The impact of COVID-19 vaccination programme in the Republic of San Marino: Focus on effectiveness of Gam-Covid-Vac.

OBJECTIVE: The adenovirus-based vaccine Gam-COVID-Vac (Sputnik V) showed promising effectiveness in a phase 3 clinical trial; however, data concerning its impact at a population level are scarce. The Republic of San Marino (RSM) conducted a SARS-CoV-2 vaccination programme mainly based (>80%) on Gam-COVID-Vac. Our aims were to investigate the impact of Gam-COVID-Vac vaccination programme and its effectiveness in a retrospective observational study based on the entire RSM population aged ≥12 years. METHODS: We calculated the incidence rate and the vaccine effectiveness (VE) in the entire RSM population not previously infected, against SARS-CoV-2 infection and COVID-19-related hospitalization, from 25 February to 1 October 2021, considering any vaccine and separately according to the vaccine used. Vaccine effectiveness was calculated using a multivariable negative binomial regression model as 1-Incidence Rate Ratio. RESULTS: During the study period, 21 568/28 791 (74.9%) not previously infected subjects received at least one dose of the Gam-COVID-Vac (84%) or BNT162b2, vaccines with 98% completing the vaccination schedule. Overall, 1634 SARS-CoV-2 infections and 166 COVID-19-related hospitalizations were observed with 17 COVID-19-related deaths reported. Incidence rates of SARS-CoV-2 infection and COVID-19-related hospitalization were 7.11 and 0.49/100 000 person-days in the fully vaccinated population, respectively. The adjusted overall VE was 67.6% (95% CI: 61.8-72.5) against SARS-CoV-2 infection and 87.9% (95% CI: 77.4-93.5) against COVID-19-related hospitalizations. Gam-COVID-Vac against SARS-CoV-2 infection VE peaked 91.8% (95% CI: 86.3-95.1) in the first bimester from the second dose, declining to 57.8% (95% CI: 42.2-69.2) at 6 months. Protection against hospitalization with COVID-19 was overall 91.6% (95% CI: 81.5-96.2), with no relevant waning trend over time. DISCUSSION: Our study demonstrated the effectiveness of overall vaccination (Gam-COVID-Vac [84%] and BNT162b2 [16%]) in the prevention SARS-CoV-2 infection (pre-Omicron variant), waning over time but still with sustainable effectiveness against COVID-19-related hospitalization in the Republic of San Marino.

Managing COVID-19 in four small countries: Initial response to the pandemic in San Marino, Montenegro, Malta and Cyprus.

The aim of this paper is to compare the impact of the COVID-19 pandemic on four small countries in the southern half of Europe with similar public health systems: San Marino, Montenegro, Malta and Cyprus, the latter two being island states. There are advantages and disadvantages in being a small nation amidst this crisis. The centralized public health administration means that small countries are faster at adapting as they learn and evolve on a weekly basis. However, small countries tend to be dependent on their bigger neighbours, and the networks they belong to, for trade, food, medical supplies as well as policies. The risk threshold taken by a small country for the transition strategy has to be less than that taken by a bigger country because if things go wrong in a border region, there is less resilience in a small country, with immediate impact on the whole country. The blow to the tourism industry, which plays a main role especially in small countries, negatively impacted the economy, and it has been a feat to reach a balance between allowing the flow of inbound tourists and keeping the local infection rates under control.

Measles and rubella elimination country profile: San Marino

Conclusions and recommendations of the European Regional Verification Commission for Measles and Rubella Elimination, based on 2018 data submitted by national verification committees.

Monitoring and managing workforce mobility in San Marino

San Marino has information on all professional health workers. At present, the country faces the challenge of finding medical doctors willing to work in San Marino to replace retiree physicians. The replacement of nurses is also an emerging problem. The development of a structured digital platform is currently underway and should provide continuous information about the health workforce. Other challenges for San Marino relate to planning the health workforce (for example, understanding numbers, specialization, workforce age). There is a problem in securing enough university training spots for San Marino’s citizens in other countries. High-school graduates in San Marino wishing to enter faculties of medicine and surgery can apply to the many Italian universities that reserve a fixed number of places for foreign students.

Postgraduate training in San Marino

In San Marino, physicians, pharmacists and biologists undergo practical training at the Institute of Social Security (2 years for physicians and 6 months for pharmacists and biologists), but there is no certification process in place. It is foreseen that a law will be passed in the near future requiring 3 years’ postgraduate training for physicians. In addition, it will be compulsory for physicians wishing to work in general practice to have worked for at least 3 years in the San Marino Hospital and the Primary Care Unit. Most health professionals in San Marino need to go abroad for specialist training. For the last 15 years, a course leading to a university degree in nursing has been available in the country.

Strongyloides stercoralis infection in San Marino Republic: first epidemiological data from an observational study.

Strongyloides stercoralis is a neglected parasite that can cause death in immunocompromised individuals. There were no data on the epidemiology of S. stercoralis infection in San Marino Republic until two patients (one of whom died) were diagnosed with severe strongyloidiasis (hyperinfection) between September 2016 and March 2017. A serology test for Strongyloides spp. was introduced in routine practice in the laboratory of the State Hospital to test patients considered to be at risk for strongyloidiasis. Between August 2017 and August 2018, of 42 patients tested with serology, two (4.8%) were positive. An additional case was found by gastric biopsy. Two of the positive cases were presumably autochthonous infections (elderly people with no significant travel history), while the other was a probable imported case (young man born in Nigeria and settled in Europe since 2003). Epidemiology of strongyloidiasis in San Marino might be similar to Northern Italy, where a relevant proportion of cases was diagnosed in immigrants (mainly from sub-Saharan Africa) and in elderly Italians with eosinophilia. Screening for strongyloidiasis might be worthwhile in inhabitants of San Marino in the same categories of individuals, particularly those at risk of immune suppression.

Epidemiology of inflammatory bowel disease in the Republic of San Marino: The "EPIMICI - San Marino" study.

BACKGROUND: The burden of Crohn's disease (CD) and ulcerative colitis (UC) has never been estimated in the Republic of San Marino, the third smallest nation of the world. AIMS: To assess the occurrence and clinical features of CD and UC in San Marino during the last 35 years. METHODS: We retrospectively evaluated the prevalence, incidence, and main clinical aspects of CD and UC from 1980 to 2014, crossing data from various sources. RESULTS: Prevalence rates (per 100,000) on December 31, were 241 for CD (263 in males and 220 in females) and 311 for UC (370 in males and 255 in females). The specific incidence of UC steadily increased from 4.6 (95% CI: 1.5-10.6) in 1980-1984 to 12.4 (95% CI: 7.6-19.1) in 2010-2014; CD incidence showed a higher proportional increase, from 1.8 (95% CI: 0.2-6.6) in 1980-1984 to 17.9 (95% CI: 12.0-25.7) in 2010-2014. The main clinical features of CD and UC (activity and location at diagnosis, extra-intestinal manifestations, disease progression overtime, therapies, and hospitalizations) were analyzed. CONCLUSIONS: This study provides the first epidemiological report on CD and UC in San Marino, showing specific traits and overall higher prevalence and incidence rates than previously reported in neighbor Areas.

Routine immunization profile: San Marino

Summary of routine immunization and vaccine-preventable diseases surveillance data, based primarily on data for 2017 submitted through the WHO/UNICEF Joint Reporting Form on Immunization.

Measles and rubella elimination country profile: San Marino

Conclusions and recommendations of the European Regional Verification Commission for Measles and Rubella Elimination, based on 2017 data submitted by national verification committees.

Participatory approaches to reaching the Sustainable Development Goals: San Marino: promoting healthy lifestyles through schools and family

In San Marino, the intersectoral approach to improving population health is a long-standing tradition. Several intersectoral projects have been under way for some time with a focus on the achievement of the Sustainable Development Goals (SDGs). In 2013, the Health and school working group was established to promote a systematic approach to health education. The aim is to create a school system in which everyone involved works together to provide students with a safe and healthy environment and positive experiences, and to promote a more sustainable and fairer lifestyle. Such an environment, involving both families and communities, is needed in tackling the burden of noncommunicable and chronic diseases and their risk factors. The adoption of the 2030 Agenda in 2015 gave San Marino the impetus to create the Intersectoral working group on implementation of the SDGs. Comprising representatives of all government departments, this working group is tasked with preparing the voluntary national review for submission to the High Level Political Forum in 2019. San Marino has also set up a strategic platform entitled “Produce health and development” to promote intersectoral policies and multi-partner cooperation, and provide leadership of the World Health Organization (WHO) Small Countries Initiative in conjunction with the WHO European Centre for Investment for Health and Development of the WHO Regional Office for Europe. The action reported in this briefing is directly linked to SDG 3 (good health and well-being), targets 3.4 and 3.5, and SDG 4 (quality education), target 4.7, and the strategic directions of the WHO European “Roadmap to implement the 2030 Agenda for Sustainable Development, building on Health 2020, the European policy for health and well-being”.

Multiple sclerosis in the Republic of San Marino, Italian peninsula: an incidence and prevalence study from a high-risk area.

Epidemiological studies on multiple sclerosis (MS) carried out in Southern Europe in the last years have shown a significant increase in the disease frequency. Previous surveys conducted in the Republic of San Marino, Northern Italian peninsula, identified that the population is at high risk for MS, with a prevalence of 51.6 per 100,000 population in 1982 and of 166.7 in 2005 and with a mean annual incidence of 7.9 per 100,000 for the period 1990-2005. The present work is a community-based intensive prevalence and incidence survey, by a complete enumeration approach, to update the prevalence and incidence of MS in the Republic of San Marino. The mean annual incidence for the period 2005-14 was 7.7 (95% CI 4.9-11.4) per 100,000, 3.3 (95% CI 1.1-7.6) for men and 11.9 (95% CI 7.2-18.6) for women. On 31 December 2014, 67 patients (19 men and 48 women), suffering from definite or probable MS and living in the Republic of San Marino, yielded a crude prevalence of 204.3 (95% CI 158.4-259.5) per 100,000, 117.8 (95% CI 70.9-183.7) for men and 288.2 (95% CI 212.4-383.3) for women. Our study has confirmed San Marino is an area at high risk for MS, in line with epidemiological data from continental Italy. The marked increase in MS prevalence over time in this population can be ascribable to increased survival and improved ascertainment, in the presence of a substantially stable, yet high, incidence rate.

Building resilience: a key pillar of Health 2020 and the Sustainable Development Goals: examples from the WHO Small Countries Initiative

This publication was developed under the framework of the WHO Small Countries Initiative, which is coordinated by the WHO European Office for Investment for Health and Development, Venice, Italy, of the WHO Regional Office for Europe. It reviews the scientific basis for strengthening resilience, which is central to Health 2020, the WHO European policy framework for health and well-being. The publication explains the concept of resilience and its implications for health at three levels (individual, community and system/society). It presents knowledge gained on strengthening resilience in three countries participating in the WHO Small Countries Initiative (Iceland, Malta and San Marino). It describes on-the-ground action taken in these countries and the main lessons learnt in strengthening resilience and developing supportive environments for population health and well-being. The material presented in this publication is intended to inform other countries participating in the WHO Small Countries Initiative and encourage them to share their own experiences in strengthening resilience for health and well-being. This publication was tabled as a background document for the Technical briefing (EUR/RC67/TD/2) during the Sixty-seventh session of the Regional Committee for Europe, Budapest, 11–14 September 2017.

Estimation of the prevalence of asymptomatic pancreatic cysts in the population of San Marino.

BACKGROUND: There has been a dramatic increase in the number of pancreatic cystic lesions observed in the past two decades but data regarding the prevalence of cysts in the general population are lacking. METHODS: All the individuals who undergo CT at the San Marino State Hospital are residents of the Republic of San Marino; their demographic distribution is available and precise. CT scans carried out over 1 year at the State Hospital were reviewed for asymptomatic pancreatic cysts. RESULTS: 1061 relevant CT scans were carried out on 814 patients; 762 individuals were eligible for the study and 650 patients underwent contrast-enhanced CT. Thirty-five patients had at least one cyst at contrast-enhanced CT (5.4%). The prevalence of cysts increased with increasing age up to 13.4% (95% CI 6.6-20) in individuals 80-89 years of age (p < .001). Cyst prevalence was significantly higher in patients who underwent CT for malignancy (p = .038) but this difference was no longer significant in multivariate analysis. The odds of a cyst being present increased by 1.05 (95% CI 1.02-1.09) for each increasing year of age (p = .002). Approximately a quarter of the patients with cysts died within 1 year after CT from non pancreas-related disease. The estimated standardized age-adjusted cyst prevalence is 2194 per 100,000 people. CONCLUSIONS: The likelihood of having a pancreatic cyst correlates with increasing age, not with the presence of extra-pancreatic malignancies. The estimated prevalence of CT-detectable asymptomatic pancreatic cysts in the general population is 2.2%.

Analgesic, antiulcer, antithrombotic drugs and organ damage: a population-based case-control study.

AIM: Oral medication is of paramount importance for pain treatment. Analgesics, antiulcer (AUDs) and antithrombotic drugs (ATDs) are often coprescribed in elderly people. Non-steroidal anti-inflammatory drugs (NSAIDs) require AUDs to lower the risk of peptic ulcer, and potentially interfere with ATDs. The aim of this study was to quantify the prevalence of NSAID use in patients with gastrointestinal, cardiac or kidney damage in the year 2013, compared to the general population. METHODS: We performed a population-based case-control study in the Republic of San Marino to evaluate the Odds-Ratios for upper gastrointestinal damage (gastroduodenal ulcers and/or erosions, GUE), ischemic heart disease (IHD), heart failure (HF), and renal function impairment (assessed using the CKD-EPI formula), in people who had taken AUDs, ATDs, or NSAIDs in the previous 90 days, versus people who had not taken such drugs in the same period of time. RESULTS: We found that AUDs decreased the OR for GUE (OR: 0.762; CI:0.598-0.972), while ATDs and NSAIDs increased the risk (OR: 1.238 and CI: 0.935-1.683; OR:1.203 and CI:0.909-1.592, respectively). NSAIDs seemed to increase the risk of IHD, although this was not statistically significant (OR=1.464; CI=0.592-3.621). AUDs and ATDs significantly increased the risk of renal function impairment (OR=1.369 and CI=1.187-1.579; OR=1.818 and CI=1.578-2.095, respectively), while this effect was not observed for NSAIDs. CONCLUSION: NSAIDs may induce gastrointestinal and cardiovascular damage, not only by themselves, but also when used concomitantly with common medications such as AUDs or ATDs, due to additive and/or synergistic effects. We performed a "pragmatic" analysis of the association of organ damage with use of NSAIDs/AUDs/ATDs, including patient age, treatment duration and dose, to allow for an immediate application of our findings to everyday clinical practice.

A roadmap to implementing Health 2020: the experience of San Marino

This publication describes San Marino's experience in developing its national health plan for 2015–2017, which integrates the core elements of Health 2020, the European policy for health and well-being. It provides a general summary of Health 2020 and descriptions of San Marino and of its national health plan, including the guiding principles, overarching goals and health objectives. It should be viewed in the content of the WHO small countries initiative, of which San Marino is the co-leader, in which eight European countries with populations of under 1 million work together to improve their citizens' health and well-being, and implement the European policy framework, Health 2020. The core of the publication is the detailed description of the development process undertaken by San Marino and other stakeholders in the small countries initiative, followed by enabling factors and challenges faced in developing and implementing the national health plan. The publication goes beyond sharing San Marino's experience to provide useful hints and key messages relevant to both small and large countries in the WHO European Region.

Canine leishmaniasis surveillance program in a San Marino Republic kennel.

The Republic of San Marino is an autonomous State that, in view of its geographical and environmental features, can be considered a part of the Northern Italian territory, where the canine leishmaniasis (CanL) is endemic. In the past, a CanL focus in the Republic's kennel was described. As a consequence of this epidemiological situation, a surveillance program was carried-out covering a 6-year period (2006-2012). A total of 1,094 sera were collected from 420 kennel dogs and examined for antibodies to Leishmania infantum by the indirect fluorescent antibody test (IFAT). Eighty-eight (21%) dogs resulted IFAT positive (antibody titre ≥1/40). The overall seroprevalence increased in the first 4 years (2006-2010), going from 5.5% to 26.8% and then decreased in the 2 following years going to 17.9%(2011) and 3.9% (2012). The cumulative incidence constantly increased from 0.6% to 2.6%. This trend could be attributed to a changed infection pressure due to the dog turnover in the kennels. According to the observed incidence values, the CanL focus seems to be stable, supported by autochthonous transmission, new case introduction and Leishmania spp. circulation in owned dogs in the same area.