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Article
Peer-Review Record

Taiwan’s Strategy Toward Measles Elimination

Vaccines 2026, 14(4), 361; https://doi.org/10.3390/vaccines14040361
by Fu-Tien Lin 1, Chin-Hui Yang 1,*, Wen-Yueh Cheng 2 and Jean-Yun Chang 1
Reviewer 1: Anonymous
Reviewer 2:
Reviewer 3: Anonymous
Vaccines 2026, 14(4), 361; https://doi.org/10.3390/vaccines14040361
Submission received: 24 March 2026 / Revised: 15 April 2026 / Accepted: 15 April 2026 / Published: 17 April 2026
(This article belongs to the Special Issue Vaccines and Immunization: Measles, Mumps, and Rubella)

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Fu-Tien Lin and the co-authors submitted the Vaccines an Article, dedicated to measles elimination in Taiwan.

The reviewer suggests some issues should be resolved before the manuscript might be recommended for publication.

1. Abstract section contains unnecessary abbreviations that should be removed.

2. A clearly stated hypothesis should be included in the Introduction. In the Discussion or Conclusion, indicate whether the hypothesis was confirmed or refuted.

3. Line 63: “Epidemiological and laboratory data were obtained from the Taiwan Centers for Disease Control (Taiwan CDC).” Specify the time period for which the data were obtained.

4. Figure 1 looks unpresentable.

5. A separate section on statistical analysis should be added to the Materials and Methods.

6. Section 2.2 describes data obtained from 2002 to 2020. Section 3.1 analyzes data from 1993 to 2024. Explain this differences.

7. Provide a Ref to “From 1993 to 2024, measles incidence remained consistently low, and the annual number of measles cases remained below 50—except in 2019, when a resurgence of global measles activity led to multiple imported cases and subsequent clusters in healthcare settings and restaurants.”

8. Figure 2 is illegible; the text is very small.

9. Whiskers should be added to all diagrams (Figs. 3, 4, 5).

10. Table 2 looks ugly, because it is formatted sloppily and carelessly, and contains many empty cells.

11. Section 3.5 presents genotyping data from 2001 to 2024. Why is there no data from 1993? The manuscript doesn't explain why some of the data is presented at different time intervals, and who and how obtained the data...

12. Please explain to which extent the data related to Taiwan can be extrapolated to other countries, add limitations of the manuscript .

13. The Discussion section is too long. All figures and tables in this section should probably be moved to the Results section.

 

The manuscript needs major revision.

Sincerely,

Author Response

Comments 1: Abstract section contains unnecessary abbreviations that should be removed.

Response 1: Thank you for the feedback. We have removed the abbreviation (VCR (vaccination coverage rates).

Comments 2: A clearly stated hypothesis should be included in the Introduction. In the Discussion or Conclusion, indicate whether the hypothesis was confirmed or refuted.

Response 2: We thank you for the valuable comments. As suggested, we have explicitly stated our hypothesis in the final paragraph of the Introduction. We propose that the specific strategies implemented in Taiwan have been the primary drivers of achieving and sustaining measles elimination, in alignment with WHO guidelines.

Comments 3: Line 63: “Epidemiological and laboratory data were obtained from the Taiwan Centers for Disease Control (Taiwan CDC).” Specify the time period for which the data were obtained.

Response 3: We appreciate your request for clarification. Although measles became a reportable disease in 1985, routine serological confirmation was not established until 1991. Subsequently, measles was classified as a notifiable communicable disease by law in 1999. Under the Communicable Disease Control Act of Taiwan, physicians have been mandated since 1999 to report cases and collect specimens (throat swabs, urine, and whole blood) simultaneously. In this study, we analyzed data from 1991 to 2024; however, it should be noted that the data became more comprehensive and standardized starting in 1999 due to these regulatory changes.

Comments 4: Figure 1 looks unpresentable.

Response 4: We appreciate your feedback regarding Figure 1. We have decided to remove this figure from the revised manuscript as it was determined to be unnecessary for the core argument.

Comments 5: A separate section on statistical analysis should be added to the Materials and Methods.

Response 5: Thank you for this valuable suggestion. A separate Statistical Analysis section has been added to the Materials and Methods (in the revised manuscript). This section now clearly describes the statistical tests applied to the 2019–2020 seroprevalence data, including analyses of differences in seropositivity across birth cohorts.

Comments 6: Section 2.2 describes data obtained from 2002 to 2020. Section 3.1 analyzes data from 1993 to 2024. Explain this difference.

Response 6: We appreciate your comment. To clarify the distinct timeframes for the analyses, we have specified that the measles case analysis and vaccination coverage span 1991 to 2024, while the seroprevalence study focuses on three key surveys conducted in Taiwan between 2002 and 2020. To avoid any potential confusion, the content of Section 2.2 has been revised as follows:

To evaluate epidemiological trends and vaccination coverage, we analyzed national measles surveillance and immunization records from 1991 to 2024. Data were derived from all notified cases maintained by the Communicable Diseases Division of Taiwan CDC and NIIS. Variables retrieved for each case included age, gender, occupation, symptom onset and diagnosis dates, clinical symptoms, and travel history. Laboratory test results were also integrated into the dataset.

Furthermore, to monitor immunity trends across age groups and establish a robust evidence base for policy refinement, three key seroprevalence surveys were conducted between 2002 and 2020. Serum measles-specific immunoglobulin G (IgG) antibodies were measured in all three seroprevalence surveys using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Two assay systems were used: Enzygnost® Anti-Measles Virus/IgG (Siemens, Germany) and Anti-Measles Virus ELISA (Euroimmun, Germany), according to the manufacturers’ instructions.

Comments 7: Provide a Ref to “From 1993 to 2024, measles incidence remained consistently low, and the annual number of measles cases remained below 50—except in 2019, when a resurgence of global measles activity led to multiple imported cases and subsequent clusters in healthcare settings and restaurants.”

Response 7: Thank you for this suggestion. The annual measles cases from 1991 to 2024 are presented in Figure 2 (Figure 1 in the revised manuscript), while a more detailed view of the annual trends from 2001 to 2024 is shown in Figure 3 (Figure 2 in the revised manuscript). To support the statement regarding the low incidence and the 2019 resurgence, we have added the following references to the revised manuscript:

•   Chang YK, Chen YH, Chang HL, Chen KT, et al. Absence of endemic measles transmission in a highly vaccinated population from 1999 to 2008: Implications of sustained measles elimination in Taiwan. 2010; Volume 28: 5332-5337.    https://doi.org/10.1016/j.vaccine.2010.05.047

•  Lai SK, Lin FT, Chen CM. The Evaluation of the San-Ma-Yi-Fong: An Overview of Measles Epidemic, Taiwan, January–May, 2019. Taiwan Epidemiology Bulletin. 2019; 35(11):135-139.

https://www.cdc.gov.tw/En/EpidemicTheme/Detail/dwCswoLnYw874U8oPrVAPA?archiveId=6opSjWOAVooBOPol-_qF4Q

Comments 8: Figure 2 is illegible; the text is very small.

Response 8: Thank you for pointing this out. Figure 2 (Figure 1 in the revised manuscript) has been revised to address the legibility issues. We have streamlined the content and increased the font size to ensure the figure is both concise and clearly readable.

Comments 9: Whiskers should be added to all diagrams (Figs. 3, 4, 5).

Response 9: Thank you for this valuable comment. We would like to clarify that Figure 3 (Figure 2 in the revised manuscript) presents the distribution of observed measles cases by year, and Figure 4 (Figure 3 in the revised manuscript) presents the distribution of observed measles case counts by birth year and age group, rather than estimated measures. Therefore, error bars (whiskers), which represent statistical uncertainty, are not applicable in this context. As these figures reflect complete observed counts rather than sample-based estimates, measures of variability such as confidence intervals are not appropriate.

Comments 10: Table 2 looks ugly, because it is formatted sloppily and carelessly, and contains many empty cells.

Response 10: We sincerely apologize for the formatting oversights in Table 2. We have completely restructured the table, removed redundant empty cells, and ensured consistent formatting to meet professional standards.

Comments 11: Section 3.5 presents genotyping data from 2001 to 2024. Why is there no data from 1993? The manuscript doesn't explain why some of the data is presented at different time intervals, and who and how obtained the data.

Response 11:

   Since 2000, laboratory confirmation has been mandatory for all suspected measles cases in Taiwan under the national surveillance system. While cases were reported prior to this, the standardized protocol for specimen collection—including throat swabs, urine, and whole blood for virologic testing—was formally established and strictly enforced at that time.

   The specimens for genotyping of measles viruses before 2000 were basically from serum samples for reported cases except for 1994, for outbreak investigation, extra sample of throat swab and whole blood were collected for isolating measles virus. And only partial reported cases were sampled for confirmation before 2000.

  The data were collected by the Taiwan Centers for Disease Control (TCDC) through the National Notifiable Disease Surveillance System. Viral isolation and sequencing were conducted by the TCDC's central laboratory using standardized RT-PCR and phylogenetic analysis protocols to determine genotypes.

Comments 12: Please explain to which extent the data related to Taiwan can be extrapolated to other countries, add limitations of the manuscript.

Response 12:

We thank this insightful comment. We have addressed the generalizability of our findings as follows:

  • Combination of genotyping data and travel history of measles cases in Taiwan helped to clarified the possible circulation measles genotype in neighboring country that cannot offer laboratory genotyping data, but the genotyping data in Taiwan before 2000 cannot be extrapolated to other countries in lacking the basic epidemic data of cases.
  • Policy Extrapolation: Taiwan’s successful measles control provides a valuable reference for neighboring countries. Key strategies include large-scale school-based catch-up campaigns, targeted follow-up vaccination policies for high-risk children, and high surveillance sensitivity maintained through active surveillance. These measures significantly enhanced population immunity and led to the early interruption of endemic transmission.
  • Data Extrapolation and Limitations: However, direct extrapolation of Taiwan’s seroprevalence data to non-elimination countries may be limited due to several factors:

Ø  Because Taiwan achieved elimination shortly after the vaccine's introduction—significantly earlier than many neighboring countries—there has been a lack of "natural boosting" from circulating wild-type viruses.

Ø  Waning Immunity: As shown in our 2007–2008 and subsequent surveys, antibody levels in cohorts vaccinated after 1981 tend to wane over time. In countries where measles remains endemic, natural exposure may maintain higher antibody levels than observed in Taiwan.

Limitations:

   We have added a dedicated "Limitations" to the revised manuscript. The primary constraints are as follows:

  1. Methodological Consistency in Data Collection: The 2007–2008 and 2019–2020 surveys were conducted by different contracted academic and research institutions with pre-defined age stratifications. Notably, the 2007–2008 data were retrieved as secondary data from a previously published study. In the absence of raw participant records from these third-party institutions, it was not feasible to recalculate or regroup the age cohorts into perfectly aligned intervals for direct comparison.
  2. Variability in Laboratory Assays: Furthermore, the two surveys utilized different commercial diagnostic kits (reagents). This variation in assay sensitivity and specificity may influence the comparability of seropositivity rates across different age groups.

These limitations have been formally incorporated into the Discussion section of the revised manuscript.

Comments 13: The Discussion section is too long. All figures and tables in this section should probably be moved to the Results section.

Response 13: We thank the reviewer for the suggestion. All figures and tables in the Discussion section have been moved to Section 3 (Results) in the revised manuscript.

Reviewer 2 Report

Comments and Suggestions for Authors

This study evaluates Taiwan’s measles elimination efforts from 1991 to 2024 using surveillance data, vaccination coverage, seroprevalence surveys, and genotyping. Since 1993, annual cases have remained below 50, and non-imported incidence has been consistently <1 per million. MMR1 and MMR2 coverage have exceeded 95% since 1998. Genotyping confirms interruption of endemic transmission after 2006. However, seroprevalence surveys show declining antibody levels among younger cohorts, with seropositivity as low as 36.7% in some groups. Despite this, importations have led to minimal secondary spread, suggesting preserved population-level immunity via immunological memory. Taiwan has sustained measles elimination through high vaccination coverage, robust surveillance, and targeted interventions. The authors conclude that targeted booster strategies for high-risk groups may be more appropriate than universal additional dosing in post-elimination settings.

This manuscript provides a comprehensive, data‑rich description of Taiwan’s measles elimination strategy over three decades. It integrates epidemiological, seroprevalence, and virologic surveillance, demonstrating sustained low incidence, high vaccination coverage, and interruption of endemic transmission. However, several issues regarding presentation, analytical depth, and critical interpretation need to be addressed before the paper meets the journal’s standards for a full research article.

1. Can the authors provide statistical tests (e.g., chi‑square for seropositivity differences, trend analysis for incidence) to support statements such as “declining antibody levels among adolescents and young adults” or “seropositivity as low as 36.7% in specific cohorts”?

2. How were the age‑group boundaries chosen for the seroprevalence tables? Aligning birth cohorts across surveys would allow for more meaningful temporal comparisons. Please justify the current grouping or consider regrouping.

3. Do we have any data coming from paired ELISA‑PRNT analyses in the Taiwanese population to validate the proportion of ELISA‑negative individuals who retain neutralizing antibodies? Without such validation, the interpretation that population immunity remains sufficient is speculative.

4. In Table 1, does this decline reflect a true reduction in suspected cases, or does it indicate under‑reporting and potential weakening of surveillance sensitivity? The authors state it was “primarily attributed to reduced clinical suspicion and reporting activity,” but how was this determined?

5. Table 3 shows sporadic genotype H1 cases until 2017, many of which were import‑related. What specific criteria were used to differentiate import‑related from possible endemic chains? Were there any years after 2006 where a chain of transmission of >12 months was identified? Clarifying this would strengthen the claim of sustained interruption.

6. How were these policy changes evaluated for their impact on coverage and immunity? Were any post‑implementation seroprevalence or outbreak data used to assess the effect of the earlier MMR2 schedule? Please consider adding a brief analysis or explanation section to previous evaluations.

Author Response

Comments 1: Can the authors provide statistical tests (e.g., chi‑square for seropositivity differences, trend analysis for incidence) to support statements such as “declining antibody levels among adolescents and young adults” or “seropositivity as low as 36.7% in specific cohorts”?

Response 1: For the 2007–2008 measles seroprevalence survey, the published study already included relevant statistical analyses. Specifically, differences in geometric mean titers (GMTs) between subgroups were assessed using an unpaired t-test. A linear regression model was applied to evaluate trends in declining antibody titers, and the trend in seropositivity across age groups was examined using the Mantel–Haenszel test.

For the 2019–2020 seroprevalence survey, we conducted additional statistical analyses based on birth cohort classification. Participants were categorized into three groups: (1) natural infection cohort (aged 45–59 years), (2) pre-campaign vaccination cohort (aged 25–44 years), and (3) post-campaign vaccination cohort (aged 3–24 years).

A Pearson’s chi-square test was used to assess the association between birth cohort and serostatus (positive vs. negative). The results demonstrated a significant association (χ² = 205.81, p < 0.001), indicating that seropositivity differed across cohorts. Furthermore, binary logistic regression analysis was performed with seropositivity (1 = positive, 0 = negative) as the dependent variable and birth cohort as a categorical independent variable, using the pre-campaign vaccination cohort as the reference group. The analysis showed that individuals in the natural infection cohort had significantly higher odds of seropositivity (OR = 8.97, 95% CI: 6.36–12.65), whereas those in the post-campaign vaccination cohort had only slightly higher odds (OR = 1.24, 95% CI: 1.02–1.50).

To further examine heterogeneity within the post-campaign vaccination cohort, a Pearson’s chi-square test (5 × 2 contingency table) was conducted across five age groups, revealing a significant difference in seropositivity (χ² = 165.3, p < 0.001). In addition, logistic regression analysis using the 15–19-year age group as the reference demonstrated that individuals aged 20-24, 10–14, 5–9, and 3–4 years had significantly higher odds of seropositivity (OR = 2.07, 3.16, 9.09 and 22.45 respectively; all p < 0.001), These results provide robust statistical support for our statements regarding variation in seropositivity across cohorts and the relatively lower antibody levels observed in adolescents aged 15–19 years.

Comments 2: How were the age‑group boundaries chosen for the seroprevalence tables? Aligning birth cohorts across surveys would allow for more meaningful temporal comparisons. Please justify the current grouping or consider regrouping.

Response 2: The age-group boundaries in our study were primarily determined by the availability and structure of the datasets from different survey periods. We appreciate your suggestion regarding birth cohort alignment; however, we encountered several logistical constraints that precluded regrouping:

  • Data Sources and Limitations: The serosurvey data for 2002–2007 were derived from residual samples of a national survey on chronic diseases ("Triple-High status") conducted by the Taiwan Bureau of Health Promotion of the Department of Health. Due to the significant time elapsed, the original raw data with individual birth dates are no longer accessible.
  • Methodological Inconsistency across Agencies: The 2007–2008 and 2019–2020 surveys were conducted by different contracted entities with pre-defined age stratifications. Specifically, the 2007–2008 data used in this study were retrieved as secondary data from a published study in Vaccine. Without access to the raw participant records from these third-party institutions, recalculating or regrouping the age cohorts into perfectly aligned intervals is not feasible.
  • Research Intent of Table 2: Despite these limitations, Table 2 aims to present the most comparable age groups and birth cohorts possible within the constraints of the available secondary data. Our primary objective was to observe the longitudinal changes in measles seroprevalence over a 12-year interval and to assess the potential waning of immunity between the "natural infection cohort" and the "vaccine-induced immunity cohort."

In summary, while we acknowledge that perfectly aligned birth cohorts would enhance temporal comparisons, the current grouping represents the highest degree of granularity allowed by the existing datasets.

Comments 3: Do we have any data coming from paired ELISA‑PRNT analyses in the Taiwanese population to validate the proportion of ELISA‑negative individuals who retain neutralizing antibodies? Without such validation, the interpretation that population immunity remains sufficient is speculative.

Response 3: Due to the time-consuming and labor-intensive nature of Plaque Reduction Neutralization Tests (PRNT), a nationwide paired ELISA-PRNT analysis has not yet been conducted in the Taiwanese population. However, previous localized studies have explored the consistency between different serological assays. For instance, a study involving elementary school students (n=856) compared two platforms and found measles seropositive rates of 82.24% via Liaison CLIA and 92.17% via NovaLisa EIA. While these results do not replace PRNT validation, the significant discrepancy between assays suggests that seroprevalence estimates are highly sensitive to the diagnostic tool used. This variation indicates that individuals testing negative on a specific ELISA platform might still possess antibodies detectable by more sensitive methods, partially addressing the concern regarding underestimated population immunity.

Comments 4: In Table 1, does this decline reflect a true reduction in suspected cases, or does it indicate under‑reporting and potential weakening of surveillance sensitivity? The authors state it was “primarily attributed to reduced clinical suspicion and reporting activity,” but how was this determined?

Response 4: Due to strict border controls during the COVID-19 pandemic, no confirmed measles cases were reported in 2020–2021. This led to a temporary decline in clinician suspicion and notification incentive, causing the annual reporting rates of discarded non-measles cases to fall below the target threshold between 2020 and 2023. Nevertheless, the Taiwan CDC maintained active surveillance through the Laboratory Surveillance System, which detected no confirmed cases as of early 2024. Following the post-pandemic border reopening, two imported cases were identified in 2023. In response, the Taiwan CDC implemented targeted interventions, including issuing press releases, sending "Letters to Doctors" (clinical alerts), and incorporating measles notification metrics into local health department performance evaluations. These efforts aimed to ensure clinicians strictly adhere to TOCC (Travel, Occupation, Contact, Cluster) history-taking and prompt reporting. Consequently, the national annual reporting rate for discarded non-measles cases recovered to 2.35 per 100,000 population in 2024.

Comments 5: Table 3 shows sporadic genotype H1 cases until 2017, many of which were import‑related. What specific criteria were used to differentiate import‑related from possible endemic chains? Were there any years after 2006 where a chain of transmission of >12 months was identified? Clarifying this would strengthen the claim of sustained interruption.

Response 5: In accordance with the Communicable Disease Control Act of Taiwan, physicians are mandated to report suspected measles cases within 24 hours of diagnosis. Epidemiological investigations must be completed within 48 hours of notification, and all records must be systematically archived.

For every confirmed case, we conduct a comprehensive investigation, including contact tracing and follow-up. To differentiate between imported, import-related, and potentially endemic cases, non-imported cases are classified based on epidemiological evidence, laboratory testing, and genotype analysis using the following criteria:

  • Importation-related case: A locally acquired infection occurring as part of a transmission chain originating from an imported case, supported by epidemiological or virological evidence.
  • Imported-virus case: A case lacking a direct epidemiological link to an imported case, but where the infecting virus is laboratory-confirmed as an imported genotype (i.e., a genotype not endemic in Taiwan).
  • Unknown source case: A confirmed case where a thorough investigation fails to identify an epidemiological or virological link to either importation or endemic transmission.
  • Endemic case: Laboratory or epidemiologically linked cases resulting from the endemic transmission of the measles virus.

Since 2006, our continuous surveillance and cluster investigations have identified no chains of transmission lasting longer than 12 months. Consequently, no cases have met the criteria for classification as "endemic" during this period, further supporting our claim of sustained interruption of measles transmission.

Comments 6: How were these policy changes evaluated for their impact on coverage and immunity? were any post‑implementation seroprevalence or outbreak data used to assess the effect of the earlier MMR2 schedule? Please consider adding a brief analysis or explanation section to previous evaluations.

Response 6: In 2012, Taiwan rescheduled the second dose of the MMR vaccine (MMR2) to ages 5–6 years (prior to primary school entry). The primary objective of this shift was to transition from mass school-based vaccinations to administration at contracted clinics. This allowed for real-time data integration into the National Immunization Information System (NIIS). Upon school entry, local health authorities can now systematically verify records and issue notifications to parents of unvaccinated children.

While this specific administrative change focused on data integrity rather than a direct boost in coverage, other strategic interventions have significantly enhanced population immunity:

  • Early Protection: Since 2009, the MMR1 schedule was adjusted from 12–15 months to exactly 12 months, effectively reducing the window of vulnerability for infants.
  • Active Surveillance and Outreach: In 2009, the Taiwan CDC integrated the NIIS with National Immigration Agency records. This system automatically alerts health agencies when a child without a documented MMR record enters the country. Public health nurses then conducts targeted follow-up.

As a result of these integrated evaluations and interventions, MMR1 coverage has consistently exceeded 97% since 2009, maintaining high herd immunity and minimizing outbreak risks.

 

Reviewer 3 Report

Comments and Suggestions for Authors

Abstract

 

Line 17. The result data should represented as of 2024, which includes the coverage rates and genotype circulation

Lines, 2021. Seroprevalence surveys revealed declining antibody levels among adolescents and young adults, with seropositivity as low as 36.7% in specific cohorts

Comment: Which seroprevalence surveys are referring to testing what?

Lines 23-24. Taiwan has successfully sustained measles elimination through high vaccination coverage (no data to support that as of 2024), robust surveillance, and targeted interventions (unclear).

Line 27. You have been informed several times in the abstract post-elimination settings, although you have stated that Taiwan has already eliminated measles. To inform the post-elimination?!

Introduction

Lines 32-36. Provide citations

Line 39. Age of 15 years or months?

Lines 41-53. Provide citations

Lines 73-74. Provide citations

Results

Lines 91-92. From 1993 to 2024, measles incidence remained consistently low, and the annual number of measles cases remained below 50.

Comment: the 50 cases should follow up the rates per million population

Line 94. A total of 534 confirmed cases… When was this outbreak notified?

Line 130...the eradication"—you mean elimination!?

Line 186. The measles seroprevalence surveys, which tests have you used?

 

Table 4 and Figure 6 This table and figure go to results

 

Discussions

Does the manuscript describe the WHO verification of measles elimination?

Line 419. The conclusion to be revisit with concise summary no repetitions and clear the way forward

 

 

Author Response

Comments 1: Line 17. The result data should represent as of 2024, which includes the coverage rates and genotype circulation.

Response 1: The relevant section has been revised as follows: From 1993 to 2024, the annual number of measles cases remained consistently below 50, except in 2019. Vaccination coverage for both MMR1 and MMR2 has exceeded 95% since 1998, with MMR1 coverage remaining above 97% between 2009 and 2024. Genotyping evidence confirms interruption of endemic transmission since 2006; furthermore, as of 2024, no continuous chains of transmission lasting longer than 12 months have been recorded.

Comments 2: Lines, 20-21. Seroprevalence surveys revealed declining antibody levels among adolescents and young adults, with seropositivity as low as 36.7% in specific cohorts Comment: Which seroprevalence surveys are referring to testing what?

Response 2: Three national surveys conducted serological testing for measles-specific Immunoglobulin G (IgG) in serum and analyzed using ELISA to assess population immunity levels. The relevant section has been revised as follows: National seroprevalence surveys monitoring measles-specific IgG antibodies revealed declining immunity among adolescents and young adults, with seropositivity as low as 36.7% in specific cohorts.

Comments 3: Lines 23-24. Taiwan has successfully sustained measles elimination through high vaccination coverage (no data to support that as of 2024), robust surveillance, and targeted interventions (unclear).

Response 3: We appreciate your comment regarding the data support.

1.High vaccination coverage: We have now updated the manuscript (see 3.2. Vaccination policy and coverage rates, Page 5) to include the latest immunization statistics from the Taiwan CDC.” The coverage for routine MMR1 and MMR2 remained high at 98.8% and 97.4% as of 2024.”

2. Surveillance system: Due to strict border controls during the COVID-19 pandemic, no confirmed measles cases were reported in 2020–2021. This led to a temporary decline in clinician suspicion and in the notification incentive, causing the annual reporting rates for discarded non-measles cases to fall below the target threshold between 2020 and 2023. Nevertheless, the Taiwan CDC maintained active surveillance through the Laboratory Surveillance System, which detected no confirmed cases as of early 2024. Following the post-pandemic border reopening, two imported cases were identified in 2023. In response, the Taiwan CDC implemented targeted interventions, including issuing press releases, sending "Letters to Doctors" (clinical alerts), and incorporating measles notification metrics into local health department performance evaluations. These efforts aimed to ensure clinicians strictly adhere to TOCC (Travel, Occupation, Contact, Cluster) history-taking and prompt reporting. Consequently, the national annual reporting rate for discarded non-measles cases recovered to 2.35 per 100,000 population in 2024.

3. Targeted interventions:

(1)2009~: Taiwan CDC has integrated data from the NIIS and the National Immigration Agency to track unvaccinated high-risk children who traveled internationally and entered Taiwan without an MMR vaccination (follow-up plan for high-risk and unvaccinated children). Under this integrated framework, the NIIS automatically alerts local health agencies when a child without a documented MMR record arrives in Taiwan. Public health nurses then conduct active follow-up and vaccination outreach. (see 3. Result ,3.6. Risk assessment and continuous prevention and control interventions, Page 11 in the revised manuscript)

(2)2009~: Requirement for proof of positive antibody for foreigners and foreign labor since 2014. (see 3.6. Risk assessment and continuous prevention and control interventions in the revised manuscript)

(2)2014~: Taiwan Advisory Committee on Immunization Practices (ACIP) recommends that infants aged 6-11 months, as well as individuals born after 1981, receive one dose of MMR vaccine prior to travel to high-risk areas. Local health centers were also instructed to offer MMR vaccination to infants aged 6-11 months, preparing for international travel. (see 3.6. Risk assessment and continuous prevention and control interventions in the revised manuscript)

 (4)2019~: Based on risk assessments derived from the 2018–2019 clusters, the Taiwan CDC identified high-risk groups for infection and transmission, including travelers to endemic areas, healthcare workers, childcare workers, and personnel with frequent professional contact with foreign nationals. A booster MMR dose is formally recommended for individuals in these high-risk categories born in or after 1981 who do not meet the immunity criteria. (see 4. Discussion, Page 11 in the revised manuscript)

Taiwan CDC integrated the MMR vaccination status of healthcare workers born in or after 1981 into the national hospital infection control audit standards. Hospitals were mandated to implement comprehensive catch-up programs, providing an additional MMR dose to healthcare workers who either lacked a two-dose history or had received their last dose more than 15 years prior. (see 4. Discussion, Page 12 in the revised manuscript)

Comments 4: Line 27. You have been informed several times in the abstract post-elimination settings, although you have stated that Taiwan has already eliminated measles. To inform the post-elimination?!

Response 4: The primary objective of this study is to analyze the critical prevention and control strategies that enabled Taiwan to achieve measles elimination efficiently. While elimination has been sustained through high vaccination coverage, our findings indicate that vaccinated cohorts lack natural boosting from exposure to the wild-type virus. Consequently, vaccine-induced immunity wanes over time, potentially creating gaps in immunity. Given the global resurgence of measles, this study evaluates the challenges of the post-elimination era and the risk of community transmission triggered by imported cases, while detailing the corresponding countermeasures implemented in Taiwan.

Comments 5: Lines 32-36. Provide citations

Response 5: In accordance with the suggestion, we have added the following reference to support the statements in lines 32–36:

• McGuinness, S. L., Lau, C. L., & Leder, K. (2025). Measles without borders: how can travel medicine help limit global resurgence? Journal of Travel Medicine, taaf056. https://doi.org/10.1093/jtm/taaf056.

Comments 6: Line 39. Age of 15 years or months?

Response 6: The relevant section has been revised as follows: Nearly all children get measles by age 15 years.

Comments 7: Lines 41-53. Provide citations

Response 7: In accordance with the suggestion, we have added the following reference to support the statements:

• Kenneth J. Bart, Feng-Ying C. Lin, Ding-Ping Liu, Hsu-Sung Kuo. The Evaluation of the San-Ma-Yi-Fong: Progress with the Programs to Eradicate Measles, Rubella, Congenital Rubella Syndrome, and to Eliminate Neonatal Tetanus. Taiwan Epidemiology Bulletin. 2010; 26(5):60-73. https://www.cdc.gov.tw/En/EpidemicTheme/Detail/hQ4XhaZAzUmNe2ksY4tjMA?archiveId=jzuzrV8QPXdQ4sF62oN6EQ

Comments 8: Lines 73-74. Provide citation

Response 8: In accordance with the suggestion, we have cited the following references:

•  Bureau of Health Promotion of the Department of Health, Taiwan. The prevalence follow-up survey of high blood pressure, hyperglycemia, and high blood lipid profile (Triple-High status) Report (2011).   https://www.hpa.gov.tw/Pages/Detail.aspx?nodeid=364&pid=6540

• Chen CJ, Lee PI, Hsieh YC, et al. Waning population immunity to measles in Taiwan. Vaccine. 2012;30(47):6721-6727. vaccine.2012.09.004. https://doi.org/10.1016/j.vaccine.2012.05.019.

•  Taiwan Centers for Disease Control. Serosurveillance of vaccine-preventable diseases in Taiwan, 2019–2020; Annual research report (2021). https://ah.cdc.gov.tw/planOne?pid=1542&lang=en-US

Comments 9: Lines 91-92. From 1993 to 2024, measles incidence remained consistently low, and the annual number of measles cases remained below 50.

Comment: the 50 cases should follow up the rates per million population

Response 9: The relevant section has been revised as follows:

From 1993 to 2024, measles incidence remained consistently low, with the annual number of cases below 50, corresponding to an incidence rate of less than 2.1 cases per million population—except in 2019.

Comments 10: Line 94. A total of 534 confirmed cases… When was this outbreak notified?

Response 10: The relevant section has been revised as follows:

Between 1993 and 2024, a total of 534 confirmed cases were reported over the 32-year period, including 342 (64%) non-imported cases and 192 (36%) imported cases.

Comments 11: Line 130...the eradication"—you mean elimination!?

Response 11: The original program, established in 1991 to support the global efforts against polio and neonatal tetanus, was formally titled “The Program to Eradicate Measles, Rubella, Congenital Rubella Syndrome, and Neonatal Tetanus.” However, to align with the WHO Western Pacific Regional Office (WPRO) guidelines, the program was reformulated in 2010 to focus specifically on measles elimination.

Comments 12: Line 186. The measles seroprevalence surveys, which tests have you used?

Response 12: Serum measles-specific immunoglobulin G (IgG) antibodies from the seroprevalence surveys were detected using a commercial enzyme-linked immunosorbent assay (ELISA). Two assay systems were used: Enzygnost® Anti-Measles Virus/IgG (Siemens, Germany) and Anti-Measles Virus ELISA (Euroimmun, Germany), according to the manufacturers’ instructions.

Comments 13: Table 4 and Figure 6 This table and figure go to results

Response 13: We thank the reviewer for the suggestion. Table 4 and Figure 6 have been moved to Section 3 (Results) in the revised manuscript.

Comments 14: Does the manuscript describe the WHO verification of measles elimination?

Response 14: In 2011, Taiwan established the National Verification Committee (NVC) for measles elimination. Following a meeting of the Measles Elimination Verification Group in 2013, committee members reviewed the evidence and unanimously confirmed that Taiwan had reached its elimination goals. Consequently, the National Documentation for Verifying Measles Elimination was submitted to the WHO Western Pacific Regional Office (WPRO) in 2014. Although the Western Pacific Regional Verification Commission for Measles and Rubella Elimination sent an email in 2018 acknowledging Taiwan’s achievements, Taiwan remains unable to receive official certification because it is not a formal member state of the WPRO.

Comments 15: Line 419. The conclusion to be revisit with concise summary no repetitions and clear the way forward.

Response 15: We thank you for the valuable comments. The conclusion has been revised as follows:

Monitoring of measles virus genotypes indicates the interruption of endemic measles transmission in Taiwan after 2006. According to WHO’s five lines evidence for verification of measles elimination, Taiwan has successfully maintained measles elimination since 2006. Although serological waning is observed, the lack of large-scale outbreaks suggests that immunological memory provides sufficient population-level protection. Consequently, two documented MCV doses are considered adequate for immunity, and a universal third MMR dose remains unnecessary—especially as secondary vaccination failure (SVF) carries an exceedingly low transmission risk. Furthermore, evidence from hospital cluster investigations and a systematic review of individuals with secondary vaccination failure (SVF) indicates that the secondary attack rate from breakthrough infections is exceedingly low. In response to the post-COVID-19 global resurgence, future efforts will transition from universal strategies to precision prevention. Based on 2019–2020 seroprevalence data, targeted boosters should prioritize high-risk groups, specifically healthcare workers more than 15 years post-vaccination. Ongoing longitudinal seroprevalence monitoring will be essential to ensure sustained vigilance against imported cases.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Manuscript might be recommended for publication after a minor revision

Reviewer 2 Report

Comments and Suggestions for Authors

I am ok with the authors' response and revision. I have no further comments.

Reviewer 3 Report

Comments and Suggestions for Authors

NIL

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