Endemic Measles Research Articles

Sustaining the Elimination of Measles, Rubella and Congenital Rubella Syndrome in the Americas, 2019-2023: From Challenges to Opportunities.

This report reviews national data from all Member States on measles, rubella, and congenital rubella syndrome (CRS) elimination in the Region of the Americas during 2019-2023. It includes an analysis of compliance with vaccination coverage, surveillance indicators, and measles outbreaks, as well as an analysis of the response capacity of the laboratory network and a country case study that meets all indicators. The sources of information were the integrated epidemiological surveillance system for measles and rubella of the Pan American Health Organization (PAHO)/World Health Organization (WHO) and the Joint Reporting Form (eJRF), among others. From 2020 to 2022, regional coverage with first (MMR-1) and second doses (MMR-2) decreased to rates below 90%. The regional suspected case notification rate was maintained above the minimum expected 2.0 suspect cases per 100,000 population, except in 2021. During 2019 to 2023, 18 countries experienced outbreaks, with two of the outbreaks resulting in re-established endemic transmission. In conclusion, two countries in the Americas have not maintained measles elimination, but by the end of 2023 no country showed endemic measles transmission. One of the countries that lost its certification of elimination in 2018 managed to be reverified in 2023; the other is pending reverification. All countries maintained rubella elimination. Despite these challenges, the sustainability of the elimination of these diseases remains a health priority in the Region.

An interregional measles outbreak in Spain with nosocomial transmission, November 2017 to July 2018.

Given sustained high vaccination coverage and enhanced surveillance for measles, Spain has been free of endemic measles transmission since 2014, achieving elimination certification from the World Health Organization in 2017. In November 2017, measles was introduced through an imported case travelling to the Valencian Community, causing an interregional outbreak. Here, we describe the outbreak using data reported to the national epidemiological surveillance network. The outbreak involved 154 cases (67 males, 87 females) notified in four regions; 148 were laboratory-confirmed and six epidemiologically linked. Most cases were adults aged 30-39 (n = 62, 40.3%) years. Sixty-two cases were hospitalised (40.3%) and 35 presented complications (22.7%). Two thirds of the cases (n = 102) were unvaccinated including 11 infants (≤ 1 year) not yet eligible for vaccination. The main route of transmission was nosocomial; at least six healthcare facilities and 41 healthcare workers and support personnel were affected. Sequencing of the viral nucleoprotein C-terminus (N450) identified genotype B3, belonging to the circulating MVs/Dublin.IRL/8.16-variant. Control measures were implemented, and the outbreak was contained in July 2018. The outbreak highlighted that raising awareness about measles and improving the vaccination coverage in under-vaccinated subgroups and personnel of healthcare facilities are key measures for prevention of future outbreaks.

Immune response to co-administration of measles, mumps, and rubella (MMR), and yellow fever vaccines: a randomized non-inferiority trial among one-year-old children in Argentina

BackgroundIn yellow fever (YF) endemic areas, measles, mumps, and rubella (MMR), and YF vaccines are often co-administered in childhood vaccination schedules. Because these are live vaccines, we assessed potential immune interference that could result from co-administration.MethodsWe conducted an open-label, randomized non-inferiority trial among healthy 1-year-olds in Misiones Province, Argentina. Children were randomized to one of three groups (1:1:1): Co-administration of MMR and YF vaccines (MMR1YF1), MMR followed by YF vaccine four weeks later (MMR1YF2), or YF followed by MMR vaccine four weeks later (YF1MMR2). Blood samples obtained pre-vaccination and 28 days post-vaccination were tested for immunoglobulin G antibodies against measles, mumps, and rubella, and for YF virus-specific neutralizing antibodies. Non-inferiority in seroconversion was assessed using a -5% non-inferiority margin. Antibody concentrations were compared with Kruskal-Wallis tests.ResultsOf 851 randomized children, 738 were correctly vaccinated, had ≥ 1 follow-up sample, and were included in the intention-to-treat population. Non-inferior seroconversion was observed for all antigens (measles seroconversion: 97.9% in the MMR1YF1 group versus 96.3% in the MMR1YF2 group, a difference of 1.6% [90% CI -1.5, 4.7]; rubella: 97.9% MMR1YF1 versus 94.7% MMR1YF2, a difference of 3.3% [-0.1, 6.7]; mumps: 96.7% MMR1YF1 versus 97.9% MMR1YF2, a difference of -1.3% [-4.1, 1.5]; and YF: 96.3% MMR1YF1 versus 97.5% YF1MMR2, a difference of -1.2% [-4.2, 1.7]). Rubella antibody concentrations and YF titers were significantly lower following co-administration; measles and mumps concentrations were not impacted.ConclusionEffective seroconversion was achieved and was not impacted by the co-administration, although antibody levels for two antigens were lower. The impact of lower antibody levels needs to be weighed against missed opportunities for vaccination to determine optimal timing for MMR and YF vaccine administration.Trial RegistrationThe study was retrospectively registered in ClinicalTrials.gov (NCT03368495) on 11/12/2017.

Lessons from the re-emergence of imported measles cases following the COVID-19 pandemic in Victoria, Australia.

Australia was declared to have eliminated endemic measles in 2014; however, imported cases continue to pose a threat of outbreaks. International travel restrictions during the coronavirus disease 2019 (COVID-19) pandemic led to a rapid decline in measles cases. The re-opening of the Australian international border to measles endemic regions returns the threat of outbreaks, which may be further compounded by disruptions in routine vaccinations during the COVID-19 pandemic. We consider lessons learned from the public health response to recent measles cases. This case series includes all confirmed measles cases meeting the national case definition reported to the Victorian Government Department of Health (the Department) between 1 January and 31 December 2022. The Department conducted active case finding and contact tracing of all cases in line with national guidelines. Cases were descriptively analysed. In 2022, six of the seven measles cases reported in Australia occurred in Victoria, all of whom resided in Australia and acquired their infection overseas. Three cases were unlinked, and three formed an epidemiologically-linked household cluster. One case was partially vaccinated, one was not eligible for vaccination, one had unknown vaccination status, and three were unvaccinated, one of whom was under 12 months old but would have been eligible for vaccination prior to travel to endemic regions. None of the cases led to secondary transmission within Australia. Following the COVID-19 pandemic, measles importations have re-commenced in Victoria. Although few measles cases occurred in 2022 and none resulted in onwards transmission, imported measles cases remain complex and require substantial public health follow-up. Delays in case diagnosis and flight contact tracing pose a significant risk for outbreaks of measles. Public health interventions are needed to maintain high vaccination rates, improve contact tracing, and ensure public health authorities and healthcare providers can rapidly identify and respond to imported measles cases.

Genetic Characteristics of Measles Viruses Isolated in Taiwan between 2015 and 2020

A genetic analysis of circulating measles virus (MeV) provides strong evidence of an interruption in endemic measles and supports the elimination status of this disease. This study investigated 219 MeVs isolated between 2015 and 2020. Based on the 450 nucleotide sequences of the nucleoprotein gene (N-450), three genotypes of the H1, D8 and B3 with 8, 18 and 6 different N-450 sequences, respectively, were identified. The H1 genotype virus has not circulated in Taiwan since 2017, and the D8 and B3 genotype MeVs became dominant between 2018 and 2019. Different D8 genotype variants were imported from neighboring countries, and the majority of MeV variants were detected only for a short period. However, MVs/Gir Somnath.IND/42.16[D8], a named strain designated by the World Health Organization (WHO), was detected over 2 years. To explore whether the endemic transmission of measles has been underestimated, another sequence window of the hypervariable, noncoding regions between the matrix (M) and fusion (F) genes (MF-NCR) was introduced to clarify the transmission chain. From the chronological sequence analysis of MeVs with N-450 and MF-NCR sequence windows, no endemic MeV variants lasted over 4 weeks, providing strong evidence to support the contention that Taiwan has reached the status for measles elimination.

A Neural-Network-Based Model Reveals Gravitational Coupling of Endemic Measles Dynamics

A Neural-Network-Based Model Reveals Gravitational Coupling of Endemic Measles Dynamics

Epidemija morbila na teritoriji Smedereva

The Republic of Serbia is a country with endemic measles transmission. Decline of MMR immunization coverage resulted in measles resurgence in Serbia at the beginning of 2023. Aim of this study is a description of measles outbreak at the territory of the City of Smederevo between January and April 2023 and identification of interventions for prevention of future measles outbreaks in the Republic of Serbia. The national active measles surveillance data were analysed. The outbreak involved 43 measles cases, of whom 42 were classified as laboratory confirmed and one as epidemiologically linked. Most of cases were aged 1 to 4 years (44.2%) and 20 to 49 years (32.6%) while the highest age-specific incidence rates were registered in children younger than 12 months (80.6/10,000) and children aged 1 to 4 years (50.5/10,000). Most of cases with known vaccination status (92.9%) were unvaccinated including 8 children younger than 12 months not yet eligible for vaccination according to the national immunization schedule. Number of hospitalized cases were 20 (46.5%) including two cases with pneumonia. Among 14 cases who contracted measles in healthcare settings 5 were employees of General Hospital Smederevo. Genom sequencing was performed in 10 cases and B3 genotype of morbilli virus was detected in all cases. In order to prevent future measles outbreaks in the Republic of Serbia it is necessary to achieve and maintain target values of coverage and timeliness of MMR vaccination. Timely notification of suspected cases and diagnosis of measles as well as immunization of susceptible employees of healthcare institutions are key strategies for prevention of measles transmission in healthcare settings.

Measles, Mumps, Rubella Vaccine (PRIORIX): Recommendations of the Advisory Committee on Immunization Practices - United States, 2022.

Vaccination is the main means for preventing measles, mumps, and rubella virus infections and their related complications (1,2). Achieving and maintaining high 2-dose measles, mumps, and rubella vaccination coverage in the United States has led to elimination of endemic measles in 2000, rubella and congenital rubella syndrome in 2004, and a sharp decrease in mumps cases. However, measles and rubella remain endemic in many countries, leading to importations of cases and occasional local transmission within the United States (3). Reported U.S. mumps cases declined >99% from the prevaccine period (4); however, mumps is endemic worldwide, and since 2006, the number of mumps cases and mumps outbreaks has increased in the United States, with wider geographic spread since 2016 (4). Given the risk for importation of measles and rubella and the resurgence of mumps, maintaining high measles, mumps, and rubella (MMR) vaccination coverage is important. Since 1978, only one MMR vaccine, M-M-R II (Merck and Co., Inc.), has been available in the United States. On June 6, 2022, the Food and Drug Administration approved a second MMR vaccine, PRIORIX (GlaxoSmithKline Biologicals), for the prevention of measles, mumps, and rubella in persons aged ≥12 months. The three live attenuated viruses contained in PRIORIX are genetically similar or identical to the corresponding components in M-M-R II (Table) (5-7). On June 23, 2022, the Advisory Committee on Immunization Practices (ACIP) unanimously recommended PRIORIX as an option to prevent measles, mumps, and rubella according to the existing recommended schedules and for off-label uses (i.e., indications not included in the package insert)* (1,2). ACIP considered PRIORIX to be safe, immunogenic, and noninferior to M-M-R II. Both PRIORIX and M-M-R II are fully interchangeable for all indications for which MMR vaccination is recommended. This report contains ACIP recommendations specific to PRIORIX and supplements the existing ACIP recommendations for MMR use (1,2).

Feasibility of measles and rubella vaccination programmes for disease elimination: a modelling study

Marked reductions in the incidence of measles and rubella have been observed since the widespread use of the measles and rubella vaccines. Although no global goal for measles eradication has been established, all six WHO regions have set measles elimination targets. However, a gap remains between current control levels and elimination targets, as shown by large measles outbreaks between 2017 and 2019. We aimed to model the potential for measles and rubella elimination globally to inform a WHO report to the 73rd World Health Assembly on the feasibility of measles and rubella eradication. In this study, we modelled the probability of measles and rubella elimination between 2020 and 2100 under different vaccination scenarios in 93 countries of interest. We evaluated measles and rubella burden and elimination across two national transmission models each (Dynamic Measles Immunisation Calculation Engine [DynaMICE], Pennsylvania State University [PSU], Johns Hopkins University, and Public Health England models), and one subnational measles transmission model (Institute for Disease Modeling model). The vaccination scenarios included a so-called business as usual approach, which continues present vaccination coverage, and an intensified investment approach, which increases coverage into the future. The annual numbers of infections projected by each model, country, and vaccination scenario were used to explore if, when, and for how long the infections would be below a threshold for elimination. The intensified investment scenario led to large reductions in measles and rubella incidence and burden. Rubella elimination is likely to be achievable in all countries and measles elimination is likely in some countries, but not all. The PSU and DynaMICE national measles models estimated that by 2050, the probability of elimination would exceed 75% in 14 (16%) and 36 (39%) of 93 modelled countries, respectively. The subnational model of measles transmission highlighted inequity in routine coverage as a likely driver of the continuance of endemic measles transmission in a subset of countries. To reach regional elimination goals, it will be necessary to innovate vaccination strategies and technologies that increase spatial equity of routine vaccination, in addition to investing in existing surveillance and outbreak response programmes. WHO, Gavi, the Vaccine Alliance, US Centers for Disease Control and Prevention, and the Bill & Melinda Gates Foundation.

Comparing and linking machine learning and semi-mechanistic models for the predictability of endemic measles dynamics.

Measles is one the best-documented and most-mechanistically-studied non-linear infectious disease dynamical systems. However, systematic investigation into the comparative performance of traditional mechanistic models and machine learning approaches in forecasting the transmission dynamics of this pathogen are still rare. Here, we compare one of the most widely used semi-mechanistic models for measles (TSIR) with a commonly used machine learning approach (LASSO), comparing performance and limits in predicting short to long term outbreak trajectories and seasonality for both regular and less regular measles outbreaks in England and Wales (E&W) and the United States. First, our results indicate that the proposed LASSO model can efficiently use data from multiple major cities and achieve similar short-to-medium term forecasting performance to semi-mechanistic models for E&W epidemics. Second, interestingly, the LASSO model also captures annual to biennial bifurcation of measles epidemics in E&W caused by susceptible response to the late 1940s baby boom. LASSO may also outperform TSIR for predicting less-regular dynamics such as those observed in major cities in US between 1932–45. Although both approaches capture short-term forecasts, accuracy suffers for both methods as we attempt longer-term predictions in highly irregular, post-vaccination outbreaks in E&W. Finally, we illustrate that the LASSO model can both qualitatively and quantitatively reconstruct mechanistic assumptions, notably susceptible dynamics, in the TSIR model. Our results characterize the limits of predictability of infectious disease dynamics for strongly immunizing pathogens with both mechanistic and machine learning models, and identify connections between these two approaches.

Measles outbreak in the sanitary area of Guadalajara (Spain): difficulty in microbiological diagnosis in the era of its elimination

IntroductionIn Spain, like in other countries where endemic measles has been eliminated, there is a need for available diagnostic tolos for confirming any cases in order to prevent and control its transmission. We describe the different microbiological tests used for the diagnosis of measles during an outbreak that occurred in 2019 in the province of Guadalajara (Spain). MethodsSerological and molecular tests were performed at the Microbiology laboratory of the Guadalajara University Hospital and at the National Center for Microbiology of the Carlos III Health Institute (Majadahonda, Spain). Patient data were obtained from the surveillance system. ResultsA total of 43 patients had a laboratory diagnosis of measles: 29 cases by PCR (pharyngeal exudate or urine) and positive specific IgM, 11 cases by PCR, and 3 cases only by a positive IgM. Genotype D8 was identified in 35 confirmed cases and genotype A in two that were discarded as post-vaccination cases. PCR was positive in the acute sera of 11 out of 14 patients with a negative IgM. Eleven confirmed cases had recieved one or two vaccine doses. Twelve adult patients were hospitalizated, all of them with a diagnostic of hepatitis. ConclusionsThe combination of molecular tests and the presence of specific IgM is necessary for a correct diagnosis of measles and also to classify patients with a breakthrough infection or vaccine failures (primary or secondary). Genotyping is essential for the correct classification of the patients in the context of a measles elimination program.

Australian vaccine preventable disease epidemiological review series: measles, 2012-2019.

Data sources, relevant to measles epidemiology from 2012 to 2019, were reviewed in the context of Australia's certification, by the World Health Organization in 2014, of the elimination of measles. Data on measles notifications, hospitalisations, and deaths were obtained from the National Notifiable Diseases Surveillance System, the National Hospital Morbidity Database, and the Australian Coordinating Registry. Data were analysed by age group, state/territory, Aboriginal and Torres Strait Islander status, genotype, place of acquisition, source of infection (importation status), and vaccination status. Between 2012 and 2019, there were 1,337 measles notifications (average annual notifications 0.7 per 100,000 population per year) and 425 hospitalisations with measles as principal diagnosis (0.3 per 100,000 population per year) were recorded. The highest annual notification rate was in 2014, when the rate in the Northern Territory was 21.4 per 100,000 population per year. Although notification and hospitalisation rates were highest in infants < 12 months (respectively 5.8 and 2.1 per 100,000 population per year), people aged 10 to 39 years (10-19y: 272 notifications; 20-29y: 347; 30-39y: 266) accounted for 66% of notified cases. Of cases with a known vaccination status, only 20/169 (11.8%) of those aged 1-9 years had received at least one dose of measles-containing vaccine, compared with 215/571 (37.7%) of those aged 10-39 years. Persons born before 1966 (at least 47 years of age during the study period) are likely to have immunity from wild-type measles infection and had the lowest notification rates in each year. Of notified cases, 98.1% were imported or import related, and of the 900 measles viruses genotyped, D8 and B3 accounted for 89.1%. This review's findings of low measles incidence, in the presence of robust surveillance and high two-dose measles vaccination coverage, provide evidence of continued elimination of endemic measles in Australia, with almost all cases imported or epidemiologically linked to an imported case. Most cases eligible for vaccination are unvaccinated, which should remain the primary focus for prevention. Potential waning immunity in older age groups requires monitoring. Continued high population immunity and high-quality public health response to cases will be needed to maintain Australia's elimination status, particularly once international borders reopen.

COVID-19 Australia: Epidemiology Report 60: Reporting period ending 10 April 2022.

Background Data sources, relevant to measles epidemiology from 2012 to 2019, were reviewed in the context of Australia’s certification, by the World Health Organization in 2014, of the elimination of measles. Methods Data on measles notifications, hospitalisations, and deaths were obtained from the National Notifiable Diseases Surveillance System, the National Hospital Morbidity Database, and the Australian Coordinating Registry. Data were analysed by age group, state/territory, Aboriginal and Torres Strait Islander status, genotype, place of acquisition, source of infection (importation status), and vaccination status. Results Between 2012 and 2019, there were 1,337 measles notifications (average annual notifications 0.7 per 100,000 population per year) and 425 hospitalisations with measles as principal diagnosis (0.3 per 100,000 population per year) were recorded. The highest annual notification rate was in 2014, when the rate in the Northern Territory was 21.4 per 100,000 population per year. Although notification and hospitalisation rates were highest in infants &lt; 12 months (respectively 5.8 and 2.1 per 100,000 population per year), people aged 10 to 39 years (10–19y: 272 notifications; 20–29y: 347; 30–39y: 266) accounted for 66% of notified cases. Of cases with a known vaccination status, only 20/169 (11.8%) of those aged 1–9 years had received at least one dose of measles-containing vaccine, compared with 215/571 (37.7%) of those aged 10–39 years. Persons born before 1966 (at least 47 years of age during the study period) are likely to have immunity from wild-type measles infection and had the lowest notification rates in each year. Of notified cases, 98.1% were imported or import related, and of the 900 measles viruses genotyped, D8 and B3 accounted for 89.1%. Conclusion This review’s findings of low measles incidence, in the presence of robust surveillance and high two-dose measles vaccination coverage, provide evidence of continued elimination of endemic measles in Australia, with almost all cases imported or epidemiologically linked to an imported case. Most cases eligible for vaccination are unvaccinated, which should remain the primary focus for prevention. Potential waning immunity in older age groups requires monitoring. Continued high population immunity and high-quality public health response to cases will be needed to maintain Australia’s elimination status, particularly once international borders reopen.

A seroepidemiologic study of a measles outbreak, Yamagata Prefecture, Japan, 2017: The estimation of spreaders using serological assays in a measles elimination setting

IntroductionIn regions where the endemic measles virus has been eliminated, early detection of contagious patients is important for preventing the spread of measles and sustaining elimination. To investigate whether serological assays can be used for the estimation of highly infectious patients with measles, we performed a seroepidemiologic study of a measles outbreak in Yamagata Prefecture, Japan, in 2017. MethodsWe tested plaque reduction neutralization (PRN), IgG avidity, and gelatin particle agglutination (PA) assays in 31 patients with measles, subdivided into two super-spreaders, three spreaders, and 26 non-spreaders. Simultaneously, these results were compared with the cycle threshold (Ct) of a semi-quantitative real-time reverse transcription PCR for the measles virus from throat swab specimens. ResultsIn the PRN assay, one super-spreader and two spreaders lacked protective antibodies. The IgG avidity assay showed that two super-spreaders and one spreader had low avidity. The PA assay indicated that two super-spreaders and two spreaders lacked protective antibodies. Comparison of the results of the three serological assays and Ct revealed that patients whose antibody titers were judged as low in the IgG avidity and PA assays showed low Ct (i.e., high viral load), whereas non-spreaders tended to show low viral load. ConclusionsOur preliminary seroepidemiologic analysis of a population of 31 patients with measles suggests that PA and IgG avidity assays may be used for the identification of super-spreader/spreader candidates. However, further investigations are necessary to validate the robustness of these serological assays in detecting contagious measles cases.

Measles Elimination Successful and Its Relevant Challenges in Iran.

Measles is an infectious childhood disease with some death annually. The expansion of the coverage of vaccination plan has significantly reduced the mortality rate of this disease. Given that the endemic measles virus is not transmitted in the country and based on Regional Verification Commission (RVC) for Measles and Rubella Elimination has declared that measles and rubella have been eliminated in three countries of Eastern Mediterranean Region including Islamic Republic of Iran, Bahrain, and Oman. Therefore, to continue and preventing from reemerging of measles in Iran, it is essential to maintaining the immunization programs, diagnose, and investigate all suspicious cases and outbreaks. This article investigates the challenges facing to measles after elimination declaration in Iran. However, the elimination of these diseases to be sustainable needs a vigorous case identification protocol and contact follow up.

Изучение напряженности поствакцинального иммунитета к кори и краснухе у студентов Республики Татарстан

The intensity of post-vaccination immunity to measles and rubella in students of medical educational institutions of the Republic of Tatarstan was studied. The study revealed the improved collective immunity to measles in this age group. At the same time, selective seromonitoring showed an excess of the values of seronegative individuals to the measles virus compared with the indicator of epidemiological well-being. In order to prevent the occurrence and spread of measles, rubella and to implement measures to eliminate endemic measles in the Russia, it is recommended to carry out additional revaccination of persons with no protective titers of antibodies to measles and rubella viruses, as well as to continue conducting research of collective immunity to this infection in this age group.

Maintenance of Measles Elimination Status in the United States for 20 Years Despite Increasing Challenges.

Measles elimination (interruption of endemic measles virus transmission) in the United States was declared in 2000; however, the number of cases and outbreaks have increased in recent years. We characterized the epidemiology of measles outbreaks and measles transmission patterns after elimination to identify potential gaps in the US measles control program. We analyzed national measles notification data from 1 January 2001 to 31 December 2019. We defined measles infection clusters as single cases (isolated cases not linked to additional cases), 2-case clusters, or outbreaks with ≥3 linked cases. We calculated the effective reproduction number (R) to assess changes in transmissibility and reviewed molecular epidemiology data. During 2001-2019, a total of 3873 measles cases, including 747 international importations, were reported in the United States; 29% of importations were associated with outbreaks. Among 871 clusters, 69% were single cases and 72% had no spread. Larger and longer clusters were reported since 2013, including 7 outbreaks with >50 cases lasting >2 months, 5 of which occurred in known underimmunized, close-knit communities. No measles lineage circulated in a single transmission chain for >12 months. Higher estimates of R were noted in recent years, although R remained below the epidemic threshold of 1. Current epidemiology continues to support the interruption of endemic measles virus transmission in the United States. However, larger and longer outbreaks in recent postelimination years and emerging trends of increased transmission in underimmunized communities emphasize the need for targeted approaches to close existing immunity gaps and maintain measles elimination.

Re-verifying the elimination of measles, rubella and congenital rubella syndrome in Canada, 2016-2020.

Elimination, in the context of measles, rubella and congenital rubella syndrome (CRS), refers to the absence of endemic measles/rubella virus transmission in a region or other defined geographic area for at least 12 months, in the presence of a high-quality surveillance system that meets targets of key performance indicators. In 1994, Canada and other countries of the World Health Organization (WHO) region of the Americas committed to the objectives of measles elimination by 2000 and rubella and CRS by 2010. Canada met these targets: eliminating measles transmission in 1998; rubella transmission in 2005; and endemically-acquired CRS in 2000. The WHO region of Americas was declared free of endemic rubella/CRS in 2015 and endemic measles in 2016. At the request of the Pan American Health Organization (PAHO), Canada’s elimination status of measles, rubella and CRS was verified in 2012 and again in 2017. Prior to submission to PAHO, the verification reports were reviewed, approved and endorsed by Canada’s National Certification Committee (NCC). The NCC is a group of experts who are not directly involved with the management of vaccine preventable diseases or immunization program implementation at the national level, but who have the expertise to assist in ensuring that Canada is meeting PAHO’S goals of elimination and eradication. Members are responsible for reviewing Canada’s current mechanisms of surveillance and progress towards elimination of targeted vaccine preventable diseases in Canada. Members have expertise in the fields of public health, infectious diseases and/or laboratory sciences.

Measles in Vaccinated People: Epidemiology and Challenges in Surveillance and Diagnosis in the Post-Elimination Phase. Spain, 2014-2020.

The MMR vaccination program was introduced in Spain in 1981. Consistently high vaccination coverage has led to Spain being declared free of endemic measles transmission since 2014. A few imported and import-related cases were reported during the post-elimination phase (2014 to 2020), with very low incidence: three cases per million of inhabitants a year, 70% in adults. In the post-elimination phase an increasing proportion of measles appeared in two-dose vaccinated individuals (up to 14%), posing a challenge to surveillance and laboratory investigations. Severity and clinical presentation were milder among the vaccinated. The IgM response varied and the viral load decreased, making the virus more difficult to detect. A valid set of samples (serum, urine and throat swab) is strongly recommended for accurate case classification. One third of measles in fully vaccinated people was contracted in healthcare settings, mainly in doctors and nurses, consistent with the important role of high intensity exposure in measles breakthrough cases. Surveillance protocols and laboratory algorithms should be adapted in advanced elimination settings. Reinforcing the immunity of people working in high exposure environments, such as healthcare settings, and implementing additional infection control measures, such as masking and social distancing, are becoming crucial for the global aim of measles eradication.

Classification of measles breakthrough cases in an elimination setting using a comprehensive algorithm of laboratory results: why sensitive and specific IgM assays are important

ObjectiveIn 2006, a measles outbreak occurred in Catalonia (Spain), six years after endemic measles was declared eliminated. This study aimed to classify 19 confirmed measles breakthrough cases (BC) using a high-performance avidity assay developed in 2010. MethodsSerum specimens were tested by indirect IgG, indirect IgM, capture IgM enzyme immunoassay, an endpoint-titer IgG avidity assay, and a plaque reduction neutralization assay. Serology and RNA detection results were combined in an algorithm for measles confirmation and classification of breakthrough cases and analyzed with clinical and epidemiological data. ResultsOf 19 samples, thirteen (68%) were conclusive with the classification of BCs, and six (32%) had false-positive IgM results on an indirect-format assay; they were classified as rash and fever illness of undetermined etiology. BCs were primary vaccine failures (seven or 54%), secondary vaccine failures (four or 31%), and two (15%) could not be classified. ConclusionsIn measles elimination settings, high-performing assays and a comprehensive algorithm of laboratory results (IgG, IgM, and RNA detection), including IgG avidity and PRN results when necessary, can assist in accurate laboratory confirmation and classification of suspected measles cases for surveillance. Highly specific IgM assays are required to minimize the number of false-positive results.