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.

Subacute sclerosing panencephalitis presenting as severe depression in an adult.

Subacute sclerosing panencephalitis (SSPE) is a fatal disorder that occurs as a rare complication of childhood measles. Symptoms typically manifest between the ages of 5 and 15. While the incidence of SSPE is declining globally, it is still prevalent in regions where measles remains common and vaccination rates are low due to poverty and lack of health education. Diagnosing SSPE can be challenging, particularly when patients exhibit unusual symptoms. A thorough clinical evaluation, including vaccination history, physical examination, electroencephalogram (EEG) and Cerebrospinal fluid (CSF) analysis, can help in making a diagnosis. We present the case of a young woman in her early 20s who initially experienced depressive symptoms, followed by myoclonus, dementia and visual impairment. The patient was ultimately diagnosed with SSPE based on characteristic EEG findings, neuroimaging results, CSF analysis and elevated serum measles antibody levels.

[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.

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.

Culturing Immortalized Human Airway Epithelial Cells at an Air-Liquid Interface for Measles Virus Infection.

Measles virus (MeV) infection of airway surface epithelial cells provides a site for final amplification before being released back into the environment via coughing and sneezing. Multiple cell lines have served as models of polarized epithelia for MeV infection, such as Caco2 cells (intestinal derived human epithelia) or MDCK cells (kidney derived canine epithelia). In this chapter, we describe the materials and air-liquid interface (ALI) culture conditions for maintaining four different cell lines derived from human airway epithelial cells: 16HBE14o-, Calu-3, H358, and NuLi-1. We provide methods for confirming transepithelial electrical resistance (TER) and preparing samples for microscopy as well as expected results from apical or basolateral MeV delivery. Polarized human airway derived cells serve as tissue culture models for investigating targeted questions about how MeV exits a human host. In addition, these methods are generalizable to studies of other respiratory viruses or the biology of ALI airway epithelial cells.

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.

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.

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.

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.

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.

Mathematical modeling and dynamics of immunological exhaustion caused by measles transmissibility interaction with HIV host.

This paper mainly addressed the study of the transmission dynamics of infectious diseases and analysed the effect of two different types of viruses simultaneously that cause immunodeficiency in the host. The two infectious diseases that often spread in the populace are HIV and measles. The interaction between measles and HIV can cause severe illness and even fatal patient cases. The effects of the measles virus on the host with HIV infection are studied using a mathematical model and their dynamics. Analysing the dynamics of infectious diseases in communities requires the use of mathematical models. Decisions about public health policy are influenced by mathematical modeling, which sheds light on the efficacy of various control measures, immunization plans, and interventions. We build a mathematical model for disease spread through vertical and horizontal human population transmission, including six coupled nonlinear differential equations with logistic growth. The fundamental reproduction number is examined, which serves as a cutoff point for determining the degree to which a disease will persist or die. We look at the various disease equilibrium points and investigate the regional stability of the disease-free and endemic equilibrium points in the feasible region of the epidemic model. Concurrently, the global stability of the equilibrium points is investigated using the Lyapunov functional approach. Finally, the Runge-Kutta method is utilised for numerical simulation, and graphic illustrations are used to evaluate the impact of different factors on the spread of the illness. Critical factors that effect the dynamics of disease transmission and greatly affect the rate and range of the disease's spread in the population have been determined through a thorough analysis. These factors are crucial in determining the expansion of the disease.