A Systematic Review of Vaccination Guidance for Humanitarian Responses

Delivering vaccines in humanitarian response requires rigourous and continuous analysis of evidence. This systematic review mapped the normative landscape of vaccination guidance on vaccine-preventable diseases in crisis-affected settings. Guidance published between 2000 and 2022 was searched for, in English and French, on websites of humanitarian actors, Google, and Bing. Peer-reviewed database searches were performed in Global Health and Embase. Reference lists of all included documents were screened. We disseminated an online survey to professionals working in vaccination delivery in humanitarian contexts. There was a total of 48 eligible guidance documents, including technical guidance (n = 17), descriptive guidance (n = 16), operational guidance (n = 11), evidence reviews (n = 3), and ethical guidance (n = 1). Most were World Health Organization documents (n = 21) targeting children under 5 years of age. Critical appraisal revealed insufficient inclusion of affected populations and limited rigour in guideline development. We found limited information on vaccines including, yellow fever, cholera, meningococcal, hepatitis A, and varicella, as well as human papilloma virus (HPV). There is a plethora of vaccination guidance for vaccine-preventable diseases in humanitarian contexts. However, gaps remain in the critical and systematic inclusion of evidence, inclusion of the concept of “zero-dose” children and affected populations, ethical guidance, and specific recommendations for HPV and non-universally recommended vaccines, which must be addressed.


Introduction
Vaccines are one of the most effective interventions to prevent morbidity and mortality [1].Currently, the World Health Organization (WHO) recommends that all countries achieve an overarching 95% coverage threshold for all routine vaccinations to achieve herd immunity levels [1].Despite this aim, global vaccination rates of children have declined.In 2021, the United Nations Children's Fund (UNICEF) reported that 25 million children did not receive lifesaving vaccinations [2].Routine vaccinations such as diphtheria-tetanuspertussis (DTP3) also saw a decline in global coverage to 81% in 2021 from 86% in 2020 [2].In 2020, 23 million children did not receive routine immunisation services, with up to 17 million of these children not receiving a single dose of a vaccine [3].Zero-dose children are defined as children who have not received any routine vaccines [3].GAVI has developed a programmatic definition for zero-dose as children who lack the first dose of diphtheria-tetanus-pertussis-containing vaccine (DTP1).Data collected prior to the coronavirus-2019 (COVID- 19) pandemic identified that more than 50% of deaths from vaccine-preventable diseases (VPDs) occur among zero-dose children [4].
It was predicted that more than 274 million individuals would require humanitarian assistance in 2022 [5].Crises including natural hazards such as floods or earthquakes, armed conflict, food insecurity, mass displacement, and epidemics present heightened risk for exposure to different types of VPDs.The Global Vaccine Alliance (GAVI) reports that nearly 50% of zero-dose children live in urban areas, remote communities, and in crisis-affected settings [4].Populations in crisis-affected settings carry the double burden of a higher risk of acquiring infectious diseases and reduced access to vaccinations.This double burden underscores the need for effective strategies for delivering vaccines to crisis-affected settings, including for zero-dose children.
Guidance documents can assist actors in responding to routine vaccination needs in crisis-affected settings using a standardised or evidence-based approach.Availability of guidance, coherence among multiple guidance sources, contextual relevance of guidance including language considerations, and credibility are identified as important considerations for guidance uptake among those responding to crisis-affected settings [6].Several studies have investigated vaccination interventions after implementation in crisis contexts [7,8].One scoping review assessed the availability of guidance targeting women's, newborns', children's and adolescents' health and nutrition in conflict settings and found seven documents specifically targeting immunisation [9].Documents lacked contextualised guidance and demonstrated a limited evidence base and limited input from affected populations during their creation.A systematic review delivering infectious disease interventions to women and children in conflict settings found significant variation in practice across NGO and UN infectious disease interventions, suggesting a lack of consensus among standard operating procedures and implementation guidance [10].To date, there has been no known review conducted to characterise the normative landscape of available guidance for vaccinating crisis-affected populations.Evaluating guideline quality and understanding the gaps and strengths of available vaccination guidance for crisis-affected settings is necessary to address gaps to support evidence-informed interventions.This review aims to systematically identify and assess available vaccination guidance for humanitarian contexts, and to identify gaps in the normative landscape for vaccination in crisis-affected settings.

Search Strategy
This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Table S1) [11].The search strategy comprised five information sources, described in detail in Table S2.
First, an anonymous survey seeking vaccination guidance was disseminated through online channels including LinkedIn, Twitter, and mailing lists between 15 July and 12 August 2022, with the aim of soliciting guidance from humanitarian health professionals involved in planning or delivering vaccination interventions in humanitarian contexts.
Second, a manual search of grey literature published in 76 agency websites was performed.Organisations (51/76, 67%) that were members of the Global Health Cluster (GHC), and other (25/76, 33%) organisations known to be involved in humanitarian responses were selected for this manual search.For websites that contained their own search function, the key terms 'vaccine', 'vaccination', 'humanitarian crises', 'conflict', 'disaster', and 'food crises' were searched to identify relevant documents.Organisational websites that did not have a search function were manually reviewed for tools, resources, and learning sections.Titles and executive summaries of documents found in these website sections were screened for inclusion criteria.
Third, searches using the key terms 'guidance', 'guideline', 'vaccine', 'vaccination', 'humanitarian crises', 'conflict', 'disaster', and 'food crises' were performed on Google and Bing search engines in English and French.The first 200 results of each search were screened.The first 200 results were chosen to be screened as Google and Bing search engine algorithms provide progressively less relevant results on subsequent search pages.
Fourthly, a search strategy for peer-reviewed publications was developed using freetext search keywords including the concepts of 'vaccination', 'vaccine preventable diseases', 'guidelines', and 'humanitarian emergency settings'.The first author (LA) searched the literature published in any language on Embase and Global Health between 1 January 2000 and 16 August 2022.
Finally, reference lists of documents that met inclusion criteria and the reference list of Aboubaker et al., were screened [9].Aboubaker et al. systematically reviewed evidence on guidance for sexual, reproductive, maternal, newborn, child, and adolescent health and nutrition in conflict settings to identify gaps in guidance published between 2008 and 2018 [9].

Inclusion and Exclusion Criteria
The inclusion criteria were as follows: (1) documents published between 1 January 2000 and 16 August 2022, (2) documents included vaccination guidance for humanitarian contexts, (3) vaccination guidance focused on at least one VPD including cholera, diphtheria, hepatitis A, hepatitis B, haemophilus influenzae type b, human papilloma virus (HPV), measles, meningococcal, mumps, pertussis, polio, pneumococcal, rotavirus, rubella, tetanus, tuberculosis, varicella, and yellow fever.Twelve of these VPDs were selected for inclusion as they are universally recommended by the WHO for all routine vaccination programmes [1].Six other non-universally WHO-recommended VPDs (yellow fever, cholera, meningococcal, mumps, hepatitis A, and varicella) were also included, as they feature an elevated risk in crisis-affected settings [12].(4) Guidance was published in either English or French.According to the Office of the United Nations High Commissioner for Human Rights (OHCHR), a humanitarian crisis is a singular event or a series of events that threaten the safety or wellbeing of a community or large group of people [13].Review-eligible typologies of crises included sudden mass displacement, armed conflict, food crises, natural or industrial disaster, complex humanitarian emergency, refugee camps, and epidemics.
The following studies were excluded: (1) older versions of an updated guidance document, (2) duplicates, (3) articles for which we were unable to retrieve full texts.
All eligible records were imported into EndNote X9 for de-duplication, screening, and data extraction.Data were then extracted into Microsoft Excel 2019.

Data Extraction
Two authors (LA and NSS) independently screened titles, abstracts, or executive summaries and excluded documents that did not meet inclusion criteria.The following metavariables were extracted from the included documents: title, first author or lead development organisation, year of publication, target user, guidance type, response type, intended beneficiary group, type of humanitarian context if specified, and type(s) of VPD(s) addressed in relation to vaccination guidance.If available, additional information was extracted for each VPD including recommended vaccine dosing, age group, modality of delivery, and whether the document referred to 'zero-dose' children or communities.The lead organisation for the development of the document was identified by the reviewer from the first page of the document or the acknowledgements section.The target users were classified as student, journalist, immunisation programme health communications team, advocacy group, health care professional, fieldworker, international non-governmental organisations (INGOs), and immunisation programme planner, manager, or policy makers based on the intended audience stated in the document.Fieldworkers could be clinical or non-clinical staff working in crisis-affected settings, whereas healthcare professionals were clinically focused.
The following definitions were used to classify guidance and were adapted from a similar review conducted by Aboubaker et al. [9] Ethical guidance: defined as normative guidance based on principles or conventions.The guidance may not be based on hard science or evidence but rather on a moral philosophical framework.

5.
Evidence reviews: defined as a synthesis of evidence or narrative review related to a specific aspect of vaccination.Guidance is typically given as a summary of findings.
Finally, documents were classified based on the crisis phase or scenarios they focused on including acute crisis, recovery, or host countries.Full definitions for terms guiding data extraction can be found in Table S4.

Critical Appraisal
Due to the heterogeneity of guidance documents identified, two forms of critical appraisal tools were used.To evaluate the quality of guidelines or documents the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool was used [14].To evaluate the quality of evidence reviews, the Scale for the Quality Assessment of Narrative Review Articles (SANRA) was used [15].

Data Analysis
Guidelines were classified according to guidance type, target users, response type, beneficiary groups, and crisis typology.A data extraction template (Table S5), created using Microsoft Excel 2019, was used.A narrative synthesis was conducted using tabulated data to systematically compare guideline characteristics for similarities and differences between classification categories.Document quality was incorporated into the overall assessment of the strength of a document's contribution to identified vaccine evidence.

Role of Funding Source
This work was funded by the Bill and Melinda Gates Foundation.The funder of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.

Characteristics of Included Studies
In total, 213 records were identified through peer-reviewed database searches, and an additional 880 records were identified from survey, search engine, reference lists, and manual website searches.After full-text screening, 48 documents (Figure 1) met inclusion criteria, of which 7 were peer-reviewed journal articles, and 41 were grey literature.Google and Bing search engines identified the greatest proportion of included documents (n = 20) followed by manual organisational website searches (n = 9), peer-reviewed database searches (n = 7), online survey (n = 3), and reviewing the reference list of included doc-uments (n = 8) and of Aboubaker et al. (n = 1) (Table S3).Two documents (4%) were in French and forty-six documents (96%) in English.Documents were published between 2004 and 2022.Almost two thirds, (60%, n = 29) of the documents were developed in the last five years (2017-2022).The concept of zero-dose was identified in 22% (n = 11) of the documents, with the majority (n = 10) of documents identifying the concept of zero-dose being published in 2020, 2021, and 2022 (Table 1).

Vaccination Delivery Recommendations
Twenty-three (48%) included documents provided specific guidance related to either dosing, age groups, or modality of vaccination delivery (Table 4).Mass vaccination was the primary modality for vaccination delivery (n = 11, 23%), followed by strengthening of routine vaccination services (n = 6, 13%).Only two documents (4%) included guidance for both mass and routine modalities.All twenty-three documents with vaccination delivery recommendations provided guidance on target age group (48%).Two documents (n = 2, 4%) targeted catch-up vaccination and varied dosing recommendations across multiple age groups.Similarly, some guidance documents focused solely on neonatal care and did not provide vaccination dosing recommendations beyond infancy (n = 2, 4%).A few documents (n = 3, 6%) included information on target age range for vaccination, but did not indicate the recommended number of doses.One document (2%) provided contextual dosing recommendations based on time following a sexual assault for tetanus and hepatitis b.

Critical Appraisal
For documents eligible for critical appraisal using the AGREE II tool (n = 45) (Table S7), the highest scores were in the domains of 'Scope and Purpose' (85%), and 'Clarity of Presentation' (71%).The lowest scores were in 'Rigour of Development' (41%) and 'Editorial Independence' (46%).Technical and operational guidelines scored similar, and descriptive documents scored lower overall than technical and operational documents (Table 5).Technical guidance scored higher in the domain of 'Applicability' (70%).The lowest scores on the 7-point Likert Scale were identified in the categories (Table S8) of 'A procedure for updating the guideline is provided' (1•5/7), 'competing interests of the guideline development group members have been recorded and addressed' (2•4/7), and 'criteria for selecting the evidence are clearly described' (2•4/7).Additionally, the category of "the views and preferences of the target population have been sought" was scored poorly (3•2/7) across documents.The highest scoring categories were 'the overall objective of the guideline are specifically described' (6•3/7), and 'the health question(s) covered by the guideline is (are) specifically described' (5•9/7).
For narrative review documents that were eligible for critical appraisal (Table 6) using the SANRA tool (n = 3), the highest scores (Table S9) were identified in the categories of 'Description of Literature Search' (100%) and 'Referencing' (100%).The items of 'Statement of Concrete Aims or Formulation of Questions' (67%) and 'Scientific Reasoning' (67%) scored lower.

Summary of Findings
To our knowledge, this is the first known review to assess the normative landscape of vaccination guidance for crisis-affected settings and to map document guidance for 18 VPDs.The review identified 48 documents that provided vaccination guidance for crisis-affected settings.There were gaps in vaccine guidance in the areas of ethics, HPV, and WHO routine vaccines not universally recommended, namely yellow fever, meningococcal, hepatitis A, mumps, and varicella.

Gaps in Guidance
Since 2000, there has been an increasing availability of evidence for effective vaccine interventions for most VPDs in crisis-affected settings [7].Despite guideline developers having a greater evidence base to inform their recommendations for vaccination, most guidance documents scored poorly in critical appraisal for the use of systematic search methods, evaluation of the current body of evidence, and reasoning for selecting evidence to inform recommendations [7].The limited reporting of methods and reasoning for the selection of evidence could be attributable to poor methodological reporting criteria for standardised organisational guideline development processes [62].Extensive transparency in the evidence selection assists in building credibility and trust towards guidance [6].Credibility is identified as an important consideration in supporting the uptake of interventions for target users and beneficiary groups in crisis-affected settings [6].
Unsurprisingly, measles, polio, and tetanus were the most frequently identified VPDs for vaccination guidance.Polio and measles are often prioritised for mass immunisation within crisis-affected settings and require a high level of vaccine coverage to achieve herd immunity [10].Understanding the incentives behind guidance development is also important.Global funding allocated towards different types of VPDs may be one such incentive.In recent years, there has been a greater global push to eradicate polio led by organisations such as the Global Polio Eradication Initiative [63].Less policy and political attention from global health governance actors towards certain diseases may conversely divert funding and widen guidance gaps.
For example, within crisis-affected settings, there is an increased prevalence of sexual violence, creating a higher exposure risk to HPV [34].Absent or weak cervical cancer screening programmes place women at greater risk of undiagnosed cancer [34].HPV is one of the only listed routine vaccines that protects against an illness that has a longer latency period, with onset of low-grade cervical cancer lesions five or more years after initial infection [34].Despite decreased immediate risk of severe health outcomes in those diagnosed with HPV, ensuring the protection of girls and women through primary prevention is critical.A recent review of vaccination in crises settings found that HPV was probably not offered to affected populations in 21 of the 25 crises reviewed [32].The lack of guidance for HPV in crisis settings may also influence how crisis responders prioritise and view the importance of providing this vaccine to crisis-affected populations.The lack of guidance for climate change-dependent VPDs such as yellow fever [7] may also be an emergent gap [64] Crisis-specific guidance on infections that have now become vaccinepreventable, including malaria and respiratory syncytial virus, may also soon become a gap.
An important consideration is that comprehensive and detailed recommendations for one VPD may have greater usability compared to less detailed recommendations for multiple VPDs.Vaccination delivery must consider contextual factors such as limited humanitarian funding, requiring prioritisation of vaccines; unclear prior immunity levels resulting from a mixture of routine vaccination, mass campaigns, and natural exposures; potential for the integration of vaccination services with other humanitarian services such as education, child protection, and distribution of relief goods; and availability of cold chains.Furthermore, catch-up vaccination dosing schedules for specific age cohorts, how to prioritise which VPDs to address, and adapting schedules to changing VPD epidemiology require greater contextual guidance.Guidance on reporting the number of vaccinations provided in humanitarian responses was limited.This information is often required by nongovernmental organisations and should be considered for inclusion in future operational guidance documents.
Included guidance in this review presented an unnecessary dichotomisation of mass and routine vaccination campaigns.There were very few guidance documents that presented both forms of vaccination campaigns or hybrid approaches.Alternative hybrid delivery modalities including leveraging other operational delivery platforms such as schools or resource distribution points should be considered [65].Hybrid approaches should also consider the role of mobile versus static clinics as delivery modalities.Mobile clinics can assist in instances of population displacement and in the delivery of booster doses.
Variations in dosing were commonly attributed to documents targeting different age ranges or vaccination timelines such as catch-up vaccination campaigns.Some guidance also created practical barriers for implementation.Notably, one document provided guidance, including dosing, for measles but did not contain dosing for mumps.The lack of inclusion of guidance for mumps creates added barriers for vaccination programmes intending to administer the MMR multivalent vaccine.
The term zero-dose has been more commonly adopted by INGOs such as GAVI and WHO in recent years into their vaccination strategies [49].The novelty of the term may explain the lack of strategies targeting zero-dose children prior to 2020 from this review.
Ethical decision making underpins a significant portion of the day-to-day work of humanitarians.Ethical challenges at the level of praxis often involve local-, cultural-, religious-, and disease-specific considerations [66].A lack of guidance to equip humanitarians can lead to increased distress for humanitarians and affected populations, a lack of recognition of ethical dilemmas, and a lack of reflection on or assessment of the appropriate next steps.Gaps in ethical guidance at the level of humanitarian praxis in relation to vaccination are consistent with and build on findings within other areas of humanitarian response [66].Moodley et al. have written the only guidance available to date on ethical considerations for vaccination programmes in acute humanitarian emergencies [20].The literature assessing guidance for outbreak management in crisis-affected settings reported that ethical guidance at the level of praxis was unevenly developed to represent a range of infectious diseases and was not specific to supporting outbreak response [66].Ethical guidance developed by the Red Cross for humanitarian professionals included guidance on assessing affected population needs and planning of interventions [67].However, no guidance is given to assist in navigating disease or intervention-specific ethical challenges [67].Another review highlighted a dissonance between ethical guidance documents and the problems confronting frontline humanitarian workers [68].Moreover, consistent with this review, none of these guidance makers consulted the populations that the ethical guidance is intended for [68].The inclusion of affected populations in guideline development can assist in supporting accessibility to mechanisms that ensure accountability of humanitarian actors.Mechanisms that promote accountability include channels to report negative reactions to humanitarian interventions, such as responses to ethical challenges or adverse medical reactions to vaccinations.This suggests a gap in the quality and availability of ethical guidance to target challenges experienced by front-line humanitarian workers and affected populations for vaccination.
A lack of inclusion of crises-affected populations in guideline development has important implications for health communication.Affected populations can provide insights for navigating ethical challenges and supporting community acceptance of vaccination.Input from affected populations can assist in understanding and mitigating potential antivaccination attitudes and enable the co-development of context-specific recommendations to support informed consent.Furthermore, health communication teams were not commonly identified as target users of these guidance documents.The inclusion of health communication teams as target users and recommendations to support effective health communication is necessary to address vaccine misconceptions and support vaccine uptake in crises settings [12].

Limitations
This review has several limitations.Notably, identifying grey literature guidance documents, although carried out systematically, was limited to a manual search of organisational websites, search engines, reference lists, and a survey.Some important documents may not be publicly available and were not captured for inclusion.Similarly, search engine algorithms may have influenced the type of results produced through searches.Guidance on websites published in languages that were not English or French were also not assessed for inclusion.Moreover, the survey may not have been accessible to all key vaccination actors and may have introduced selection bias in the types of documents identified.The largest proportion of documents were published by the WHO, which may have biased the quality appraisal of the documents as the WHO has a process for guideline development that may have made the results of the data extraction and quality appraisal more homogenous [10].Data extracted were consistent with the terminology that the guidance document identified.There may be useful guidance for other target users or intended beneficiary groups (ex: policy makers or students, etc.) within documents that were not explicitly identified by document developers.

Conclusions
Implications for policy include greater collaboration with individuals affected by humanitarian crises in guideline development and strengthening the systematic rigour of guideline development to create high-quality and evidence-based guidelines targeting contextual challenges.Individuals working at the level of humanitarian praxis, as well as those affected by crises, should be consulted in the development of ethical guidance for front-line vaccination delivery.
Future research should build on the findings of this review and target vaccines not identified in this review such as Japanese encephalitis, tick-borne encephalitis, rabies, dengue, typhoid, and malaria [1].These VPDs have greater disease burden within certain regions and certain high-risk populations affected by crises.Assessment of documents for guidance related to vaccine contraindications as well as how to navigate administering vaccines when information on previous vaccination is not available should also be explored.Future research should also assess characteristics of guidance documents that facilitate the usability in practice.Evaluating programme implementers' abilities to translate evidence into practice is key to equitably and effectively meeting vaccination needs in humanitarian contexts.
The nature of delivering routine vaccines in crisis-affected settings is complex and demands effective, evidence-based guidelines with flexible and contextual approaches which support the translation of recommendations into practice.Several vaccination guidance documents for crisis-affected settings currently exist; however, the inclusion of vaccine-specific guidance is inconsistent.Addressing gaps in guidance towards routine immunisation delivery, ethical guidance, and antigens such as HPV as well as non-universally recommended WHO routine vaccines will assist effective and evidence-informed delivery of vaccines.

Figure 1 .
Figure 1.Flowchart of the vaccination guidance in humanitarian settings search according to PRISMA guidelines.

Figure 1 .
Figure 1.Flowchart of the vaccination guidance in humanitarian settings search according to PRISMA guidelines.The largest share of documents (Figure 2) were published by the WHO (n = 21), followed by INGOs (n = 12), authors in academic journals (n = 7), other non-WHO United Nations (UN) agencies (n = 6), and national governments (n = 2).

Figure 2 .
Figure 2. Vaccination guidance for humanitarian settings classified according to lead development organisation.* Includes documents published in academic journals such as evidence reviews.

Figure 2 .
Figure 2. Vaccination guidance for humanitarian settings classified according to lead development organisation.* Includes documents published in academic journals such as evidence reviews.

Figure 2 .
Figure 2. Vaccination guidance for humanitarian settings classified according to lead development organisation.* Includes documents published in academic journals such as evidence reviews.

Figure 3 .
Figure 3. Number of vaccination guidance documents classified according to humanitarian crisis type and setting.

Vaccines 2023 , 29 Figure 3 .
Figure 3. Number of vaccination guidance documents classified according to humanitarian crisis type and setting.

Figure 4 .
Figure 4. Intended target user identified by vaccination guidance document.

Figure 4 .
Figure 4. Intended target user identified by vaccination guidance document.

Table 1 .
Characteristics of eligible guidance documents.

Table 2 .
Percentage of vaccine guidance for VPD mapped to corresponding WHO routine vaccines recommended for all immunisation programmes (1).

Table 2 .
Percentage of vaccine guidance for VPD mapped to corresponding WHO routine vaccines recommended for all immunisation programmes (1).

Table 3 .
(1)centage of other vaccines assessed in review mapped according to WHO non-universal routine vaccine programme recommendations(1).

Table 5 .
AGREE II quality appraisal scores by guidance type.

Table 6 .
SANRA quality appraisal scores for evidence reviews.

Mean SANRA Scores for Six Items Document Type Number of Documents Eligible for SANRA Justification of the Article's Importance for the Readership Statement of Concrete Aims or Formulation of Questions
: Data extraction classification definitions; Table S5: Data extraction framework; Table S6: Vaccine-preventable diseases included in guidance documents; Table S7: AGREE II critical appraisal by domain; Table S8: AGREE II Critical appraisal disaggregated by individual domain indicators; Table S9: SANRA Critical appraisal by item.