High rates of hepatic involvement associated with new epidemic measles strains in Romania.

Similar to other European countries, a measles epidemic dominated by D8 genotype strains is ongoing since 2022 in our country. Recent reports of liver involvement associated with new measles virus (MeV) strains are scarce. The aim of the study was to compare the clinical characteristics between hospitalized patients with measles from the current epidemic and those from the previous outbreak and to analyze the risk factors associated with hepatic involvement. Data were collected retrospectively for all consecutive adult ( ≥18 years old) patients admitted between October 2022-April 2024 and January 2018-December 2019. A number of 228 patients from the current and 130 from the previous MeV epidemic were included. The main statistically significant differences were those regarding hepatic involvement (77.2% vs. 45.4%, p < 0.001) and significant hepatocellular injury (23.6% vs. 10.7%, p = 0.003). Compared to cases without liver involvement (123), patients with hepatocytolysis (235) had a higher prevalence of keratoconjunctivitis (42.5% vs. 28.4%, p = 0.01), thrombocytopenia (47.6% vs. 34.9%, p = 0.02), severe lymphopenia (51% vs. 35.7%, p = 0.007) and high fibrinogen levels (58.7% vs. 47.1%, p = 0.04). MeV strains from the 2022-2024 epidemic were the strongest predictors of hepatic involvement in the multivariable analysis (odds ratio = 4.3, 95% confidence interval: 2.5-7.4, p < 0.001). The mortality rate of patients with hepatocellular injury was 1.2%. The current measles epidemic is dominated by high rates of hepatic involvement compared to the previous outbreak. Although not associated with a significant mortality, the potential change in MeV hepatotropism could have important clinical implications and warrants further monitoring.

Estimating the risk and spatial spread of measles in populations with high MMR uptake: Using school-household networks to understand the 2013 to 2014 outbreak in the Netherlands.

BACKGROUND: Measles outbreaks are still routine, even in countries where vaccination coverage exceeds the guideline of 95%. Therefore, achieving ambitions for measles eradication will require understanding of how unvaccinated children interact with others who are unvaccinated. It is well established that schools and homes are key settings for both clustering of unvaccinated children and for transmission of infection. In this study, we evaluate the potential for contacts between unvaccinated children in these contexts to facilitate measles outbreaks with a focus on the Netherlands, where large outbreaks have been observed periodically since the introduction of mumps, measles and rubella (MMR). METHODS AND FINDINGS: We created a network of all primary and secondary schools in the Netherlands based on the total number of household pairs between each school. A household pair are siblings from the same household who attend a different school. We parameterised the network with individual level administrative school and household data provided by the Dutch Ministry for Education and estimates of school level uptake of the MMR vaccine. We analysed the network to establish the relative strength of contact between schools and found that schools associated with low vaccine uptake are highly connected, aided by a differentiated school system in the Netherlands (Coleman homophily index (CHI) = 0.63). We simulated measles outbreaks on the network and evaluated the model against empirical measles data per postcode area from a large outbreak in 2013 (2,766 cases). We found that the network-based model could reproduce the observed size and spatial distribution of the historic outbreak much more clearly than the alternative models, with a case weighted receiver operating characteristic (ROC) sensitivity of 0.94, compared to 0.17 and 0.26 for models that do not account for specific network structure or school-level vaccine uptake, respectively. The key limitation of our framework is that it neglects transmission routes outside of school and household contexts. CONCLUSIONS: Our framework indicates that clustering of unvaccinated children in primary schools connected by unvaccinated children in related secondary schools lead to large, connected clusters of unvaccinated children. Using our approach, we could explain historical outbreaks on a spatial level. Our framework could be further developed to aid future outbreak response.

Assessing measles risk transmission in Iran: a utilization of the World Health Organization's programmatic risk assessment tool,2022.

BACKGROUND: Despite successful efforts to eliminate measles in Iran, imported measles cases continue to be reported. Because measles is endemic in neighboring countries. This research aims to evaluate the risk of measles transmission in different regions of Iran. METHODS: Measles case-based surveillance data of the Expanded Program of Immunization containing 31 provinces and 463 districts from 2019 to 2021 were assessed. The WHO Measles Programmatic Risk Assessment tool was used to evaluate the risk of disease transmission in four domains: population immunity, surveillance quality, program delivery performance, and threat assessment. scores were categorized as low, medium, high, or very high risk. RESULTS: During 2019-2021, the average incidence of measles was 1.9 per 1 million. Chabahar and Mashhad with 76 and ./6per million reported the highest and lowest incidence respectively. All 463 districts were categorized as low risk in risk assessment. Andimeshk, Chabahar, and Bojnurd obtained the highest risk scores with 27, 24, and 25 respectively. All districts were classified as low risk for population immunity. The average coverage of (MMR1) and (MMR2) was 95% or higher. All districts received the minimum points for surveillance quality. CONCLUSION: All regions are placed at a low level of disease transmission risk. However, the tool is not able to assess the risk at the rural or peripheral sectors level. The indicators used in this tool are the same for all countries with different epidemiological features (elimination, endemic). Sensitivity analysis can optimize the use of this tool for countries with different disease conditions.

Crisis-Related Measles Outbreaks in Low-Income Countries and the Need for Increased Health Systems Resilience.

The measles is a highly contagious disease that can be prevented by vaccination. During and after crises, vaccination against measles decreases in low-income countries, leading to outbreaks. It is possible for developed countries to be at risk from these outbreaks through travel. Low-income countries' health systems are not resilient to crises. Lack of capacity among these countries causes a decrease in vaccinations. As a result, we provide some recommendations for increasing the resilience of the health system in low-income countries in this letter.

[Analysis of serum IgM antibody and viral nucleic acid test results in measles and rubella cases in China from 2014 to 2023].

Objective: To analyze the results of serum IgM antibody and viral nucleic acid testing in measles and rubella cases in China from 2014 to 2023. Methods: Surveillance data on measles and rubella during 2014-2023 were obtained from the Chinese Disease Prevention and Control Information System, and cases that underwent measles/rubella IgM antibody testing and viral nucleic acid testing were included in the study. Information on the number of cases, vaccination status, and laboratory test results was collected, and laboratory test results were compared among cases with different times of rash or onset and different doses of vaccination. Results: From 2014 to 2023, the total number of measles and rubella surveillance cases was 581 746, and the number of measles and rubella cases that underwent both IgM antibody and viral nucleic acid testing was 39 124 and 21 766, respectively, with a double-positive rate of IgM antibody and viral nucleic acid testing of 63.73% (for measles) and 41.68% (for rubella). The single-positive rate for IgM antibody was 21.12% (for measles) and 27.15% (for rubella). The single-positive rate for viral nucleic acid tests was 13.84% (for measles) and 28.19% (for rubella). According to different days of rash or onset (0-3, 4-5, 6-10 and >10), samples of 24 629 (62.95%) measles cases and 15 785 (72.52%) rubella cases were from within 3 days of rash or onset, and the single positive rate of viral nucleic acid detection was 16.90% (for measles) and 32.07% (for rubella). The single positive rate of IgM antibody increased gradually with the time of onset (measles: χ2trend=314.098, P<0.001, rubella: χ2trend=763.846, P<0.001), and reached 31.66% (for measles) and 53.12% (for rubella) after 10 days of rash or onset. Depending on the number of vaccination doses (1, 2,≥3), the single positive rate of viral nucleic acid detection ranged from 12.93% to 20.29% (for measles) and from 25.30% to 27.88% (for rubella). The single positive rate of IgM antibody detection ranged from 36.89% to 47.47% (for measles) and from 22.81 to 41.15% (for rubella). Conclusions: Combined testing of serum IgM antibody and viral nucleic acids could facilitate laboratory confirmation of measles and rubella cases and was also important for measles and rubella elimination efforts.

Spatio-temporal modeling of co-dynamics of smallpox, measles, and pertussis in pre-healthcare Finland.

Infections are known to interact as previous infections may have an effect on risk of succumbing to a new infection. The co-dynamics can be mediated by immunosuppression or modulation, shared environmental or climatic drivers, or competition for susceptible hosts. Research and statistical methods in epidemiology often concentrate on large pooled datasets, or high quality data from cities, leaving rural areas underrepresented in literature. Data considering rural populations are typically sparse and scarce, especially in the case of historical data sources, which may introduce considerable methodological challenges. In order to overcome many obstacles due to such data, we present a general Bayesian spatio-temporal model for disease co-dynamics. Applying the proposed model on historical (1820-1850) Finnish parish register data, we study the spread of infectious diseases in pre-healthcare Finland. We observe that measles, pertussis, and smallpox exhibit positively correlated dynamics, which could be attributed to immunosuppressive effects or, for example, the general weakening of the population due to recurring infections or poor nutritional conditions.

Long-term waning of vaccine-induced immunity to measles in England: a mathematical modelling study.

BACKGROUND: Among people infected with measles in England between 2010 and 2019, the proportion of cases who had previously received two doses of vaccine has increased, especially among young adults. Possible explanations include rare infections in vaccinated individuals who did not gain immunity upon vaccination, made more common because fewer individuals in the population were born in the endemic era, before vaccination was introduced, and exposed as part of endemic transmission, or the waning of vaccine-induced immunity, which would present new challenges for measles control in near-elimination settings. We aimed to evaluate whether measles dynamics observed in England between 2010 and 2019 were in line with a waning of vaccine-induced immunity. METHODS: We used a compartmental mathematical model stratified by age group, region, and vaccine status, fitted to individual-level case data reported in England from 2010 to 2019 and collected by the UK Health Security Agency. The deterministic model was fitted using Monte Carlo Markov Chains under three scenarios: without the waning of vaccine-induced immunity, with waning depending on time since vaccination, and with waning depending on time since vaccination, starting in 2000. We generated stochastic simulations from the fitted parameter sets to evaluate which scenarios could replicate the transmission dynamics observed in vaccinated cases in England. FINDINGS: The scenario without waning overestimated the number of one-dose recipients among measles cases, and underestimated the number of two-dose recipients among cases older than 15 years (median 75 cases [95% simulation interval (SI) 44-124] in simulations without waning, 196 [95% SI 122-315] in simulations when waning was included, 188 [95% SI 118-301] in simulations when waning started in 2000, and 202 observed cases). The number of onward transmissions from vaccinated cases was 83% (95% credible interval 72-91%) of the number of transmissions from unvaccinated cases. The estimated waning rate was slow (0·039% per year of age; 95% credible interval 0·034-0·044% per year in the best-fitting scenario with waning starting in 2000), but sufficient to increase measles burden. INTERPRETATION: Measles case dynamics in England are consistent with scenarios assuming the waning of vaccine-induced immunity. Since measles is highly infectious, slow waning leads to a heightened burden in outbreaks, increasing the number of measles cases in people who are both vaccinated and unvaccinated. Our findings show that although the vaccine remains highly protective against measles infections for decades and most transmission is connected to people who are unvaccinated, breakthrough infections are increasingly frequent for individuals aged 15 years and older who have been vaccinated twice. FUNDING: National Institute for Health and Care Research and Wellcome Trust.

Epidemiology of measles outbreaks, incidence and associated risk factors in Ethiopia from 2000 to 2023: a systematic review and meta-analysis.

BACKGROUND: Although a universal vaccine is available and Ethiopia is working outstandingly towards measles elimination, a recurrent measles outbreak has occurred each year in different parts of the country. Therefore, understanding the epidemiology of measles cases, the incidence of confirmed measles virus cases and related risk factors is crucial. Here, we conducted a systematic review and meta-analysis to summarize information regarding the epidemiology, measles incidence rate and risk factors for national measles infections occurring in the past two decades, from 2000 to 2023. METHODS: Data from electronic databases, including PubMed, African Journal Online, WHO databases and Google Scholars, were searched to identify studies describing measles outbreaks, incidence rates and associated factors in Ethiopia that occurred between 2000 and 2023. Important basic information was extracted in an Excel spreadsheet and imported into Comprehensive Meta-analysis Software version 3 to evaluate the associations between measles outbreaks and different risk factors. We pooled the odds ratios (ORs) and 95% confidence intervals (CIs) for every included risk factor to evaluate the associations with measles outbreaks. RESULTS: We included 36 studies involving 132,502 patients with confirmed measles cases in Ethiopia. The results of this systematic review and meta-analysis revealed that measles outbreaks were more frequently reported in the Oromia region (73,310 (33.1%)), followed by the Southern Nation Nationalities of Ethiopia region (29,057 (13.4%)). The overall pooled analysis indicated that the prevalence of measles susceptibility was 67.5% (95% CI: 67.3-67.8%), with an I2 of 99.86% and a p value for heterogeneity < 0.0001. The non-vaccinated status of the children, their contact history with measles cases, their travel history, the presence of cases in family or neighbors, and malnourished patients were identified as factors associated with the high prevalence and recurrent measles infections in Ethiopia. CONCLUSION: The results of this systematic review and meta-analysis indicated that the pooled prevalence of measles infection was high, which is a public health concern in Ethiopia. Thus, strengthening healthcare services, regular vaccination campaigns, and the integration of health education activities with other services may decrease the incidence rate.

Hospital-acquired infections and unvaccinated children due to chronic diseases: an investigation of the 2017-2019 measles outbreak in the northern region of Vietnam.

BACKGROUND: Measles remains a major public health burden worldwide. Parents often hesitate to vaccinate children with chronic diseases. We investigated the association between the percentage of vaccination and chronic diseases and explore hospital infections' role in the 2017-2019 measles outbreak across northern Vietnam provinces. METHODS: A total of 2,064 children aged 0-15 years old admitted for measles to the National Children's Hospital during the outbreak were included in the study. Demographic information, clinical characteristics, vaccination statuses and laboratory examination were extracted from electronic medical records, vaccination records, or interviews with parents when other sources were unavailable. RESULTS: The incidence rate that provincial hospitals sent to the National Children's Hospital was proportional to the population density of their provinces of residence. Early nosocomial transmission of measles was observed before community-acquired cases emerged in many provinces. Among patients aged over 18 months, those with chronic diseases had a proportion of vaccination of 9.4%, lower than patients without chronic diseases at 32.4%. Unvaccinated patients had a higher proportion of hospital-acquired infections with aOR = 2.42 (1.65-3.65), p < 0.001 relative to vaccinated patients. The proportion of hospital-acquired infections was higher among children with chronic diseases compared to those without, with aOR = 3.81 (2.90-5.02), p < 0.001. CONCLUSION: Measles spread in healthcare settings prior to community cases that occurred in several provinces. We recommend enhancing hospital infection control by increasing staff training and improving early detection and isolation during non-outbreak periods. Measles patients with chronic diseases exhibited lower proportions of vaccination and faced a higher risk of hospital-acquired infections. It is crucial to establish comprehensive vaccination guidelines and enhance parental awareness regarding the significance and safety of measles vaccination to protect these vulnerable individuals.

Measles in the Modern Era: A Review.

Measles is a viral illness considered eliminated in the United States; however, outbreaks still occur even in this modern era where vaccines are readily available for every child under government-sponsored financing programs. The most recent measles outbreak was reported in March 2024 in Chicago, Illinois. Many of these patients were children younger than age 5 years with unvaccinated or unknown vaccine status, and this outbreak was associated with a migrant shelter. Measles bears a resemblance to other exanthemic diseases of childhood. In populations where there is high vaccine coverage, measles is less likely to be in the differential diagnosis for most physicians; however, cases of vaccine failure have been described, and populations have risk factors for developing complications associated with measles. Therefore, this quick review aims to describe an illustrative case, followed by epidemiology, clinical manifestations, complications, diagnosis, and vaccines associated with measles. By the end of this article, clinicians should be able to recognize a potential measles case, select the most appropriate test to confirm the diagnosis, and thus, prevent the spreading of this highly contagious disease. [Pediatr Ann. 2024;53(9):e345-e350.].

Assessing the impact of COVID-19 non-pharmaceutical interventions and relaxation policies on Class B respiratory infectious diseases transmission in China.

This study investigates the incidence of Class B respiratory infectious diseases (RIDs) in China under the Coronavirus disease 2019 (COVID-19) epidemic and examines variations post-epidemic, following the relaxation of non-pharmaceutical interventions (NPIs). Two-stage evaluation was used in our study. In the first stage evaluation, we established counterfactual models for the pre-COVID-19 period to estimate expected incidences of Class B RIDs without the onset of the epidemic. In the second stage evaluation, we constructed seasonal autoregressive integrated moving average intervention (SARIMA-Intervention) models to evaluate the impact on the Class B RIDs after NPIs aimed at COVID-19 pandemic were relaxed. The counterfactual model in the first stage evaluation suggested average annual increases of 10.015%, 78.019%, 70.439%, and 67.799% for tuberculosis, scarlet fever, measles, and pertussis respectively, had the epidemic not occurred. In the second stage evaluation, the total relative reduction in 2023 of tuberculosis, scarlet fever, measles and pertussis were - 35.209%, - 59.184%, - 4.481%, and - 9.943% respectively. The actual incidence declined significantly in the first stage evaluation. However, the results of the second stage evaluation indicated that a rebound occurred in four Class B RIDs after the relaxation of NPIs; all of these showed a negative total relative reduction rate.

A historical syndemic? The impact of synergistic epidemics of measles and scarlet fever on life expectancy in Victoria, Australia (1860s-1870s).

OBJECTIVES: To explore whether synergistic epidemics of measles and scarlet fever in 1860s-1870s Victoria, Australia could be characterized as syndemics, we apply the methods of Sawchuk, Tripp, and Samakaroon (Social Science & Medicine 2022, 295, 112956) to quantify the impact of each of the two major co-occurring epidemic events (1867, 1875) in terms of life expectancy (LE) changes. Sawchuk et al. posit the presence of a harvesting effect, indicated by a statistically significant increase in LE in the immediate post-epidemic "fallow period", as a criterion for identification of a historical syndemic. We test an alternate hypothesis that the same methods can identify a short-term scarring effect. MATERIALS AND METHODS: Using annual age- and cause-specific death statistics and census population data, we constructed abridged period life tables for baseline period, potential syndemic year, and "fallow" year for each of the two periods (1860s and 1870s). We compared LE at birth using Z-tests. We decomposed age-cause-specific mortality according to Arriaga's method to identify age-and cause-specific contributions to LE change. RESULTS: LE was significantly lower than baseline (1864-1865) in 1867 but not in the "fallow" year (1869). LE in 1875 and the 1878 "fallow" year were both significantly below baseline (1871-1873). Age-cause-specific decomposition showed similar patterns for 1867 and 1875 for measles and scarlet fever combined effects. DISCUSSION: Evidence of a scarring effect following the 1875 measles/scarlet fever combined peak supports the interpretation of this event as a syndemic. We suggest the short-term scarring effect can be a useful additional criterion for identifying historical syndemics.

Quantifying the long-term effects of measles infection-a retrospective cohort study.

OBJECTIVES: To assess whether measles infection has an impact on the rate of non-measles infectious diseases over an extended period. METHODS: This retrospective matched cohort study included 532 measles-diagnosed patients who were exactly matched with 2128 individuals without a previous measles diagnosis. Adjusted OR for any all-cause infectious diagnosis and any viral infection diagnosis ≤2 years after measles diagnosis between the measles and control groups was obtained from a conditional logistic regression model. The Cox proportional hazards model was used to estimate the hazard ratio. RESULTS: Previous measles virus (MeV) exposure was associated with an increased risk for all-cause non-measles infectious disease diagnosis (OR: 1.83, 95% CI: 1.26-2.64, p 0.001), with 492 diagnoses in the MeV-exposed group and 1868 diagnoses in the control group. Additionally, previous MeV exposure was linked to a higher risk of viral infection diagnosis (OR: 1.23, 95% CI: 1.01-1.59, p < 0.05), with 302 viral infection diagnoses in the MeV-exposed group and 1107 diagnoses in the control group. The hazard ratio for viral diagnosis in the MeV-exposed group compared with the control group was 1.54 (95% CI: 1.18-2.02, p < 0.001). DISCUSSION: Individuals diagnosed with measles had a moderately increased risk of being diagnosed with all-cause non-measles infectious disease or viral infection. This observational individual-level study supports previous ecological and individual population-level studies.

Impact of the COVID-19 Pandemic on Measles Vaccination Coverage and Estimated Catch-up Efforts for Serbia.

BACKGROUND: Measles is highly infectious, requiring ≥95% vaccine coverage rate (VCR) to prevent outbreaks. This study aimed to understand the impact of the COVID-19 pandemic on routine measles-containing vaccine (MCV) VCRs in Serbia and estimate national and regional catch-up vaccination required to prevent outbreaks. METHODS: A multiplier model was used to calculate annual MCV dose 1 (MCV1) and MCV dose 2 (MCV2) VCRs for children 1-6 and 6-12 years of age, respectively, for 2011-2022. Postpandemic (2023-2024) VCRs were modeled. The numbers of administered doses were compared to prepandemic and postpandemic, and monthly catch-up rates were calculated for 12-, 18- and 24-month campaigns. RESULTS: Between prepandemic and pandemic periods, national MCV1 VCR decreased from 88% to 81%, while MCV2 VCR decreased from 92% to 89%, corresponding to 20,856 missed MCV1 and 8760 missed MCV2 doses. Assuming national VCRs returned to prepandemic levels post-2022, 18% of children 1-6 years of age and 11% of children 6-12 years of age would have missed their MCV1 and MCV2 doses, respectively, by 2024. To catch up missed doses under this scenario, most regions would require monthly catch-up rates of 25%, 16% or 12% for MCV1 and 14%, 9% or 7% for MCV2, considering 12-, 18- or 24-month campaigns, respectively. CONCLUSIONS: The pandemic negatively impacted MCV VCRs in Serbia, leaving a sizeable proportion of children with missed doses. Significant catch-up efforts are required to recover VCRs to prepandemic levels and avoid future measles outbreaks, with increased monthly administration rates versus those in prepandemic periods.

Onward transmission of measles virus among vaccinated cases in a large community outbreak in Auckland, New Zealand, 2019.

BACKGROUND: Isolation of cases and quarantining of non-immune contacts are the mainstay of measles outbreak management in elimination settings. Serology testing of exposed contacts may not be feasible in large outbreaks; therefore, vaccination history is used as a proxy for determining immunity to measles and thus prevention of onward virus transmission. This study sought to investigate the risk of measles virus transmission from individuals with a history of one or two doses of measles-containing vaccine (MCV). METHODS:  Retrospective analysis of data from measles cases reported to Auckland Regional Public Health Service during the 2019 Auckland region measles outbreak. Vaccination history was verified using patient records and the New Zealand National Immunisation Register. Onward transmission was determined through case interviews and assessment of exposed contacts. RESULTS:  1451 measles cases were assessed as eligible for vaccination at the time of measles outbreak. Of these, 1015 (70.0%) were unvaccinated, 220 (15.2%) had unknown vaccination status, 139 (9.6%) had received only one dose of MCV and 77 (5.3%) had received two doses of the vaccine. Compared to unvaccinated cases, the odds of onward transmission were lower among those with one dose only (OR 0.41, 95% CI: 0.20-0.75) or two doses of MCV (OR 0.44, 95% CI: 0.17-0.95). Median time since vaccination was longer among those with onward transmission compared to those without onward transmission for one and two doses of the vaccine, suggesting a potential effect of waning immunity among this cohort. CONCLUSION:  These findings support the hypothesis that measles cases with a history of prior vaccination are less likely to transmit the virus to others compared to unvaccinated cases. Such information can be used to support decisions around quarantine requirements for vaccinated contacts in future measles outbreaks.