Seroepidemiology of measles and rubella among Hong Kong young adults and the humoral responses of an MMR booster among participants with low antibody levels.

BACKGROUND: Some individuals may not retain adequate immunity against measles and rubella years after two doses of measles, mumps, and rubella (MMR) vaccination due to vaccine failure. This study aimed to investigate the rates of vaccine failure and seroconversion by administering an MMR booster to young adults. METHODS: We first assessed measles and rubella antibody levels using the Luminex multiplex assay, VIDAS IgG assay, and plaque reduction neutralization test (PRNT) among individuals aged 18-30 years old who had received two doses of MMR vaccine. Participants with low measles and/or rubella antibody levels as confirmed by VIDAS received an MMR booster. Antibody levels were measured at 1-month post-booster. RESULTS: Among 791 participants, the measles and rubella seroprevalence rates were 94.7% (95% CI: 92.9%-96.0%) and 97.3% (95% CI: 96.0%-98.3%), respectively. Lower seroprevalence rates were observed among older participants. 113 participants who received an MMR booster acquired higher measles and rubella antibody levels at 1-month post-booster compared to baseline. CONCLUSIONS: Although measles and rubella vaccine failures were observed among 5.3% and 2.7% of young adults, respectively, an MMR booster triggered a significant antibody response.

Epidemiology of measles in southern Iran: trends, challenges, and vaccination insights.

Background: Measles, a highly contagious and vaccine-preventable disease, continues to present global public health challenges. This retrospective study focused on measles outbreaks in Hormozgan province, southern Iran, spanning from 2014 to 2019. Methods: Between 2014 and 2019, patients suspected of having measles, as reported by medical centers in Hormozgan, were subject to a comprehensive evaluation. The diagnosis of measles was conclusively established through the use of real-time polymerase chain reaction (RT-PCR) testing. A detailed collection of pertinent data was undertaken. SPSS software, version 21, was employed for statistical analysis. Results: In the current study, out of 1291 clinically suspected measles cases, 151 were PCR-confirmed, with an average age of 16.77 years (±10.46), comprising 50.9% males and 49.1% females. The annual distribution showed varied incidence: 8.4% in 2014, peaking at 18.8% in 2015, then fluctuating to 11.4% in 2016, 0.8% in 2017, and 17.9% in 2018, with no cases in 2019. Among confirmed cases, 16.5% were vaccinated, while 68.2% were not, and 15.23% had unknown vaccination status. Conclusion: This retrospective study highlights the ongoing challenge of measles in Hormozgan province, Iran, from 2014 to 2019. Despite measles being preventable by vaccination, a significant number of cases were confirmed among both vaccinated and unvaccinated individuals, indicating gaps in immunization coverage and effectiveness. The fluctuating annual incidence, with a peak in 2015 and no cases in 2019, suggests variable success in disease control efforts. This underscores the need for enhanced surveillance, improved vaccination strategies, and public health interventions to effectively combat measles outbreaks in this region.

A Semiquantitative Protein-Fragment Complementation Assay to Study Protein-Protein Interactions of the Polymerase Complex in Cellula.

Protein-fragment complementation assays (PCAs) are powerful tools to investigate protein-protein interactions in a cellular context. These are especially useful to study unstable proteins and weak interactions that may not resist protein isolation or purification. The PCA based on the reconstitution of the Gaussia princeps luciferase (split-luc) is a sensitive approach allowing the mapping of protein-protein interactions and the semiquantitative measurement of binding affinity. Here, we describe the split-luc protocol we used to map the viral interactome of measles virus polymerase complex.

Optical Control of Mononegavirus Gene Expression and Replication.

Mononegaviruses are promising tools as oncolytic and transgene vectors for gene therapy and regenerative medicine. However, when mononegaviruses are used for therapeutic applications, the viral activity must be strictly controlled due to concerns about toxicity and severe side effects. With this technology, mononegavirus vectors can be grown where they are intended and can be easily removed when they are no longer needed. In particular, a photoswitch protein called Magnet (consisting of two magnet domains) is incorporated into the hinge region between the connector and methyltransferase domains of the mononegavirus polymerase protein (L protein) to disrupt the L protein functions. Blue light (470 ± 20 nm) irradiation causes the dimerization of the two magnet domains, and the L protein is restored to activity, allowing viral gene expression and virus replication. Since the magnet domains' dimerization is reversible, viral gene expression and replication cease when blue light irradiation is stopped.

Investigating Liquid-Liquid Phase Separation in Virus-Generated Inclusion Bodies Using Fluorescence Recovery After Photobleaching of Fluorescently Labeled Host Proteins.

Many negative-sense single-stranded RNA viruses within the order Mononegavirales harm humans. A common feature shared among cells infected by these viruses is the formation of subcellular membraneless structures called biomolecular condensates, also known as inclusion bodies (IBs), that form through a process called liquid-liquid phase separation (LLPS). Like many other membraneless organelles, viral IBs enrich a specific subset of viral and host proteins involved in the formation of viral particles. Elucidation of the properties and regulation of these IBs as they mature throughout the viral replication process are important for our understanding of viral replication, which may also lead to the development of alternative antiviral treatments. The protocol outlined in this chapter aims to characterize the intrinsic properties of LLPS within the measles virus (MeV, a member of Mononegavirales) IBs by using an imaging approach that fluorescently tags an IB-associated host protein. This method uses common laboratory techniques and is generalizable to any host factors as well as other viral systems.

Applying Reverse Genetics to Study Measles Virus Interactions with the Host.

The study of virus-host interactions is essential to achieve a comprehensive understanding of the viral replication process. The commonly used methods are yeast two-hybrid approach and transient expression of a single tagged viral protein in host cells followed by affinity purification of interacting cellular proteins and mass spectrometry analysis (AP-MS). However, by these approaches, virus-host protein-protein interactions are detected in the absence of a real infection, not always correctly compartmentalized, and for the yeast two-hybrid approach performed in a heterologous system. Thus, some of the detected protein-protein interactions may be artificial. Here we describe a new strategy based on recombinant viruses expressing tagged viral proteins to capture both direct and indirect protein partners during the infection (AP-MS in viral context). This way, virus-host protein-protein interacting co-complexes can be purified directly from infected cells for further characterization.

Dual RNA-seq Analysis of Patients' Cells and Viral Genome After Measles Infection.

During the infection of a host cell by an infectious agent, a series of gene expression changes occurs as a consequence of host-pathogen interactions. Unraveling this complex interplay is the key for understanding of microbial virulence and host response pathways, thus providing the basis for new molecular insights into the mechanisms of pathogenesis and the corresponding immune response. Dual RNA sequencing (dual RNA-seq) has been developed to simultaneously determine pathogen and host transcriptomes enabling both differential and coexpression analyses between the two partners as well as genome characterization in the case of RNA viruses. Here, we provide a detailed laboratory protocol and bioinformatics analysis guidelines for dual RNA-seq experiments focusing on - but not restricted to - measles virus (MeV) as a pathogen of interest. The application of dual RNA-seq technologies in MeV-infected patients can potentially provide valuable information on the structure of the viral RNA genome and on cellular innate immune responses and drive the discovery of new targets for antiviral therapy.

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.

Histopathological Analysis of Brains from Dogs Infected with Canine Distemper Virus.

We describe the use of conventional histology and immunohistochemistry against canine distemper virus (CDV) to examine the brains of domestic dogs with a confirmed diagnosis of CDV infection. Histologically, to identify the main typical lesions, we used conventional H&E stain; to evaluate the progressive demyelination, we used Luxol Fast Blue stain; and to identify the presence of viral particles in these affected regions, we used immunohistochemistry against CDV. We confirm that the histopathological analysis of brains of distemper-infected dogs is a powerful tool to evaluate the typical brain lesions and could be used as an interesting natural model to continue studying the pathogenesis of canine distemper in different species and/or other morbillivirus infections, like measles.

Measles Foci Reduction Neutralization Test (FRNT).

The plaque reduction neutralization test (PRNT) and the enzyme-linked immunosorbent assay (ELISA) are both widely used to assess immunity to infectious diseases such as measles, but they use two different measurement principles: ELISA measures the ability of antibodies to bind to virus components, while the PRNT detects the aptitude of antibodies to prevent the infection of a susceptible cell. As a result, detection of measles virus (MV) neutralizing antibodies is the gold standard for assessing immunity to measles. However, the assay is laborious and requires experience and excellent technical skills. In addition, the result is only available after several days. Therefore, the classical PRNT is not suitable for high-throughput testing. By using an immunocolorimetric assay (ICA) to detect MV-infected cells, the standard PRNT has been developed into a focus reduction neutralization test (FRNT). This assay is faster and has improved specificity. The FRNT described here is extremely useful when immunity to measles virus needs to be assessed in patients with a specific medical condition, such as immunocompromised individuals in whom presumed residual immunity needs to be assessed. The FRNT is not generally recommended for use with large numbers of specimens, such as in a seroprevalence study.

Measles IgG Avidity Assay.

Measles IgG avidity assays determine the overall strength of molecular binding between measles-specific IgG antibodies and measles virus antigens. Avidity results can distinguish recent from distant measles virus infections. Individuals who are immunologically naïve to measles virus develop low-avidity antibodies upon measles virus infection or first-time vaccination. Within 4-6 months, antibodies mature to high avidity. Measles avidity assays are most useful in the context of measles elimination. In such settings, avidity and epidemiological and clinical information are used to classify measles breakthrough infections for control and surveillance purposes and to assist in case confirmation when other laboratory results are inconclusive or nonexistent. We present a highly accurate end-titer measles avidity assay that delivers results based on IgG quality (avidity) that are independent of IgG concentration.

Multiplex Bead Assay for the Serological Surveillance of Measles and Rubella.

There is increasing interest in evaluating antibody responses to multiple antigen targets in a single assay. Immunity to measles and rubella are often evaluated together because immunity is provided through combined vaccines and because routine immunization efforts and surveillance for measles and rubella pathogens are combined in many countries. The multiplex bead assay (MBA) also known as the multiplex immunoassay (MIA) described here combines the measurement of measles- and rubella-specific IgG antibodies in serum quantitatively according to international serum standards and has been successfully utilized in integrated serological surveillance.

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.

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.

Determinants of second-dose measles vaccination dropout in Ethiopia: A community-based matched case-control study.

Background: Measles vaccination is the most important public health intervention and a cost-effective strategy to reduce morbidity and mortality in under-five children. Although Ethiopia's government developed a measles elimination strategic plan by 2020, the full coverage of immunization was 43 %. Therefore, this study aimed to identify determinants of second-dose measles vaccination (MCV2) dropout among children aged 24-35 months in East Bale Zone, Ethiopia. Method: A community-based matched case-control study was conducted among 351 children (117 cases and 234 controls). Children who received the first dose of measles vaccine but did not receive the second dose were cases, and children who received both doses of measles vaccine were control. The matches were based on age and residence. The data were collected using a structured questionnaire, entered into Epi Data 3.1, cleaned, exported, and analyzed using Stata version 16.1. A multivariable conditional logistic regression analysis was performed. Variables with a P value of <0.05 were considered significant determinants of the dependent variable at the 95 % confidence level. Results: Mothers who were unable to read and write (mAOR: 4.0; 95 % CI: 1.59-10.2), did not receive counseling (mAOR: 3.19; 95 % CI: 1.62-6.27), spent ≥30 min to reach health facilities (mAOR; 2.76, 95 % CI: 1.25-6.1), and did not attend postnatal care (mAOR; 3.46, 95 % CI: 1.58-7.57) were significantly and positively associated with second-dose measles vaccination dropout. In addition, mothers who had poor knowledge of second-dose measles vaccination (mAOR; 3.20, 95 % CI: 1.50-6.70) and waited more than an hour for measles vaccination at health facilities (mAOR; 2.61, 95 % CI: 1.0-6.20) were significantly more likely to experience second-dose measles vaccine dropout. Conclusions: The key factors associated with second-dose measles vaccination dropout are maternal illiteracy, lack of PNC, inadequate maternal knowledge and poor counseling about MCV2 vaccination, long distances travel to healthcare facilities and extended waiting times at vaccination providing sites. Health extension workers emphasize strengthening home visit programs in catchment households to improve mothers' awareness of measles vaccination.

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.

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.

Predictors on parent's attitudes toward the measles-rubella (MR) vaccine in Jordan: An education program.

BACKGROUND: Vaccine hesitancy is considered 1 of the top 10 threats to global health. This study aims to assess the impact of an education program on parents' attitudes toward the measles-rubella vaccine. METHODS: A study was conducted with 250 parents using a randomized controlled trial design. The intervention group (125 parents) received training, education programs, and video, while the control group (125 parents) only received video. The Parent Attitudes about Childhood Vaccines (PACV) scale, including its behavior, safety and efficacy, and trust subscales, was used for pre-post assessment. This allowed for comparison between the groups and measurement of score differences. The PACV scale (range 0-42) identified vaccine hesitancy, with a score below 21 indicating "non-hesitant" and 21 or higher indicating "hesitant." RESULTS: The intervention group had a significant decrease in PACV scores after the program (17.54 ± 4.7, P = .001), mainly in behavior, safety, efficacy, and trust (6.4 ± 3.6, 9.8 ± 4.7, 3.9 ± 2; P = .001, .011, .002). The control group showed no changes (23.6 ± 3.5; P = .402). Postintervention PACV score differences were significant (t = 11.562, P = .001). DISCUSSION: Findings indicate that the education program had a positive effect on changing vaccine hesitancy. CONCLUSIONS: The education programs promoted vaccine acceptance among parents.