Responding to COVID-19 vaccine-related safety events: WHO Western Pacific regional experience and lessons learned.

Problem: Novel vaccines were developed in an unprecedentedly short time in response to the global coronavirus disease (COVID-19) pandemic, which triggered concerns about the safety profiles of the new vaccines. This paper describes the actions and outcomes of three major adverse events of special interest (AESIs) reported in the World Health Organization's (WHO's) Western Pacific Region: anaphylaxis, thrombosis with thrombocytopenia syndrome (TTS) and post-vaccination death. Context: During the large-scale introduction of various novel COVID-19 vaccines, robust monitoring of and response to COVID-19 vaccine safety events were critical. Action: We developed and disseminated information sheets about anaphylaxis and TTS; provided tailor-made training for anaphylaxis monitoring and response, webinars about TTS and AESIs, and an algorithm to support decision-making about AESIs following immunization; as well as provided country-specific technical support for causality assessments, including for possible vaccination-related deaths. Outcome: Each major vaccine event and situation of high concern was responded to appropriately and in a timely manner with comprehensive technical support from WHO. Our support activities have not only strengthened countries' capacities for vaccine safety surveillance and response, but also enabled countries to decrease the negative impact of these events on their immunization programmes and maintain the confidence of health-care professionals and the general population through proactive delivery of risk communications. Discussion: This paper summarizes selected, major AESIs following COVID-19 vaccination and responses made by WHO's Regional Office for the Western Pacific to support countries. The examples of responses to vaccine safety events during the pandemic and unprecedented mass vaccination campaigns could be useful for countries to adopt, where applicable, to enhance their preparation for activities related to monitoring vaccine safety.

COVID-19 vaccine-related adverse events following immunization in the WHO Western Pacific Region, 2021-2022.

The speed at which new vaccines against coronavirus disease (COVID-19) were developed and rolled out as part of the global response to the pandemic was unprecedented. This report summarizes COVID-19 vaccine-related safety data in the World Health Organization Western Pacific Region. Data for 1 March 2021 to 31 March 2022 from 36 out of 37 countries and areas in the Western Pacific Region are presented. More than 732 million doses of eight COVID-19 vaccines were administered; reporting rates of adverse events following immunization (AEFIs) and serious AEFIs were 130.1 and 5.6 per 100 000 doses administered, respectively. Anaphylaxis, thrombosis with thrombocytopenia syndrome, and myocarditis/pericarditis were the most frequent COVID-19 adverse events of special interest (AESIs) reported. The reported rates of AESIs in the Western Pacific Region were within the range of expected or background rates. Vaccine benefits far outweigh the risk of reported serious adverse reactions and serious outcomes of COVID-19. Continued AEFI surveillance is recommended to better understand and ensure the safety profiles of novel COVID-19 vaccines.

Anaphylaxis: Revision of the Brighton collaboration case definition.

The Brighton Collaboration (BC) has formulated a number of case definitions which have primarily been applied to adverse events of special interest in the context of vaccine safety surveillance. This is a revision of the 2007 BC case definition for anaphylaxis. Recently, the BC definition has been widely used for evaluating reports of suspected anaphylaxis following COVID-19 vaccination. This has led to debate about the performance of the BC definition in comparison with those from the US National Institute of Allergy and Infectious Disease/Food Allergy Anaphylaxis Network (NIAID/FAAN) and the World Allergy Organization (WAO). BC convened an expert working group to revise the case definition based on their usual process of literature review and expert consensus. This manuscript presents the outcome of this process and proposes a revised case definition for anaphylaxis. Major and minor criteria have been re-evaluated with an emphasis on the reporting of observable clinical signs, rather than subjective symptoms, and a clearer approach to the ascertainment of levels of certainty is provided. The BC case definition has also been aligned with other contemporary and international case definitions for anaphylaxis.

Use of a catch-up programme to improve routine immunization in 13 provinces of Papua New Guinea, 2020-2022.

Objective: Routine immunization coverage in Papua New Guinea has decreased in the past 5 years. This persistently low routine immunization coverage has resulted in low population immunity and frequent outbreaks of vaccine-preventable disease across the country. We describe the use of a catch-up programme to improve routine immunization during the coronavirus disease pandemic in Papua New Guinea during 2020-2022. Methods: In June 2020, 13 provinces of Papua New Guinea were selected to undergo a vaccination catch-up programme, with technical support from the World Health Organization (WHO) and the United Nations Children's Fund. Twelve provinces received financial and logistic support through the Accelerated Immunization and Health Systems Strengthening programme, and one received support from WHO. All stakeholders were involved in planning and implementing the catch-up programme. Results: Between July 2020 and June 2022, about 340 health facilities conducted catch-up activities. The highest number of children aged under 1 year were vaccinated in 2022 (n = 33 652 for third dose of pentavalent vaccine). The national coverage of routine immunization (including the catch-up vaccinations) increased between 2019 and 2020 - by 5% for the third dose of pentavalent vaccine, 11% for the measles-rubella vaccine and 16% for the inactivated poliovirus vaccine. The coverage declined slightly in 2021 before increasing again in 2022. Discussion: The catch-up programme was an instrumental tool to improve routine immunization coverage between 2020 and 2022 and during the pandemic in Papua New Guinea. With appropriate technical and logistic support, including financial and human resources, catch-up programmes can strengthen routine immunization coverage across the country.

Assessing perceptions of establishing a vaccine pooled procurement mechanism for the Western Pacific Region.

This study explored the demand and interest among countries in the World Health Organization Western Pacific Region (WPR) to establish and participate in a regional vaccine pooled procurement mechanism. National counterparts affiliated with Ministries of Health that are involved in the national procurement of vaccines within the WPR were identified and invited to complete surveys. Out of 80 counterparts invited, 17 (21%) responded, representing 13 of the 27 WPR countries. Five countries expressed interest in participating in a regional pooled procurement mechanism, 3 expressed lack of interest and 5 did not respond to the question. Preferred characteristics of the procurement mechanism, included flexible participation (i.e. non-compulsory), payment in local currency before receipt of goods and a fixed price for vaccines (i.e. not tiered pricing). Vaccine pricing disparities were noted among upper middle-income and high-income countries for five of the 13 routine vaccines surveyed. Eight countries listed budget planning, quality of vaccines, timely delivery, cost-saving and payment after receipt as potential benefits of pooled procurement.

An approach for preparing and responding to adverse events following immunization reported after hepatitis B vaccine birth dose administration.

The success of immunization programs in lowering the incidence of vaccine preventable diseases (VPDs) has led to increased public attention on potential health risks associated with vaccines. As a result, a scientifically rigorous response to investigating reported adverse events following immunization (AEFI) and effective risk communications strategies are critical to ensure public confidence in immunization. Globally, an estimated 257 million people have chronic hepatitis B virus (HBV) infection, which causes more than 686,000 premature deaths from liver cancer and cirrhosis. Hepatitis B vaccination is the most effective way to prevent mother-to-child transmission of HBV infection, especially when a timely birth dose is given within 24 h of birth. However, an infant's risk of dying is highest in the neonatal period, and thus, administering HepB-BD within 24 h of birth overlaps with the most fragile period in an infant's life. A working group formed in July 2016 following the publication of the case reports of the effects on vaccination coverage of media reports of infant deaths after HepB-BD administration in China and Vietnam. The goal of the working group was to create a framework and describe best practices for preparing for and responding to AEFI reported after HepB-BD administration, using existing resources. The framework includes six steps, including three preparation steps and three response steps. This document is written for national and regional immunization program staff. Prior to using the framework for preparation and response to AEFIs reported after HepB-BD administration, staff members should be familiar with how AEFI are detected, reported, and investigated in the country. The document might also be of interest to national regulatory staff members who monitor vaccine safety within the country.

Engagement of private providers in immunization in the Western Pacific region.

Financial sustainability of national immunization programmes (NIPs) in the Western Pacific is a growing concern. In the face of decreasing donor support for public immunization programmes, the role of private providers is becoming growingly important in attaining and sustaining programme achievements. Two-thirds of Member States in the Region have engaged the private sector in their immunization programmes, however little is known about the range and type of engagement. A survey was conducted in 2016 to map the scope and characteristics of private provider involvement, in order to inform guidance for decision makers. 14 countries participated, with responses from NIPs, national regulatory agencies, national immunization technical advisory groups (NITAGs), and private providers (defined as any entity other than the government). Findings revealed that most countries have policies and regulations concerning private providers, but 50% of private provider respondents were unaware that such policies are available. In most countries private providers' contribution is limited to less than 10% of the total target population. Private providers in only 6 countries surveyed follow the vaccination schedule recommended by the NIP, with demand by vaccine recipients being the main cause of deviation. A majority (>70%) of private provider respondents believe that clients seeks their services not because of perception of quality, but to access new vaccines unavailable through the NIP. Private providers in all countries received vaccines from the NIP at no cost, for which they only charge clients a service fee. The majority of private providers received training from the NIP, whereas only around 25% of them received training from their own institutions. Private providers from 11 countries share EPI performance data and adverse events following immunization, however, NIPs perceive this data as suboptimal. Private providers have a limited role in decision making processes, such as NITAGs. Further effective engagement of private sector providers has the potential to improve overall efficiency of immunization service delivery.

Analysis of Dengue Serotype 4 in Sri Lanka during the 2012-2013 Dengue Epidemic.

The four serotypes of dengue virus (DENV-1, -2, -3, and -4) have had a rapidly expanding geographic range and are now endemic in over 100 tropical and subtropical countries. Sri Lanka has experienced periodic dengue outbreaks since the 1960s, but since 1989 epidemics have become progressively larger and associated with more severe disease. The dominant virus in the 2012 epidemic was DENV-1, but DENV-4 infections were also commonly observed. DENV-4 transmission was first documented in Sri Lanka when it was isolated from a traveler in 1978, but has been comparatively uncommon since dengue surveillance began in the early 1980s. To better understand the molecular epidemiology of DENV-4 infections in Sri Lanka, we conducted whole-genome sequencing on dengue patient samples from two different geographic locations. Phylogenetic analysis indicates that all sequenced DENV-4 strains belong to genotype 1 and are most closely related to DENV-4 viruses previously found in Sri Lanka and those recently found to be circulating in India and Pakistan.

A Spatial Hierarchical Analysis of the Temporal Influences of the El Niño-Southern Oscillation and Weather on Dengue in Kalutara District, Sri Lanka.

Dengue is the major public health burden in Sri Lanka. Kalutara is one of the highly affected districts. Understanding the drivers of dengue is vital in controlling and preventing the disease spread. This study focuses on quantifying the influence of weather variability on dengue incidence over 10 Medical Officer of Health (MOH) divisions of Kalutara district. Weekly weather variables and data on dengue notifications, measured at 10 MOH divisions in Kalutara from 2009 to 2013, were retrieved and analysed. Distributed lag non-linear model and hierarchical-analysis was used to estimate division specific and overall relationships between weather and dengue. We incorporated lag times up to 12 weeks and evaluated models based on the Akaike Information Criterion. Consistent exposure-response patterns between different geographical locations were observed for rainfall, showing increasing relative risk of dengue with increasing rainfall from 50 mm per week. The strongest association with dengue risk centred around 6 to 10 weeks following rainfalls of more than 300 mm per week. With increasing temperature, the overall relative risk of dengue increased steadily starting from a lag of 4 weeks. We found similarly a strong link between the Oceanic Niño Index to weather patterns in the district in Sri Lanka and to dengue at a longer latency time confirming these relationships. Part of the influences of rainfall and temperature can be seen as mediator in the causal pathway of the Ocean Niño Index, which may allow a longer lead time for early warning signals. Our findings describe a strong association between weather, El Niño-Southern Oscillation and dengue in Sri Lanka.

Laboratory-Enhanced Dengue Sentinel Surveillance in Colombo District, Sri Lanka: 2012-2014.

INTRODUCTION: Dengue has emerged as a significant public health problem in Sri Lanka. Historically surveillance was passive, with mandatory dengue notifications based on clinical diagnosis with only limited laboratory confirmation. To obtain more accurate data on the disease burden of dengue, we set up a laboratory-based enhanced sentinel surveillance system in Colombo District. Here we describe the study design and report our findings of enhanced surveillance in the years 2012-2014. METHODS: Three outpatient clinics and three government hospitals in Colombo District that covered most of the Colombo metropolitan area were selected for the sentinel surveillance system. Up to 60 patients per week presenting with an undifferentiated fever were enrolled. Acute blood samples from each patient were tested by dengue specific PCR, NS1 ELISA and IgM ELISA. A sub-set of samples was sent to Duke-NUS Singapore for quality assurance, virus isolation and serotyping. Trained medical research assistants used a standardized case report form to record clinical and epidemiological data. Clinical diagnoses by the clinicians-in-charge were recorded for hospitalized cases. RESULTS: Of 3,127 febrile cases, 43.6% were PCR and/or NS1 positive for dengue. A high proportion of lab confirmed dengue was observed from inpatients (IPD) (53.9%) compared to outpatient (clinics in hospitals and general practice) (7.6%). Dengue hemorrhagic fever (DHF) was diagnosed in 11% of patients at the time of first contact, and the median day of illness at time of presentation to the sentinel sites was 4. Dengue serotype 1 was responsible for 85% of the cases and serotype 4 for 15%. The sensitivity and specificity of the clinicians' presumptive diagnosis of dengue was 84% and 34%, respectively. CONCLUSION: DENV-1, and to a lesser degree DENV-4, infection were responsible for a high proportion of febrile illnesses in Colombo in the years 2012 to 2014. Clinicians' diagnoses were associated with high sensitivity, but laboratory confirmation is required to enhance specificity.