Frequently asked questions on seven rare adverse events following immunization.

Routine mass immunization programs have contributed greatly to the control of infectious diseases and to the improvement of the health of populations. Over the last decades, the rise of antivaccination movements has threatened the advances made in this field to the point that vaccination coverage rates have decreased and outbreaks of vaccine-preventable diseases have resurfaced. One of the critical points of the immunization debate revolves around the level of risk attributable to vaccination, namely the possibility of experiencing serious and possibly irreversible adverse events. Unfortunately, the knowledge about adverse events, especially rare ones, is usually incomplete at best and the attribution of a causal relationship with vaccinations is subject to significant uncertainties. The aim of this paper is to provide a narrative review of seven rare or very rare adverse events: hypotonic hyporesponsive episode, multiple sclerosis, apnea in preterm newborns, Guillain-Barré syndrome, vasculitides, arthritis/ arthralgia, immune thrombocytopenic purpura. We have selected these adverse events based on our experience of questions asked by health care workers involved in vaccination services. Information on the chosen adverse events was retrieved from Medline using appropriate search terms. The review is in the form of questions and answers for each adverse event, with a view to providing useful and actionable concepts while not ignoring the uncertainties that remain. We also highlight in the conclusion possible future improvements to adverse event detection and assessment that could help identify individuals at higher risk against the probable future backdrop of ever-greater abandonment of compulsory vaccination policies.

Effect of mass media on influenza vaccine coverage in the season 2014/2015: a regional survey in Lazio, Italy.

INTRODUCTION: Adherence to vaccination program for Influenza virus is an important issue of Public Health in presence of many no-vaccine tendencies. The media event about some deaths, occurring after MF59 adjuvanted vaccine administration, has characterized the season 2014/15 vaccination program in Italy. Aim of the study is vaccination adherence assessment of the current season with regards to local health units (LHU) coordinators's perceptions in Lazio Region (IT). METHODS: LHU coordinators's perceptions were collected from a questionnaire that was send via email to the all 12 LHU coordinators. The questionnaire was built with 4 questions concerning the impression about the vaccination adherence of elderly people in the current season. Data from questionnaire was compared with the official coverage rate obtained by the Regional Authority. Severe adverse events were collected by 1 LHU. RESULTS: All the 12 LHU coordinators answered to our questionnaire: 7/12 (50%) predicted a coverage rate of at least 50%; 3/12 (25%) referred a coverage rate around 40-45%; 2/12 (17%) predicted a reduction of 5-10% less than the previous season. Indeed, a mean 49.1% vaccination coverage in the elderly has been reported by the Regional Authority highlighting a reduction of 10% less than the 2013/14 season coverage. No severe adverse events were observed. DISCUSSION: In our survey an important effect of media event on anti-flu vaccination program adherence has been evidenced, with a failure in communication and joint management of Public Health Institutions in Italy about efficacy and safety information of flu vaccine.

Knowledge and worry as basis for different behaviors among university students: the case of pandemic flu H1N1v.

INTRODUCTION: Attitudes towards the pandemic were different across countries and cultures and confounding news caused some to question whether unnecessary alarm and public panic resulted. The aim of this study was to detect behavior, perception and worry about pandemic flu among undergraduate students considered a group at major risk to contract and spread the infection. MATERIALS AND METHODS: In November 2009, during the pandemic peak in Italy, we conducted a survey about pandemic flu by means of anonymous multiple choice self-administered questionnaires among students, attending different courses at the Tor Vergata University in Rome. To investigate the relationship between the level of concern about H1N1v and the attitude to prevention the sample was divided in three groups based on the level of the declared worry. RESULTS: Among the 436 students that answer the questionnaires a statistical correlation was found between the level of worry and the disposition to change habits and the will to undergo vaccination. Males were less worried than females and more students living outside Rome would accept the vaccine. DISCUSSION AND CONCLUSIONS: The results of the study, generally in agreement with those of similar research, confirmed the need to know the relationship between fear and attitude in order to organize effective preventive campaigns.

Opinions and attitudes of Italian healthcare workers towards recommended but not compulsory rotavirus vaccination.

Rotaviruses (RVs) are a leading cause of viral gastroenteritis among children younger than 5. The incidence of RV disease can be reduced through the widespread use of vaccination, but coverage is low in many countries, including Italy. This fact reflects the poor consideration given to the RV vaccine, both by the population and by healthcare workers. Peoples' opinions are strictly dependent on the attitude of doctors and nurses. The aim of this work is the evaluation of healthcare workers' knowledge, attitudes and opinions regarding RV vaccination. The results of two surveys were compared; the first was carried out in 2017, soon after the Italian National Immunization Plan introduced the recommendation for the RV vaccine. The second was performed at the end of 2018, approximately 1 year after the adoption of a Law that introduced new compulsory vaccinations, not including the RV vaccine. In 2017, 182 questionnaires were collected, and 111 in 2018. An increase was observed in the percentage of participants who reported recommending the RV vaccine and a significant increase was found in the coverage the participants claimed to reach. Education of healthcare workers after the introduction of compulsory vaccination may prompt them to actively offer also recommended vaccines.

[Vaccinations in the multicultural Italian scenario]. / Le vaccinazioni del bambino nello scenario multiculturale italiano.

Foreign citizens living in Italy with residence permit represent about 7,2% of the population even if the international migration started recently in the Country. Sanitary problems of children and families whose lifestyle and disease awareness strongly differ from the typical approach of the industrialized world are important also in the acceptance of the immuneprophylaxis. This aspect has to be taken in account when considering the integration of vaccination schedules. Public Health Services will be able to respond adequately to the health demand only identifying the need of foreign children and offering them the appropriate intervention.

[Vaccines and adverse events between risk and fear]. / Vaccini ed eventi avversi tra rischio reale e paura immotivata.

The decrease in the incidence of infectious diseases caused by vaccination is responsible for the huge importance given to adverse reactions from both population and health care personnel. Generally no real relationship exists between the true risks associated with vaccines and the risk perceived by the population. This aspect is confirmed by the results of a survey performed in 2009 among 376 students of the University of Roma Tor Vergata and 84 health care workers of the vaccination centers in Lazio Region.

Strategies for elimination of rubella in pregnancy and of congenital rubella syndrome in high and upper-middle income countries.

Rubella infection generally leads to mild symptoms; otherwise, in pregnant women it can cause severe damages. The only way to prevent rubella is vaccine. Before the introduction of the vaccine, up to 4 babies in 1000 live births were born with CRS. This work aims to review the most important strategies for the elimination of CRS in upper and high-income countries. Papers were selected through a PubMed search up to January 2019, using keywords rubella, congenital rubella syndrome and epidemiology. Articles published in the last 12 years and referred to upper income and high-income countries in title or abstract were included. Sixty-five papers were selected dealing with one or more of the following strategies: increasing of rubella vaccination coverage in childbearing age women, males, immigrants; exploitation of all appropriate occasions; improving of rubella surveillance. Despite numerous suggestions and indications for valid strategies to eliminate rubella in pregnancy and congenital rubella syndrome, a practical application is often missing.

Nosocomial rotavirus infection: An up to date evaluation of European studies.

Rotavirus (RV) is worldwide considered as the most important viral agent of acute gastroenteritis in children less than 5 y. Since 2006, the availability of anti-RV vaccines has deeply modified the incidence and economic burden of RV infection. In Europe, some countries have introduced an anti-RV vaccination program in the last 10 y. Although community acquired RV (CARV) disease is the most studied condition of RV infection, recently some authors have highlighted the importance of nosocomial RV (nRV) disease as an emerging public health issue. The aim of this review is to summarize the epidemiology of both CARV and nRV, in order to discuss the difficulty of a clear evaluation of the burden of the disease in absence of comparable data. In particular, we focused our attention to European studies regarding nRV in terms of divergences related to definition, report of incidence rate and methodological issues.

Age-specific prevalence of hepatitis B virus infection among teenagers in Sardinia.

In 1989, the prevalence of hepatitis B virus (HBV) markers was studied using Elisa method in a sample of 1357 healthy high school 14-19 year old teenagers in Sardinia. The overall prevalence of any HBV marker was 4.7%, increasing from 3.6% among 14-16 year old teenagers to 5.7% in 17-19 year olds. The overall prevalence of hepatitis B surface antigen (HBsAg) was 1.1%, similar in both age groups. A slight male preponderance was observed (5% versus 4.4% for any HBV marker and 1.7% versus 0.6% for HBsAg, respectively). The prevalence of any HBV marker was not associated with the family size (O.R. 1.5; CI 95% = 0.6-4.5), but it was inversely related to the number of years of education received by the father. Teenagers whose fathers had received less than six years of schooling had a 2.3 fold risk (CI 95% = 1.1-5.2) of previous exposure to HBV infection. Comparing these findings with recent results in children and adults in the same area, a cohort effect is likely evident.

Comparison of indirect immunofluorescence and radioimmunoassay for detecting antibodies against hepatitis A virus of the IgG and IgM classes.

Indirect Immunofluorescence test (IIF) and Radioimmunoassay (RIA) were compared for determining anti-Hepatitis A virus (HAV) IgG and IgM. 142 sera were tested for anti-HAV IgG and 16 for anti-HAV IgM, both with IIF and RIA techniques. The correlation between the results reached 98.6% for anti-HAV IgG and 93.75% for anti-HAV IgM detection, confirming the specificity and sensibility of IIF.

Hepatitis A virus infection in children in Sardinia, Italy.

The prevalence of antibody to hepatitis A virus (anti-HAV) in a sample of 1662 Sardinian children aged 3 to 11 years was estimated by ELISA. The overall anti-HAV prevalence was 3.8 per cent; it increased from zero among children of 3 to 7.2 per cent in children of 11 years. A slight male predominance was observed (4 versus 3.6 per cent). Anti-HAV prevalence was inversely related to the number of years of education received by the father and positively related to the number of households in the sample. Children whose fathers had received less than six years of schooling, had a 6.2-fold risk (Cl 95 per cent = 2.6-15.3) and children with five or more households under one roof had a 2.6-fold risk (Cl 95 per cent = 1.4-5.0) of previous exposure to hepatitis A virus (HAV) infection. These findings suggest that exposure of Sardinian children to hepatitis A virus is relatively low, probably because of improvements in socioeconomic conditions in recent years in the island. However, overcrowding and poor education in the father of schooling appear to be important determinants of infection.

Indirect immunofluorescence application in the epidemiological study of hepatitis A.

We used IIF test for seroepidemiological study on 531 sera divided in age-groups obtained from apparently healthy subjects of Rome. Our results confirm the endemicity of HAV (Hepatitis A virus) infection in Rome with a prevalence of more than 50%. The application of the anti-HAV IIF (Indirect Immunofluorescence) test to a large number of sera demonstrated its usefulness as a quantitative and qualitative test in the epidemiological field.

Viral hepatitis in the Bhutanese population: preliminary results of a seroepidemiological investigation.

A seroepidemiological study of the prevalence of markers related to the most common forms of viral hepatitis was carried out in Bhutan on 1,666 healthy people of both sexes, from the general population. A group of 440 pregnant women were screened separately. Our results suggest that in Bhutan, hepatitis A and hepatitis B are widespread, while there is a low prevalence of hepatitis C and E. Anti-HAV (anti-hepatitis A virus) was found in all 171 tested subjects over 12 years of age, and anti-HBc (anti-hepatitis B core antigen) in 63.1% of 1,666 tested people. On the other hand, anti-HEV proved positive in 2.0% of 257 tested subjects, and anti-HCV in only 1.3% of 611 tested subjects. Hepatitis B surface antigen (HBsAg) was found in 5.9% of the sample from the general population (5.2% in children, 5.6% in young people and 6.3% in adults) and in 5.4% of the pregnant women. Furthermore, 29.1% of HBsAg-positive pregnant women were HBeAg- and HBV DNA-positive, too. Comparing the pregnant women's prevalence data to those found in children, we suggest that the main route of HBV transmission in the Bhutanese population is vertical, from mother to child; this finding is important for the implementation of a correct anti-HBV vaccination strategy in Bhutan.

Genital herpes infection in outpatients attending a sexually transmitted disease clinic in Italy.

Prevalence of Herpes Simplex, type 2, specific antibodies was estimated in sexually transmitted disease outpatients: 783 heterosexuals and 158 homosexual-bisexuals. The anti-HSV-2 prevalence rates were 69% in the homosexual-bisexuals and 35% in the heterosexuals. In both groups positive association with age of anti-HSV-2 prevalence was found: only in the homosexual-bisexuals negative association with education level was detected. No difference exists between the two groups regarding the symptomatic/asymptomatic ratio of HSV-2 infection.

Hepatitis B and Delta virus infection among heterosexuals, homosexuals and bisexual men.

The hepatitis B virus (HBV) and hepatitis Delta virus (HDV) infection rates were estimated in patients attending a venereal disease outpatient clinic: 759 heterosexuals and 154 homosexual-bisexual men. The anti-HBc prevalence was higher in homo-bisexual men (68.8 per 100) than in heterosexuals (41.8 per 100), whereas HBsAg was roughly the same in the two groups (about 6 per 100). The anti-HBc prevalence rate among heterosexuals was higher than that estimated in hospital personnel from the same geographical area. A positive association between anti-HBc prevalence and present or past sexually transmitted diseases (STD) was found among homo-bisexual men. Anti-HBc was also positively associated with herpes simplex type 2 antibodies in both heterosexuals and homo-bisexual men. These data are consistent with the hypothesis that sexual behavior also plays a role in the spread of infection among heterosexuals. Ten of the 46 HBsAg-positive subjects were anti-HDV positive: 6 of the 36 heterosexuals and 4 of the 10 homosexuals. All HDV-positive subjects had present or past STDs. These findings suggest sexual transmission of HDV infection.

Hepatitis A, B, C and D in a community in Italy of immigrants from NE Africa.

A total of 213 subjects from a community in Italy of immigrants from Somalia and other NE African countries were enrolled in this study to evaluate the prevalence of HAV, HBV, HCV and HDV infections and to assess their possible risk factors. Of the subjects, 45 per cent (96) were female and 24 per cent (52) were under 12 years old. The age range was from 1 to 67 years and the mean age was 24 years. Eighty-three per cent (177 subjects) were born in Somalia, 10 per cent (21 subjects) in Ethiopia, and the rest in Djibouti, Egypt or Saudi Arabia. The 213 subjects were administered a questionnaire which covered socio-demographic characteristics and risk factors resulting from Western medical practice, traditional medicine, personal behaviour and living conditions. Blood was drawn from 209 subjects to ascertain the presence of HbsAg, HBeAg, anti-HAV, anti-HBc, anti-HBs, anti-HCV and anti-HDV. The results of this study show an HAV prevalence of 96 per cent (an 87.5 per cent prevalence in children under 12), and an HBV prevalence of 32 per cent (a 3.3 per cent prevalence of HBsAg carriers). No subject under 11 was HBV positive and no woman tested positive for HBeAg, confirming the extreme unlikelihood of vertical transmission of HBV. The prevalence of HBV is closely correlated with age (ranging from 2 per cent in those under 12 to 59 per cent in subjects over 39).(ABSTRACT TRUNCATED AT 250 WORDS)

Immune response at birth, long-term immune memory and 2 years follow-up after in-utero anti-HBV DNA immunization.

Infections occurring at the end of pregnancy, during birth or by breastfeeding are responsible for the high toll of death among first-week infants. In-utero DNA immunization has demonstrated the effectiveness in inducing specific immunity in newborns. A major contribution to infant immunization would be achieved if a vaccine proved able to be protective as early as at the birth, preventing the typical 'first-week infections'. To establish its potential for use in humans, in-utero DNA vaccination efficiency has to be evaluated for short- and long-term safety, protection at delivery, efficacy of boosts in adults and effective window/s for modulation of immune response during pregnancy, in an animal model suitable with human development. Here we show that a single intramuscular in-utero anti-HBV DNA immunization at two-thirds of pig gestation produces, at birth, antibody titers considered protective in humans. The boost of antibody titers in every animal following recall at 4 and 10 months demonstrates the establishment of immune memory. The safety of in-utero fetus manipulation is guaranteed by short-term (no fetus loss, lack of local alterations, at-term spontaneous delivery, breastfeeding) and long-term (2 years) monitoring. Treatment of fetuses closer to delivery results in immune ignorance without induction of tolerance. This result highlights the repercussion of selecting the appropriate time point when this approach is used to deliver therapeutic genes. All these findings illustrate the relevance of naked DNA-based vaccination technology in therapeutic efforts aimed to prevent the high toll of death among first-week infants.

HAV and HEV infection in hospitalised hepatitis patients in Alexandria, Egypt.

A total of 202 serum and stool samples from acute hepatitis patients attending the Fever Hospital of Alexandria, Egypt, have been studied to reveal markers of hepatitis virus infection. Anti-HAV IgM were detected in 21 out of 202 sera (10.4%), whereas 201 sera (99.5%) had anti-HAV IgG. The first age attack was in the class-age 0-9 years with 64.7% of anti-HAV IgM positive sera. Among 202 patients, anti-hepatitis E IgG (sample/over cut off > 1.0) was identified in 90 patients (44.5%). The anti-HEV seropositivity ranged from 17.6% to 60.0% in the different age groups, with the highest level in the class-age 20 29 years. Anti-hepatitis E IgM were identified in 49 patients with the first age attack in the class-age 10-19 years (39.4%). HAV RNA was identified by nested PCR in 7 samples out of 15, whereas HEV RNA was present in 4 out of 75 stool samples. Direct DNA sequence of the latter PCR products confirmed the presence of the HEV genome; comparison of the sequences of the isolates from Egypt with those in data banks revealed the highest homology to the Burma strain. Our data confirm that HAV and HEV are common causes of acute sporadic hepatitis in Alexandria but with different peak age positivity. Occasionally, but not infrequently, dual infections (HAV-HEV and HEV-enteric viruses) were also found. The risk analysis indicates that patients living in rural areas are exposed to a higher risk of hepatitis E infection compared to the urban population, whereas the presence of anti-HEV IgG was significantly associated with consumption of common village water and use of indoor dry pit and oral therapy for schistosomiasis.