Lessons learnt from implementation of the International Health Regulations: a systematic review
Amitabh B Suthar a, Lisa G Allen b, Sara Cifuentes c, Christopher Dye d & Jason M Nagata e
a. South African Centre for Epidemiological Modelling and Analysis, University of Stellenbosch, Private Bag X1, Matieland, Stellenbosch, 7602, South Africa.
b. TMF Health Quality Institute, Austin, United States of America (USA).
c. Center for Public Health Initiatives, University of Pennsylvania, Philadelphia, USA.
d. Department of Strategy, Policy and Information, World Health Organization, Geneva, Switzerland.
e. Department of Pediatrics, University of California San Francisco, San Francisco, USA.
Correspondence to Amitabh B. Suthar (email: firstname.lastname@example.org).
(Submitted: 28 November 2016 – Revised version received: 26 October 2017 – Accepted: 14 November 2017 – Published online: 11 December 2017.)
Bulletin of the World Health Organization 2018;96:110-121E. doi: http://dx.doi.org/10.2471/BLT.16.189100
While bi- and multilateral communication and collaboration are the foundation for global control of infectious disease epidemics, they are strengthened by the International Health Regulations (IHR). First introduced in 1969, IHR is global legislation requiring countries to link and coordinate specific actions.1 These regulations were originally designed to control cholera, plague, yellow fever, smallpox, relapsing fever and typhus. Given the need to expand the scope to include new epidemics and to improve global coordination, the regulations were revised in 2005, as IHR (2005).2 One of the key changes was the requirement for countries to notify the World Health Organization (WHO) of all events that may constitute a public health emergency of international concern and to respond to requests for verification of information about these events.2 Since IHR (2005) was adopted by WHO States’ Parties, several outbreaks, epidemics and pandemics have been declared public health emergencies of international concern: the H1N1 pandemic influenza in 2009, wild poliovirus in 2014, Ebola virus disease in 2014, and Zika virus and increases in neurological disorders and neonatal malformations in 2016.3–6
IHR (2005) also requires all countries to develop, strengthen and maintain eight core public health capacities.2,7 These core capacities cover: (i) national legislation, policy and financing; (ii) coordination and national focal point communications; (iii) surveillance; (iv) response; (v) preparedness; (vi) risk communication; (vii) human resources; and (viii) laboratory.8 Given varying levels of health and socioeconomic development across countries, there have been challenges in implementing these requirements. By the original deadline of June 2012, only 42 (22%) of the 192 WHO Member States had met the core capacity requirements.9 Yet substantial progress has been made in some areas. These include establishing a 24-hour presence of a national focal point to communicate with all relevant sectors within government, all national stakeholders and WHO; increased transparency in reporting events; using early warning systems more systematically; and better communication and collaboration between the animal and human health sectors. Nevertheless, by the end of 2015, 127 of the 192 countries had not meet all IHR (2005) core capacity requirements.9,10
Although IHR (2005) describes what must be achieved by countries, there is limited knowledge on how countries should proceed in achieving the core capacities. To fill this gap and accelerate implementation of IHR (2005), the World Health Assembly in 2015 identified a need to evaluate and share the lessons learnt from countries that have implemented IHR (2005).11 While country exchanges and regional meetings are one mechanism to achieve this, we systematically evaluated published literature and reports for lessons learnt from national experience in implementing IHR (2005).
This systematic review was conducted in accordance with Enhancing Transparency in Reporting the Synthesis of Qualitative Research guidelines, using a predefined protocol (International Prospective Register of Systematic Reviews identification number: CRD42016038719).12,13 We systematically searched the PubMed®, Embase®, Global Health, Scopus and WHO Global Index Medicus databases without any limitations of language, publication type or date on 13 November 2015. We searched all databases for the terms “IHR” or “International Health Regulations” to ensure we captured articles focusing specifically on IHR implementation. We did not search additional terms for the core capacities since this would decrease the number of results from the databases and potentially decrease the sensitivity of the search strategy. We also searched updates from the WHO bulletin on IHR implementation and abstracts from the International Society for Disease Surveillance annual conferences.14,15 Studies were included when they summarized national experience in implementing any of the IHR (2005) core capacities or their components (Box 1).8 We excluded studies that referred to IHR (1969) or were theoretical and not rooted in national experience.
Box 1. Core capacities and components of the International Health Regulations (2005)
Core capacity 1: National legislation, policy and financing
Component 1A: National legislation and policy
Component 1B: Financing
Core capacity 2: Coordination and national focal point communications
Component 2A: IHR coordination, communication and advocacy
Core capacity 3: Surveillance
Component 3A: Indicator-based surveillance
Component 3B: Event-based surveillance
Core capacity 4: Response
Component 4A: Rapid response capacity
Component 4B: Case management
Component 4C: Infection control
Component 4D: Disinfection, decontamination and vector control
Core capacity 5: Preparedness
Component 5A: Public health emergency preparedness and response
Component 5B: Risk and resource management for IHR preparedness
Core capacity 6: Risk communication
Component 6A: Policy and procedures for public communications
Core capacity 7: Human resources
Component 7A: Human resource capacity
Core capacity 8: Laboratory
Component 8A: Policy and coordination of laboratory services
Component 8B: Laboratory diagnostic and confirmation capacity
Component 8C: Laboratory biosafety and laboratory biosecurity (biorisk management)
Component 8D: Laboratory-based surveillance
IHR: International Health Regulations.
Source: International Health Regulations (2005).7
Two authors independently screened all abstracts, articles and reports and then matched the full texts selected during screening against the inclusion criteria. The reference lists of relevant articles and reviews were also searched for additional studies and reports. Articles meeting the inclusion criteria were included in the review. Three authors completed the data extraction using standardized extraction tables.
Two authors independently read and assessed the quality of included studies using the Critical Appraisal Skills Programme qualitative research checklist.16 Disagreements in quality assessment between reviewers were resolved through discussion. In case new insights, grounded in data, might be generated in studies classified as low methodological quality, no studies were excluded on the basis of the quality assessment.17,18
We used the Cochrane qualitative systematic review method, including meta-ethnography, to synthesize qualitative data.17,19–22 Meta-ethnography involved three steps: (i) reciprocal translational analysis (comparison); (ii) refutational synthesis (contrast); and (iii) line of argument synthesis (high-level synthesis).23,24 We extracted key quotations from each study into an Excel spreadsheet (Microsoft Corporation, Redmond, United States of America) and organized these into facilitators or barriers to implementation for each component of the eight IHR core capacities.25 Each quotation was summarized into a theme. For reciprocal translation analysis, we compared similar themes from individual studies within each core capacity and synthesized lessons learnt that reflected themes from multiple studies. For refutational synthesis, we contrasted themes between individual studies within each core capacity and noted disagreements. Line of argument synthesis was used to identify lessons learnt that were relevant to multiple core capacities (i.e. cross-cutting themes).24
We identified 1075 abstracts through database searches. After removing duplicates and screening out non-relevant abstracts, we assessed 93 full-text articles for eligibility and excluded 45. We identified three abstracts from the International Society for Disease Surveillance’s annual conferences. In total 51 articles, published from 2007 to 2015,26–77 met the eligibility criteria (Fig. 1; Table 1 and Table 2 (both available at: http://www.who.int/bulletin/volumes/96/2/16-189100). A more detailed summary of the included articles and themes identified is available from the corresponding author. Some articles reported national experience in IHR (2005) implementation in multiple countries. In total, 77 countries were represented from all WHO Regions: 23 from Western Pacific, 16 from Europe, 14 from Africa, 11 from the Americas, eight from Eastern Mediterranean and five from South-East Asia (Fig. 2). A total of 44 lessons learnt were synthesized from the eligible articles (Box 2; Box 3).
Fig. 1. Flowchart on the selection of articles for the systematic review on the implementation of the International Heath Regulations (2005)
Table 1. Summary of articles included in the systematic review of the implementation of the International Health Regulations (2005)
Table 2. Quality assessment of studies included in the systematic review of the implementation of the International Health Regulations (2005)
Fig. 2. Country location of studies and reports included in the systematic review of implementation of the International Heath Regulations (2005), by World Health Organization Region
Box 2. Lessons learnt synthesized from the systematic review of national implementation of the International Health Regulations (2005), organized by core capacities 1–4
Core capacity 1: National legislation, policy and financing
1. It is important to mobilize and sustain political commitment to developing the core capacities of IHR (2005) from central government, subnational levels of government, civil society and the scientific community.40,59
4. For sustainable financing, detailed long-term national strategic plans with budget allocations should be developed in partnership between government, national stakeholders, and non-state actors (i.e. companies, high net-worth individuals and philanthropic foundations).47,52,71
5. The national health system and sociocultural context of a country will determine priorities for funding and other resource needs for IHR (2005) core capacity development, emergency response and the health workforce.64,70
Core capacity 2: Coordination and national focal point communications
3. Establishing roles, responsibilities and terms of reference of national focal points within national legislation, and disseminating information inside government, to national stakeholders, and to WHO, improves coordination and communication.27,51,74
4. Adequately resourced communication channels and standard operating procedures, from the subnational to the inter-governmental level, facilitate the timely transmission and retrieval of information.26,29,57,73
Core capacity 3: Surveillance
3. Key communicable diseases need to be categorized based on epidemiological context (e.g. endemic diseases, target for disease elimination or eradication, epidemic-prone diseases and novel diseases).26,30,60
4. Surveillance at the subnational level can be sustained by developing legislation that outlines the requirements, mechanisms (e.g. indicator- or syndromic-based surveillance7) and frequency of reporting, stratified by communicable disease category and supported by guidelines and standard operating procedures.33,38
6. A unified and dynamic surveillance system to track alerts, updates and early warnings and response, and using technologies appropriate to the national context (e.g. electronic, open-source, internet-based, real-time, mobile phone platform), encourages appropriate information use and accurate reporting.28,33,37
7. Standardizing passive data collection, management and validation procedures across all reporting sites, and actively searching for potential surveillance intelligence through local communication channels (e.g. community leaders, print media, internet, television), improves the usability and timeliness of data.36,55,59,63
Core capacity 4: Response
1. Defining criteria for an emergency public health event (e.g. seriousness, impact, unexpectedness, risk for international spread, risk for trade or travel) assists with the initiation of an appropriate and timely response.36,39
2. Establishing roles, responsibilities and terms of reference for a multidisciplinary response unit supports coordination of public health emergency responses at the national and subnational levels.26,27,36,53
4. Designing and resourcing health facilities to minimize nosocomial infection transmission improves the efficacy of response without encouraging further spread (e.g. building isolation rooms, ensuring adequate ventilation, providing personal protective equipment).26,73
Box 3. Lessons learnt synthesized from the systematic review of national implementation of the International Health Regulations (2005), organized by core capacities 5–8 and cross-cutting themes
Core capacity 5: Preparedness
Core capacity 6: Risk communication
Core capacity 7: Human resources
1. Identifying competency gaps in the workforce ensures that training and resources are targeting the highest priority needs (e.g. epidemiology, problem-solving, management and leadership, technical expertise in pandemic and epidemic diseases).54,61,74
Core capacity 8: Laboratory
1. It is important to create a governmental entity at the national level to coordinate national strategic plans for laboratory response and develop national standards, guidelines and operating procedures for laboratory surveillance at national and subnational levels.26,34,52,54,73
5. Bidirectional flows of data, specimens and communication between national and subnational levels of government improve laboratory system effectiveness and adequate public health investigation.27,29
IHR (2005): International Health Regulations, 2005 revision: WHO: World Health Organization.
Notes: Framework for the analysis was based on the eight core capacities of the International Health Regulations (2005).7
Implementation of core capacities
A total of 33 articles from 60 countries reported experience implementing the national legislation, policy and financing core capacity.27,29–31,34–41,44,47,50–54,56,57,59–61, 64,66,68,70–74 In Cambodia, India and Uganda, the need to develop basic health-system functions (e.g. expanding access to health services that are essential for treating patients and for disease surveillance) had to be balanced against the commitment to meeting IHR (2005) requirements.30 Some low- and middle-income countries were concerned that large inflows of external funding for IHR (2005) would create vertical programmes that could not be fully incorporated within their health systems.30 In the USA, stakeholders need to ensure coverage and enforcement of legislation within private health-care facilities, where most citizens receive health services.34 In Brazil, creation of legislation, policy and guidelines was found to be insufficient without training and mechanisms to enforce implementation of IHR (2005).51
Experience implementing the coordination and communications capacity was reported in 33 articles from 51 countries.26–31,33,36,38–43,46–48,50–52,56,57, 59,61,63,64,66,68,70,71,73,76,77 In Cambodia, India and Uganda, failing to coordinate through the national focal point led to duplication of surveillance strengthening efforts.30 In Papua New Guinea, capacity to govern is variable at the subnational level, and the reach of the national focal point needs to be expanded to local partners beyond the health sector.33
Forty articles from 63 countries reported experience implementing the surveillance core capacity.26–43,45–47,50,51,53–55,57, 59,60,62,63,65,67,68,71,73–76 In the European Union, researchers identified a need for manuals of surveillance standards, guidelines, case definitions and protocols for reporting and disease notification.38,39 Reports from France, Iceland Indonesia and Madagascar noted the complementary nature of early warning systems, event-based surveillance and syndromic surveillance for detecting different types of epidemics.55,63,75 Experience in Papua New Guinea reinforced the need for periodic evaluations of syndromic and event-based surveillance systems.33 A study from the Pacific Islands identified a need to adapt surveillance information systems to the local context.59
Experience implementing the response core capacity was reported by 27 articles from 47 countries.26–36,39,42,43,45,46,51–54, 56,60,62,68,71,73,74 Experience from the Republic of Moldova reinforced the importance of interdisciplinary rapid response teams (e.g. epidemiologists, microbiologists, hygienists, environmental health professionals and laboratory technicians).36 In Uganda, a command centre was created to house the rapid response team and to receive, evaluate and distribute information.29 Experience from Chile indicated the importance of having infection control committees composed of staff from different levels of the health system (e.g. hospital, provincial and national).26 A report from the United Kingdom of Great Britain and Northern Ireland and its territories emphasized the need for response plans to be reviewed and updated regularly to respond to all hazards: zoonotic, food safety, chemical, radionuclear and antimicrobial resistance threats.39
Thirteen articles from 37 countries reported experience implementing the preparedness core capacity.26,27,29,32,34–36,40,45, 49,50,52,56,73,74,76 In the United Republic of Tanzania, failure to create specific budget lines for public health preparedness hampered preparedness planning.27 Experience from Asia during the H1N1 influenza pandemic found that, in addition to national plans, regions may need to develop multicountry preparedness plans focused on real-time information sharing.50
A total of 23 articles from 36 countries reported on implementing the risk communication core capacity.26–29,33,35,36,42,45,46,50–53, 55,57,59,68,71,73,76 Experience from Papua New Guinea and the USA found that regular interactions with the media helped to build relationships, trust and functioning communication streams for use in times of emergency.33,42 In the Republic of Moldova and sub-Saharan Africa, bi-directional communication streams allowed central authorities to communicate with subnational levels to raise awareness, receive information from subnational authorities, and ultimately conduct investigations on disease epidemics.36
A total of 37 articles from 49 countries reported experience implementing the human resources core capacity.26,27,29–31,33–39,41,42,44–46,49–54,56–59,61–64,68,71–74 Experience from Cambodia, India, Uganda and the United Kingdom indicated that traditional curricula, competencies and training did not prepare the workforce to implement IHR (2005) and that additional knowledge transfer and skill-building is needed to ensure reporting and data use at subnational levels.30,39 The sociocultural context influenced learning preferences; for example, in Morocco face-to-face learning was preferred, while in India and the United Kingdom electronic learning was preferred.39,45,61 In China, Morocco, South Africa and the United Kingdom, interactive and skill-building sessions were preferred over static knowledge transfer.41,61,74 Settings that had high staff turnover (e.g. rural areas, those with armed conflicts) faced staff shortages and required unique mechanisms for continual retraining.31,39,59,63
Experience implementing the laboratory core capacity was reported in 26 articles from 44 countries.26–31,34,36,39–42,45,46,50, 52–54,56,57,62,68,71,73,77 Studies in Afghanistan, Uganda and the United Kingdom identified a need to develop laboratory capacity for basic tasks such as collection, transportation and analysis of specimens.31,39,73 Several sub-Saharan counties needed laboratory accreditation systems, supported by training and mentoring, and external quality assurance systems in place, as well as laboratory information systems that directly influence public health action.54
We identified five global lessons learnt that related to multiple IHR (2005) core capacities (Box 2). Some major cross-cutting themes included the need for mobilizing and sustaining political commitment; for adapting global requirements based on the local sociocultural, epidemiological, health system and economic contexts; and for conducting baseline and follow-up assessments to monitor IHR (2005) status.
We found substantial documentation of lessons learnt from implementing IHR (2005) core capacities globally. Although many factors affected implementation in a country, the structure of the health system, sociocultural factors, economic status and type of governance, we were able to extract some common themes. We found few gaps in implementation in direct relation to the IHR (2005) core capacities. Nonetheless, additional research could be useful in evaluating countries’ core capacity performance against actual disease epidemics. Specifically, we did not identify any documentation evaluating IHR (2005) core capacity development with national performance in preventing, detecting and responding to disease epidemics. This type of evaluation could provide useful data for future revisions of the IHR. Moreover, defining fundamental data needs for new treatments and vaccines could help develop national research capacity to shorten the development window during future disease epidemics. Finally, additional documentation of experience from Eastern Europe and Africa could help fill knowledge gaps.
Countries had different national health plans outlining how to organize their systems and strategies for managing threats and hazards.78 National plans typically outlined how health priorities will be managed and linked to programme-specific strategic plans, such as those for primary health care, maternal and child health, human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS). To avoid having only vertical programmes, countries will have to decide how to integrate IHR (2005) core capacity development within existing strategic plans, such as those for the health workforce or laboratory systems. Integration of IHR (2005) into national legislation is also required. To achieve this, WHO proposed that countries need to consider how the IHR (2005) are to be implemented based on their national legal and governance context; to assess existing legislation for IHR (2005) implementation; to revise existing legislation or adopt new legislation; and to enforce nationally adapted legislation.69,79
Most countries reported some experience in implementing communicable disease surveillance as part of IHR (2005).80 Although core capacity requirements for surveillance are the same for all countries, the means to achieve them differed. For example, real-time systems worked well in settings with good electronic and telecommunications infrastructure, while delays were common in settings with more limited infrastructure.59 Such delays were acute in rural settings where health staff face logistic challenges in reporting events and may not be fully aware of the benefits of reporting events.33 Nevertheless, minimizing delays in discovering and declaring disease outbreaks remains a global priority.81 Prospectively, vertical disease surveillance systems (e.g. population-based surveys for HIV/AIDS, case reporting for malaria and cohort monitoring for tuberculosis) could be used and adapted when developing and maintaining the surveillance core capacity of IHR (2005).30
Although complementary in nature, the preparedness and response core capacities were often implemented independently of one another. For example, areas requiring coordination across both of these core capacities, such as case management or infection control, were not well-documented. Taking a holistic approach to IHR (2005) core capacity development could avoid these issues.26,45,52 Moreover, there were cases in which it was difficult to implement national IHR (2005) policies. For example, in the United Republic of Tanzania protocols for isolating patients with certain diseases were developed, but due to shortages of public-sector health facilities private sector hospitals had to be used during epidemics.27 This highlights the need to adapt global core capacities requirements to locally appropriate policies and solutions.
Risk communication focuses primarily on effective communication strategies during disease epidemics. Some of the articles we identified primarily discussed communication systems.33,46,59 For example, while many countries documented positive experience with internet-based communication strategies, inconsistent access to electricity and telecommunications in the United Republic of Tanzania made this challenging.27 More documentation of risk communication lessons learnt during epidemics are needed. For example, there was delayed notification and underreporting of cases from the national to international level during the severe acute respiratory syndrome epidemic in China in 2002.16 This delay may have contributed to preventable transmission of the virus and galvanized international interest in revising IHR(2005) to ensure transparency and timeliness of communication during disease epidemics.82,83
The World Health Assembly recently approved the Global strategy on human resources for health: workforce 2030.84 Development of human resources required by IHR (2005) could be included within national strategies for human resource development. Initial quantification of needs could be completed through the use of WHO recommended tools such as the Workload Indicators of Staffing Need.85 Most health workforce strategies are long-term and require development and revision of curricula, competencies, professional continuing education and licensing. Although international support plays a role in training local staff, Indonesia and South Africa, among others, noted that this mechanism was often resource-intensive and unsustainable.41,42,44 Moreover, given that front-line health staff may be resistant to additional administrative duties and responsibilities without increased remuneration, it is essential to reduce redundancies in roles and responsibilities across different disease programmes.30
Laboratory networks are an essential part of national and regional health systems. Global laboratory networks are in place for polio, immunization programmes and influenza.86–88 It could be worthwhile to adapt and integrate these existing networks to meet IHR (2005) requirements. The issue of limited capacity to develop laboratory infrastructure in rural areas was raised.39 In these settings, disease-specific point-of-care assays may be needed, even if they do not contribute to overall strengthening of the laboratory system. Decentralized laboratory assays that contribute to control of multiple diseases (e.g. nucleic acid amplification that could be used for HIV/AIDS, tuberculosis, viral hepatitis, novel influenza strains and Ebola virus disease), rather than disease-specific assays, may be a better way to strengthen laboratory systems.89
Given the many priorities in development, and limited national budgets to achieve them, external funding opportunities often help mobilize political commitment and national action. Experience from South Africa suggested that while external funding sources can be inflexible and unsustainable within national governance frameworks, such funding could create momentum in generating domestic financing and accelerate progress in implementing IHR (2005).41 Therefore, identifying adequate funding is the first step to developing, strengthening and maintaining national IHR (2005) core capacities. Global eradication of polio and global elimination of HIV/AIDS, tuberculosis and malaria were all costed and have been successful in mobilizing political commitment.90–93 Estimating the global and national costs of meeting IHR (2005) core capacities could also help in identifying external funding sources. Various frameworks and tools are available to cost IHR core capacity development.94,95 Depending on the setting and context, the World Bank, the International Monetary Fund, regional development banks, bilateral partners and non-state actors (i.e. companies, high net-worth individuals and philanthropic foundations) could all make substantial contributions towards advancing global implementation of IHR (2005).96–101
Along with financial and technical support, additional international measures could help accelerate IHR (2005) core capacity development. For example, since past disease epidemics affected regional and global economic growth, economic issues are relevant.102,103 Allowing countries that meet IHR (2005) core capacity requirements to participate in regional and global trade agreements, or have access to grants or low-interest loans through bilateral partnerships or international financing institutions, could help mobilize political commitment and action. Conversely, if there remain persistent challenges in meeting the agreed IHR (2005) core capacity deadlines, trade tariffs, sanctions or embargoes might be needed to ensure countries collaborate fully in sustaining global health security. These different measures could also be used during disease epidemics in response to countries’ compliance or lack of compliance with IHR (2005) requirements. This could help, for example, accelerate the timeliness of providing essential surveillance data to the global health community. This would represent a shift in current enforcement of IHR (2005) core capacity development that may require discussion and consensus outside of the health sector.104 Regardless of whether macroeconomic measures are implicated with IHR (2005), failure to implement IHR (2005) core capacities could adversely affect the international image of a country and also increase its susceptibility to economic losses due to disease epidemics.
This study has several limitations. We focused only on IHR (2005) core capacities and not on the core capabilities of points of entry, zoonotic events, food safety, chemical events and radiation emergencies.105 Future studies should evaluate these additional aspects of IHR (2005). The databases we used only have the capacity to search the titles and abstracts of articles and may have missed articles that only mentioned IHR-related keywords in the full text. Using databases that have the capacity to search the full text may identify additional studies.106 There is little consensus on the use of quality appraisal in qualitative meta-ethnography and we therefore did not exclude any qualitative studies based on quality rating.18 In addition, given the limited availability of formal qualitative research, we included all documentation related to IHR (2005) irrespective of study design. We relied on publicly available documentation from countries; some countries or institutions may not have published their experiences in implementing IHR (2005) due to competing priorities, limited capacity or lack of awareness on the importance of sharing their experience. After completion of this systematic review, Joint External Evaluation guidance became publicly available.107 Their mission reports provide valuable information that should be included in updates to this review.108 Furthermore, annual submissions on IHR (2005) from Member States to the World Health Assembly likely contain relevant information, but are not publicly available.
Despite considerable progress, countries that are yet to implement IHR (2005) core capacities may have insufficient human and financial resources to meet their obligations in the near future. Recent global epidemics have galvanized high-level political commitment towards ensuring global health security. We can leverage this commitment by mobilizing resources and securing wider collaboration to apply the lessons outlined here and accelerate the development of IHR (2005) core capacities globally.
JMN is also affiliated with Department of Paediatrics, Stanford University School of Medicine, Stanford, USA.
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