Role of the National Immunisation Technical Advisory Groups in 13 European countries in the decision-making process on vaccine recommendations.

In Europe, National Immunisation Technical Advisory Groups (NITAGs) were established in most countries to promote evidence-informed decision-making in introducing new or improved vaccines or changing recommendations for existing ones. Still, the role, activities and outcomes of NITAGs have not been optimally implemented across Europe. Within the European Joint Action on Vaccination (EU-JAV), we conducted a survey to collect information on decision-making process including the main criteria for the introduction of new vaccines or changes to recommendations on their use. Between December 2021 and January 2022, 13 of the 28 European countries invited participated in an online survey. The criteria ranked as most relevant were disease burden and availability of financial resources. Only one country specified that the NITAG recommendations were binding for the government or the health authority. Vaccinations more often reported for introduction or recommendation changes were those against herpes zoster, influenza, human papillomavirus infection, pneumococcal and meningococcal disease. The planned changes will mainly address children and adolescents (2-18 years) and adults (≥ 45-65 years). Our findings show potential overlaps in the activities of NITAGs between countries; and therefore, collaboration between NITAGs may lead to optimisation of the workload and better use of resources.

Relative effectiveness of bivalent Original/Omicron BA.4-5 mRNA vaccine in preventing severe COVID-19 in persons 60 years and above during SARS-CoV-2 Omicron XBB.1.5 and other XBB sublineages circulation, Italy, April to June 2023.

During predominant circulation of SARS-CoV-2 Omicron XBB.1.5 and other XBB sublineages (April-June 2023), we found that a second or third booster of Comirnaty bivalent Original/Omicron BA.4-5 mRNA vaccine, versus a first booster received at least 120 days earlier, was effective in preventing severe COVID-19 for more than 6 months post-administration in persons 60 years and above. In view of autumn 2023 vaccination campaigns, use of bivalent Original/Omicron BA.4-5 mRNA vaccines might be warranted until monovalent COVID-19 vaccines targeting Omicron XBB.1 sublineages become available.

Relative effectiveness of monovalent and bivalent mRNA boosters in preventing severe COVID-19 due to omicron BA.5 infection up to 4 months post-administration in people aged 60 years or older in Italy: a retrospective matched cohort study.

BACKGROUND: Limited evidence is available on the additional protection conferred by second mRNA vaccine boosters against severe COVID-19 caused by omicron BA.5 infection, and whether the adapted bivalent boosters provide additional protection compared with the monovalent ones. In this study, we aimed to estimate the relative effectiveness of a second booster with monovalent or bivalent mRNA vaccines against severe COVID-19 in Italy. METHODS: Linking data from the Italian vaccination registry and the SARS-CoV-2 surveillance system, between Sept 12, 2022, and Jan 7, 2023, we matched 1:1 each person aged 60 years or older receiving a second booster with a person who had received the first booster only at least 120 days earlier. We used hazard ratios, estimated through Cox proportional hazard models, to compare the hazard of severe COVID-19 between the first booster group and each type of second booster (monovalent mRNA vaccine targeting the original strain of SARS-CoV-2, bivalent mRNA vaccine targeting the original strain plus omicron BA.1 [bivalent original/BA.1], and bivalent mRNA vaccine targeting the original strain plus omicron BA.4 and BA.5 [bivalent original/BA.4-5]). Relative vaccine effectiveness (rVE) was calculated as (1-hazard ratio) × 100. FINDINGS: We analysed a total of 2 129 559 matched pairs. The estimated rVE against severe COVID-19 with the bivalent original/BA.4-5 booster was 50·6% (95% CI 46·0-54·8) in the overall time interval 14-118 days post-administration. Overall, rVE was 49·3% (43·6-54·4) for the bivalent original/BA.1 booster and 26·9% (11·8-39·3) for the monovalent booster. For the bivalent original/BA.4-5 booster, we did not observe relevant differences in rVE between the 60-79-year age group (overall, 53·6%; 46·8-59·5) and those aged 80 years or older (overall, 48·3%; 41·9-54·0). INTERPRETATION: These findings suggest that a second booster with mRNA vaccines provides additional protection against severe COVID-19 due to omicron BA.5 (the predominant circulating subvariant in Italy during the study period) in people aged 60 years or older. Although rVE decreased over time, a second booster with the original/BA.4-5 mRNA vaccine, currently the most used in Italy, was found to be still providing protection 4 months post-administration. FUNDING: NextGenerationEU-MUR-PNRR Extended Partnership initiative on Emerging Infectious Diseases (project number PE00000007, INF-ACT). TRANSLATION: For the Italian translation of the abstract see Supplementary Materials section.

Assessment of Pertussis Underreporting in Italy.

A study was conducted to assess the degree of pertussis underreporting in Italy. An analysis was performed to compare the frequency of pertussis infections estimated using seroprevalence data with the pertussis incidence based on reported cases among the Italian population. For this purpose, the proportion of subjects who had an anti-PT ≥ 100 IU/mL (indicative of B. pertussis infection within the last 12 months) was compared with the reported incidence rate among the Italian population ≥5 years old, divided into two age groups (6-14 and ≥15 years old), obtained from the European Centre for Disease Prevention and Control (ECDC) database. The pertussis incidence rate in the Italian population ≥5 years old reported by the ECDC in 2018 was 6.75/100,000 in the 5-14 age group and 0.28/100,000 in the ≥15 age group. The proportion of subjects recruited in the present study with an anti-PT ≥ 100 IU/mL was 0.95% in the 6-14 age group and 0.97% in the ≥15 age group. The estimated rate of pertussis infections based on seroprevalence was approximately 141-fold and 3452-fold higher than the reported incidence in the 6-14 age group and in the ≥15 age group, respectively. Quantification of underreporting can allow for the burden of pertussis, as well as the impact of ongoing vaccination, to be better evaluated.

Protection against severe COVID-19 after second booster dose of adapted bivalent (original/Omicron BA.4-5) mRNA vaccine in persons ≥ 60 years, by time since infection, Italy, 12 September to 11 December 2022.

Effectiveness against severe COVID-19 of a second booster dose of the bivalent (original/BA.4-5) mRNA vaccine 7-90 days post-administration, relative to a first booster dose of an mRNA vaccine received ≥ 120 days earlier, was ca 60% both in persons ≥ 60 years never infected and in those infected > 6 months before. Relative effectiveness in those infected 4-6 months earlier indicated no significant additional protection (10%; 95% CI: -44 to 44). A second booster vaccination 6 months after the latest infection may be warranted.

Sero-Epidemiological Study of Varicella in the Italian General Population.

The aim of this study was to analyze the seroprevalence of varicella in Italy and to evaluate the impact of varicella vaccination, which has been mandatory for newborns since 2017. The levels of VZV-specific IgG antibodies were determined by the ELISA method in residual serum samples obtained from subjects aged between 6 and 64 years and residing in 13 Italian regions. Overall, 3746 serum samples were collected in the years 2019 and 2020. The overall seroprevalence was 91.6% (89.9% in males and 93.3% in females; p = 0.0002). Seroprevalence showed an increasing trend (p < 0.0001) starting in the younger age groups: 6-9 years: 84.1%; 10-14 years: 88.7%; 15-19 years: 89.3%; 20-39 years: 93.1% and >40 years: 97.0%. The seroprevalence data obtained in the present study were compared with those relating to previous sero-epidemiological surveys conducted, respectively, in the years 1996-1997, 2003-2004 and 2013-2014, taking into consideration only data from regions monitored in all surveillance campaigns. The comparison highlighted for the period 2019-2020 showed significantly higher values in the age groups 6-9 (p < 0.001), 10-14 (p = 0.018) and 15-19 years (p = 0.035), while in adults, the trend did not change over time (ns). These results highlight the positive impact of varicella vaccination in Italy.

Decline in reported measles cases in Italy in the COVID-19 era, January 2020 - July 2022: The need to prevent a resurgence upon lifting non-pharmaceutical pandemic measures.

From January 2020 to July 2022, 120 measles cases were reported to the Italian national surveillance system, of which 105 had symptom onset in 2020, nine in 2021 and six in the first seven months of 2022. This represents a sharp decline compared to the time period immediately preceding the COVID-19 pandemic, most likely due to the non-pharmaceutical interventions implemented to prevent SARS-CoV2 transmission. Of 105 cases reported in 2020, 103 acquired the infection before a national lockdown was instituted on 9 March 2020. Overall, one quarter of cases reported at least one complication. As non-pharmaceutical pandemic measures are being eased worldwide, and considering measles seasonality, infectiousness, and its potential severity, it is important that countries ensure high vaccination coverage and close immunity gaps, to avoid risk of future outbreaks.

Relative effectiveness of a 2nd booster dose of COVID-19 mRNA vaccine up to four months post administration in individuals aged 80 years or more in Italy: A retrospective matched cohort study.

Several countries started a 2nd booster COVID-19 vaccination campaign targeting the elderly population, but evidence around its effectiveness is still scarce. This study aims to estimate the relative effectiveness of a 2nd booster dose of COVID-19 mRNA vaccine in the population aged ≥ 80 years in Italy, during predominant circulation of the Omicron BA.2 and BA.5 subvariants. We linked routine data from the national vaccination registry and the COVID-19 surveillance system. On each day between 11 April and 6 August 2022, we matched 1:1, according to several demographic and clinical characteristics, individuals who received the 2nd booster vaccine dose with individuals who received the 1st booster vaccine dose at least 120 days earlier. We used the Kaplan-Meier method to compare the risks of SARS-CoV-2 infection and severe COVID-19 (hospitalisation or death) between the two groups, calculating the relative vaccine effectiveness (RVE) as (1 - risk ratio)X100. Based on the analysis of 831,555 matched pairs, we found that a 2nd booster dose of mRNA vaccine, 14-118 days post administration, was moderately effective in preventing SARS-CoV-2 infection compared to a 1st booster dose administered at least 120 days earlier [14.3 %, 95 % confidence interval (CI): 2.2-20.2]. RVE decreased from 28.5 % (95 % CI: 24.7-32.1) in the time-interval 14-28 days to 7.6 % (95 % CI: -14.1 to 18.3) in the time-interval 56-118 days. However, RVE against severe COVID-19 was higher (34.0 %, 95 % CI: 23.4-42.7), decreasing from 43.2 % (95 % CI: 30.6-54.9) to 27.2 % (95 % CI: 8.3-42.9) over the same time span. Although RVE against SARS-CoV-2 infection was much reduced 2-4 months after a 2nd booster dose, RVE against severe COVID-19 was about 30 %, even during prevalent circulation of the Omicron BA.5 subvariant. The cost-benefit of a 3rd booster dose for the elderly people who received the 2nd booster dose at least four months earlier should be carefully evaluated.

Sero-Epidemiological Study of Bordetella pertussis Infection in the Italian General Population.

A multicenter study was conducted to estimate the prevalence of pertussis IgG antibodies (anti-PTx) in the Italian population. Serum samples (4154) collected in the years 2019−2020 from subjects aged 6 to 90 years were tested. The anti-PTx IgG levels were determined by ELISA test. The limit of detection was 5 IU/mL (International Units per milliliter); values ≥ 40 IU/mL and ≥100 IU/mL indicate an infection that has occurred in recent years and a recent infection (occurred during the last year), respectively. The mean concentration of anti-PTx IgG antibodies in the tested samples was 13 IU/mL; 1.0% of subjects had a titer ≥ 100 IU/mL, 5.3% a titer between 40 and 100 IU/mL, and 38.9% a titer < 5 IU/mL. The mean antibody concentration was significantly higher in males than in females. The age group 25−39 years had the lowest percentage of negative subjects (36.9%) and the highest prevalence of subjects with antibody titers ≥ 100 IU/mL (1.3%). In the age group ≥ 65 years, the prevalence of subjects with titers between 40 and 100 IU/mL (6.7%) and the percentage of negative subjects (44.8%) was higher than in the other age groups. The results highlight the possible role of adolescents and adults in the transmission of B. pertussis.

Characteristics of COVID-19 cases in Italy from a sex/gender perspective.

INTRODUCTION: Coronavirus disease 19 (COVID-19) is an infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To date, few data on clinical features and risk factors for disease severity and death by gender are available. AIM: The current study aims to describe from a sex/gender perspective the characteristics of the SARS-CoV-2 cases occurred in the Italian population from February 2020 until October 2021. METHOD AND RESULTS: We used routinely collected data retrieved from the Italian National Surveillance System. The highest number of cases occurred among women between 40 and 59 years, followed by men in the same age groups. The proportion of deaths due to COVID-19 was higher in men (56.46%) compared to women (43.54%). Most of the observed deaths occurred in the elderly. Considering the age groups, the clinical outcomes differed between women and men in particular in cases over 80 years of age; with serious or critical conditions more frequent in men than in women. CONCLUSIONS: Our data clearly demonstrate a similar number of cases in women and men, but with more severe disease and outcome in men, thus confirming the importance to analyse the impact of sex and gender in new and emerging diseases.

Understanding the vaccine stance of Italian tweets and addressing language changes through the COVID-19 pandemic: Development and validation of a machine learning model.

Social media is increasingly being used to express opinions and attitudes toward vaccines. The vaccine stance of social media posts can be classified in almost real-time using machine learning. We describe the use of a Transformer-based machine learning model for analyzing vaccine stance of Italian tweets, and demonstrate the need to address changes over time in vaccine-related language, through periodic model retraining. Vaccine-related tweets were collected through a platform developed for the European Joint Action on Vaccination. Two datasets were collected, the first between November 2019 and June 2020, the second from April to September 2021. The tweets were manually categorized by three independent annotators. After cleaning, the total dataset consisted of 1,736 tweets with 3 categories (promotional, neutral, and discouraging). The manually classified tweets were used to train and test various machine learning models. The model that classified the data most similarly to humans was XLM-Roberta-large, a multilingual version of the Transformer-based model RoBERTa. The model hyper-parameters were tuned and then the model ran five times. The fine-tuned model with the best F-score over the validation dataset was selected. Running the selected fine-tuned model on just the first test dataset resulted in an accuracy of 72.8% (F-score 0.713). Using this model on the second test dataset resulted in a 10% drop in accuracy to 62.1% (F-score 0.617), indicating that the model recognized a difference in language between the datasets. On the combined test datasets the accuracy was 70.1% (F-score 0.689). Retraining the model using data from the first and second datasets increased the accuracy over the second test dataset to 71.3% (F-score 0.713), a 9% improvement from when using just the first dataset for training. The accuracy over the first test dataset remained the same at 72.8% (F-score 0.721). The accuracy over the combined test datasets was then 72.4% (F-score 0.720), a 2% improvement. Through fine-tuning a machine-learning model on task-specific data, the accuracy achieved in categorizing tweets was close to that expected by a single human annotator. Regular training of machine-learning models with recent data is advisable to maximize accuracy.

Effectiveness of BNT162b2 vaccine against SARS-CoV-2 infection and severe COVID-19 in children aged 5-11 years in Italy: a retrospective analysis of January-April, 2022.

BACKGROUND: By April 13, 2022, more than 4 months after the approval of BNT162b2 (Pfizer-BioNTech) for children, less than 40% of 5-11-year-olds in Italy had been vaccinated against COVID-19. Estimating how effective vaccination is in 5-11-year-olds in the current epidemiological context dominated by the omicron variant (B.1.1.529) is important to inform public health bodies in defining vaccination policies and strategies. METHODS: In this retrospective population analysis, we assessed vaccine effectiveness against SARS-CoV-2 infection and severe COVID-19, defined as an infection leading to hospitalisation or death, by linking the national COVID-19 surveillance system and the national vaccination registry. All Italian children aged 5-11 years without a previous diagnosis of infection were eligible for inclusion and were followed up from Jan 17 to April 13, 2022. All children with inconsistent vaccination data, diagnosed with SARS-CoV-2 infection before the start date of the study or without information on the municipality of residence were excluded from the analysis. With unvaccinated children as the reference group, we estimated vaccine effectiveness in those who were partly vaccinated (one dose) and those who were fully vaccinated (two doses). FINDINGS: By April 13, 2022, 1 063 035 (35·8%) of the 2 965 918 children aged 5-11 years included in the study had received two doses of the vaccine, 134 386 (4·5%) children had received one dose only, and 1 768 497 (59·6%) were unvaccinated. During the study period, 766 756 cases of SARS-CoV-2 infection and 644 cases of severe COVID-19 (627 hospitalisations, 15 admissions to intensive care units, and two deaths) were notified. Overall, vaccine effectiveness in the fully vaccinated group was 29·4% (95% CI 28·5-30·2) against SARS-CoV-2 infection and 41·1% (22·2-55·4) against severe COVID-19, whereas vaccine effectiveness in the partly vaccinated group was 27·4% (26·4-28·4) against SARS-CoV-2 infection and 38·1% (20·9-51·5) against severe COVID-19. Vaccine effectiveness against infection peaked at 38·7% (37·7-39·7) at 0-14 days after full vaccination and decreased to 21·2% (19·7-22·7) at 43-84 days after full vaccination. INTERPRETATION: Vaccination against COVID-19 in children aged 5-11 years in Italy showed a lower effectiveness in preventing SARS-CoV-2 infection and severe COVID-19 than in individuals aged 12 years and older. Effectiveness against infection appears to decrease after completion of the current primary vaccination cycle. FUNDING: None. TRANSLATION: For the Italian translation of the summary see Supplementary Materials section.

How the Italian Twitter Conversation on Vaccines Changed During the First Phase of the Pandemic: A Mixed-Method Analysis.

In the context of the European Joint Action on Vaccination, we analyzed, through quantitative and qualitative methods, a random sample of vaccine-related tweets published in Italy between November 2019 and June 2020, with the aim of understanding how the Twitter conversation on vaccines changed during the first phase of the pandemic, compared to the pre-pandemic months. Tweets were analyzed by a multidisciplinary team in terms of kind of vaccine, vaccine stance, tone of voice, population target, mentioned source of information. Multiple correspondence analysis was used to identify variables associated with vaccine stance. We analyzed 2,473 tweets. 58.2% mentioned the COVID-19 vaccine. Most had a discouraging stance (38.1%), followed by promotional (32.5%), neutral (22%) and ambiguous (2.5%). The discouraging stance was the most represented before the pandemic (69.6%). In February and March 2020, discouraging tweets decreased intensely and promotional and neutral tweets dominated the conversation. Between April and June 2020, promotional tweets remained more represented (36.5%), followed by discouraging (30%) and neutral (24.3%). The tweets' tone of voice was mainly polemical/complaining, both for promotional and for discouraging tweets. The multiple correspondence analysis identified a definite profile for discouraging and neutral tweets, compared to promotional and ambiguous tweets. In conclusion, the emergence of SARS-CoV-2 caused a deep change in the vaccination discourse on Twitter in Italy, with an increase of promotional and ambiguous tweets. Systematic monitoring of Twitter and other social media, ideally combined with traditional surveys, would enable us to better understand Italian vaccine hesitancy and plan tailored, data-based communication strategies.

Case Report: First Report of Fatal Legionella pneumophila and Klebsiella pneumoniae Coinfection in a Kidney Transplant Recipient.

A very rare case of pulmonary Klebsiella pneumoniae-Legionella pneumophila coinfection in a double kidney transplanted man affected by the chronic renal disease is described. Cases of Legionnaires' disease with an incubation period of 14 days have rarely been documented. Despite the long period of hospitalization, typing of clinical and environmental L. pneumophila strains demonstrated that the patient's home water distribution system was the source of infection, highlighting that Legionella house contamination can be a hidden risk, especially for immune-compromised people.

Risk and protective factors for SARS-CoV-2 reinfections, surveillance data, Italy, August 2021 to March 2022.

We explored the risk factors associated with SARS-CoV-2 reinfections in Italy between August 2021 and March 2022. Regardless of the prevalent virus variant, being unvaccinated was the most relevant risk factor for reinfection. The risk of reinfection increased almost 18-fold following emergence of the Omicron variant compared with Delta. A severe first SARS-CoV-2 infection and age over 60 years were significant risk factors for severe reinfection.

Winning during a pandemic: epidemiology of SARS-CoV-2 during EURO2020 in Italy.

INTRODUCTION: EURO2020 generated a growing media and population interest across the month period, that peaked with large spontaneous celebrations across the country upon winning the tournament. METHODS: We retrospectively analysed data from the national surveillance system (indicator-based) and from event-based surveillance to assess how the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) changed in June-July 2021 and to describe cases and clusters linked with EURO2020. RESULTS: Widespread increases in transmission and case numbers, mainly among younger males, were documented in Italy, none were linked with stadium attendance. Vaccination coverage against SARS-CoV-2 was longer among cases linked to EURO2020 than among the general population. CONCLUSIONS: Transmission increased across the country, mainly due to gatherings outside the stadium, where, conversely, strict infection control measures were enforced. These informal 'side' gatherings were dispersed across the entire country and difficult to control. Targeted communication and control strategies to limit the impact of informal gatherings occurring outside official sites of mass gathering events should be further developed.

Effectiveness of an mRNA vaccine booster dose against SARS-CoV-2 infection and severe COVID-19 in persons aged ≥60 years and other high-risk groups during predominant circulation of the delta variant in Italy, 19 July to 12 December 2021.

BACKGROUND: Consolidated information on the effectiveness of COVID-19 booster vaccination in Europe are scarce. RESEARCH DESIGN AND METHODS: We assessed the effectiveness of a booster dose of an mRNA vaccine against any SARS-CoV-2 infection (symptomatic or asymptomatic) and severe COVID-19 (hospitalization or death) after over two months from administration among priority target groups (n = 18,524,568) during predominant circulation of the Delta variant in Italy (July-December 2021). RESULTS: Vaccine effectiveness (VE) against SARS-CoV-2 infection and, to a lesser extent, against severe COVID-19, among people ≥60 years and other high-risk groups (i.e. healthcare workers, residents in long-term-care facilities, and persons with comorbidities or immunocompromised), peaked in the time-interval 3-13 weeks (VE against infection = 67.2%, 95% confidence interval (CI): 62.5-71.3; VE against severe disease = 89.5%, 95% CI: 86.1-92.0) and then declined, waning 26 weeks after full primary vaccination (VE against infection = 12.2%, 95% CI: -4.7-26.4; VE against severe disease = 65.3%, 95% CI: 50.3-75.8). After 3-10 weeks from the administration of a booster dose, VE against infection and severe disease increased to 76.1% (95% CI: 70.4-80.7) and 93.0% (95% CI: 90.2-95.0), respectively. CONCLUSIONS: These results support the ongoing vaccination campaign in Italy, where the administration of a booster dose four months after completion of primary vaccination is recommended.

Genome analysis of Legionella pneumophila ST23 from various countries reveals highly similar strains.

Legionella pneumophila serogroup 1 (Lp1) sequence type (ST) 23 is one of the most commonly detected STs in Italy where it currently causes all investigated outbreaks. ST23 has caused both epidemic and sporadic cases between 1995 and 2018 and was analysed at genomic level and compared with ST23 isolated in other countries to determine possible similarities and differences. A core genome multi-locus sequence typing (cgMLST), based on a previously described set of 1,521 core genes, and single-nucleotide polymorphisms (SNPs) approaches were applied to an ST23 collection including genomes from Italy, France, Denmark and Scotland. DNAs were automatically extracted, libraries prepared using NextEra library kit and MiSeq sequencing performed. Overall, 63 among clinical and environmental Italian Lp1 isolates and a further seven and 11 ST23 from Denmark and Scotland, respectively, were sequenced, and pangenome analysed. Both cgMLST and SNPs analyses showed very few loci and SNP variations in ST23 genomes. All the ST23 causing outbreaks and sporadic cases in Italy and elsewhere, were phylogenetically related independent of year, town or country of isolation. Distances among the ST23s were further shortened when SNPs due to horizontal gene transfers were removed. The Lp1 ST23 isolated in Italy have kept their monophyletic origin, but they are phylogenetically close also to ST23 from other countries. The ST23 are quite widespread in Italy, and a thorough epidemiological investigation is compelled to determine sources of infection when this ST is identified in both LD sporadic cases and outbreaks.

Are vaccine shortages a relevant public health issue in Europe? Results from a survey conducted in the framework of the EU Joint Action on Vaccination.

National immunisation programmes require an adequate supply of vaccines to function properly but many countries, globally and in Europe, have reported vaccine shortages. A comprehensive view of vaccine shortages and stockouts in the EU/EEA is missing in the published literature. This study was conducted in the framework of the European Joint Action on Vaccination (EU-JAV). Twenty-eight countries, including 20 EU-JAV consortium member states and an additional 8 EU/EEA countries, were invited to participate in a survey aimed at collecting information on vaccine shortages and stock-outs experienced from 2016 to 2019, their main causes, actions taken, and other aspects of vaccine supply. Twenty-one countries completed the survey (response rate 75%), of which 19 reported at least one shortage/stock-out event. Overall, 115 events were reported, 28 of which led to a change in the national immunisation programme. The most frequently involved vaccines were DT- and dT-containing combination vaccines, hepatitis B, hepatitis A, and BCG vaccines. The median duration of shortages/stock-outs was five months (range <1 month-39 months). Interruption in supply and global shortage were the most frequently indicated causes. Only about half of countries reported having an immunization supply chain improvement plan. Similarly, only about half of countries had recommendations or procedures in place to address shortages/stockouts. The survey also identified the occurrence of shortages/stockouts of other biological products (e.g. diphtheria antitoxin in 12 countries). Public health strategies to assure a stable and adequate vaccine supply for immunization programmes require coordinated actions from all stakeholders, harmonized definitions, strengthening of reporting and monitoring systems, the presence of an immunization supply chain improvement plan in all countries, and procedures or recommendations in place regarding the use of alternative vaccines or vaccination schedules in case of shortages/stockouts.

Vaccine Procurement: A Conceptual Framework Based on Literature Review.

Ensuring timely access to affordable vaccines has been acknowledged as a global public health priority, as also recently testified by the debate sparked during the COVID-19 pandemic. Effective vaccine procurement strategies are essential to reach this goal. Nevertheless, this is still a neglected research topic. A narrative literature review on vaccine procurement was conducted, by retrieving articles from four academic databases (PubMed/MEDLINE, Scopus, Embase, WebOfScience), 'grey' literature reports, and institutional websites. The aim was to clarify key concepts and definitions relating to vaccine procurement, describe main vaccine procurement methods, and identify knowledge gaps and future perspectives. A theoretical conceptual framework was developed of the key factors involved in vaccine procurement, which include quality and safety of the product, forecasting and budgeting, procurement legislation, financial sustainability, and plurality of manufacture, contracting, investment in training, storage and service delivery, monitoring and evaluation. This information can be useful to support policymakers during planning, implementation, and evaluation of regional and national vaccine procurement strategies and policies.