Review of Israel’s action and response during the COVID-19 pandemic and tabletop exercise for the evaluation of readiness and resilience—lessons learned 2020–2021

BackgroundReevaluating response plans is essential to ensuring consistent readiness and resilience to the COVID-19 pandemic. The “During Action Review” and Tabletop (DART) methodology provides a retrospective and prospective assessment to inform the adaptive response. Israel introduced COVID-19 vaccinations in December 2020 and was the first country to implement booster vaccination to address waning immunity and surges caused by new variants. We assessed Israel’s readiness and resilience related to COVID-19 response while capturing the pre-vaccination and vaccination periods.MethodsA DART analysis was conducted between December 2020 and August 2021 among experts involved in the management of the COVID-19 pandemic in Israel. During the retrospective stage, a role-based questionnaire and discussions were undertaken in a participant-led review of the response, focusing on epidemiology and surveillance, risk communication, and vaccines. The prospective stage included tabletop exercises to evaluate short to long-term simulated scenarios.ResultsParticipants emphasized the pivotal role of Israel globally by sharing experiences with the pandemic, and vaccination. Perceived strengths included multi-sectoral collaboration between the Ministry of Health, healthcare providers, academia, military, and others, stretching capacities, expanding laboratory workload, and establishing/maintaining surveillance. The vaccine prioritization plan and strong infrastructure, including computerized databases, enabled real-life assessment of vaccine uptake and impact. Challenges included the need to change case definitions early on and insufficient staffing. Quarantine of patients and contacts was particularly challenging among underprivileged communities. Risk communication approaches need to focus more on creating norms in behavior. Trust issues and limited cooperation were noted, especially among ethnic and religious minorities. To ensure readiness and resiliency, participants recommended establishing a nationally deployed system for bringing in and acting upon feedback from the field, especially concerning risk communication and vaccines.ConclusionOur study appraised strengths and weaknesses of the COVID-19 pandemic response in Israel and led to concrete recommendations for adjusting responses and future similar events. An efficient response comprised multi-sectoral collaboration, policy design, infrastructure, care delivery, and mitigation measures, including vaccines, while risk communication, trust issues, and limited cooperation with minority groups were perceived as areas for action and intervention

Epidemiological and Virological Characterization of Influenza B Virus Infections

While influenza A viruses comprise a heterogeneous group of clinically relevant influenza viruses, influenza B viruses form a more homogeneous cluster, divided mainly into two lineages: Victoria and Yamagata. This divergence has complicated seasonal influenza vaccine design, which traditionally contained two seasonal influenza A virus strains and one influenza B virus strain. We examined the distribution of the two influenza B virus lineages in Israel, between 2011-2014, in hospitalized and in non-hospitalized (community) influenza B virus-infected patients. We showed that influenza B virus infections can lead to hospitalization and demonstrated that during some winter seasons, both influenza B virus lineages circulated simultaneously in Israel. We further show that the influenza B virus Yamagata lineage was dominant, circulating in the county in the last few years of the study period, consistent with the anti-Yamagata influenza B virus antibodies detected in the serum samples of affected individuals residing in Israel in the year 2014. Interestingly, we found that elderly people were particularly vulnerable to Yamagata lineage influenza B virus infections

Enhanced Control of Mycobacterium tuberculosis Extrapulmonary Dissemination in Mice by an Arabinomannan-Protein Conjugate Vaccine

Currently there are a dozen or so of new vaccine candidates in clinical trials for prevention of tuberculosis (TB) and each formulation attempts to elicit protection by enhancement of cell-mediated immunity (CMI). In contrast, most approved vaccines against other bacterial pathogens are believed to mediate protection by eliciting antibody responses. However, it has been difficult to apply this formula to TB because of the difficulty in reliably eliciting protective antibodies. Here, we developed capsular polysaccharide conjugates by linking mycobacterial capsular arabinomannan (AM) to either Mtb Ag85b or B. anthracis protective antigen (PA). Further, we studied their immunogenicity by ELISA and AM glycan microarrays and protection efficacy in mice. Immunization with either Abg85b-AM or PA-AM conjugates elicited an AM-specific antibody response in mice. AM binding antibodies stimulated transcriptional changes in Mtb. Sera from AM conjugate immunized mice reacted against a broad spectrum of AM structural variants and specifically recognized arabinan fragments. Conjugate vaccine immunized mice infected with Mtb had lower bacterial numbers in lungs and spleen, and lived longer than control mice. These findings provide additional evidence that humoral immunity can contribute to protection against Mtb

Attack Rates Assessment of the 2009 Pandemic H1N1 Influenza A in Children and Their Contacts: A Systematic Review and Meta-Analysis

Background: The recent H1N1 influenza A pandemic was marked by multiple reports of illness and hospitalization in children, suggesting that children may have played a major role in the propagation of the virus. A comprehensive detailed analysis of the attack rates among children as compared with their contacts in various settings is of great importance for understanding their unique role in influenza pandemics. Methodology/Principal Findings: We searched MEDLINE (PubMed) and Embase for published studies reporting outbreak investigations with direct measurements of attack rates of the 2009 pandemic H1N1 influenza A among children, and quantified how these compare with those of their contacts. We identified 50 articles suitable for review, which reported school, household, travel and social events. The selected reports and our meta-analysis indicated that children had significantly higher attack rates as compared to adults, and that this phenomenon was observed for both virologically confirmed and clinical cases, in various settings and locations around the world. The review also provided insight into some characteristics of transmission between children and their contacts in the various settings. Conclusion/Significance: The consistently higher attack rates of the 2009 pandemic H1N1 influenza A among children, as compared to adults, as well as the magnitude of the difference is important for understanding the contribution of children to disease burden, for implementation of mitigation strategies directed towards children, as well as more precise mathematical modeling and simulation of future influenza pandemics

Effectiveness of Influenza Vaccine in Preventing Medically-Attended Influenza Virus Infection in Primary Care, Israel, Influenza Seasons 2014/15 and 2015/16

IntroductionInfluenza vaccine is recommended for the entire population in Israel. We assessed influenza vaccine effectiveness (VE) for the 2014/15 and 2015/16 seasons in Israel, for the first time. Methods: Combined nose and throat swab specimens were collected from patients with influenza-like illness (ILI) presenting to sentinel primary care clinics and tested for influenza virus by RT-PCR. VE of the trivalent inactivated vaccine (TIV) was assessed using test-negative case-control design. Results: During the 2014/15 season 1,142 samples were collected; 327 (28.6%) were positive for influenza, 83.8% A(H3N2), 5.8% A(H1N1)pdm09, 9.2% B and 1.2% A un-subtyped. Adjusted VE against all influenza viruses for this influenza season was -4.8% (95% confidence interval (CI): -54.8 to 29.0) and against influenza A(H3N2), it was -15.8% (95% CI: -72.8 to 22.4). For the 2015/16 season, 1,919 samples were collected; 853 (44.4%) were positive for influenza, 43.5% A(H1N1)pdm09, 57% B, 0.7% A(H3N2) and 11 samples positive for both A(H1N1)pdm09 and B. Adjusted VE against all influenza viruses for this influenza season was 8.8% (95% CI: -25.1 to 33.5), against influenza A(H1N1)pdm09, it was 32.3% (95% CI: (-4.3 to 56.1) and against influenza B, it was -2.2% (95% CI: (-47.0 to 29.0). Conclusions: Using samples from patients with ILI visiting sentinel clinics in Israel, we demonstrated the feasibility of influenza VE estimation in Israel

Influenza vaccine compatibility among hospitalized patients during and after the COVID-19 pandemic

IntroductionFollowing the significant decrease in SARS-CoV-2 cases worldwide, Israel, as well as other countries, have again been faced with a rise in seasonal influenza. This study compared circulating influenza A and B in hospitalized patients in Israel with the influenza strains in the vaccine following the 2021–2022 winter season which was dominated by the omicron variant.MethodsNasopharyngeal samples of 16,325 patients were examined for the detection of influenza A(H1N1)pdm09, influenza A(H1N1)pdm09 and influenza B. Phylogenetic trees of hemagglutinin were then prepared using sanger sequencing. Vaccine immunogenicity was also performed using the hemagglutination inhibition test.ResultsOf the 16,325 nasopharyngeal samples collected from hospitalized patients between September 2021 (Week 40) and April 2023 (Week 15), 7.5% were found to be positive for influenza. Phylogenetic analyses show that in the 2021–2022 winter season, the leading virus subtype was influenza A(H3N2), belonging to clade 3C.2a1b.2a.2. However, the following winter season was dominated by influenza A(H1N1)pdm09, which belongs to clade 6B.aA.5a.2. The circulating influenza A(H1N1)pdm09 strain showed a shift from the vaccine strain, while the co-circulating influenza A(H3N2) and influenza B strains were similar to those of the vaccine. Antigenic analysis coincided with the sequence analysis.DiscussionInfluenza prevalence during 2022–2023 returned to typical levels as seen prior to the emergence of SARS-CoV-2, which may suggest a gradual viral adaptation to SARS-CoV-2 variants. Domination of influenza A(H1N1)pdm09 was observed uniquely in Israel compared to Europe and USA and phylogenetic and antigenic analysis showed lower recognition of the vaccine with the circulating influenza A(H1N1)pdm09 in Israel compared to the vaccine

Forty Five Percent of the Israeli Population were Infected with the Influenza B Victoria virus During the Winter season 2015-16

While infection with influenza A viruses has been extensively investigated, infections with influenza B viruses which are commonly categorized into the highly homologous Victoria and Yamagata lineages, are less studied, despite their considerable virulence. Here we used RT-PCR assays, hemagglutination inhibition assays and antibody titers to determine the levels of influenza B infection. We report of high influenza B Victoria virus prevalence in the 2015-16 winter season in Israel, affecting approximately half of the Israeli population. We further show that the Victoria B virus infected individuals of all ages and that it was present in the country throughout the entire winter season. The vaccine however included the inappropriate Yamagata virus. We propose that a quadrivalent vaccine, that includes both Yamagata and Victoria lineages, should be considered for future influenza vaccination

Genetic Divergence of Influenza A(H3N2) Amino Acid Substitutions Mark the Beginning of the 2016-2017 Winter Season in Israel

BACKGROUND: Influenza vaccine composition is reevaluated each year due to the frequency and accumulation of genetic changes that influenza viruses undergo. The beginning of the 2016-2017 influenza surveillance period in Israel has been marked by the dominance of influenza A(H3N2). OBJECTIVES: To evaluate the type, subtype, genetic evolution and amino acid substitutions of influenza A(H3N2) viruses detected among community patients with influenza-like illness (ILI) and hospitalized patients with respiratory illness in the first weeks of the 2016-2017 influenza season. STUDY DESIGN: Respiratory samples from community patients with influenza-like illness and from hospitalized patients underwent identification, subtyping and molecular characterization. Hemagglutinin sequences were compared to the vaccine strain, phylogenetic tree was created, and amino acid substitutions were determined. RESULTS: Influenza A(H3N2) predominated during the early stages of the 2016-2017 influenza season. Noticeably, approximately 20% of community patients and 36% of hospitalized patients, positive for influenza CONCLUSIONS: Characterization of the 2016-2017 A(H3N2) influenza viruses is imperative for determining the future influenza vaccine composition