Transmission Pattern of Measles Virus Circulating in China During 1993-2021: Genotyping Evidence Supports That China Is Approaching Measles Elimination.

BACKGROUND: To provide useful insights into measles elimination progress in China, measles surveillance data were reviewed, and the transmission patterns of measles viruses circulating in China during 1993-2021 were analyzed. METHODS: Measles incidence data from the National Notifiable Disease Reporting System of the China Center for Disease Control and Prevention were analyzed. A total of 17 570 strains were obtained from 30 of 31 provinces in mainland China during 1993-2021. The recommended genotyping window was amplified. Genotyping analysis was conducted for comparison with the reference strains. Phylogenetic analyses were performed to identify genetic relationships among different lineages within the genotypes. RESULTS: With high coverage of routine immunization and intensive supplementary immunization activities, measles incidence has shown a downward trend since 1993, despite 2 resurgences, reaching a historic low level in 2020-2021 (average 0.5 per million). During 1993-2021, 9 genotypes including domestic genotype H1; imported genotypes B3, D4, D8, D9, D11, G3, and H2; and vaccine-associated genotype A were identified. Among them, the genotype H1 strain circulated endemically in China for more than 25 years; the last strain was detected in Yunnan Province in September 2019. Multiple imported genotypes have been identified since 2009 showing different transmission patterns. Since April 2020, no imported strains have been detected, while vaccine-associated genotype A continues to be detected. CONCLUSIONS: The evidence of low incidence during 2020-2021 and virological surveillance data in this study confirm that China is currently approaching measles elimination.

In Elimination Settings, Measles Antibodies Wane After Vaccination but Not After Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: We conducted a systematic review to assess whether measles humoral immunity wanes in previously infected or vaccinated populations in measles elimination settings. METHODS: After screening 16 822 citations, we identified 9 articles from populations exposed to wild-type measles and 16 articles from vaccinated populations that met our inclusion criteria. RESULTS: Using linear regression, we found that geometric mean titers (GMTs) decreased significantly in individuals who received 2 doses of measles-containing vaccine (MCV) by 121.8 mIU/mL (95% confidence interval [CI], -212.4 to -31.1) per year since vaccination over 1 to 5 years, 53.7 mIU/mL (95% CI, -95.3 to -12.2) 5 to 10 years, 33.2 mIU/mL (95% CI, -62.6 to -3.9), 10 to 15 years, and 24.1 mIU/mL (95% CI, -51.5 to 3.3) 15 to 20 years since vaccination. Decreases in GMT over time were not significant after 1 dose of MCV or after infection. Decreases in the proportion of seropositive individuals over time were not significant after 1 or 2 doses of MCV or after infection. CONCLUSIONS: Measles antibody waning in vaccinated populations should be considered in planning for measles elimination.

The impact of local vaccine coverage and recent incidence on measles transmission in France between 2009 and 2018.

BACKGROUND: Subnational heterogeneity in immunity to measles can create pockets of susceptibility and result in long-lasting outbreaks despite high levels of national vaccine coverage. The elimination status defined by the World Health Organization aims to identify countries where the virus is no longer circulating and can be verified after 36 months of interrupted transmission. However, since 2018, numerous countries have lost their elimination status soon after reaching it, showing that the indicators defining elimination may not be associated with lower risks of outbreaks. METHODS: We quantified the impact of local vaccine coverage and recent levels of incidence on the dynamics of measles in each French department between 2009 and 2018, using mathematical models based on the "Endemic-Epidemic" regression framework. After fitting the models using daily case counts, we simulated the effect of variations in the vaccine coverage and recent incidence on future transmission. RESULTS: High values of local vaccine coverage were associated with fewer imported cases and lower risks of local transmissions, but regions that had recently reported high levels of incidence were also at a lower risk of local transmission. This may be due to additional immunity accumulated during recent outbreaks. Therefore, the risk of local transmission was not lower in areas fulfilling the elimination criteria. A decrease of 3% in the 3-year average vaccine uptake led to a fivefold increase in the average annual number of cases in simulated outbreaks. CONCLUSIONS: Local vaccine uptake was a reliable indicator of the intensity of transmission in France, even if it only describes yearly coverage in a given age group, and ignores population movements. Therefore, spatiotemporal variations in vaccine coverage, caused by disruptions in routine immunisation programmes, or lower trust in vaccines, can lead to large increases in both local and cross-regional transmission. The incidence indicator used to define the elimination status was not associated with a lower number of local transmissions in France, and may not illustrate the risks of imminent outbreaks. More detailed models of local immunity levels or subnational seroprevalence studies may yield better estimates of local risk of measles outbreaks.

The impact of supplementary immunization activities on measles transmission dynamics and implications for measles elimination goals: A mathematical modelling study.

BACKGROUND: Measles has re-emerged globally due to the accumulation of susceptible individuals and immunity gap, which causes challenges in eliminating measles. Routine vaccination and supplementary immunization activities (SIAs) have greatly improved measles control, but the impact of SIAs on the measles transmission dynamics remains unclear as the vaccine-induced immunity wanes. METHODS: We developed a comprehensive measles transmission dynamics model by taking into account population demographics, age-specific contact patterns, seasonality, routine vaccination, SIAs, and the waning vaccine-induced immunity. The model was calibrated by the monthly age-specific cases data from 2005 to 2018 in Jiangsu Province, China, and validated by the dynamic sero-prevalence data. We aimed to investigate the short-term and long-term impact of three-time SIAs during 2009-2012 (9.68 million and 4.25 million children aged 8 months-14 years in March 2009 and September 2010, respectively, and 140,000 children aged 8 months-6 years in March 2012) on the measles disease burden and explored whether additional SIAs could accelerate the measles elimination. RESULTS: We estimated that the cumulative numbers of measles cases from March 2009 to December 2012 (in the short run) and to December 2018 (in the long run) after three-time SIAs (base case) were 6,699 (95% confidence interval [CI]: 2,928-10,469), and 22,411 (15,146-29,675), which averted 45.0% (42.9%-47.0%) and 34.3% (30.7%-37.9%) of 12,226 (4,916-19,537) and 34,274 (21,350-47,199) cases without SIAs, respectively. The fraction of susceptibles for children aged 8-23 months and 2-14 years decreased from 8.3% and 10.8% in March 2009 to 5.8% and 5.8% in April 2012, respectively. However, the fraction of susceptibles aged 15-49 years and above 50 years increased gradually to about 15% in 2018 irrespective of SIAs due to the waning immunity. The measles elimination goal would be reached in 2028, and administrating additional one-off SIAs in September 2022 to children aged 8-23 months, or young adolescents aged 15-19 years could accelerate the elimination one year earlier. CONCLUSIONS: SIAs have greatly reduced the measles incidence and the fraction of susceptibles, but the benefit may wane over time. Under the current interventions, Jiangsu province would reach the measles elimination goal in 2028. Additional SIAs may accelerate the measles elimination one year earlier.

Decreasing measles burden by optimizing campaign timing.

Measles remains a major contributor to preventable child mortality, and bridging gaps in measles immunity is a fundamental challenge to global health. In high-burden settings, mass vaccination campaigns are conducted to increase access to vaccine and address this issue. Ensuring that campaigns are optimally effective is a crucial step toward measles elimination; however, the relationship between campaign impact and disease dynamics is poorly understood. Here, we study measles in Pakistan, and we demonstrate that campaign timing can be tuned to optimally interact with local transmission seasonality and recent incidence history. We develop a mechanistic modeling approach to optimize timing in general high-burden settings, and we find that in Pakistan, hundreds of thousands of infections can be averted with no change in campaign cost.

Measles and rubella serosusceptibity among population vaccinated with different schedules: the potential impact on measles-rubella elimination in Iran.

BACKGROUND: Iranian children were vaccinated with the scheduled two doses of monovalent measles vaccine (mMV) from 1984. In December 2003, a nationwide campaign of measles-rubella (MR) immunization was established to vaccinate 5-25 year- old individuals. In 2004, the mMV was replaced with measles- mumps- rubella (MMR) vaccine. Despite the high vaccination coverage, the outbreaks of measles still occur in the country. In this Study, the MR immunity status of various age groups, vaccinated with different schedules was investigated, and the immunologic response of seronegative subjects to revaccination was examined. METHODS: This cross-sectional study was conducted among 7-33-year-old healthy individuals with a documented history of measles vaccination from November 2017 to June 2018. The subjects were categorized as follows: group A, including 20-33 year-old individuals; vaccinated with 1-2 doses of mMV at ages 9 and 15 months, and revaccinated with MR, group B, including 15-19-year-old individuals, vaccinated with two doses of mMV at 9 and 15 months of age, and received additional dose of MMR upon school entrance, group C, including 11-14 year-old individuals, vaccinated with two-doses of MMR at the ages of 15 months and 6 years, and group D, including 7-10 year-old individuals vaccinated with two-doses of MMR vaccine at the ages 12 and 18 months, respectively. Levels of antimeasles- antirubella IgG antibodies in the collected sera were measured. Also antimeasles- antirubella IgM and IgG of seronegative individuals were reexamined at 4-6 weeks after MMR revaccination. The collected data were analyzed using descriptive statistical methods. RESULTS: A total of 635 individuals were investigated in this study. Group A, 98; group B, 295; group C, 139; and group D, 103 persons. Overall, 12.3 and 18.4% of the population were seronegative for measles and rubella antibodies. This rate varied greatly between the 4 groups: group A, 0/0-2%; group B,15.2-25.0%; group C,11.5-17.2%; and groupD,14.6-18.4%. After revaccination, 92 and 94.9% of seronegative individuals showed IgG response to measles and rubella vaccines, respectively. CONCLUSION: Despite the high coverage rate of M-R containing vaccines, a significant number of vaccinated subjects were seronegative for measles and rubella, possibly because of secondary vaccine failure; this may negatively affect measles-rubella elimination targets in the country. If these findings are confirmed in similar future studies, a more robust regional/national supplementary immunization activity will be considered.

Emergence of Attenuated Measles Illness Among IgG-positive/IgM-negative Measles Cases: Victoria, Australia, 2008-2017.

BACKGROUND: Waning measles immunity among vaccinated individuals may result in an attenuated illness. This study compares the epidemiological, clinical, and laboratory profile of measles cases with waning immunity with other measles cases. METHODS: Polymerase chain reaction-positive (+) measles cases notified to Victoria's Department of Health and Human Services from 2008 to 2017 with immunoglobulin (Ig) M and IgG tested at diagnosis were classified according to serology at diagnosis: IgG negative (-) (nonimmune), IgM+/IgG+ (indeterminate), or IgM-/IgG+ (waning immunity). RESULTS: Between 2008 and 2017, 297 measles cases were notified, of whom 190 (64%) were included; 151 of 190 (79%) were nonimmune at diagnosis, 26 (14%) were indeterminate, and 13 (7%) had waning immunity. Between 2008-2013 and 2014-2017, the proportion of cases with waning immunity increased from 0 of 87 (0%) to 13 of 103 (13%) (P < .001) and the diagnostic sensitivity of initial IgM fell from 93% to 81% (P = .012), respectively. Seven (54%) waning immunity cases reported receiving measles-containing vaccines; 1 case had 2 documented doses. Compared with nonimmune and indeterminate cases, waning immunity cases were more likely to be male; less likely to report fever, coryza, and cough; and had lower burden of virus (higher cycle threshold values). Waning immunity cases had higher IgG titers than indeterminate cases (mean optical density values, 1.96 vs 0.71; P = .004). Onward transmission from 1 waning immunity case was documented. CONCLUSIONS: Waning immunity among measles cases, associated with secondary vaccine failure and modified clinical illness, is emerging in Victoria with transmission potential.

Challenges to Achieving Measles Elimination, Georgia, 2013-2018.

Controlling measles outbreaks in the country of Georgia and throughout Europe is crucial for achieving the measles elimination goal for the World Health Organization's European Region. However, large-scale measles outbreaks occurred in Georgia during 2013-2015 and 2017-2018. The epidemiology of these outbreaks indicates widespread circulation and genetic diversity of measles viruses and reveals persistent gaps in population immunity across a wide age range that have not been sufficiently addressed thus far. Historic problems and recent challenges with the immunization program contributed to outbreaks. Addressing population susceptibility across all age groups is needed urgently. However, conducting large-scale mass immunization campaigns under the current health system is not feasible, so more selective response strategies are being implemented. Lessons from the measles outbreaks in Georgia could be useful for other countries that have immunization programs facing challenges related to health-system transitions and the presence of age cohorts with historically low immunization coverage.

International Importations of Measles Virus into the United States During the Postelimination Era, 2001-2016.

BACKGROUND: Although measles was declared eliminated from the United States in 2000, measles cases and outbreaks continue to occur, resulting from importations of the disease from countries where it remains endemic. METHODS: We describe the epidemiology of international importations of measles virus into the United States during the postelimination era. RESULTS: From 2001 to 2016, 553 imported measles cases were reported to the Centers for Disease Control and Prevention. A median of 28 importations occurred each year (range: 18-80). The median age of imported case-patients was 18 years (range: 3 months-75 years); 87% were unvaccinated or had an unknown vaccination status. US residents (as opposed to foreign visitors) accounted for 62% of imported measles cases. Overall, 62% of all imported case-patients reported travel to countries in the Western Pacific and European Regions of the World Health Organization during their exposure periods. The number of measles importations from specific countries was related to the incidence of measles in and the volume of travel to and from the source country. CONCLUSIONS: Our findings emphasize the importance of measles vaccination of US residents aged ≥6 months before international travel according to the Advisory Committee on Immunization Practices recommendations and supporting global measles elimination efforts.

The introduction of 'No jab, No school' policy and the refinement of measles immunisation strategies in high-income countries.

BACKGROUND: In recent years, we witnessed a resurgence of measles even in countries where, according to WHO guidelines, elimination should have already been achieved. In high-income countries, the raise of anti-vaccination movements and parental vaccine hesitancy are posing major challenges for the achievement and maintenance of high coverage during routine programmes. Italy and France approved new regulations, respectively in 2017 and 2018, aimed at raising immunisation rates among children by introducing mandatory vaccination at school entry. METHODS: We simulated the evolution of measles immunity profiles in seven distinct countries for the period 2018-2050 and evaluated the effect of possible adjustments of immunisation strategies adopted in the past on the overall fraction and age distribution of susceptible individuals in different high-income demographic settings. The proposed model accounts for country-specific demographic components, current immunity gaps and immunisation activities in 2018. Vaccination strategies considered include the enhancement of coverage for routine programmes already in place and the introduction of a compulsory vaccination at primary school entry in countries where universal school enrolment is likely achieved. RESULTS: Our model shows that, under current vaccination policies, the susceptible fraction of the population would remain below measles elimination threshold only in Singapore and South Korea. In the UK, Ireland, the USA and Australia either the increase of coverage of routine programmes above 95% or the introduction of a compulsory vaccination at school entry with coverage above 40% are needed to maintain susceptible individuals below 7.5% up to 2050. Although the implementation of mandatory vaccination at school entry would be surely beneficial in Italy, strategies targeting adults would also be required to avoid future outbreaks in this country. CONCLUSIONS: Current vaccination policies are not sufficient to achieve and maintain measles elimination in most countries. Strategies targeting unvaccinated children before they enter primary school can remarkably enhance the fulfilment of WHO targets.

Evaluation of measles immunity in Turkey: is it still a threat?

Background/aim: Measles is one of the important vaccine-preventable diseases with many complications in childhood. This study presents cross-sectional seroepidemiological data, beginning from neonatal cord blood in infants to children under 6 years of age, about waning of measles antibody and tries to suggest the proper time for measles immunization. Materials and methods: A total of 564 blood samples consisting of neonatal cord blood and samples taken from infants and children at ages of 6, 9, 24­48, and 49­72 months were analyzed for measles seropositivity in a period of 6 months. Results: Measles seropositivity rate was 72.5% in 109 cord blood samples, 2.6% in 117 infants of 6 months of age, and 3.6% in 111 infants of 9 months of age. Seropositivity was determined in 118 children at 24­48 months and in 109 children at 49­72 months and was 80.5% and 66%, respectively (P = 0.001). These children were vaccinated in the 12th month. Conclusion: Though measles immunization coverage is 97% in Turkey, population immunity is somewhat lower than expected. Increases of measles cases in Europe and the refugee problem in the country could easily lead to outbreaks. Implementing the first dose of the immunization at 9 months may be an option.

The declining antibody level of measles virus in China population, 2009-2015.

BACKGROUND: To eliminate measles, the coverage of more than 90% vaccine is required in China. Nonetheless, the measles incidence still reached to 3.88 per 100,000 in 2014, which is far more than the target of 1 per 1,000,000. Moreover, there is little national surveillance to measles antibody level indicating herd immunity status in China. METHODS: We detected the level of antibody to measles using commercially available indirect enzyme-linked immunosorbent IgG assays, and calculated the protection rate of population (PRP) to measles virus infection among health peoples in China. RESULTS: During the years 2009-2015, among the Chinese population aged 0-56, PRP was 94.7, 91.6, 91.6, 84.2, 82.1, 81.0, 75.4%, respectively. Among all age bands, the PRP is lowest among children less than 12-month-age, followed by people over 15 years old. CONCLUSION: Measles antibody level among healthy population has been declined since 2012, supplemented measles vaccination activity may be necessary to eliminate measles in China.

National, Regional and Global Certification Bodies for Polio Eradication: A Framework for Verifying Measles Elimination.

The Global Certification Commission (GCC), Regional Certification Commissions (RCCs), and National Certification Committees (NCCs) provide a framework of independent bodies to assist the Global Polio Eradication Initiative (GPEI) in certifying and maintaining polio eradication in a standardized, ongoing, and credible manner. Their members meet regularly to comprehensively review population immunity, surveillance, laboratory, and other data to assess polio status in the country (NCC), World Health Organization (WHO) region (RCC), or globally (GCC). These highly visible bodies provide a framework to be replicated to independently verify measles and rubella elimination in the regions and globally.

Use of a Diagonal Approach to Health System Strengthening and Measles Elimination after a Large Nationwide Outbreak in Mongolia.

Measles is a highly transmissible infectious disease that causes serious illness and death worldwide. Efforts to eliminate measles through achieving high immunization coverage, well-performing surveillance systems, and rapid and effective outbreak response mechanisms while strategically engaging and strengthening health systems have been termed a diagonal approach. In March 2015, a large nationwide measles epidemic occurred in Mongolia, 1 year after verification of measles elimination in this country. A multidisciplinary team conducted an outbreak investigation that included a broad health system assessment, organized around the Global Health Security Agenda framework of Prevent-Detect-Respond, to provide recommendations for evidence-based interventions to interrupt the epidemic and strengthen the overall health system to prevent future outbreaks of measles and other epidemic-prone infectious threats. This investigation demonstrated the value of evaluating elements of the broader health system in investigating measles outbreaks and the need for using a diagonal approach to achieving sustainable measles elimination.

Optimal vaccine schedules to maintain measles elimination with a two-dose routine policy.

Measles was eliminated in the Americas in 2002 by a combination of routine immunizations and supplementary immunization activities. Recent outbreaks underscore the importance of reconsidering vaccine policy in order to maintain elimination. We constructed an age-structured dynamical model for the distribution of immunity in a population with routine immunization and without disease, and analysed the steady state for an idealized age structure and for real age structures of countries in the Americas. We compared the level of immunity maintained by current policy in these countries to the level maintainable by an optimal policy. The optimal age target for the first routine dose of measles vaccine depends on the timing and coverage of both doses. Similarly, the optimal age target for the second dose of measles vaccine depends on the timing and coverage of the first dose. The age targets for the first and second doses of measles vaccine should be adjusted for the post-elimination era, by specifically accounting for current context, including realized coverage of both doses, and altered maternal immunity. Doing so can greatly improve the proportion immune within a population, and therefore the chances of maintaining measles elimination, without changing coverage.

A paired measles-rubella catch-up campaign in Sichuan China to stop an outbreak and strengthen local immunization programs.

BACKGROUND: China has been working towards measles elimination, but in 2017, measles outbreaks occurred in Ganzi and Aba prefectures of Sichuan province, representing 95% of all provincial cases and jeopardizing measles elimination. METHODS: During March and April 2017, high-performing prefectures were paired with outbreak and other interested counties to jointly conduct a measles-rubella (MR) catch-up campaign, build population immunity, and strengthen the counties' programs. RESULTS: House-to-house search identified 88,383 children in Ganzi that lacked MCV vaccination; 85,144 (96.34%) were vaccinated. Search identified 33,683 children in Aba who were not vaccinated against measles; 33,074 (98.19%) were vaccinated. The supporting prefectures helped install Immunization Information Systems and enroll unvaccinated children into the immunization program.The outbreak ended within a month and incidence has remained low for the subsequent six years. CONCLUSION: A paired catch-up campaign represents an effective model of using measles elimination strategies to strengthen local immunization programs for long-term program effectiveness.

M-F noncoding region sequences of H1 genotype measles virus provide higher resolution for virus transmission tracing.

As countries and regions move toward measles elimination, extended sequence window including noncoding region located between the matrix and fusion protein genes (M - F NCR) was considered to be used in molecular surveillance. The molecular resolution of M - F NCR was evaluated with 192 genotype H1 strains circulating during 2011-2018 in China. Phylogenetic analyses of the N450 and M - F NCR targets indicated that both two targets could confirm epi-linked outbreak, while M - F NCR target could further improve resolution of the molecular characterization: (1) it could differentiate the strains with identical N450 circulated in one county within one month of disease onset; (2) different transmission chains could be distinguished for strains with identical N450; (3) better spatial-temporal consistency with topology could be provided among sporadic cases with inconsistent N450. Accordingly, M - F NCR could be used to complement the information from N450 to address the specific questions in tracking the virus transmission chains.

Challenges for Sustaining Measles Elimination: Post-Verification Large-Scale Import-Related Measles Outbreaks in Mongolia and Cambodia, Resulting in the Loss of Measles Elimination Status.

The Western Pacific Region's pursuit of measles elimination has seen significant progress and setbacks. Mongolia and Cambodia were the first two middle-income countries in the Western Pacific to be verified as having eliminated measles by the Western Pacific Regional Verification Commission for Measles and Rubella Elimination, in March 2014 and 2015, respectively. However, both countries experienced large-scale or prolonged importation-related measles outbreaks shortly afterwards, leading to the re-establishment of endemic transmission. We describe the path to initial elimination in both countries and explore these outbreaks' characteristics, factors contributing to the loss of elimination status, and implications for broader elimination efforts. Data sources include case-based epidemiological and laboratory surveillance reports, historical immunization coverage, genotype data, and published reports of in-depth outbreak investigations. In Mongolia, a single prolonged and large-scale outbreak revealed a hidden immunity gap among young adults and was driven in part by nosocomial transmission, leading to significant morbidity and mortality and loss of elimination status. Cambodia suffered multiple importations from neighboring endemic countries during the global measles resurgence in 2018-2019, complicated by cross-border mobility and significant nosocomial amplification, and the country was ultimately unable to sufficiently distinguish independent chains of transmission, leading to loss of elimination status. Our findings highlight the importance of broadening population immunity assessments beyond children to include adults and specific high-risk groups. Robust routine immunization programs, supplemented by tailored SIAs, are crucial for preventing and managing outbreaks. Additionally, strong outbreak preparedness plans, rapid response strategies, and cross-border collaboration and the global effort to prevent multiple resurgences and large-scale importation-induced outbreaks are vital for maintaining elimination status. The experiences of Mongolia and Cambodia underscore the challenges of sustaining measles elimination in the face of importation risks, shared borders with endemic countries, healthcare system gaps, and population movements. Strengthening the global coordination and synchronization of measles elimination activities is imperative to protect the gains achieved and prevent future setbacks.

Breakthrough Measles among Vaccinated Adults Born during the Post-Soviet Transition Period in Mongolia.

Mongolia experienced a nationwide measles outbreak during 1 March 2015-31 December 2016, with 49,077 cases reported to the WHO; many were among vaccinated young adults, suggesting a possible role of vaccine failure. Advanced laboratory methods, coupled with detailed epidemiological investigations, can help classify cases as vaccine failure, failure to vaccinate, or both. In this report, we conducted a study of cases to identify risk factors for breakthrough infection for a subset of laboratory-confirmed measles cases. Of the 193 cases analyzed, only 19 (9.8%) reported measles vaccination history, and 170 (88%) were uncertain. Measles-specific IgG avidity testing classified 120 (62%) cases as low IgG avidity, indicating no prior exposure to measles. Ten of these cases with low IgG avidity had a history of measles vaccination, indicating primary vaccine failure. Overall, sixty cases (31%) had high IgG avidity, indicating breakthrough infection after prior exposure to measles antigen through vaccination or natural infection, but the IgG avidity results were highly age-dependent. This study found that among young children aged 9 months-5 years, breakthrough infection was rare (4/82, 5%); however, among young adults aged 15-25 years, breakthrough infection due to secondary vaccine failure (SVF) occurred on a large scale during this outbreak, accounting for the majority of cases (42/69 cases, 61%). The study found that large-scale secondary vaccine failure occurred in Mongolia, which highlights the potential for sustained outbreaks in post-elimination settings due to "hidden" cohorts of young adults who may have experienced waning immunity. This phenomenon may have implications for the sustainability of measles elimination in countries that remain vulnerable to the importation of the virus from areas where it is still endemic. Until global measles elimination is achieved, enhanced surveillance and preparedness for future outbreaks in post- or peri-elimination countries may be required.

Achieving measles elimination and emerging modified measles: Longitudinal measles epidemiology from 1982 to 2021 in Osaka Prefecture, Japan.

BACKGROUND: Measles is a contagious viral disease causing infant mortality in developing countries without vaccination programs. In Japan, measles vaccination was launched in 1978, surveillance commenced in 1981, and elimination was achieved in 2015. This was due to improved, legally required surveillance methods and vaccine programs. METHODS: The data sets of sentinel (1982-2007) and notifiable (2008-2021) disease surveillance, as well as the vaccination coverage, detected genotypes, and seroepidemiology during the study period in Osaka Prefecture, were analyzed. Additionally, the trend under the current notifiable surveillance was compared before (2008-2014) and after (2015-2021) measles elimination. RESULTS: Under sentinel surveillance, 51,107 cases were reported, predominantly infants aged 1-4 years (63.6 %). Under notifiable disease surveillance, the 781 patients were predominantly in their 20s-30s (43.7 %). From 2000, the age of the major susceptible group increased due to the rise in vaccination coverage, which exceeded 95% for the first dose in 1998 and 90% for the second dose in 2009. Consistent with these data, seroprevalence exceeded 95% in 2011. However, the geometric mean of the antibody titer showed a decreasing trend with a falling number of patients. Compared with before and after measles elimination, the number of modified measles cases increased from 10.1% to 48.2%. During the study period, 398 strains comprising eight genotypes were identified, and the dominant type changed over time. After measles elimination, genotypes B3 and D8, derived from imported cases, became predominant. CONCLUSIONS: Improved vaccination coverage and surveillance reduced measles cases and increased herd immunity. However, the lack of a booster effect due to the low incidence of measles caused waning antibody titers despite high seroprevalence, which may contribute to the rising rate of vaccine failures causing modified measles. Careful monitoring of measles incidence and herd immunity are necessary for measles eradication.