comparative and included 90 COVID-19-positive children aged nine months to 12 years. The study was registered under the clinical trials registry of India (CTRI/2021/01/030363). COVID-19 antibody titers were measured at two weeks, six weeks, and 12 weeks, along with the assessment of MR antibody titers. COVID-19 antibody titers and disease severity were compared between MR-vaccinated and MR-unvaccinated children. The comparison of COVID-19 antibody titers between recipients of a single dose and two doses of MR vaccine was also conducted. RESULTS: The results showed significantly higher median COVID-19 antibody titers at all time points during follow-up in the MR-vaccinated group (P<0.05). However, the two groups had no significant difference in the disease severity. Moreover, there was no difference in the antibody titers of MR one dose and two dose recipients. CONCLUSION: Exposure to even a single dose of MR-containing vaccine enhances the antibody response against COVID-19. However, randomized trials are necessary to further explore this subject.

Measles and Varicella Vaccination Program in a Hospital: Implementation and Impact on Contact Tracing.

Healthcare workers are recommended to get vaccinated against measles and varicella. This study aims to describe the implementation process of a measles and varicella vaccination program and report on the reduction in the number of susceptible healthcare workers exposed to measles, varicella, and disseminated herpes zoster at a tertiary hospital. The Consolidated Framework for Implementation Research (CFIR) model was used to describe the vaccination program implemented from October 2015 to September 2018. The number of exposed, reviewed, and susceptible healthcare workers during contact tracing for exposure to (a) measles and (b) varicella and disseminated herpes zoster in 2016, 2017, and 2018 is reported. A total of 6770 (95%) out of 7083 healthcare workers completed their immunization review by 2018. In 2016, 20 (10%) out of 198 healthcare workers exposed to measles were considered susceptible. In 2018, no one was found susceptible out of the 51 staff members exposed to measles (p < 0.01). For exposure to varicella and disseminated herpes zoster, seven (5%) out of 154 exposed healthcare workers were susceptible in 2016. In comparison, only two (1%) out of 377 exposed healthcare workers in 2018 were susceptible (p < 0.01). The vaccination program effectively reduced number of healthcare workers susceptible to measles, varicella, and disseminated zoster.

'I was terrified for my child': understanding the link between the Dengvaxia® controversy and the measles vaccine hesitancy in Pasay City, Philippines.

BACKGROUND: The Dengvaxia® (dengue vaccine) controversy has been identified as one of the main reasons for the measles vaccine hesitancy in the Philippines. Our study aimed to identify various issues related to the Dengvaxia® controversy and to link these issues with the social perspective of measles vaccine refusal. METHODS: Semi-structured interviews and a focus group discussion using ethnography research were conducted with 41 parents and healthcare workers in Pasay City. Using Victor Turner's Social Drama Theory, our study identified existing social issues relating to the different angles of the Dengvaxia® controversy and the measles vaccine hesitancy. RESULTS: Misinformation on the failed Dengvaxia® rollout implementation has challenged the fundamental understanding of the importance of immunization programs. Our findings on vaccine hesitancy in the community showed a complex problem with compounded factors, including medical populism, moral panics and other social views. We described how Pasay City's clinic waiting room became a significantly important scenario where individuals often discuss information, concerns and experiences on vaccines and vaccine hesitancy. CONCLUSION: Our study suggests that the Dengvaxia® controversy may reduce the measles vaccination confidence in the Philippines. Lack of transparency played a crucial role in this dilemma, producing a cascading effect on the other vaccines' safety.

Overall effect of a campaign with measles vaccine on the composite outcome mortality or hospital admission: A cluster-randomized trial among children aged 9-59 months in rural Guinea-Bissau.

OBJECTIVES: Campaigns with measles vaccine (C-MV) are conducted to eradicate measles, but prior studies indicate that MV reduces non-measles mortality and hospital admissions too. We hypothesized that C-MV reduces death/hospital admission by 30%. METHODS: Between 2016-2019, we conducted a non-blinded cluster-randomized trial randomizing village clusters in rural Guinea-Bissau to a C-MV targeting children aged 9-59 months. In Cox proportional hazards models, we assessed the effect of C-MV, obtaining hazard ratios (HR) for the composite outcome (death/hospital admission). We also examined potential effect modifiers. RESULTS: Among 18,411 children (9636 in 111 intervention clusters/8775 in 110 control clusters), 379 events occurred (208 intervention/171 control) during a median follow-up period of 22 months. C-MV did not reduce the composite outcome (HR 1.12, 95% confidence interval 0.88-1.41). Mortality among enrolled children (5.3 intervention and 4.6 control, per 1000 person-years) was approximately half the pre-trial mortality rate (11.1 intervention and 8.9 control, per 1000 person-years). Neither planned nor explorative analyses of potential effect modifiers explained the contrasting results to prior studies. CONCLUSION: C-MV did not reduce overall mortality or hospital admission. This might be explained by changes in disease patterns, baseline differences in health status, and/or modifying effects of other campaigns during follow-up.

Why Parents Say No to Having Their Children Vaccinated against Measles: A Systematic Review of the Social Determinants of Parental Perceptions on MMR Vaccine Hesitancy.

Ongoing outbreaks of measles threaten its elimination status in the United States. Its resurgence points to lower parental vaccine confidence and local pockets of unvaccinated and undervaccinated individuals. The geographic clustering of hesitancy to MMR indicates the presence of social drivers that shape parental perceptions and decisions on immunization. Through a qualitative systematic review of published literature (n = 115 articles; 7 databases), we determined major themes regarding parental reasons for MMR vaccine hesitancy, social context of MMR vaccine hesitancy, and trustworthy vaccine information sources. Fear of autism was the most cited reason for MMR hesitancy. The social drivers of vaccine hesitancy included primary care/healthcare, education, economy, and government/policy factors. Social factors, such as income and education, exerted a bidirectional influence, which facilitated or hindered vaccine compliance depending on how the social determinant was experienced. Fear of autism was the most cited reason for MMR hesitancy. Vaccine hesitancy to MMR and other childhood vaccines clustered in middle- to high-income areas among mothers with a college-level education or higher who preferred internet/social media narratives over physician-based vaccine information. They had low parental trust, low perceived disease susceptibility, and were skeptical of vaccine safety and benefits. Combating MMR vaccine misinformation and hesitancy requires intersectoral and multifaceted approaches at various socioecological levels to address the social drivers of vaccine behavior.

Second Dose Measles Vaccination Utilization and Associated Factors in Jabitehnan District, Northwest Ethiopia.

Background: Herd immunity against measles is essential to interrupt measles transmission, and this can only be attained by reaching at least 95% coverage for each of the 2 doses of measles vaccine provided in infancy and early childhood age group. It is important to provide everyone with 2 doses of the measles vaccine in order to effectively safeguard the population. Despite this, little is known about the second dosage of the measles vaccine utilization status and the factors that affect it. Therefore, this study aimed to assess second dose of measles vaccination utilization and its associated factors among children aged 24-35 months in Jabitehnan district, 2020. Methods: A community-based cross-sectional study design was conducted at Jabitehnan District, Northwest Ethiopia, from September 1st, 2020 to October 1st, 2020. Systematic random sampling technique was used to select 845 mothers/caregivers who had children aged 24-35 months. Both bi-variable and multivariable logistic regression was fitted to identify the determinant factors of second dose measles vaccination utilization. Finally, the statistical significant variables were declared by using 95% CI and P value less than .05 in the multivariable logistic regression analysis. The Hosmer and Lemeshow test was used to check the model's fit to the data, and the variance inflation factor was used to assess multi-collinearity. Results: The overall second dose of measles vaccination utilization was 48.1%, (95% CI: 44.7-51.6). Mothers with primary school education (AOR = 1.91, 95% CI: 1.15-3.17), information about MCV2 (AOR = 6.53, 95% CI: 4.22-10.08), distance from vaccination site (AOR = 3.56, 95% CI: 2.46-5.14), knowledge about immunization (AOR = 1.935, 95% CI: 1.29-2.90), and favorable attitude about immunization (AOR = 5.19, 95% CI: 3.25-8.29) were significantly associated factors with second dose of measles vaccination utilization. Conclusion: Second dose measles vaccination utilization in the district was lower than the national target. Maternal education, distances from vaccination site, information about MCV2, and knowledge about immunization were significantly associated variables with second dose measles vaccination utilization. Therefore, in order to increase the utilization of the second dose of the measles vaccine, improved health education and service expansion to difficult-to-reach areas are required.

Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model.

Oncolytic virotherapy constitutes a promising treatment option for many solid cancers, including peritoneal carcinomatosis (PC), which still represents a terminal stage of many types of tumors. To date, the in vitro efficacy of oncolytic viruses is mostly tested in 2D-cultured tumor cell lines due to the lack of realistic 3D in vitro tumor models. We have investigated the feasibility of virotherapy as a treatment option for PC in a human ex vivo peritoneum co-culture model. Human HT-29 cancer cells stably expressing marker genes GFP and firefly luciferase (GFP/luc) were cultured on human peritoneum and infected with two prototypic oncolytic viruses (GLV-0b347 and MeV-DsRed). Both viral constructs were able to infect HT-29 cells in patient-derived peritoneum with high tumor specificity. Over time, both GFP signal and luciferase activity decreased substantially, thereby indicating successful virus-induced oncolysis. Furthermore, immunohistochemistry stainings showed specific virotherapeutic infections of HT-29 cells and effective tumor cell lysis in infected co-cultures. Thus, the PC model established here provides a clinically relevant screening platform to evaluate the therapeutic efficacy of virotherapeutic compounds and also to investigate, in an autologous setting, the immunostimulatory potential of oncolytic viruses for PC in a unique human model system superior to standard 2D in vitro models.