The new Italian National Immunization Technical Advisory Group (NITAG) and its commitment to endorse a new efficient National Immunization Plan in COVID-19 times.

Among the objectives of the WHO Global Vaccination Action Plan 2020-2025, there is the establishment, in all countries, of a National Immunization Technical Advisory Group (NITAG), an independent body with the aim of supporting and harmonising vaccination policies. Italy firstly established a NITAG in 2017; it contributed to the nation's immunization policies but fell short of its goal of becoming a true reference group. The newly appointed NITAG, made up of 28 independent experts, has the ambitious goal to promote the new National Immunization Prevention Plan (PNPV), to harmonise the current vaccination schedule with the anti-COVID-19 campaign, and to recover the vaccination coverage decline that occurred during the pandemic. The contact with the ECDC EU/EEA, the WHO Global NITAG networks, and all the national stakeholders needs to be reinforced in order to accomplish these aims. This paper describes the structure, organisation, and strategy of the new Italian NITAG.

Analysis of COVID-19 Risk Following a Ring Vaccination Intervention to Address SARS-CoV-2 Alpha Variant Transmission in Montreal, Canada.

Importance: Given limited COVID-19 vaccine availability early in the pandemic, optimizing immunization strategies was of paramount importance. Ring vaccination has been used successfully to control transmission of other airborne respiratory viruses. Objective: To assess the association of a ring vaccination intervention on COVID-19 spread in the initial epicenter of SARS-CoV-2 Alpha variant transmission in Montreal, Canada. Design, Setting, and Participants: This cohort study compared COVID-19 daily disease risk in 3 population-based groups of neighborhoods in Montreal, Canada, defined by their intervention-specific vaccine coverage at the neighborhood level: the primary intervention group (500 or more vaccinated persons per 10 000 persons), secondary intervention group (95 to 499), and control group (0 to 50). The groups were compared within each of 3 time periods: before intervention (December 1, 2020, to March 16, 2021), during and immediately after intervention (March 17 to April 17, 2021), and 3 weeks after the intervention midpoint (April 18 to July 18, 2021). Data were analyzed between June 2021 and November 2021. Exposures: Vaccination targeted parents and teachers of children attending the 32 schools and 48 childcare centers in 2 adjacent neighborhoods with highest local transmission (case counts) of Alpha variant shortly after its introduction. Participants were invited to receive 1 dose of mRNA vaccine between March 22 and April 9, 2021 (before vaccine was available to these age groups). Main Outcomes and Measures: COVID-19 risk in 3 groups of neighborhoods based on intervention-specific vaccine coverage. Results: A total of 11 794 residents were immunized, with a mean (SD) age of 43 (8) years (range, 16-93 years); 5766 participants (48.9%) lived in a targeted neighborhood, and 9784 (83.0%) were parents. COVID-19 risk in the primary intervention group was significantly higher than in the control group before (unadjusted risk ratio [RR], 1.58; 95% CI 1.52-1.65) and during (RR, 1.63; 95% CI, 1.52-1.76) intervention, and reached a level similar to the other groups in the weeks following the intervention (RR, 1.03; 95% CI, 0.94-1.12). A similar trend was observed when restricting to SARS-CoV-2 variants and persons aged 30 to 59 years (before: RR, 1.72; 95% CI, 1.63-1.83 vs after: RR, 1.01; 95% CI, 0.88-1.17). Conclusions and Relevance: Our findings show that ring vaccination was associated with a reduction in COVID-19 risk in areas with high local transmission of Alpha variant shortly after its introduction. Ring vaccination may be considered as an adjunct to mass immunization to control transmission in specific areas, based on local epidemiology.

Measles.

Measles is a highly contagious, potentially fatal, but vaccine-preventable disease caused by measles virus. Symptoms include fever, maculopapular rash, and at least one of cough, coryza, or conjunctivitis, although vaccinated individuals can have milder or even no symptoms. Laboratory diagnosis relies largely on the detection of specific IgM antibodies in serum, dried blood spots, or oral fluid, or the detection of viral RNA in throat or nasopharyngeal swabs, urine, or oral fluid. Complications can affect many organs and often include otitis media, laryngotracheobronchitis, pneumonia, stomatitis, and diarrhoea. Neurological complications are uncommon but serious, and can occur during or soon after the acute disease (eg, acute disseminated encephalomyelitis) or months or even years later (eg, measles inclusion body encephalitis and subacute sclerosing panencephalitis). Patient management mainly involves supportive therapy, such as vitamin A supplementation, monitoring for and treatment of secondary bacterial infections with antibiotics, and rehydration in the case of severe diarrhoea. There is no specific antiviral therapy for the treatment of measles, and disease control largely depends on prevention. However, despite the availability of a safe and effective vaccine, measles is still endemic in many countries and causes considerable morbidity and mortality, especially among children in resource-poor settings. The low case numbers reported in 2020, after a worldwide resurgence of measles between 2017 and 2019, have to be interpreted cautiously, owing to the effect of the COVID-19 pandemic on disease surveillance. Disrupted vaccination activities during the pandemic increase the potential for another resurgence of measles in the near future, and effective, timely catch-up vaccination campaigns, strong commitment and leadership, and sufficient resources will be required to mitigate this threat.

Review of Oral Rabies Vaccination of Dogs and Its Application in India.

Oral rabies vaccines (ORVs) have been in use to successfully control rabies in wildlife since 1978 across Europe and the USA. This review focuses on the potential and need for the use of ORVs in free-roaming dogs to control dog-transmitted rabies in India. Iterative work to improve ORVs over the past four decades has resulted in vaccines that have high safety profiles whilst generating a consistent protective immune response to the rabies virus. The available evidence for safety and efficacy of modern ORVs in dogs and the broad and outspoken support from prominent global public health institutions for their use provides confidence to national authorities considering their use in rabies-endemic regions. India is estimated to have the largest rabies burden of any country and, whilst considerable progress has been made to increase access to human rabies prophylaxis, examples of high-output mass dog vaccination campaigns to eliminate the virus at the source remain limited. Efficiently accessing a large proportion of the dog population through parenteral methods is a considerable challenge due to the large, evasive stray dog population in many settings. Existing parenteral approaches require large skilled dog-catching teams to reach these dogs, which present financial, operational and logistical limitations to achieve 70% dog vaccination coverage in urban settings in a short duration. ORV presents the potential to accelerate the development of approaches to eliminate rabies across large areas of the South Asia region. Here we review the use of ORVs in wildlife and dogs, with specific consideration of the India setting. We also present the results of a risk analysis for a hypothetical campaign using ORV for the vaccination of dogs in an Indian state.

Equitable and Feasible Distribution of SARS-CoV-2 Vaccines for All in Africa.

As the fight against the coronavirus disease 2019 (COVID-19) pandemic continues, the necessity for wide-scale, global vaccine rollout to reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and slow its mutation rate remains unassailable. The COVID-19 Vaccines Global Access (COVAX) initiative's campaign involves a proportional framework to finance and distribute SARS-CoV-2 vaccines in low- and middle-income countries. However, the COVAX framework has critical limitations, including limited funding and the failure to account for the special epidemic risks and needs of its participating nations, as recommended by the World Health Organization's Strategic Advisory Group of Experts on Immunization framework. These drawbacks disproportionately impact Africa, where many nations rely on COVAX as their main source of vaccines. The current plan to vaccinate only up to 20% of participating nations' populations is short-sighted from both epidemiologic and moral perspectives. COVAX must commit to vaccinating all of Africa and its initiative must be modified to account for the health and economic infrastructures in these countries. Lessons learned from successful vaccination campaigns, including the West African Ebola outbreak, have shown that vaccinating all of Africa is possible and feasible, and that infrastructure and human resources can support mass vaccination. To halt this global pandemic, global responsibility must be accepted to finance and equitably distribute SARS-CoV-2 vaccines to African nations. We urge COVAX to act swiftly to prevent Africa from becoming the new face of a persisting pandemic.

Accounting for the spread of vaccination behavior to optimize influenza vaccination programs.

Vaccination is the most efficient means of preventing influenza infection and its complications. While previous studies have considered the externalities of vaccination that arise from indirect protection against influenza infection, they have often neglected another key factor-the spread of vaccination behavior among social contacts. We modeled influenza vaccination as a socially contagious process. Our model uses a contact network that we developed based on aggregated and anonymized mobility data from the cellphone devices of ~1.8 million users in Israel. We calibrated the model to high-quality longitudinal data of weekly influenza vaccination uptake and influenza diagnoses over seven years. We demonstrate how a simple coupled-transmission model accurately captures the spatiotemporal patterns of both influenza vaccination uptake and influenza incidence. Taking the identified complex underlying dynamics of these two processes into account, our model determined the optimal timing of influenza vaccination programs. Our simulation shows that in regions where high vaccination coverage is anticipated, vaccination uptake would be more rapid. Thus, our model suggests that vaccination programs should be initiated later in the season, to mitigate the effect of waning immunity from the vaccine. Our simulations further show that optimally timed vaccination programs can substantially reduce disease transmission without increasing vaccination uptake.

COVID-19 optimal vaccination policies: A modeling study on efficacy, natural and vaccine-induced immunity responses.

About a year into the pandemic, COVID-19 accumulates more than two million deaths worldwide. Despite non-pharmaceutical interventions such as social distance, mask-wearing, and restrictive lockdown, the daily confirmed cases remain growing. Vaccine developments from Pfizer, Moderna, and Gamaleya Institute reach more than 90% efficacy and sustain the vaccination campaigns in multiple countries. However, natural and vaccine-induced immunity responses remain poorly understood. There are great expectations, but the new SARS-CoV-2 variants demand to inquire if the vaccines will be highly protective or induce permanent immunity. Further, in the first quarter of 2021, vaccine supply is scarce. Consequently, some countries that are applying the Pfizer vaccine will delay its second required dose. Likewise, logistic supply, economic and political implications impose a set of grand challenges to develop vaccination policies. Therefore, health decision-makers require tools to evaluate hypothetical scenarios and evaluate admissible responses. Following some of the WHO-SAGE recommendations, we formulate an optimal control problem with mixed constraints to describe vaccination schedules. Our solution identifies vaccination policies that minimize the burden of COVID-19 quantified by the number of disability-adjusted years of life lost. These optimal policies ensure the vaccination coverage of a prescribed population fraction in a given time horizon and preserve hospitalization occupancy below a risk level. We explore "via simulation" plausible scenarios regarding efficacy, coverage, vaccine-induced, and natural immunity. Our simulations suggest that response regarding vaccine-induced immunity and reinfection periods would play a dominant role in mitigating COVID-19.

Optimal allocation of limited vaccine to control an infectious disease: Simple analytical conditions.

When allocating limited vaccines to control an infectious disease, policy makers frequently have goals relating to individual health benefits (e.g., reduced morbidity and mortality) as well as population-level health benefits (e.g., reduced transmission and possible disease eradication). We consider the optimal allocation of a limited supply of a preventive vaccine to control an infectious disease, and four different allocation objectives: minimize new infections, deaths, life years lost, or quality-adjusted life years (QALYs) lost due to death. We consider an SIR model with n interacting populations, and a single allocation of vaccine at time 0. We approximate the model dynamics to develop simple analytical conditions characterizing the optimal vaccine allocation for each objective. We instantiate the model for an epidemic similar to COVID-19 and consider n=2 population groups: one group (individuals under age 65) with high transmission but low mortality and the other group (individuals age 65 or older) with low transmission but high mortality. We find that it is optimal to vaccinate younger individuals to minimize new infections, whereas it is optimal to vaccinate older individuals to minimize deaths, life years lost, or QALYs lost due to death. Numerical simulations show that the allocations resulting from our conditions match those found using much more computationally expensive algorithms such as exhaustive search. Sensitivity analysis on key parameters indicates that the optimal allocation is robust to changes in parameter values. The simple conditions we develop provide a useful means of informing vaccine allocation decisions for communicable diseases.

Considerations for fair prioritization of COVID-19 vaccine and its mandate among healthcare personnel.

With current COVID-19 vaccine demand outweighing supply and the emergency authorization/rollout of three novel vaccines in the United States, discussions continue regarding fair prioritization among various groups for this scarce resource. The US federal government's recommended vaccination schedule, meant to assist states with vaccine allocation, demonstrates fair ethical considerations; however, difficulties remain comparing various groups to determine fair vaccine access and distribution. Although strides have been taken to analyze risks versus benefits of early vaccination across certain high-risk populations, prioritizing vulnerable populations versus essential workers remains challenging for multiple reasons. Similarly, as COVID-19 vaccine allocation and distribution continues in the US and in other countries, topics that require continued consideration include sub-prioritization among currently prioritized groups, prioritization among vulnerable groups disproportionately affected by the COVID-19 pandemic, like ethnic minorities, and holistic comparisons between groups who might receive various and disparate benefits from vaccination. Although all current COVID-19 vaccines are emergency authorization use only and a vaccine mandate would be considered only once these vaccines are licensed by the US Food and Drug Administration, future vaccination policies require time and deliberation. Similarly, given current vaccine hesitancy, mandatory vaccination of certain groups, like healthcare personnel, may need to be considered when these vaccines are licensed, especially if voluntary vaccination proves insufficient. Continued discussions regarding risks versus benefits of mandatory COVID-19 vaccination and the unique role of healthcare personnel in providing a safe healthcare environment could lead to better deliberation regarding potential policies. This commentary aims to address both questions of fair prioritization and sub-prioritization of various groups, as well as ethical considerations for mandatory COVID-19 vaccination among healthcare personnel.

Influenza-associated disease burden in mainland China: a systematic review and meta-analysis.

Influenza causes substantial morbidity and mortality. Many original studies have been carried out to estimate disease burden of influenza in mainland China, while the full disease burden has not yet been systematically reviewed. We did a systematic review and meta-analysis to assess the burden of influenza-associated mortality, hospitalization, and outpatient visit in mainland China. We searched 3 English and 4 Chinese databases with studies published from 2005 to 2019. Studies reporting population-based rates of mortality, hospitalization, or outpatient visit attributed to seasonal influenza were included in the analysis. Fixed-effects or random-effects model was used to calculate pooled estimates of influenza-associated mortality depending on the degree of heterogeneity. Meta-regression was applied to explore the sources of heterogeneity. Publication bias was assessed by funnel plots and Egger's test. We identified 30 studies eligible for inclusion with 17, 8, 5 studies reporting mortality, hospitalization, and outpatient visit associated with influenza, respectively. The pooled influenza-associated all-cause mortality rates were 14.33 and 122.79 per 100,000 persons for all ages and ≥ 65 years age groups, respectively. Studies were highly heterogeneous in aspects of age group, cause of death, statistical model, geographic location, and study period, and these factors could explain 60.14% of the heterogeneity in influenza-associated mortality. No significant publication bias existed in estimates of influenza-associated all-cause mortality. Children aged < 5 years were observed with the highest rates of influenza-associated hospitalizations and ILI outpatient visits. People aged ≥ 65 years and < 5 years contribute mostly to mortality and morbidity burden due to influenza, which calls for targeted vaccination policy for older adults and younger children in mainland China.

Risk factors for HPV infection and high-grade cervical disease in sexually active Japanese women.

In Japan, recommendations for HPV vaccines were suspended in 2013 due to unfounded safety fears. Although vaccine opponents claim modifying sexual behavior can prevent cervical cancer, no comprehensive data exist on sexual behavior and the risk of high-grade cervical disease in a Japanese population. This study investigates sexual behavior and the risk of HPV infection and cervical disease in 3968 women aged 20-41 yrs undergoing cervical screening between April 2014 and March 2016. Mean age at first intercourse was 18.4 yrs ± 2.8 and 32% of women reported ≥ 6 lifetime sexual partners. In regression analyses, number of partners was a significant risk factor for HPV infection. However, for high-grade disease (CIN2+), when HPV genotype was adjusted for, number of partners was not statistically significant. The greatest risk factor was an HPV16/18 infection (adjusted odds ratio 113.7, 95% CI: 40.8-316.9). In conclusion, we found that having an HPV16/18 infection and not sexual behavior was the most significant risk factor for high grade cervical disease in young Japanese women. These infections can be prevented by a highly effective vaccine and we recommend that the Japanese government resume proactive recommendations for the HPV vaccine immediately.

Summary of evidence to reduce the two-dose infant priming schedule to a single dose of the 13-valent pneumococcal conjugate vaccine in the national immunisation programme in the UK.

Pneumococcal conjugate vaccines (PCVs) are highly effective in preventing invasive and non-invasive pneumococcal infections in all age groups through a combination of direct and indirect protection. In many industrialised countries with established PCV programmes, the maximum benefit of the PCV programme has already been achieved, with most cases now due to non-PCV serotypes. On Jan 1, 2020, the UK changed its childhood pneumococcal immunisation programme from a two-dose infant priming schedule with the 13-valent PCV at 8 and 16 weeks after birth, to a single priming dose at 12 weeks after birth, while retaining the 12-month booster. This decision was made after reviewing the evidence from surveillance data, clinical trials, epidemiological analyses, vaccine effectiveness estimates, and modelling studies to support the reduced schedule. In this Review, we summarise the epidemiology of pneumococcal disease in the UK, the evidence supporting the decision to implement a reduced schedule, and the national and global implications of the proposed schedule.

Assessment of A20 infectious laryngotracheitis vaccine take in meat chickens using swab and dust samples following mass vaccination in drinking water.

Infectious laryngotracheitis, caused by the alphaherpesvirus infectious laryngotracheitis virus (ILTV), is an important disease of chickens. Partial control of this disease in meat chickens is commonly achieved by mass vaccination with live virus in drinking water. There is a need for a practical test to evaluate vaccination outcomes. For the Serva ILTV vaccine, quantitative real-time PCR (qPCR) enumeration of ILTV genome copies (GC) in flock level dust samples collected at 7-8 days post vaccination (dpv) can be used to differentiate flocks with poor and better vaccine take. This study aimed to validate this approach for A20, another widely used ILT vaccine in Australia. In four meat chicken flocks vaccinated with A20 in water using two different water stabilization times (20 or 40 min), swabs from the trachea and choanal cleft and dust samples were collected at 0, 7, 14 and 21 dpv. ILTV GC detection in swabs and dust was highest at 7 dpv and at this time ILTV GC load in dust was strongly and positively associated with vaccine take in individual birds assessed by swab samples. Choanal cleft swabs provided significantly fewer ILTV positive results than paired tracheal swab samples but the level of ILTV GC detected was similar. Water stabilization time had only minor effects on vaccination response in favour of the shorter time. Location of dust collection had no effect on viral load measured in dust samples. Dust samples collected at 0 and 7 dpv can be used to assess the vaccination status of flocks.