Immunization stress-related responses

ISRS

In December 2015, GACVS received reports from mainstream and social media in several countries in which clusters of anxiety-related reactions after immunization had adversely affected immunization programmes.6 Subsequently, GACVS commissioned a group of experts to explore and determine the etiology and characteristics of those events and to prepare a guidance document to help guide public health programmes to prevent, recognize and manage them.

During the meeting in December 2017, the expert group presented the findings of a systematic review of the literature and social media and the outcome of discussions with subject experts.7 GACVS reviewed a draft manual to support programme managers in preventing, identifying and responding to stress-related events associated with immunization. It had become clear that the term, “immunization anxiety-related reaction” would not cover the entire spectrum of these events and that a broader term was required; initially “immunization- triggered stress response” was proposed, as it would incorporate all the stress-related symptoms and signs that manifest just before, during and after immunization.

GACVS recommended that the draft manual be circulated for review to relevant stakeholders, which was conducted in several rounds during 2018. Feedback was incorporated into a revised manual, which was presented to GACVS for discussion. A new term was proposed, as it was considered that “immunization -triggered stress response” would strongly assign causality to the immunization, whereas such responses are not specific to immunization. The term “immunization stress-related responses (ISRR)” was considered more appropriate, as it encompasses the broad range of responses that can be experienced in relation to immunization, without implying that they are causally related. The WHO causality assessment process should then be followed to determine the relation between immunization and the event.8 GACVS made additional recommendations, in particular that the manual should address not only programme managers but all health care professionals, that use of “responses” rather than “reaction” in the new term would be appropriate, and that postural orthostatic tachycardia syndrome, chronic fatigue syndrome and complex regional pain syndrome are not part of the ISRR spectrum. As the relation of these entities with some vaccine products has been discussed recently, GACVS concluded that the fact that there is currently insufficient evidence to include them in ISRR should be explicitly stated.

GACVS agreed that the manual should be prominently featured in the vaccine safety landscape, as prevention, diagnosis and management of ISRR are fundamental to avoid mistrust in immunization programmes. Communication strategies were also discussed. The comprehensive manual will be made available in several languages on the WHO website, and a synopsis will be proposed for publication in an international, peer-reviewed journal to increase awareness among health care professionals of the existence of ISRR, with a link to the full manual. Publication of the ISRR manual will also be accompanied by appropriate training materials.

⁶ See No. 91, 2016, pp. 21–23.

⁷ See No. 93, 2018, pp. 27–28.

⁸ Causality assessment of an adverse event following immunization (AEFI): user manual for the revised WHO classification. Second edition. Geneva: World Health Organization; 2018.

Full report of GACVS meeting of 5-6 December 2018, published in the WHO Weekly Epidemiological Record on 25 January 2019

Guidance on prevention and management of immunization-triggered stress responses

During its December 2015 meeting, GACVS was presented with literature and mainstream and social media reports from several countries where clusters of anxiety-related reactions following immunization affected immunization programmes had drawn negative attention from the media and public.¹⁵ Following the meeting, GACVS convened an expert working group to explore and understand the etiology of such events and their characteristics, and prepare a guidance document that would help guide public health efforts and programme managers and immunization staff in prevention and management.

The expert working group systematically reviewed the available literature along with information gathered from social media, and used the findings to initiate discussion with subject experts. The group prepared a draft guidance document aimed to equip immunization programme managers and health-care providers at local, regional and national levels with the knowledge to manage both individual and clusters of such events. The emphasis was to obtain clarity on the spectrum of anxiety-related manifestations, including their epidemiology and associated risk factors, and to better understand the context of their occurrence. The objective was to produce a document providing a framework and guidance to understand, prevent, diagnose and manage such events; to explain the context of their occurrence; to clarify the reporting mechanisms and the communication approaches when such events occur; and to identify research gaps and strategies to move forward.

GACVS was presented with a draft manual for programme managers to prevent, identify and respond to stress related events associated with immunization. During discussions, it was clarified that the term, “immunization anxiety related reaction” did not capture the spectrum of such events. A new term, “Immunization Triggered Stress Response” (ITSR) was therefore proposed which incorporates all events that manifest just prior to, during, or after immunization. ITSR can be subcategorized to peri-immunization stress response, post-immunization stress response and other disorders or syndromes that can occur post-immunization, such as the occurrence of anxiety, fear, phobia with immunization, and associated anxiety disorders including “needle phobias” and conversion disorders. Complex syndromes that may have a stress component are also considered in possible relation to immunization and outlined in the document in a biopsychosocial context.

GACVS discussed the proposed terminologies and the classification. It was clear that further research is still needed to better understand the rate of occurence of such events, their relationship to age and mechanisms of occurence. There is a need to link ITSR with pain mitigation and pain management following injections. Better guidance to prevent stress-related events is needed, particularly for parents, vaccinators and health-care providers to address the needs of older children, adolescents and adults prior to vaccination. The exploitation of ITSR by anti-vaccine groups was also mentioned. To avoid mismanagement, screening to differentiate between ITSR and actual vaccine reactions, such as anaphylaxis, is critical; incorporating this into training materials for health-care providers will be helpful. GACVS recommended that the manual be circulated for consultation to relevant stakeholders and that training materials be developed to accompany the new document.

¹⁵ See No. 03, 2016, pp. 21–23.

Full report of GACVS meeting of 6-7 December 2017, published in the WHO Weekly Epidemiological Record of 19 January 2018

Clusters of anxiety-related reactions following immunization

Clusters of anxiety-related reactions following immunization have affected immunization programmes in several countries and drawn the attention of media and the public globally. Understanding such events, their characteristics, and why they may occur will help to better guide public health efforts to prevent and manage them.

The Committee was provided with updated information on the occurrence of such events in the relevant scientific literature and the media and social media reports from several countries including: Iran (tetanus toxoid vaccine 1992); Italy (hepatitis B vaccine 1995); Jordan (diphtheria tetanus vaccine 1998); India (tetanus toxoid vaccine 2001); Viet Nam (oral cholera vaccine 2001); Australia (HPV vaccine 2007); Taiwan, China (H1N1 influenza 2009); and the United States of America (H1N1 influenza 2010). The GACVS observed that these clusters occurred in rural and urban settings both in high and low income countries from all continents and involved different vaccines. Children of both sexes were affected, though with a higher frequency of girls than boys in some studies. Occurrence of reactions was usually within the first 15 minutes of vaccination and involved mostly school-age children. The reactions manifested with a wide variety of symptoms. Most clusters involved introduction of a new vaccine or a change in the routine programme such as new age group or new setting. A small cluster that started in a group setting could spread quickly to form a larger outbreak involving several clusters. Response to such clusters varied in different countries, as did its impact on vaccination programmes. Public health interventions to regain community trust after such events were often costly and resource-intensive.

A survey carried out in 12 low and middle income countries in October 2015 found that many countries are aware of such events. Fainting events are most commonly reported. The survey also found that short-term consequences included a decrease in public confidence in vaccines, resulting in decreased coverage and concerns and fear among health-care personnel to vaccinate; however, there were no long-term or major impacts on their immunization programmes, mainly due to prompt responses. It was observed that there are gaps in surveillance systems for adverse events following immunization (AEFI) in countries, such that various anxiety-related AEFIs are not well defined and reported or are grouped with other AEFIs, therefore not capturing the true burden.

The use of terms suggesting psychological disorders for severe anxiety reactions were observed to be problematic for vaccinees because of the stigma and consequences that were related to such labelling. Failure to differentiate between the clinical manifestations of fainting, anxiety and associated hyperventilation and other conditions such as anaphylaxis, resulted in mismanagement of cases and thereby additional avoidable harm.

GACVS also reviewed in detail the cluster immunization anxiety reactions that recently occurred on the occasion of a mass measles immunization campaign in a European country. There are increasing reports of occurrence of such reactions with expansion of age of immunization to school children and young adults. Little knowledge and understanding of such events by health workers was also documented. Fast spreading of rumours, fears and concerns of “unknown events” through media and social networking using modern communication technologies was observed and may have aggravated the situation. These events have high visibility and, if not adequately assessed and managed, can convert from a cluster of immunization anxiety events that can be easily managed onsite into a real medical problem with a detrimental impact on the individual affected and on the immunization programme. It was observed that good pre-campaign preparation, such as creating awareness of such events and training of health staff, engagement of communities and appropriate media and communication strategies were important for prevention of such events.

GACVS acknowledged that the magnitude of the impact of immunization anxiety reactions is not currently recognized in the medical literature. Several gaps have been identified including the need for case definitions that span the different degrees of anxiety reactions and for guidance on how to recognize, manage and prevent immunization anxiety reactions. It is also important to identify communication strategies tailored to the audience and plan interventions for first responders, hospitals and immunization programmes in order to improve recognition and management of immunization anxiety clusters, and limit their continuation and spread. There is need to conduct research on predisposing factors for such clusters, outbreaks and the role of social media. Other key areas that need to be addressed include defining effective practices for prevention and intervention in different settings. It was also noted that such clusters need not be immunization-specific and may occur in several other contexts. Finally, GACVS also noted that lack of recognition, lack of early onsite intervention, excessive hospitalization and overreaction by health-care providers and programme managers to such episodes have the potential to aggravate the problem.

Full report of GACVS meeting of 2-3 December 2015, published in the WHO Weekly Epidemiological Record of 22 January 2016