**6. What Is Needed to Sustainably Reach Zero-Dose Children?**

The Immunization Agenda 2030 and the supporting Gavi 2021–2025 Strategy [24] have ambitious targets to reduce the number of zero-dose children by 25% by 2025 and 50% by 2030 as compared to 2019 levels. These targets are even more challenging following two years of backsliding in vaccination coverage during 2020 and 2021, resulting in an additional 5 million zero-dose children globally. Moreover, coverage disruptions due to COVID-related lockdowns in 2020 illustrated that gains in coverage among zero-dose children can be tenuous, as 95% of the increase in the number of underimmunized children in low- and lower-middle-income countries was due to an increase in zero-dose children [8]. Population growth presents another challenge. The 15 countries that had a zero-dose prevalence of 30% or more in 2021, accounting for 40% of all zero-dose children globally, are expected to see nearly a 10% increase in their birth cohorts in 2030 as compared to 2021 [8,25]. Thus, it will be important to design robust programs to sustainably reach zero-dose children to reach 2030 targets while avoiding a "one size fits all" approach.

The Identify-Reach-Monitor-Measure-Advocate (IRMMA) framework offers a way to develop strategies to reach zero-dose children and missed communities [26]. The IRMMA framework involves diving deeper into subnational- and community-level inequities and identifying where unvaccinated children live and what barriers to immunization they face. As the majority of zero-dose children tend to live in countries still developing their health information systems, data triangulation is often necessary, though imperfect. Tailored strategies appropriate for the local context then need to be designed and operationalized to overcome identified barriers. For example, strategies to sustainably reach zero-dose children with immunization services in urban slums would be different from those for nomadic populations or for children in cross-border settings. This will often require addressing gender barriers to immunization, and opportunities for integrated service delivery should be sought out to increase efficiency and sustainability and to take advantage of opportunities opened by vaccination. Supplemental immunization activities should also include the purposeful linking of newly reached zero-dose children back to the routine

immunization system to ensure children go on to receive a full complement of vaccines. Such approaches also provide an opportunity to improve the data systems that enable the program's ability to monitor and measure progress. Robust monitoring and measurement are critical for refining delivery approaches and advocating for pro-equity investments. Political will is necessary to initiate and sustain the program and should be secured with a purposeful and inclusive advocacy approach.

Several data and evidence gaps also warrant attention. These include the need for investment in improved demographic and immunization coverage data to enable the identification and monitoring of efforts to reach zero-dose children. To the extent that data from household surveys are used to quantify the distribution and characteristics of zero-dose children, in cases where survey sampling frames are outdated, the picture may be incomplete, and new methods relying on gridded population survey sampling warrant consideration [27]. New innovative methods to overcome barriers to immunization should also be tried, documented, and shared. This should include information on program costs. While there are estimates of average immunization delivery costs [28], data on the incremental costs associated with expanding the reach of immunization systems are very limited [29] but likely higher for hard-to-reach populations [30].

#### **7. Impact of Reaching Zero-Dose Children and Missed Communities**

Reaching zero-dose children with a full complement of vaccines has the potential to substantially reduce child mortality, as nearly half of all vaccine-preventable deaths in LMICs occur among zero-dose children [26]. The impact of vaccination is potentially highest in zero-dose children, as they would otherwise be receiving no protection against vaccine-preventable diseases, be more susceptible to infection, and be the least likely to benefit from timely and high-quality treatment if they fall ill. In an analysis conducted by Gavi, the Vaccine Alliance based on data from the Vaccine Impact Modelling Consortium [2], immunizing zero-dose children would account for 53% of incremental impact in Gavisupported countries through routine immunization between 2021 and 2025, with the remainder of the impact coming from scaling up new childhood vaccines among nonzero-dose children and HPV vaccination (Figure 2) [31]. A modeling study focused on 41 LMICs from 2021 to 2030 estimated that vaccination among the two poorest wealth quintiles would avert 1.2 to 3.8 times as many future deaths per person vaccinated as compared to vaccination in the two wealthiest quintiles [32]. The same study projected that vaccination would avert 24 million cases of medical impoverishment in 2021–2030, with more than 40% of the impact occurring within the poorest wealth quintile for many vaccines. Sustainably reaching communities currently missed by immunization would also help prevent future outbreaks, including the resurgence of measles and polio, and remove the need for repeated disease-specific supplemental immunization activities.

The potential impact of reaching zero-dose children and their communities goes beyond vaccine-preventable diseases. Nearly one-third of all-cause under-five child deaths in LMICs occur in households with a zero-dose child [33], so they must be a focus as countries strive for the SDG child mortality target of fewer than 25 under-five deaths per 1000 live births. Achieving the SDGs thus requires addressing the multiple deprivations faced by zero-dose children and missed communities through strengthened and integrated primary care, as well as improved water, sanitation, nutrition, and education.

**Figure 2.** Potential incremental future deaths averted in 57 Gavi-supported countries through routine immunization, 2021–2025. Analysis based on Vaccine Impact Modeling Consortium impact ratios and immunization coverage as estimated in the WUENIC July 2021 release, ignoring the impact of maintaining coverage at 2020 levels and assuming Gavi 5.0 targets are met.

#### **8. Conclusions**

Zero-dose children account for over 70% of underimmunized children and must be reached with sustainable immunization services to meet ambitious targets for 2030. Identifying and understanding zero-dose children and missed communities will be key for designing effective interventions to reach them, which will often require tailoring to the local context. As zero-dose children and their families face multiple deprivations, with a high burden of morbidity and mortality, the potential for impact is great if they can be reached. By doing so, countries would be taking a key step toward ensuring no one is left behind in the Sustainable Development Goal era.

**Author Contributions:** Conceptualization, D.H. and A.G.; Analysis, D.H. and A.G.; writing—original draft preparation, D.H.; writing—review and editing, D.H. and A.G. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Data sharing not applicable.

**Acknowledgments:** The authors thank Taylor Holroyd, Joshua Lorin, and Todi Mengistu for data analysis support.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**


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