Zero-dose Children in Timor-leste: Household-level Risk Factors and Implications for the Immunization Agenda 2030

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Methods This retrospective cohort study analyzed national immunization data from the Timor-Leste EPI Factsheet 2024 and WHO/UNICEF Estimates of National Immunization Coverage 2023. Zero-dose children were defined according to the IA2030 standards (no first dose of DTP-containing vaccine). The primary outcome was the zero-dose prevalence in the 2023 birth cohort. Indicators corresponding to risk factors from a multi-country analysis of 82 low- and middle-income countries were extracted and descriptively compared with global estimates from the Global Burden of Disease Study 2023. This study adhered to the STROBE guidelines for observational research. Results In 2023, Timor-Leste had 33,260 live births and 3254 zero-dose children (9.8% of the birth cohort), a 22% reduction from 4184 (13.1%) in 2022. Neonatal tetanus protection improved to 85% (from 83%), with 15% unprotected—a group with three times the odds of being zero-dose (OR 3.00; 95% CI: 2.72–3.30). Skilled birth attendance was 57%, with 43% home deliveries—a group with nearly twice the odds of being zero-dose (OR 1.87; 95% CI: 1.70–2.05). All 14 districts (100%) now have updated micro-plans; zero districts show a > 10% DTP1-to-DTP3 dropout rate, a complete elimination from five districts (38%) in 2022. The number of districts achieving > 90% MCV1 coverage increased from five (38%) to ten (71%). The pneumococcal conjugate vaccine was introduced in January 2023. Conclusions Timor-Leste's 22% zero-dose reduction demonstrates that targeted microplanning and district accountability are effective strategies for addressing zero-dose children. However, the prevalence of 9.8% exceeds the global average, with access to maternal healthcare remaining the predominant risk factor. Achieving IA2030s 50% reduction target requires integrating maternal-child health services with immunization programs and reaching 43% of families delivering at home. These findings generate hypotheses for future prospective studies on integrated service delivery models in Southeast Asia. Epidemiology Zero-dose children immunization coverage Timor-Leste maternal health vaccine-preventable diseases Southeast Asia public health clinical epidemiology Figures Figure 1 INTRODUCTION Routine immunization prevents 2–3 million deaths annually [ 1 ]; however, zero-dose children—those who have not received the first dose of diphtheria-tetanus-pertussis (DTP)-containing vaccines —remain a critical challenge for the Immunization Agenda 2030 (IA2030) [ 2 ]. Vaccine-preventable diseases continue to cause significant morbidity and mortality in Southeast Asia, with DTP1-zero-dose children susceptible to pertussis, diphtheria, and tetanus, the latter being particularly relevant where maternal and neonatal tetanus protection gaps persist [ 3 ]. Therefore, understanding zero-dose epidemiology is essential for clinical infectious disease control and public health practices. Globally, an estimated 15.7 million children were zero-dose in 2023, with the majority concentrated in low- and middle-income countries (LMICs) [ 3 ]. The Global Burden of Disease Study 2023 documented that the COVID-19 pandemic caused sharp declines in vaccination coverage across all regions since 2020, with incomplete recovery as of 2023 [ 3 ]. As the world commemorates 50 years of the Expanded Programme on Immunization (EPI), understanding the progress and persistent challenges in diverse settings is essential [ 4 , 5 ]. Timor-Leste, a Southeast Asian nation with 1.34 million people, has maintained its EPI since 1978 [ 6 ]. The country faces the typical challenges of a post-conflict, lower-middle-income setting: mountainous terrain, a dispersed population, and health system infrastructure that is still under development. Despite these challenges, national immunization coverage has steadily improved, although sub-national disparities persist [ 7 ]. The IA2030 sets an ambitious target of a 50% reduction in zero-dose children by 2030, compared to 2019 baseline levels [ 2 ]. To achieve this, countries must accelerate progress, identify the remaining barriers, and implement evidence-based strategies tailored to local contexts. A multi-country analysis of 82 LMICs identified household-level risk factors for zero-dose status, including limited maternal healthcare access, low maternal education, household poverty, and geographic remoteness [ 8 ]. However, no study has specifically examined zero-dose epidemiology in Timor-Leste or assessed progress toward the IA2030 targets using standardized methodologies. The integration of maternal and child health services with routine immunization has been identified as a key strategy for improving coverage and equity [ 9 ]. Evidence from systematic reviews indicates that integrated service delivery can improve outcomes for linked services while maintaining or improving immunization coverage when implementation considerations are adequately addressed [ 10 ]. We aimed to estimate zero-dose prevalence in Timor-Leste using 2023 data, identify household-level risk factors by comparing national indicators with global patterns, and assess progress toward the IA2030 50% reduction target. METHODS Study design and rationale This retrospective cohort study analyzed publicly available national immunization data from Timor-Leste (2022–2023) and descriptively compared the findings with global estimates from multi-country analyses and the Global Burden of Disease Study 2023. While IJID Regions preferentially publishes prospective randomized controlled trials, this retrospective study provides essential epidemiological evidence from a lower-middle-income country, where such data are currently scarce. This study adhered to the (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for observational research (see Supplementary Material). Data sources We analyzed data from the Timor-Leste Expanded Programme on Immunization (EPI) Factsheet 2024, published by the WHO Regional Office for South-East Asia, which provides national immunization data, health system indicators, and district-level coverage estimates for 2023 [ 11 ]. The WHO/UNICEF Estimates of National Immunization Coverage (WUENIC) 2023 provided validated national coverage estimates for DTP1 and other antigens [ 12 , 13 ]. For global comparison, we utilized findings from (i) a multi-country analysis of 82 LMICs examining household-level risk factors for zero-dose immunization using Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) data spanning 2011–2020 [ 8 ], and (ii) the GBD 2023 Vaccine Coverage Collaborators study, which provided global, regional, and national estimates of routine childhood vaccine coverage from 1980 to 2023 with forecasts to 2030 for 204 countries and territories [ 3 ]. We also incorporated insights from the recent literature commemorating 50 years of the EPI [ 4 , 5 , 14 ]. As this study used only publicly available aggregate data, informed consent was not applicable, and ethical approval was not required. Procedures Following the IA2030 IG 2.1 standards, zero-dose children were defined as those who did not receive the first dose of a DTP-containing vaccine [ 15 ]. The number of zero-dose children was calculated as follows: Zero-dose children = Estimated surviving infants – Number of children receiving DTP1 The estimated number of surviving infants was derived from the United Nations Population Division birth cohort estimates, and DTP1 vaccination data were obtained from the WUENIC. For Timor-Leste, we utilized the published estimate of 3254 zero-dose children from the EPI Factsheet 2024, which applied this methodology to the 2023 data [ 11 ]. We extracted Timor-Leste indicators corresponding to the risk factors identified in the global multi-country analysis and GBD 2023, organized into five domains: maternal healthcare access (skilled birth attendance and neonatal tetanus protection), health system characteristics (district-level coverage, dropout rates, microplanning status, and new vaccine introductions), demographic context (birth cohort), and vaccine-preventable disease burden. Global comparison data included odds ratios (OR) with 95% confidence intervals (CIs) from multivariate logistic regression models [ 8 ] and GBD 2023 estimates of coverage trends, zero-dose counts, and forecasts [ 3 ]. These are presented for descriptive comparison only, as our study did not perform an independent multivariate analysis. Outcomes The primary outcome was zero-dose prevalence (proportion of the annual birth cohort receiving no DTP1) in Timor-Leste in 2023. The secondary outcomes included (i) change in zero-dose prevalence from 2022 to 2023, (ii) district-level immunization performance indicators (DTP1-to-DTP3 dropout rates, MCV1, and MCV2 coverage), (iii) maternal healthcare access indicators (skilled birth attendance and neonatal tetanus protection), and (iv) descriptive comparison of Timor-Leste indicators with global risk factor patterns. Statistical analysis This study used only descriptive statistics. Zero-dose prevalence was calculated as a simple proportion: the number of zero-dose children divided by the total birth cohort, expressed as a percentage. Changes between 2022 and 2023 were calculated as absolute and relative percentage differences. District-level data are presented as counts and percentages to show the number and proportion of districts that meet specific performance thresholds (e.g., > 10% dropout rate, > 90% coverage). Changes between the years were described narratively. To compare with global findings, we qualitatively assessed Timor-Leste's indicators against global risk factor patterns and GBD trends. Global odds ratios from the multi-country analysis [ 8 ] are presented alongside Timor-Leste's corresponding indicators to facilitate descriptive comparison. These odds ratios were not calculated from Timor-Leste data but are shown to contextualize local findings within established global patterns. All data are presented as numbers, percentages, or published odds ratios with 95% confidence intervals from the source literature. No inferential statistical tests were conducted. All analyses were performed using Microsoft Excel (version 16.8). RESULTS In 2023, Timor-Leste had an estimated 33,260 live births, an increase from 31,832 in 2022 (Table 1 ) [ 11 ]. Applying the IA2030 IG 2.1 methodology, the country had 3254 zero-dose children, representing 9.8% of the birth cohort. This marks a substantial improvement from 2022, when 4184 children (13.1% of the birth cohort) were zero-dose, a 22% reduction in absolute numbers and a 3.3 percentage point reduction in prevalence within a single year. At 9.8%, Timor-Leste's zero-dose prevalence falls between the average for low-income (10.4%) and lower-middle-income countries (7.0%), having moved closer to the latter [ 8 ]. The 3254 zero-dose children represent 0.02% of the global 15.7 million zero-dose burden, proportionate to the country's population size [ 3 ]. Table 1 Baseline characteristics and immunization indicators for Timor-Leste (2022–2023) Characteristic 2022 2023 Population Live births 31,832 33,260 Zero-dose children 4184 (13.1%) 3254 (9.8%) Maternal healthcare access Skilled birth attendance 57% 57% Home deliveries 43% 43% Neonatal tetanus protection 83% 85% Neonatal tetanus unprotected 17% 15% District-level performance Districts with > 10% DTP1–DTP3 dropout 5 (38%) 0 (0%) Districts with updated micro-plans 13 (93%) 14 (100%) Districts with > 90% MCV1 coverage 5 (38%) 10 (71%) Districts with > 90% MCV2 coverage 4 (31%) 10 (71%) New vaccine introductions Pneumococcal conjugate vaccine (PCV) Not introduced Introduced Jan 2023 Data are presented as n, n (%), or percentages. DTP=diphtheria-tetanus-pertussis. MCV: measles-containing vaccine. Sources: Timor-Leste EPI Factsheets, 2023, and 2024 [ 11 ]. The global multi-country analysis identified a lack of maternal healthcare access as the strongest predictor of zero-dose status (Table 2 ) [ 8 ]. Timor-Leste's 2023 indicators show modest improvements but persistent challenges. Skilled birth attendance remained at 57%, unchanged from 2022, indicating that 43% of deliveries still occurred at home without skilled care [ 11 ]. Globally, children delivered at home had nearly twice the odds of being zero-dose compared to those delivered at facilities (OR 1.87; 95% CI: 1.70–2.05) [ 8 ]. Neonatal tetanus protection improved to 85% of neonates protected at birth (up from 83% in 2022); however, 15% remained unprotected [ 11 ]. Globally, children whose mothers received no tetanus injections had three times the odds of being zero-dose (OR 3.00; 95% CI: 2.72–3.30) compared with those whose mothers received ≥ 2 injections [ 8 ]. Table 2 Descriptive comparison of Timor-Leste maternal healthcare indicators with global risk factors Indicator Timor-Leste 2023 Global odds ratio (95% CI)* Home delivery (vs facility) 43% 1.87 (1.70–2.05) No maternal tetanus protection (vs ≥ 2 doses) 15% 3.00 (2.72–3.30) *Odds ratios from multivariate logistic regression models in 82 LMICs (Farrenkopf et al., 2023) [ 8 ]. These are presented for descriptive comparison only and were not calculated using Timor-Leste data. The most striking improvement in Timor-Leste's immunization system from 2022 to 2023 was the complete elimination of districts with high dropout rates (Fig. 1). In 2023, zero districts had > 10% DTP1-to-DTP3 dropout, compared with five districts (38%) in 2022—a reduction from five to zero districts. This achievement demonstrates the effectiveness of targeted microplanning [ 16 ]. Additional health system strengthening achievements included updated micro-plans now covering all 14 districts (100%, up from 13 in 2022), districts achieving > 90% MCV1 coverage increasing from five (38%) to ten (71%), and districts achieving > 90% MCV2 coverage increasing from four (31%) to ten (71%) [ 11 ]. Figure 1: District-level DTP1-to-DTP3 dropout rates in Timor-Leste, 2022 vs 2023 Data represent the number of districts. DTP=diphtheria-tetanus-pertussis. DISCUSSION This analysis revealed that Timor-Leste achieved remarkable progress in reducing its zero-dose burden, from 4184 children (13.1% of the birth cohort) in 2022 to 3254 children (9.8%) in 2023—a 22% reduction in a single year. This exceeds the annualized progress needed to achieve the IA2030 50% reduction target by 2030, demonstrating that focused health system strengthening can yield rapid results in Southeast Asia. The most dramatic improvement was the complete elimination of districts with high dropout rates—from five districts (38%) with > 10% DTP1-to-DTP3 dropout in 2022 to none in 2023. This achievement, alongside substantial increases in districts achieving > 90% MCV1 and MCV2 coverage, demonstrates the effectiveness of targeted microplanning and district-level accountability—approaches that other Southeast Asian countries with similar health system structures could adopt [ 16 ]. Clinical implications These findings have direct clinical relevance for infectious disease control in Timor-Leste and similar settings. Neonatal tetanus risk : Approximately 15% of neonates (approximately 5000 infants annually) unprotected against tetanus at birth remain vulnerable to this preventable fatal disease. Every antenatal care contact should ensure tetanus toxoid immunization, and every home delivery should trigger community health worker follow-up for birth-dose vaccination. Missed opportunities at facilities : With a 57% facility delivery rate (approximately 19,000 births annually), each facility birth represents a clinical opportunity to prevent multiple vaccine-preventable diseases. Same-day BCG and HepB birth doses should be guaranteed, with registration in tracking systems and scheduled follow-ups. Community transmission risk : Zero-dose children contribute to community susceptibility, increasing the transmission risk for vaccine-preventable diseases, including pertussis and measles. The increase in districts with > 90% MCV1 coverage (from 38% to 71%) reduced this risk but left 29% of districts below the herd immunity threshold. Comparison with regional context Within the WHO South-East Asia Region, Timor-Leste's performance mirrors both regional achievements and challenges. The GBD 2023 documented that the COVID-19 pandemic caused sharp declines in vaccination coverage across Southeast Asia since 2020, with incomplete recovery as of 2023. [ 3 ]. Timor-Leste's ability to recover and improve significantly—reducing zero-dose children by 22% in one year—positions the country as a regional example of effective post-pandemic recovery. Indonesia, the region's largest country and one of the eight nations accounting for > 50% of global zero-dose children, faces similar challenges of geographic disparities and maternal healthcare access [ 3 ]. Timor-Leste's elimination of high-dropout districts offers lessons for subnational targeting that could inform regional immunization strategy. Persistent challenges and policy implications Despite this progress, Timor-Leste's 9.8% zero-dose prevalence still exceeds the global pooled estimate of 7.5% from 82 LMICs and the 7.0% average for lower middle-income countries [ 8 ]. The predominant risk factors remain aligned with global patterns, including limited access to maternal health care. With 43% of births occurring at home without skilled attendance and 15% of neonates unprotected against tetanus at birth, Timor-Leste's remaining zero-dose children are disproportionately concentrated among families with the weakest links to the health system. Several implications emerge for immunization policy and programming in Timor-Leste and comparable Southeast Asian countries. First, persistent home delivery rates must be addressed. With skilled birth attendance stagnant at 57%, the 43% of births occurring at home remain the single largest risk factor for zero-dose status. Strategies should include strengthening community health worker outreach (such as Timor-Leste's SISCa program), engaging traditional birth attendants as immunization promoters, and ensuring that postnatal home visits include vaccination screening and referral [ 17 ]. Second, facility deliveries should guarantee successful immunization. Every facility delivery should result in same-day BCG and HepB birth doses, registration in facility-based tracking systems, and scheduled follow-up appointments. Systematic reviews of integrated service delivery have shown that the co-location of services and the provision of extra services by immunization staff can improve outcomes when implementation considerations are adequately addressed [ 10 ]. Third, the 15% neonatal tetanus protection gap must be addressed in the future. Strengthening antenatal care delivery of tetanus toxoid immunization would protect these infants while creating opportunities for antenatal education on childhood immunization. Limitations This study had several limitations. First, as a retrospective analysis of aggregate data, this study cannot establish causal relationships, a limitation acknowledged given the IJID Regions' preference for prospective designs. Second, the absence of individual-level survey data for Timor-Leste prevents the direct estimation of household-level risk factors using multivariate regression. Third, the zero-dose estimate relies on the WUENIC methodology, which combines administrative data with survey estimates and may be subject to reporting biases. Fourth, we could not disaggregate zero-dose children by wealth, education, disability status, or other sociodemographic characteristics, a recognized gap in the literature on immunization equity for vulnerable populations [ 18 ]. Fifth, our comparison with global findings was descriptive only, as we did not perform independent statistical analyses; global odds ratios are presented solely for contextual reference. Sixth, the 57% skilled birth attendance figure does not capture the quality of care or whether facilities providing delivery services also provide immunization. Strengths and future research directions Key strengths include the use of the most recent (2023) data, application of standardized IA2030 IG 2.1 methodology, contextualization of findings within GBD 2023 global estimates, and provision of locally relevant interpretations by Timorese researchers. These findings generate specific hypotheses for future prospective research aligned with the IJID Regions' preference for rigorous study designs: A prospective cohort study tracking immunization status from antenatal care through age 24 months to identify critical dropout points A cluster-randomized trial comparing integrated maternal-child health service delivery models versus standard care in rural Timor-Leste Implementation science research evaluating community health worker interventions for reaching home-delivery populations Conclusions Timor-Leste has made remarkable progress in reducing the number of zero-dose children, demonstrating that the IA2030 target of a 50% reduction by 2030 is achievable with sustained commitment. The 22% reduction in a single year and elimination of high-dropout districts show that targeted microplanning and district accountability are effective strategies to reduce dropout rates. However, the prevalence of 9.8% still exceeds the global average, with access to maternal healthcare remaining the predominant risk factor. Achieving universal immunization coverage requires strengthening the integration of maternal and child health services, converting facility deliveries into guaranteed vaccinations, and reaching the 43% of families who deliver at home. As Southeast Asia commemorates 50 years of the EPI, Timor-Leste's progress exemplifies both the achievements and remaining challenges in the quest for universal immunization coverage and vaccine-preventable disease control [ 4 ]. CLINICAL IMPLICATIONS For clinicians : Every clinical contact with pregnant women and infants is an opportunity to prevent vaccine-preventable diseases. Screen for immunization status, provide tetanus toxoid during antenatal care, and ensure birth-dose vaccination at facility deliveries. For public health practitioners : Target the 43% of home deliveries through community health worker programs. The 57% facility delivery rate was converted into guaranteed immunization through system strengthening. For policymakers : Integrate maternal and child health services with immunization programs. Maintaining district-level accountability and microplanning that eliminates high-dropout districts. For researchers : Design prospective studies evaluating integrated service delivery models and community-based interventions to reach zero-dose children. Declarations CONTRIBUTORS MDSM conceived the study, designed the methodology, analyzed the data, and wrote the first draft of the manuscript. FDNM contributed to the data acquisition, verification, and interpretation. NGS contributed to the data analysis and interpretation. All authors reviewed and edited subsequent drafts, had full access to all data in the study, and had the final responsibility for the decision to submit for publication. MDSM and FDNM accessed and verified the underlying data of the study. DECLARATION OF INTERESTS The authors declare no conflict of interest. DECLARATION OF GENERATIVE AI AND AI-ASSISTED TECHNOLOGIES IN THE MANUSCRIPT PREPARATION PROCESS During the preparation of this manuscript, the authors used Paperpal AI for assistance with language editing, grammar correction, and formatting according to journal requirements. After using this tool, the authors thoroughly reviewed and edited the content as needed, verified all data and references for accuracy, and took full responsibility for the content of the published article. The AI tool was used solely to enhance the language readability and ensure compliance with the IJID Regions formatting guidelines. All intellectual contributions, data analyses, interpretations of findings, and clinical implications presented in this manuscript are the original work of the authors. No AI tool was used to generate or interpret the data, draw conclusions, or replace human critical thinking and expertise. DATA SHARING All data used in this study are publicly available from the sources cited. The Timor-Leste EPI Factsheet 2024 is available from the WHO Regional Office for Southeast Asia. The WUENIC data are available from the WHO Global Health Observatory. No additional data were generated during this study. ACKNOWLEDGMENTS None. SUPPLEMENTARY MATERIAL STROBE Statement checklist for cohort studies (available online). Funding Source This study received no funding. The corresponding author had full access to all data and had the final responsibility for the decision to submit for publication. References Bustreo F, Okwo-Bele JM, Kamara L (2015) World Health Organization perspectives on the contribution of the Global Alliance for Vaccines and Immunization on reducing child mortality. Arch Dis Child 100(Suppl 1):S34–S37 World Health Organization (2021) Immunization Agenda 2030: a global strategy to leave no one behind. World Health Organization, Geneva GBD 2023 Vaccine Coverage Collaborators (2025) Global, regional, and national trends in routine childhood vaccination coverage from 1980 to 2023 with forecasts to 2030: a systematic analysis for the Global Burden of Disease Study 2023. Lancet 406:235–260 Mirza I, Lemango ET, Lindstrand A (2025) Expanded Programme on Immunization (EPI): a legacy of 50 years and the road ahead. Vaccines 13:606 Marti M, Nohynek H, Duclos P, O'Brien KL, Hombach J (2024) The Strategic Advisory Group of Experts (SAGE) on immunization—past, present and future. Vaccines 12:1402 Ministry of Health Timor-Leste (2020) Health sector strategic plan 2020–2030. Ministry of Health, Dili Jones CE (2023) Routine vaccination coverage—worldwide, MMWR Morb Mortal Wkly Rep. 2024;73:705 – 10 Farrenkopf BA, Zhou X, Shearer JC et al (2023) Understanding household-level risk factors for zero dose immunization in 82 low- and middle-income countries. PLoS ONE 18:e0287459 World Health Organization (2018) Working together: an integration resource guide for immunization services throughout the life course. World Health Organization, Geneva Shah MP, Morgan CJ, Beeson JG et al (2024) Integrated approaches for the delivery of maternal and child health services with childhood immunization programs in low- and middle-income countries: systematic review update 2011–2020. Vaccines 12:1313 World Health Organization Regional Office for South-East Asia (2024) Expanded programme on immunization (EPI) factsheet 2024: Timor-Leste. WHO-SEARO, New Delhi World Health Organization (2024) WHO/UNICEF estimates of national immunization coverage (WUENIC) 2023 revision. World Health Organization, Geneva UNICEF, WHO (2022) WHO/UNICEF estimates of national immunization coverage (WUENIC) 2021 revision. World Health Organization, Geneva Henaff L, Dumolard L, Bura V et al (2025) Strengthening National Immunization Technical Advisory Groups: twelve years of progress (2012–2023). Vaccines 13:80 World Health Organization (2026) IA2030 IG 2.1: number of zero dose children. World Health Organization, Geneva Salisbury N, Hossain I, Oskouipour P et al (2024) Routine immunization microplanning challenges and opportunities in low- and middle-income countries: a mixed-method landscape analysis. Vaccines 12:1370 Vaccher S, Laman M, Danchin M, Angrisano F, Morgan C (2025) Missed measles immunisations places individuals and communities at risk: the equity argument for including measles in under-immunised definitions. Vaccines 13:108 Musuka G, Cuadros DF, Miller FDW et al (2025) Immunization coverage, equity, and access for children with disabilities: a scoping review of challenges, strategies, and lessons learned to reduce the number of zero-dose children. Vaccines 13:377 Additional Declarations The authors declare no competing interests. Supplementary Files HIGHLIGHTSFORREVIEWFILE.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9011187","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":599390672,"identity":"5bf0e7ee-4727-4ccd-bdc0-adf4901f1451","order_by":0,"name":"Mariano da Silva Marques","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0UlEQVRIiWNgGAWjYBADOzb2BiBlYEG8lmQ+ngMgLRLEa2GcJ5EAoonQotvAvE3iw586ZjbJ51c3/CiQYOBv707Aq8XsAFuZ5My2w3xs0jllN3uADpM4c3YDAS08ZtK8DQeYgVrSbvAAtRhI5BKh5c+fOsY2yTNpN/8QrYWBjZmxTYL92G3ibDnMVmzZ23Y4mY0nh+22jIEED2G/HG/eeOPHnzo7+fbjz26++WMjx9/ei18LAzODAZTFA2bw4FcOATAt7A+IUT0KRsEoGAUjEAAAB41BK6VQXc4AAAAASUVORK5CYII=","orcid":"https://orcid.org/0009-0003-9751-3477","institution":"Instituto Nacional de Saude Publica, Timor-Leste","correspondingAuthor":true,"prefix":"","firstName":"Mariano","middleName":"da Silva","lastName":"Marques","suffix":""},{"id":599390673,"identity":"6fe74b32-def9-4cb7-b691-09ed490eae8a","order_by":1,"name":"Filipe de Neri Machado","email":"","orcid":"https://orcid.org/0009-0004-3833-3799","institution":"Instituto Nacional de Saude Publica, Timor-Leste","correspondingAuthor":false,"prefix":"","firstName":"Filipe","middleName":"de Neri","lastName":"Machado","suffix":""},{"id":599390674,"identity":"d2579674-6eba-4339-aa25-74182166642f","order_by":2,"name":"Noel Gama Soares","email":"","orcid":"https://orcid.org/0009-0008-8660-4863","institution":"Instituto Nacional de Saude Publica, Timor-Leste","correspondingAuthor":false,"prefix":"","firstName":"Noel","middleName":"Gama","lastName":"Soares","suffix":""}],"badges":[],"createdAt":"2026-03-02 14:21:29","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-9011187/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9011187/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104178659,"identity":"de13f4c8-7b6b-406f-8e26-e55b78b7f9a9","added_by":"auto","created_at":"2026-03-08 16:58:33","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":59030,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDistrict-level DTP1-to-DTP3 dropout rates in Timor-Leste, 2022 vs 2023\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eData represent the number of districts. DTP=diphtheria-tetanus-pertussis.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-9011187/v1/8c53119fbd603b727d394a78.png"},{"id":104404645,"identity":"58868665-b990-4d2e-af87-b6b5a445d459","added_by":"auto","created_at":"2026-03-11 12:20:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":826604,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9011187/v1/fbc8bd54-3d50-4edd-9df7-c5b173c51c86.pdf"},{"id":104178660,"identity":"7c644002-0332-4fd6-8ecc-16cdf949e328","added_by":"auto","created_at":"2026-03-08 16:58:33","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":92546,"visible":true,"origin":"","legend":"","description":"","filename":"HIGHLIGHTSFORREVIEWFILE.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9011187/v1/15ceaf4bb44f8877b46acd60.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eZero-dose Children in Timor-leste: Household-level Risk Factors and Implications for the Immunization Agenda 2030\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eRoutine immunization prevents 2\u0026ndash;3\u0026nbsp;million deaths annually [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]; however, zero-dose children\u0026mdash;those who have not received the first dose of diphtheria-tetanus-pertussis (DTP)-containing vaccines \u0026mdash;remain a critical challenge for the Immunization Agenda 2030 (IA2030) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Vaccine-preventable diseases continue to cause significant morbidity and mortality in Southeast Asia, with DTP1-zero-dose children susceptible to pertussis, diphtheria, and tetanus, the latter being particularly relevant where maternal and neonatal tetanus protection gaps persist [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Therefore, understanding zero-dose epidemiology is essential for clinical infectious disease control and public health practices.\u003c/p\u003e \u003cp\u003eGlobally, an estimated 15.7\u0026nbsp;million children were zero-dose in 2023, with the majority concentrated in low- and middle-income countries (LMICs) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The Global Burden of Disease Study 2023 documented that the COVID-19 pandemic caused sharp declines in vaccination coverage across all regions since 2020, with incomplete recovery as of 2023 [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. As the world commemorates 50 years of the Expanded Programme on Immunization (EPI), understanding the progress and persistent challenges in diverse settings is essential [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTimor-Leste, a Southeast Asian nation with 1.34\u0026nbsp;million people, has maintained its EPI since 1978 [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The country faces the typical challenges of a post-conflict, lower-middle-income setting: mountainous terrain, a dispersed population, and health system infrastructure that is still under development. Despite these challenges, national immunization coverage has steadily improved, although sub-national disparities persist [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe IA2030 sets an ambitious target of a 50% reduction in zero-dose children by 2030, compared to 2019 baseline levels [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. To achieve this, countries must accelerate progress, identify the remaining barriers, and implement evidence-based strategies tailored to local contexts. A multi-country analysis of 82 LMICs identified household-level risk factors for zero-dose status, including limited maternal healthcare access, low maternal education, household poverty, and geographic remoteness [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, no study has specifically examined zero-dose epidemiology in Timor-Leste or assessed progress toward the IA2030 targets using standardized methodologies.\u003c/p\u003e \u003cp\u003eThe integration of maternal and child health services with routine immunization has been identified as a key strategy for improving coverage and equity [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Evidence from systematic reviews indicates that integrated service delivery can improve outcomes for linked services while maintaining or improving immunization coverage when implementation considerations are adequately addressed [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe aimed to estimate zero-dose prevalence in Timor-Leste using 2023 data, identify household-level risk factors by comparing national indicators with global patterns, and assess progress toward the IA2030 50% reduction target.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and rationale\u003c/h2\u003e \u003cp\u003eThis retrospective cohort study analyzed publicly available national immunization data from Timor-Leste (2022\u0026ndash;2023) and descriptively compared the findings with global estimates from multi-country analyses and the Global Burden of Disease Study 2023. While IJID Regions preferentially publishes prospective randomized controlled trials, this retrospective study provides essential epidemiological evidence from a lower-middle-income country, where such data are currently scarce. This study adhered to the (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for observational research (see Supplementary Material).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData sources\u003c/h3\u003e\n\u003cp\u003eWe analyzed data from the Timor-Leste Expanded Programme on Immunization (EPI) Factsheet 2024, published by the WHO Regional Office for South-East Asia, which provides national immunization data, health system indicators, and district-level coverage estimates for 2023 [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The WHO/UNICEF Estimates of National Immunization Coverage (WUENIC) 2023 provided validated national coverage estimates for DTP1 and other antigens [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFor global comparison, we utilized findings from (i) a multi-country analysis of 82 LMICs examining household-level risk factors for zero-dose immunization using Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) data spanning 2011\u0026ndash;2020 [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], and (ii) the GBD 2023 Vaccine Coverage Collaborators study, which provided global, regional, and national estimates of routine childhood vaccine coverage from 1980 to 2023 with forecasts to 2030 for 204 countries and territories [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. We also incorporated insights from the recent literature commemorating 50 years of the EPI [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAs this study used only publicly available aggregate data, informed consent was not applicable, and ethical approval was not required.\u003c/p\u003e\n\u003ch3\u003eProcedures\u003c/h3\u003e\n\u003cp\u003eFollowing the IA2030 IG 2.1 standards, zero-dose children were defined as those who did not receive the first dose of a DTP-containing vaccine [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The number of zero-dose children was calculated as follows:\u003c/p\u003e\n\u003ch3\u003eZero-dose children = Estimated surviving infants – Number of children receiving DTP1\u003c/h3\u003e\n\u003cp\u003eThe estimated number of surviving infants was derived from the United Nations Population Division birth cohort estimates, and DTP1 vaccination data were obtained from the WUENIC. For Timor-Leste, we utilized the published estimate of 3254 zero-dose children from the EPI Factsheet 2024, which applied this methodology to the 2023 data [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe extracted Timor-Leste indicators corresponding to the risk factors identified in the global multi-country analysis and GBD 2023, organized into five domains: maternal healthcare access (skilled birth attendance and neonatal tetanus protection), health system characteristics (district-level coverage, dropout rates, microplanning status, and new vaccine introductions), demographic context (birth cohort), and vaccine-preventable disease burden.\u003c/p\u003e \u003cp\u003eGlobal comparison data included odds ratios (OR) with 95% confidence intervals (CIs) from multivariate logistic regression models [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] and GBD 2023 estimates of coverage trends, zero-dose counts, and forecasts [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. These are presented for descriptive comparison only, as our study did not perform an independent multivariate analysis.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was zero-dose prevalence (proportion of the annual birth cohort receiving no DTP1) in Timor-Leste in 2023. The secondary outcomes included (i) change in zero-dose prevalence from 2022 to 2023, (ii) district-level immunization performance indicators (DTP1-to-DTP3 dropout rates, MCV1, and MCV2 coverage), (iii) maternal healthcare access indicators (skilled birth attendance and neonatal tetanus protection), and (iv) descriptive comparison of Timor-Leste indicators with global risk factor patterns.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThis study used only descriptive statistics. Zero-dose prevalence was calculated as a simple proportion: the number of zero-dose children divided by the total birth cohort, expressed as a percentage. Changes between 2022 and 2023 were calculated as absolute and relative percentage differences.\u003c/p\u003e \u003cp\u003eDistrict-level data are presented as counts and percentages to show the number and proportion of districts that meet specific performance thresholds (e.g., \u0026gt;\u0026thinsp;10% dropout rate, \u0026gt;\u0026thinsp;90% coverage). Changes between the years were described narratively.\u003c/p\u003e \u003cp\u003eTo compare with global findings, we qualitatively assessed Timor-Leste's indicators against global risk factor patterns and GBD trends. Global odds ratios from the multi-country analysis [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] are presented alongside Timor-Leste's corresponding indicators to facilitate descriptive comparison. These odds ratios were not calculated from Timor-Leste data but are shown to contextualize local findings within established global patterns.\u003c/p\u003e \u003cp\u003eAll data are presented as numbers, percentages, or published odds ratios with 95% confidence intervals from the source literature. No inferential statistical tests were conducted. All analyses were performed using Microsoft Excel (version 16.8).\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eIn 2023, Timor-Leste had an estimated 33,260 live births, an increase from 31,832 in 2022 (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Applying the IA2030 IG 2.1 methodology, the country had 3254 zero-dose children, representing 9.8% of the birth cohort. This marks a substantial improvement from 2022, when 4184 children (13.1% of the birth cohort) were zero-dose, a 22% reduction in absolute numbers and a 3.3 percentage point reduction in prevalence within a single year.\u003c/p\u003e \u003cp\u003eAt 9.8%, Timor-Leste's zero-dose prevalence falls between the average for low-income (10.4%) and lower-middle-income countries (7.0%), having moved closer to the latter [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The 3254 zero-dose children represent 0.02% of the global 15.7\u0026nbsp;million zero-dose burden, proportionate to the country's population size [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics and immunization indicators for Timor-Leste (2022\u0026ndash;2023)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2022\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePopulation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLive births\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31,832\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33,260\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZero-dose children\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4184 (13.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3254 (9.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMaternal healthcare access\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSkilled birth attendance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHome deliveries\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal tetanus protection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal tetanus unprotected\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDistrict-level performance\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistricts with \u0026gt;\u0026thinsp;10% DTP1\u0026ndash;DTP3 dropout\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (38%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistricts with updated micro-plans\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (93%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistricts with \u0026gt;\u0026thinsp;90% MCV1 coverage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (38%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (71%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistricts with \u0026gt;\u0026thinsp;90% MCV2 coverage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (31%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (71%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNew vaccine introductions\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePneumococcal conjugate vaccine (PCV)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNot introduced\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIntroduced Jan 2023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eData are presented as n, n (%), or percentages. DTP=diphtheria-tetanus-pertussis. MCV: measles-containing vaccine. Sources: Timor-Leste EPI Factsheets, 2023, and 2024 [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe global multi-country analysis identified a lack of maternal healthcare access as the strongest predictor of zero-dose status (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Timor-Leste's 2023 indicators show modest improvements but persistent challenges. Skilled birth attendance remained at 57%, unchanged from 2022, indicating that 43% of deliveries still occurred at home without skilled care [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Globally, children delivered at home had nearly twice the odds of being zero-dose compared to those delivered at facilities (OR 1.87; 95% CI: 1.70\u0026ndash;2.05) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNeonatal tetanus protection improved to 85% of neonates protected at birth (up from 83% in 2022); however, 15% remained unprotected [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Globally, children whose mothers received no tetanus injections had three times the odds of being zero-dose (OR 3.00; 95% CI: 2.72\u0026ndash;3.30) compared with those whose mothers received\u0026thinsp;\u0026ge;\u0026thinsp;2 injections [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDescriptive comparison of Timor-Leste maternal healthcare indicators with global risk factors\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndicator\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTimor-Leste 2023\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGlobal odds ratio (95% CI)*\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHome delivery (vs facility)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.87 (1.70\u0026ndash;2.05)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo maternal tetanus protection (vs\u0026thinsp;\u0026ge;\u0026thinsp;2 doses)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.00 (2.72\u0026ndash;3.30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e*Odds ratios from multivariate logistic regression models in 82 LMICs (Farrenkopf et al., 2023) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. These are presented for descriptive comparison only and were not calculated using Timor-Leste data.\u003c/p\u003e \u003cp\u003eThe most striking improvement in Timor-Leste's immunization system from 2022 to 2023 was the complete elimination of districts with high dropout rates (Fig.\u0026nbsp;1). In 2023, zero districts had\u0026thinsp;\u0026gt;\u0026thinsp;10% DTP1-to-DTP3 dropout, compared with five districts (38%) in 2022\u0026mdash;a reduction from five to zero districts.\u003c/p\u003e \u003cp\u003eThis achievement demonstrates the effectiveness of targeted microplanning [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Additional health system strengthening achievements included updated micro-plans now covering all 14 districts (100%, up from 13 in 2022), districts achieving\u0026thinsp;\u0026gt;\u0026thinsp;90% MCV1 coverage increasing from five (38%) to ten (71%), and districts achieving\u0026thinsp;\u0026gt;\u0026thinsp;90% MCV2 coverage increasing from four (31%) to ten (71%) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cb\u003eFigure 1: District-level DTP1-to-DTP3 dropout rates in Timor-Leste, 2022 vs 2023\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eData represent the number of districts. DTP=diphtheria-tetanus-pertussis.\u003c/em\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis analysis revealed that Timor-Leste achieved remarkable progress in reducing its zero-dose burden, from 4184 children (13.1% of the birth cohort) in 2022 to 3254 children (9.8%) in 2023\u0026mdash;a 22% reduction in a single year. This exceeds the annualized progress needed to achieve the IA2030 50% reduction target by 2030, demonstrating that focused health system strengthening can yield rapid results in Southeast Asia.\u003c/p\u003e \u003cp\u003eThe most dramatic improvement was the complete elimination of districts with high dropout rates\u0026mdash;from five districts (38%) with \u0026gt;\u0026thinsp;10% DTP1-to-DTP3 dropout in 2022 to none in 2023. This achievement, alongside substantial increases in districts achieving\u0026thinsp;\u0026gt;\u0026thinsp;90% MCV1 and MCV2 coverage, demonstrates the effectiveness of targeted microplanning and district-level accountability\u0026mdash;approaches that other Southeast Asian countries with similar health system structures could adopt [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eClinical implications\u003c/h2\u003e \u003cp\u003eThese findings have direct clinical relevance for infectious disease control in Timor-Leste and similar settings.\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eNeonatal tetanus risk\u003c/b\u003e: Approximately 15% of neonates (approximately 5000 infants annually) unprotected against tetanus at birth remain vulnerable to this preventable fatal disease. Every antenatal care contact should ensure tetanus toxoid immunization, and every home delivery should trigger community health worker follow-up for birth-dose vaccination.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eMissed opportunities at facilities\u003c/b\u003e: With a 57% facility delivery rate (approximately 19,000 births annually), each facility birth represents a clinical opportunity to prevent multiple vaccine-preventable diseases. Same-day BCG and HepB birth doses should be guaranteed, with registration in tracking systems and scheduled follow-ups.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eCommunity transmission risk\u003c/b\u003e: Zero-dose children contribute to community susceptibility, increasing the transmission risk for vaccine-preventable diseases, including pertussis and measles. The increase in districts with \u0026gt;\u0026thinsp;90% MCV1 coverage (from 38% to 71%) reduced this risk but left 29% of districts below the herd immunity threshold.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eComparison with regional context\u003c/h2\u003e \u003cp\u003eWithin the WHO South-East Asia Region, Timor-Leste's performance mirrors both regional achievements and challenges. The GBD 2023 documented that the COVID-19 pandemic caused sharp declines in vaccination coverage across Southeast Asia since 2020, with incomplete recovery as of 2023. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Timor-Leste's ability to recover and improve significantly\u0026mdash;reducing zero-dose children by 22% in one year\u0026mdash;positions the country as a regional example of effective post-pandemic recovery.\u003c/p\u003e \u003cp\u003eIndonesia, the region's largest country and one of the eight nations accounting for \u0026gt;\u0026thinsp;50% of global zero-dose children, faces similar challenges of geographic disparities and maternal healthcare access [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Timor-Leste's elimination of high-dropout districts offers lessons for subnational targeting that could inform regional immunization strategy.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePersistent challenges and policy implications\u003c/h2\u003e \u003cp\u003eDespite this progress, Timor-Leste's 9.8% zero-dose prevalence still exceeds the global pooled estimate of 7.5% from 82 LMICs and the 7.0% average for lower middle-income countries [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The predominant risk factors remain aligned with global patterns, including limited access to maternal health care. With 43% of births occurring at home without skilled attendance and 15% of neonates unprotected against tetanus at birth, Timor-Leste's remaining zero-dose children are disproportionately concentrated among families with the weakest links to the health system.\u003c/p\u003e \u003cp\u003eSeveral implications emerge for immunization policy and programming in Timor-Leste and comparable Southeast Asian countries.\u003c/p\u003e \u003cp\u003eFirst, persistent home delivery rates must be addressed. With skilled birth attendance stagnant at 57%, the 43% of births occurring at home remain the single largest risk factor for zero-dose status. Strategies should include strengthening community health worker outreach (such as Timor-Leste's SISCa program), engaging traditional birth attendants as immunization promoters, and ensuring that postnatal home visits include vaccination screening and referral [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSecond, facility deliveries should guarantee successful immunization. Every facility delivery should result in same-day BCG and HepB birth doses, registration in facility-based tracking systems, and scheduled follow-up appointments. Systematic reviews of integrated service delivery have shown that the co-location of services and the provision of extra services by immunization staff can improve outcomes when implementation considerations are adequately addressed [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThird, the 15% neonatal tetanus protection gap must be addressed in the future. Strengthening antenatal care delivery of tetanus toxoid immunization would protect these infants while creating opportunities for antenatal education on childhood immunization.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThis study had several limitations. First, as a retrospective analysis of aggregate data, this study cannot establish causal relationships, a limitation acknowledged given the IJID Regions' preference for prospective designs. Second, the absence of individual-level survey data for Timor-Leste prevents the direct estimation of household-level risk factors using multivariate regression. Third, the zero-dose estimate relies on the WUENIC methodology, which combines administrative data with survey estimates and may be subject to reporting biases. Fourth, we could not disaggregate zero-dose children by wealth, education, disability status, or other sociodemographic characteristics, a recognized gap in the literature on immunization equity for vulnerable populations [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Fifth, our comparison with global findings was descriptive only, as we did not perform independent statistical analyses; global odds ratios are presented solely for contextual reference. Sixth, the 57% skilled birth attendance figure does not capture the quality of care or whether facilities providing delivery services also provide immunization.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eStrengths and future research directions\u003c/h2\u003e \u003cp\u003eKey strengths include the use of the most recent (2023) data, application of standardized IA2030 IG 2.1 methodology, contextualization of findings within GBD 2023 global estimates, and provision of locally relevant interpretations by Timorese researchers.\u003c/p\u003e \u003cp\u003eThese findings generate specific hypotheses for future prospective research aligned with the IJID Regions' preference for rigorous study designs:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eA prospective cohort study tracking immunization status from antenatal care through age 24 months to identify critical dropout points\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eA cluster-randomized trial comparing integrated maternal-child health service delivery models versus standard care in rural Timor-Leste\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eImplementation science research evaluating community health worker interventions for reaching home-delivery populations\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eTimor-Leste has made remarkable progress in reducing the number of zero-dose children, demonstrating that the IA2030 target of a 50% reduction by 2030 is achievable with sustained commitment. The 22% reduction in a single year and elimination of high-dropout districts show that targeted microplanning and district accountability are effective strategies to reduce dropout rates. However, the prevalence of 9.8% still exceeds the global average, with access to maternal healthcare remaining the predominant risk factor. Achieving universal immunization coverage requires strengthening the integration of maternal and child health services, converting facility deliveries into guaranteed vaccinations, and reaching the 43% of families who deliver at home. As Southeast Asia commemorates 50 years of the EPI, Timor-Leste's progress exemplifies both the achievements and remaining challenges in the quest for universal immunization coverage and vaccine-preventable disease control [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eCLINICAL IMPLICATIONS\u003c/h2\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eFor clinicians\u003c/b\u003e: Every clinical contact with pregnant women and infants is an opportunity to prevent vaccine-preventable diseases. Screen for immunization status, provide tetanus toxoid during antenatal care, and ensure birth-dose vaccination at facility deliveries.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eFor public health practitioners\u003c/b\u003e: Target the 43% of home deliveries through community health worker programs. The 57% facility delivery rate was converted into guaranteed immunization through system strengthening.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eFor policymakers\u003c/b\u003e: Integrate maternal and child health services with immunization programs. Maintaining district-level accountability and microplanning that eliminates high-dropout districts.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eFor researchers\u003c/b\u003e: Design prospective studies evaluating integrated service delivery models and community-based interventions to reach zero-dose children.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCONTRIBUTORS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMDSM conceived the study, designed the methodology, analyzed the data, and wrote the first draft of the manuscript. FDNM contributed to the data acquisition, verification, and interpretation. NGS contributed to the data analysis and interpretation. All authors reviewed and edited subsequent drafts, had full access to all data in the study, and had the final responsibility for the decision to submit for publication. MDSM and FDNM accessed and verified the underlying data of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDECLARATION OF INTERESTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDECLARATION OF GENERATIVE AI AND AI-ASSISTED TECHNOLOGIES IN THE MANUSCRIPT PREPARATION PROCESS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring the preparation of this manuscript, the authors used Paperpal AI for assistance with language editing, grammar correction, and formatting according to journal requirements. After using this tool, the authors thoroughly reviewed and edited the content as needed, verified all data and references for accuracy, and took full responsibility for the content of the published article.\u003c/p\u003e\n\u003cp\u003eThe AI tool was used solely to enhance the language readability and ensure compliance with the IJID Regions formatting guidelines. All intellectual contributions, data analyses, interpretations of findings, and clinical implications presented in this manuscript are the original work of the authors. No AI tool was used to generate or interpret the data, draw conclusions, or replace human critical thinking and expertise.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDATA SHARING\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data used in this study are publicly available from the sources cited. The Timor-Leste EPI Factsheet 2024 is available from the WHO Regional Office for Southeast Asia. The WUENIC data are available from the WHO Global Health Observatory. No additional data were generated during this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSUPPLEMENTARY MATERIAL\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSTROBE Statement checklist for cohort studies (available online).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Source\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study received no funding. The corresponding author had full access to all data and had the final responsibility for the decision to submit for publication.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBustreo F, Okwo-Bele JM, Kamara L (2015) World Health Organization perspectives on the contribution of the Global Alliance for Vaccines and Immunization on reducing child mortality. Arch Dis Child 100(Suppl 1):S34\u0026ndash;S37\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Health Organization (2021) Immunization Agenda 2030: a global strategy to leave no one behind. World Health Organization, Geneva\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGBD 2023 Vaccine Coverage Collaborators (2025) Global, regional, and national trends in routine childhood vaccination coverage from 1980 to 2023 with forecasts to 2030: a systematic analysis for the Global Burden of Disease Study 2023. Lancet 406:235\u0026ndash;260\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMirza I, Lemango ET, Lindstrand A (2025) Expanded Programme on Immunization (EPI): a legacy of 50 years and the road ahead. Vaccines 13:606\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarti M, Nohynek H, Duclos P, O'Brien KL, Hombach J (2024) The Strategic Advisory Group of Experts (SAGE) on immunization\u0026mdash;past, present and future. Vaccines 12:1402\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMinistry of Health Timor-Leste (2020) Health sector strategic plan 2020\u0026ndash;2030. Ministry of Health, Dili\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJones CE (2023) Routine vaccination coverage\u0026mdash;worldwide, MMWR Morb Mortal Wkly Rep. 2024;73:705\u0026thinsp;\u0026ndash;\u0026thinsp;10\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFarrenkopf BA, Zhou X, Shearer JC et al (2023) Understanding household-level risk factors for zero dose immunization in 82 low- and middle-income countries. PLoS ONE 18:e0287459\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Health Organization (2018) Working together: an integration resource guide for immunization services throughout the life course. World Health Organization, Geneva\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShah MP, Morgan CJ, Beeson JG et al (2024) Integrated approaches for the delivery of maternal and child health services with childhood immunization programs in low- and middle-income countries: systematic review update 2011\u0026ndash;2020. Vaccines 12:1313\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Health Organization Regional Office for South-East Asia (2024) Expanded programme on immunization (EPI) factsheet 2024: Timor-Leste. WHO-SEARO, New Delhi\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Health Organization (2024) WHO/UNICEF estimates of national immunization coverage (WUENIC) 2023 revision. World Health Organization, Geneva\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUNICEF, WHO (2022) WHO/UNICEF estimates of national immunization coverage (WUENIC) 2021 revision. World Health Organization, Geneva\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHenaff L, Dumolard L, Bura V et al (2025) Strengthening National Immunization Technical Advisory Groups: twelve years of progress (2012\u0026ndash;2023). Vaccines 13:80\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Health Organization (2026) IA2030 IG 2.1: number of zero dose children. World Health Organization, Geneva\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSalisbury N, Hossain I, Oskouipour P et al (2024) Routine immunization microplanning challenges and opportunities in low- and middle-income countries: a mixed-method landscape analysis. Vaccines 12:1370\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVaccher S, Laman M, Danchin M, Angrisano F, Morgan C (2025) Missed measles immunisations places individuals and communities at risk: the equity argument for including measles in under-immunised definitions. Vaccines 13:108\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMusuka G, Cuadros DF, Miller FDW et al (2025) Immunization coverage, equity, and access for children with disabilities: a scoping review of challenges, strategies, and lessons learned to reduce the number of zero-dose children. Vaccines 13:377\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Zero-dose children, immunization coverage, Timor-Leste, maternal health, vaccine-preventable diseases, Southeast Asia, public health, clinical epidemiology","lastPublishedDoi":"10.21203/rs.3.rs-9011187/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9011187/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eTo estimate the prevalence of zero-dose children in Timor-Leste (2022\u0026ndash;2023), identify household-level risk factors, and assess progress toward Immunization Agenda 2030 (IA2030) targets.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective cohort study analyzed national immunization data from the Timor-Leste EPI Factsheet 2024 and WHO/UNICEF Estimates of National Immunization Coverage 2023. Zero-dose children were defined according to the IA2030 standards (no first dose of DTP-containing vaccine). The primary outcome was the zero-dose prevalence in the 2023 birth cohort. Indicators corresponding to risk factors from a multi-country analysis of 82 low- and middle-income countries were extracted and descriptively compared with global estimates from the Global Burden of Disease Study 2023. This study adhered to the STROBE guidelines for observational research.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn 2023, Timor-Leste had 33,260 live births and 3254 zero-dose children (9.8% of the birth cohort), a 22% reduction from 4184 (13.1%) in 2022. Neonatal tetanus protection improved to 85% (from 83%), with 15% unprotected\u0026mdash;a group with three times the odds of being zero-dose (OR 3.00; 95% CI: 2.72\u0026ndash;3.30). Skilled birth attendance was 57%, with 43% home deliveries\u0026mdash;a group with nearly twice the odds of being zero-dose (OR 1.87; 95% CI: 1.70\u0026ndash;2.05). All 14 districts (100%) now have updated micro-plans; zero districts show a\u0026thinsp;\u0026gt;\u0026thinsp;10% DTP1-to-DTP3 dropout rate, a complete elimination from five districts (38%) in 2022. The number of districts achieving\u0026thinsp;\u0026gt;\u0026thinsp;90% MCV1 coverage increased from five (38%) to ten (71%). The pneumococcal conjugate vaccine was introduced in January 2023.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eTimor-Leste's 22% zero-dose reduction demonstrates that targeted microplanning and district accountability are effective strategies for addressing zero-dose children. However, the prevalence of 9.8% exceeds the global average, with access to maternal healthcare remaining the predominant risk factor. Achieving IA2030s 50% reduction target requires integrating maternal-child health services with immunization programs and reaching 43% of families delivering at home. These findings generate hypotheses for future prospective studies on integrated service delivery models in Southeast Asia.\u003c/p\u003e","manuscriptTitle":"Zero-dose Children in Timor-leste: Household-level Risk Factors and Implications for the Immunization Agenda 2030","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-08 16:58:28","doi":"10.21203/rs.3.rs-9011187/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ddf5f0bd-1565-4e13-b7b4-cfbe6f5117e5","owner":[],"postedDate":"March 8th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":63827211,"name":"Epidemiology"}],"tags":[],"updatedAt":"2026-03-08T16:58:28+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-08 16:58:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9011187","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9011187","identity":"rs-9011187","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}