Measles has reemerged as a significant global public health threat, with increasing morbidity and mortality associated with declining vaccination rates. This review summarizes current global outbreaks, history of measles, vaccination and elimination status, vaccine hesitancy, and outbreak response and lessons learned highlighting different novel digital epidemiological tools. Measles continues to surge worldwide with an estimated 11 million infections in 2024, which is more than prepandemic levels. Developing and developed countries are both facing measles outbreaks, with the United States at risk of losing measles elimination status. Recent studies have showed that worldwide percentages of two-dose measles vaccination were lower than 95% that is required to interrupt measles transmission in all WHO regions. Novel epidemiological tools such as interactive simulators, real-time use of dynamic models, serosurveillance, and others are transforming measles outbreak response and enable earlier outbreak detection, tracking, and targeted public health interventions. Vaccine hesitancy is one of the top global health threats and developing a tailored evidence-based approach is necessary to establish and maintain measles elimination.
In February 2026, two travel-associated cases of measles were reported to the Wisconsin Department of Health Services (WDHS). Public health investigations for each case included wastewater (sewage) surveillance for wild-type measles, which was first implemented by the WDHS Wastewater Monitoring Program in June 2025. The virus from one case, caused by measles genotype D8, was detected by a wastewater surveillance assay before the case was identified by local health authorities, leading to public health notifications and action. Measles virus from the second case, caused by measles genotype B3, was not detected by the assay. Additional analysis of the measles wastewater assay, which is among the most widely used assays in the United States, revealed that the assay was not able to detect an internationally circulating variant of the measles B3 genotype. Two alternative assays confirmed that measles virus was present and detectable in the wastewater. The assay developers designed and released a modified assay that incorporated an additional probe that could detect the B3 variant. These cases demonstrate the potential benefit of wastewater surveillance in detecting wild-type measles virus from a single case, while also highlighting the importance of regularly monitoring wastewater assays with respect to available genomic data. These activities should be supported by up-to-date libraries of publicly available whole-genome sequencing data.
Recent studies indicate that declining levels of measles-specific IgG antibodies among vaccinated individuals without exposure to wild-type virus may reflect changes in population-level serological profiles, rather than direct measures of protective immunity. Such findings may have implications for understanding population susceptibility following viral introduction in measles-eliminated settings. This study aimed to analyze changes in the age distribution of protective measles antibodies in the population of Salvador, Brazil, between 2000 and 2024. A population-based seroprevalence study was conducted using a household-based cluster sampling design across 30 sentinel areas in Salvador, Brazil. A total of 1,508 individuals were included, and a comparable survey had been conducted in 2000. Data on sociodemographic characteristics, vaccination history, and prior measles infection were collected through household interviews. Venous blood samples were obtained for measurement of measles-specific IgG antibodies using ELISA. Seroprevalence estimates were calculated by age group, and logistic regression analysis was performed to identify factors associated with measles seropositivity. ELISA-based IgG detection does not directly measure functional neutralizing antibodies or protective immunity. Overall measles IgG seroprevalence was 82.4%, with antibody concentrations predominantly ranging from 275 to 1,000 IU/L. The highest seroprevalence was observed among individuals aged over 50 years (92.1%), whereas the highest proportion of seronegative individuals occurred in the 20-29-year age group (39.6%). This age group also showed the most pronounced decline in seropositivity between 2000 and 2024, from 95.7% to 60.4%. In multivariable analysis, only previous measles infection was positively associated with seropositivity (OR = 1.67; 95% CI: 1.04-2.66; p = 0.032). Although seroprevalence was higher than seronegativity in the study population, the observed levels remain below those generally considered sufficient to interrupt measles transmission (≈ 92-95%). These findings indicate important immunity gaps among young adults and children that may facilitate outbreak occurrence following virus introduction in large urban centers.
Children with sickle cell anemia (SCA) may have decreased antibody responses after some routine vaccines, but it is not known if this affects the response to measles vaccination. It is critical to determine if children with SCA develop adequate seroprotection after measles vaccination considering the rise in measles infections in the United States and persistent transmission globally, particularly in regions with high SCA prevalence. It is also unknown if concurrent hydroxyurea treatment affects the measles antibody response to vaccination. We conducted a retrospective cohort study of children with SCA enrolled on the TREAT trial (NCT02286154) to determine anti-measles seroprotection (IgG ≥ 200 IU/L via ELISA) after first (MV1) and second (MV2) measles vaccine. Seroprotection was reached by 33 of 35 children (94%) after MV1 and by 46 of 50 (92%) after MV2. Each additional year of age at MV2 was associated with decreased odds of seroprotection (odds ratio (OR) 0.25, p=0.02). Hydroxyurea treatment at the time of vaccination did not reduce seroprotection; rather, earlier hydroxyurea initiation was associated with increased seroprotection (OR 4.4, p=0.02). The majority of children with SCA are adequately protected following measles vaccination, similar to the general population, and seroprotection is increased with timely vaccination and early hydroxyurea treatment.
This study aimed to develop a measles risk estimation tool to predict municipal-level occurrences in Brazil's most populous state, São Paulo. Measles risk for the 645 municipalities of the State of São Paulo was estimated by using public data spanning 2007-2023, integrated via the use and selection of machine learning models. Five machine-learning prediction models were trained via K-fold stratified cross validation using publicly available demographic, mobility, socioeconomic, and vaccination data to predict annual measles occurrence per municipality. Model-specific decision thresholds to classify municipalities into high/low risk were obtained from the Receiver Operating Characteristic (ROC) curve evaluated on validation data. Shapley Additive Explanations (SHAP) on test data were used to identify the most influential features. All models showed similar performances across metrics like AUC-ROC, F1-Score and Brier Score on training and test data. The highest measles risk was consistently identified in the São Paulo municipality metropolitan region (state capital) and in Santos (largest South American port). Using the decision threshold for the Random Forest model, a total of 2 municipalities were highlighted as high risk. Passenger arrivals at international airports, WHO-reported cases along with municipal population size and population density were the most influential features, consistent with the current non-endemic measles scenario in São Paulo State. A measles risk-estimation tool is proposed for estimating measles risk in São Paulo State. Because it relies on publicly available data, the proposed framework may serve as a basis for similar initiatives in other Brazilian states or regions.
Eswatini has been implementing measles and rubella elimination strategies, aligning with the WHO African Regional goal. This report reviews the immunization coverage and surveillance data to evaluate the country's progress towards the elimination goals. We reviewed routine immunisation coverage data, supplemental immunisation activity coverage data, and case based and laboratory surveillance data for measles and rubella. Routine immunization coverage for the first and second dose was 85% and 82% respectively in 2023 according to the WHO UNICEF coverage estimates. Eswatini implemented regular nationwide preventive supplemental immunisation activities, with the most recent one in 2021 attaining 97% administrative coverage. Eswatini has consistently met the performance targets for the principal indicators since 2008. The incidence of both measles and rubella have been maintained at less than 5 cases per million for more than 10 years, with zero incidence of measles documented over multiple years. Eswatini has made immense progress towards measles and rubella elimination. The country will need to address programmatic gaps that may negatively impact population immunity and will need to maintain high quality measles and rubella surveillance, including molecular surveillance in order to attain and maintain the verification of measles and rubella elimination.
Measles remains a significant public health concern in Romania, with recurrent ongoing nationwide outbreaks despite the availability of the measles-mumps-rubella (MMR) vaccine. This study investigates the epidemiological, clinical, and sociocultural dimensions of measles among Romanian adults, with a particular focus on a vulnerable group, the Roma population. We conducted a retrospective cohort study using clinical data from a tertiary hospital in Bucharest, Romania. The study included adult patients hospitalized with measles between July 2023 and April 2024. In a subsequent phase, we carried out a cross-sectional survey among hospitalized measles patients to assess their perception and understanding of measles and the MMR vaccine, with particular attention to responses from Roma participants. A retrospective investigation of 100 hospitalized adult patients with laboratory-confirmed diagnoses of measles demonstrated frequent complications such as hepatic involvement (85/100), pneumonia (68/100), and respiratory failure (21/100). Only 6/100 of patients were fully vaccinated. Rhabdomyolysis was significantly more common in unvaccinated individuals and women. No deaths were recorded, and no ICU admissions occurred. Among the hospitalized patients, 49 adults responded to a vaccine centered questionnaire. We report a notable vaccine hesitancy, particularly among the Roma respondents. Socioeconomic factors such as low income, limited education, and lack of health insurance were significantly associated with negative perceptions of the MMR vaccine. A statistically significant association was observed between Roma ethnicity and the belief that the MMR vaccine causes autism. These findings highlight the urgent need for targeted public health interventions with culturally adapted education campaigns to improve vaccination coverage and thereby protect vulnerable adult populations in Romania.
The basic reproduction number, R0, is an epidemiological measure to describe the transmissibility of infectious diseases and evaluate the potential effect of interventions. Measles R0 has historically been considered to be between 12-18, with contextual factors contributing to its heterogeneity, but has rarely been estimated using data across multiple countries. Our study aims to estimate measles R0 in low- and middle-income countries using a standardised database of population-based serosurveys. We fitted an age-structured compartmental model of measles transmission dynamics and vaccination (DynaMICE) to the age-specific seroprevalence data extracted from a recent systematic review. Using Markov Chain Monte Carlo, we estimated setting-specific posterior distributions of R0 in 172 studies with unique survey years and locations from 57 countries. Bootstrapped samples of R0 estimates were pooled by study characteristics, including survey period, geography, and overall bias in sampling, measurement, and reporting results. Measles R0 estimates varied substantially across serostudies, ranging from 0.93 (95% credible interval (CrI): 0.70-1.00) to 147 (95% CrI: 76.5-208), with fewer than 13% of studies having median R0 values in the range of 12-18. Pooled R0 estimates showed smaller medians and variation in serostudies conducted after 2000 or including the adult population, while no distinguishable variation was identified across the World Health Organization regions. Our revised estimates demonstrated the wide range of measles R0 across low- and middle-income settings and highlighted the importance of considering the heterogeneity in measles transmissibility when modelling epidemics and planning interventions and vaccination strategies.
The United States declared endemic measles eliminated in 2000. However, outbreaks continued, with resurgences in 2019 and 2025. In 2025, more than 2200 cases across 48 outbreaks, the most since 1992, were reported. In the first half of 2026, 2073 cases were reported. Declining measles, mumps, and rubella vaccination rates have increased susceptibility among children. Acute and critical care nurses are central to early recognition and management of measles for optimal outcomes. To summarize current evidence on measles epidemiology, pathophysiology, clinical presentation, complications, treatment strategies, and acute and critical care nursing implications, emphasizing preparedness amid rising case numbers. A literature review was conducted using PubMed and CINAHL databases and websites of Centers for Disease Control and Prevention, World Health Organization, professional organizations, and pediatric hospitals. English-language sources published from 2015 to August 2025 were prioritized; relevant earlier studies were included. Reference lists were searched for additional articles. Measles is among the most contagious human diseases. Typical features include fever, cough, coryza, conjunctivitis, and morbilliform rash. Severe respiratory and neurological complications may require critical care hospitalization. Complications like encephalitis may present weeks to years after acute infection. Management remains supportive, with vitamin A supplementation recommended. Acute and critical care nursing priorities include early recognition, isolation precautions, specimen collection, respiratory and hemodynamic support, neurological monitoring, serial assessments, hydration, nutrition, and caregiver education. Measles is resurging in the United States despite being vaccine preventable. Nurse preparedness, including knowledge of clinical features, complications, and infection control, is essential to mitigate morbidity and mortality and to support outbreak prevention. (Critical Care Nurse. Published online ahead of print July 17, 2026).
Prevention and control of vaccine-preventable infections is a key component of maintaining public health, and the overall state of immunity is the determining factor. To study herd immunity of the Armenian population to measles, rubella, mumps, and diphtheria. The study involved 5,513 individuals from all regions aged from 1 year and above. A cohort of volunteers, stratified into 9 age groups, was formed including by region and activity using a web application. For each infection, the presence and/or levels of immunoglobulin G were determined by the enzyme immunoassay method using Russian-made test systems. The cohort average seroprevalence values for measles, rubella, mumps, and diphtheria were 88.3%, 97.2, 83.2, and 56.3%, respectively. The least protected age groups were: children <5 years (80.7% seropositive) and adults 30-49 years (82-83%) regarding measles; adolescents and adults <49 years (73-79%) regarding mumps; and the older adults (34.4%) regarding diphtheria. Most volunteers had: low or moderate measles Ab levels (0.18-1 IU/mL); high levels of rubella Abs (>200 IU/mL); and a basic protective level of diphtheria toxin Abs (0.1-1 IU/mL). With age, a trend is seen: seropositivity for the viral pathogens (measles, mumps, and rubella) increased to maximum values; and diphtheria seropositivity decreased to minimum values. The level of herd immunity in Armenia is sufficient only for rubella, as confirmed by the absence of cases. Currently, immunity to measles and mumps is present, which prevents outbreaks but may not be fully preventive of sporadic cases. Despite the absence of diphtheria, insufficient protection in older adults makes them a risk group for incidence and severity. However, immunity levels in our study were assessed based only on humoral immunity, which may underrepresent the full immunological response, including that mediated by cellular immunity.
Globally, measles remains a major cause of child mortality, and rubella is the leading cause of birth defects among all infectious diseases. In Mainland Tanzania, eliminating measles and rubella remains challenging due to geographical diversity, uneven healthcare facilities distribution, and socio-economic disparities across regions. Understanding spatial patterns and associated determinants of vaccination coverage is essential for improving campaign effectiveness. This study aimed to explore the spatial distribution and associated factors of measles-rubella campaign coverage among children aged 9-59 months in Mainland Tanzania. A cross-sectional survey was conducted following the implementation of the February 2024 measles-rubella (MR) vaccination campaign to assess the spatial distribution and factors influencing MR vaccination coverage among children aged 9-59 months in Mainland Tanzania. Spatial autocorrelation was evaluated using Moran's I to detect clustering, while Local Indicators of Spatial Association (LISA) was used to identify High-High and Low-Low clusters. Hotspot and cold-spot analyses were performed using Getis-Ord Gi* statistics at the 95% confidence level, consistent with standard epidemiological reporting practices, to identify statistically significant spatial clusters. To identify factors associated with the campaign coverage, we used a multivariable logistic regression model. The study included 16,703 children, of whom 81.5% received the MR vaccine during the campaign. Vaccination coverage varied notably between regions, with Tabora and Pwani having a low coverage rate of 58.8% (95% CI: 51.3%-65.9%) and 61.0% (95% CI: 45.0%-75.0%) respectively. Njombe and Mbeya demonstrated high MR vaccination coverage of 97.4% (95% CI: 90.5-99.3%) and 95.6% (95% CI: 90.9-97.9%), respectively. The household wealth quintile and place of residence, caregiver's education, caregiver's age, and their marital status were associated with receiving MR vaccination during the campaign among children aged 9-59 months in Mainland Tanzania. Spatial distribution revealed significant clustering of vaccination coverage (Moran's I = 0.34, p < 0.01). The LISA identified two distinct categories of clusters: High-High Clusters (high-coverage) and Low-Low Clusters (low-coverage). High-High Clusters, which indicate regions with high MR vaccine rates surrounded by similar neighbors, are concentrated in regions such as Njombe and parts of Mbeya, whereas Low-Low Clusters, representing regions with low MR coverage, are found in areas like Tabora, Katavi, Dar es Salaam and Pwani. The Getis-Ord Gi* hotspot analysis shows significant clustering, with high-confidence hotspots in the southern highlands (Njombe and Mbeya) and notable cold spots in western Tanzania (Tabora and Katavi) and parts of eastern Tanzania. This study demonstrates substantial spatial heterogeneity in measles-rubella vaccination coverage across Mainland Tanzania, with persistent geographic inequities driven by socio-economic and demographic factors. These findings demonstrate how integrating geospatial insights with equity-focused planning can support precision public health planning, enabling targeted interventions to close coverage gaps and accelerate progress toward measles and rubella elimination.
Measles is a highly contagious vaccine-preventable disease that was once controlled with measles, mumps, and rubella vaccinations but has reemerged in the United States and globally as a public health emergency. Despite availability of a safe and effective vaccine, declining vaccination rates driven by vaccine hesitancy, access issues, and clustering of unvaccinated individuals have led to measles outbreaks. Since January 2026 in the United States, both the International Vaccine Access Center (IVAC; 1,654 cases) and the Centers for Disease Control (CDC; 1,671 cases) have reported a high number of cases (IVAC, March 27, 2026; CDC, April 3, 2026) that will exceed the reported cases (2,286) in 2025 (CDC, April 3, 2026). The Pan American Health Organization (PAHO) reported an epidemiological alert on measles in the Americas Region (PAHO, February 3, 2026). Emergency Nurse Practitioners must identify, manage, and initiate control measures. This review covers clinical manifestations, vaccination guidelines, management, and complications of measles.
Measles remains a leading cause of vaccine-preventable mortality, particularly in low- and middle-income countries. Despite Rwanda's high routine immunization coverage and introduction of a two-dose measles-rubella schedule, persistent immunity gaps continue to drive localized outbreaks. Understanding how age influences hospitalization duration during outbreaks is critical for optimizing clinical management and resource allocation, yet evidence using robust time-to-event methods remains limited. We conducted a retrospective cohort analysis of 56 confirmed measles cases identified during an outbreak in Nyanza District, Southern Province, Rwanda (February 16 - April 17, 2026). Demographic, clinical, and geographic data were extracted from routine surveillance records. Kaplan-Meier survival curves described time to hospital discharge stratified by age group. Among the 56 cases, infants under 9 months formed the largest proportion (44.6%), followed by adults over 15 years (25%). Geographic clustering was concentrated in Busasamana sector (51.7%). Age significantly predicted hospitalization duration (log-rank p = 0.00049), with children aged 5-15 years demonstrating the most rapid discharge by day 5, while infants under 9 months. Age was a significant determinant of measles hospitalization duration, with infants and adolescents experiencing the most prolonged clinical courses while school-aged children recovered fastest. These findings support age-targeted clinical triage and resource planning during measles outbreak response.
In recent years, global outbreaks of measles and mumps have re-emerged as herd immunity declines. Pediatric heart transplant recipients are at increased risk for severe vaccine-preventable infections, yet live vaccines have historically been avoided due to safety concerns. Data on post-transplant measles-mumps-rubella (MMR) vaccination remain limited. We conducted a retrospective single-center cohort study of pediatric heart transplant recipients who received live-attenuated MMR vaccination between January 2022 and January 2026 under a structured post-transplant vaccination protocol. Eligibility required clinical stability, >6 months post-transplantation, no recent rejection, and predefined immune parameters. Safety, immunosuppressive status, and serologic response were assessed. Twenty-nine recipients received 49 MMR doses at a median of 9.8 years post-transplant. Vaccination was well tolerated, with no vaccine-related adverse events, rejection episodes, or graft complications. Post-vaccination serologic data was available for 23 recipients. Overall seroconversion rates were 61% for measles, 65% for mumps, and 100% for rubella, with higher measles responses after two doses (68% vs. 43%). Seroconversion was not associated with age, time from transplantation, immunosuppression, or immune parameters. Most patients (65%) would not have met 2019 International Pediatric Transplantation Association criteria for standard live vaccination eligibility. In carefully selected pediatric heart transplant recipients, MMR vaccination was safe and provided acceptable immunogenicity. These findings challenge the historical exclusion of this population from live vaccination and suggest current eligibility criteria may be overly restrictive.
Measles elimination remains elusive in many countries, and resurgences occur even in previously controlled settings. We assessed age-specific clinical and epidemiological factors associated with laboratory-confirmed measles among suspected cases. In this test-negative case-control study, we analyzed surveillance data from Diyarbakır, Türkiye (2012-2024). Cases and controls were defined by measles-specific IgM results. Cases were stratified into two age groups, individuals aged ≤ 1 year and individuals aged > 1 year, with controls selected using systematic sampling at a case-control ratio of 1:3. Univariable and multivariable logistic regression analyses estimated odds ratios (ORs) for demographic factors, vaccination status, seasonality, epidemic year, clinical symptoms, and hospitalization. Among 3,868 individuals (967 cases, 2,901 controls), 32% of cases were ≤ 1 year of age. In infants, predictors included hospitalization (OR: 7.95; 95% CI:4.21-15), upper respiratory tract symptoms (OR: 3.20; 95% CI:1.87-5.48), age 7-9 months (OR: 4.16; 95% CI:2.33-7.41) and 10-12 months (OR: 5.28; 95% CI:3.03-9.20), and spring-summer season (OR: 2.08; 95% CI:1.14-3.82). Among individuals aged > 1 year, significant predictors were receipt of a single dose (OR: 3.64; 95% CI:1.09-12.15); being unvaccinated (OR: 16.13; 95% CI:4.77-54.54) or having unknown vaccination status (OR: 17.26; 95% CI:5.14-57.88); epidemic year (OR: 4.06; 95% CI:2.74-6.02); spring-summer season (OR: 1.80; 95% CI:1.21-2.69); fever (OR: 1.89; 95% CI:1.20-2.95); and hospitalization (OR: 2.24; 95% CI:1.39-3.62). Among suspected cases, age-specific predictors of laboratory-confirmed measles may support clinical suspicion, surveillance alertness, and prioritization of laboratory testing when interpreted alongside the local epidemiological context, including seasonality, vaccination coverage, and individual vaccination status. These findings may help guide regionally tailored surveillance and control efforts.
Despite sustained public-health efforts, measles continues to re-emerge in Europe. According to the ECDC, 1045 measles cases were reported in Italy in 2024. We describe epidemiological trends and characteristics of measles cases in the Tuscany Region from 2019 to 2024. We conducted a population-based retrospective study using cases reported through the national surveillance system (PREMAL). Incidence rates were calculated using demographic data from the Italian National Institute of Statistics (ISTAT). Cases were stratified by year, sex, age group, vaccination status (2024), and hospital admission; temporal, demographic, and clinical trends were analysed. From 2019 to 2024, 204 cases were reported, corresponding to a mean annual incidence of 0.93 per 100,000 population (95% CI: 0.80-1.07) and a cumulative incidence of 5.58 per 100,000 (95% CI: 4.78-6.31). Females accounted for 63.2% of cases (n = 129). After a peak in 2019 (n = 116), with an incidence of 3.13 per 100,000 (95% CI: 2.56-3.71), cases sharply declined during 2020-2023, followed by a resurgence in 2024 (n = 75), with an incidence of 2.05 per 100,000 (95% CI: 1.59-2.51). Children aged 0-4 years represented 7.4% of cases but had the highest age-specific incidence (12.19 per 100,000). Adults aged 25-64 years accounted for 70.1% of all cases, indicating the greatest absolute burden. Incidence was higher among individuals aged 25-44 years (11.56 per 100,000) than among those aged 45-64 years (4.30 per 100,000). Overall, 41.7% of cases required hospitalization. In 2024, most cases occurred in unvaccinated individuals (n = 56), while vaccination status was unknown for five cases. The 2024 measles resurgence in Tuscany mainly affected unvaccinated adults. These findings highlight persistent immunity gaps among adults, suggesting that protection and prevention measures are also needed in the population (0-4 y).
AbstractThe ongoing 2025-2026 outbreak of measles in Utah is the state's largest in 40 years. To characterize the epidemiology and clinical features of hospitalized patients, we conducted a chart review of patients admitted to Utah hospitals between June 20, 2025, and April 14, 2026. Of the 602 measles cases reported during that period, we identified 49 patients (8%) who were hospitalized. Most hospitalized patients (44, 90%) were unvaccinated. The most common reasons for hospitalization were dehydration and hypoxemia. These findings highlight the preventable health care burden associated with measles in Utah.
Bangladesh's 2026 measles outbreak followed an abrupt decline in measles-rubella vaccination coverage-from above 95% to approximately 57% within a single programme cycle-after more than a decade of stable high performance. This commentary argues that the collapse reflects institutional disruption linked to health sector restructuring in 2025, rather than demand side failure or vaccine hesitancy. Administrative reorganisation weakened accountability, disrupted logistics, and led to the cancellation of planned catch up activities, removing key compensatory mechanisms at a critical moment. Routine monitoring failed to prevent collapse because coverage data were not linked to predefined thresholds or enforceable response protocols. The Bangladesh case highlights a broader policy lesson: immunisation programmes are institutional functions whose continuity depends on governance arrangements. Where demand side failure is unsupported, measles resurgences should prompt systematic review of governance and accountability.
An ongoing measles outbreak in Israel, involving ≈3,200 cases and 16 deaths, threatens the country's measles elimination status and reflects declining vaccination rates observed globally and within Israel. Epidemiologic investigations supported by sequencing suggest that a single importation triggered the outbreak, underscoring the critical role of rapid genomic surveillance in outbreak control.
Measles virus (MeV) and human respiratory syncytial virus (HRSV) remain significant causes of global morbidity and mortality; measles in unvaccinated children, HRSV in infants below 6 months, immunocompromised, and the elderly. Despite the availability of vaccines and prophylactic monoclonal antibodies, there is a need for novel antiviral therapeutics. Both MeV and HRSV depend on correct glycosylation of surface glycoproteins (F and H for MeV, F and G for HRSV) for receptor interaction, entry, fusion, and cell-to-cell spread. Host endoplasmic reticulum (ER) α-glucosidases enable the proper folding of these N-linked viral enveloped glycoproteins via the calnexin pathway. Therefore, targeting those host-enzymes offers a promising broad-spectrum antiviral strategy. Here we demonstrate that the iminosugars MON-DNJ and NB-DNJ, which are inhibitors of ER α-glucosidases I and II, exert antiviral activity against both MeV and HRSV in vitro using different treatment protocols. Both compounds reduced viral spread as measured by infected cell surface area, decreased viral titers, and, in the case of HRSV, preserved cell viability in a dose-dependent manner. Gene set enrichment analysis of MeV and HRSV infection datasets revealed specific enrichment of MON-DNJ-modulated gene set, suggesting overlap in host transcriptional response. Antiviral activity to HRSV was confirmed in human airway organoids. These findings support the further development of iminosugars as host-directed antivirals against MeV and HRSV.