Prevalence and management of rubella susceptibility in healthcare workers in Italy: A systematic review and meta-analysis.

Introduction: In the pre-vaccination era, all adults acquired immunity status due to natural infections during childhood and adolescence, whereas universal mass vaccination has changed the seroepidemiology of rubella among adults, showing lack of immunity in some subgroups. National and international guidelines recommend evaluating all healthcare workers (HCWs) for their immune status to rubella and possibly vaccinating those who are seronegative. We conducted a systematic review and meta-analysis to estimate the susceptibility rate to rubella among HCWs in Italy and to explore possible options for the management of those found to be susceptible. Methods: Eight studies were included in the meta-analysis, selected from scientific papers available in the MEDLINE/PubMed and Google Scholar (till page 10) databases between January 1, 2015 and November 30, 2021. The following terms were used for the search strategy: (sero* OR seroprevalence OR prevalence OR susceptibilit* OR immunit* OR immunogenict*) AND (healthcare worker* OR health personnel OR physician* OR nurse OR student*) AND (rubella OR german measles OR TORCH) AND (Italy). Results: The prevalence of rubella-susceptible HCWs was 9.0 % (95 %CI: 6.4-12.1 %). In a comparison of female vs. male serosusceptible HCWs, the RR was 0.67 (95 %CI = 0.51-0.88). Occupational medicine examinations for rubella screening with possible subsequent vaccination of seronegatives and exclusion of susceptible HCWs from high-risk settings were common management strategies. Conclusions: HCWs susceptible to rubella are an important epidemiological concern in Italy, and efforts to identify and actively offer the vaccine to this population should be increased.

Effectiveness and Safety of a Probiotic-Mixture for the Treatment of Infantile Colic: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial with Fecal Real-Time PCR and NMR-Based Metabolomics Analysis.

INTRODUCTION: To investigate the effectiveness and the safety of a probiotic-mixture (Vivomixx®, Visbiome®, DeSimone Formulation®; Danisco-DuPont, Madison, WI, USA) for the treatment of infantile colic in breastfed infants, compared with a placebo. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in exclusively breastfed infants with colic, randomly assigned to receive a probiotic-mixture or a placebo for 21 days. A structured diary of gastrointestinal events of the infants was given to the parents to complete. Samples of feces were also collected to evaluate microbial content and metabolome using fecal real-time polymerase chain reaction (qPCR) and Nuclear magnetic resonance (NMR)-based analysis. Study registered at ClinicalTrials.gov (NCT01869426). RESULTS: Fifty-three exclusively-breastfed infants completed three weeks of treatment with a probiotic-mixture (n = 27) or a placebo (n = 26). Infants receiving the probiotic-mixture had less minutes of crying per day throughout the study by the end of treatment period (68.4 min/day vs. 98.7 min/day; p = 0.001). A higher rate of infants from the probiotic-mixture group responded to treatment (defined by reduction of crying times of ≥50% from baseline), on day 14, 12 vs. 5 (p = 0.04) and on day 21, 26 vs. 17 (p = 0.001). A higher quality of life, assessed by a 10-cm visual analogue scale, was reported by parents of the probiotic-mixture group on day 14, 7.1 ± 1.2 vs. 7.7 ± 0.9 (p = 0.02); and on day 21, 6.7 ± 1.6 vs. 5.9 ± 1.0 (p = 0.001). No differences between groups were found regarding anthropometric data, bowel movements, stool consistency or microbiota composition. Probiotics were found to affect the fecal molecular profile. No adverse events were reported. CONCLUSIONS: Administration of a probiotic-mixture appears safe and reduces inconsolable crying in exclusively breastfed infants.

Are pre-terms born timely and right immunized? Results of an Italian cohort study.

The aim of this study is to evaluate the vaccination coverage at 24 months of chronological age in a sample of preterm infants discharged by the Neonatal Intensive Care Unit (NICU) of the Bari Policlinico University General Hospital in Italy. The list of infants preterm born discharged during 2013 by the NICU was obtained by hospital database. Vaccination status of each subject at 24 months of chronological age was acquired by the Apulian Regional Vaccination Register (GIAVA). 159 preterm borns were enrolled in this study. 98.1% received the 1st dose of hexavalent vaccine and 98.7% the 1st dose of pneumococcal conjugate vaccine. The 8.8% of hexavalent vaccinations were performed during hospitalization. The percentage of immunized subjects decreased to 91.2% and 87.3% for the 2nd and 3rd dose of hexavalent vaccine and to 90.6% and 86.1% for the 2nd and 3rd dose of pneumococcal conjugate vaccine. Coverage for MMR, MEN C and Varicella vaccines were, respectively 76.4%, 86.0% and 80.9%. Pre-terms received the vaccinations later than the age recommended by public health guidelines. Age at the immunization, for all vaccines, seems to increase for lower gestational age and birth weight and for higher length of hospitalization. This study shows a high risk of vaccine delay among pre-terms born. There is a strong need to improve specific vaccination strategies for this group. Neonatologists might play a key role in informing parents about the vaccination schedule at the moment of NICU discharge and during follow-up, also preparing correct time schedule.

Systematic causality assessment of adverse events following HPV vaccines: Analysis of current data from Apulia region (Italy).

Since 2013, World Health Organization (WHO) recommended that adverse events following immunization (AEFIs) should be evaluated by a standardized algorithm for causality assessment, however the use of WHO procedure is rarely adopted. In Italy, AEFIs (classified only by temporal criteria) are registered in the National Drug Authority (AIFA) database, but causality assessment is not mandatory. Every year AIFA publishes the AEFIs report, that doesn't contain information about causal correlation between events and vaccines. From AIFA database, we selected AEFIs following human papillomavirus vaccination (HPV) reported in Apulia (about 4,000,000 inhabitants) during 2008-2016. For serious AEFIs, we applied WHO causality assessment criteria; for cases hospitalized, we repeated the assessment getting additional information from health documentation. In 2008-2016, 100 HPV AEFIs (reporting rate: 17.8 per 100,000 doses) were registered of which 19 were serious (rate: 3.4 per 100,000 doses) and 12 led to hospitalization. After causality assessment, for 9 AEFIs the classification was "consistent causal association to immunization", for 3 indeterminate, for 5 "inconsistent causal association to immunization" and for 2 not-classifiable. Among hospitalized patients, 5 AEFIs were consistent, 5 inconsistent, 1 not-classifiable and 1 indeterminate; adding information from health documentation, the results were similar except for indeterminate and not classifiable AEFIs that turned into "not consistent". Only half of severe AEFIs could be associated with vaccination and this suggests that AIFA report provides a incomplete picture of HPV vaccine safety, with a risk for readers to confound "post hoc" and "propter hoc" approach without considering the causality assessment results. In the view of the systematic use of WHO causality assessment algorithm in the AEFI surveillance, the efforts of Public Health must be focused on the improvement of the quality of the information provided to reduce conclusions inter-observer variability; the routine follow-up of reports, also to collect additional information, must be guaranteed.

Vaccination coverage in patients affected by chronic diseases: A 2014 cross-sectional study among subjects hospitalized at Bari Policlinico General Hospital.

Subjects affected by at least 1 chronic disease are the target of influenza vaccination strategies because they are at high risk of influenza complications or death. The aim of this cross-sectional study is to evaluate flu and pneumococcal vaccination coverage (VC) in a sample of patients hospitalized at Bari Policlinico General Hospital (South Italy). According to national public health guidelines, these patients should have been vaccinated at hospital discharge by general practitioners. There were 540 patients involved in the study, and the average age was of 46.9 ± 13.4 years (range, 0-64 years). We assessed the vaccination status of 412 of 540 (76.3%) patients. The overall VC was 22.8% (94/412) for influenza and 7.2% (30/412) for pneumococcal vaccine. Doctor recommendation has a pivotal importance in vaccine acceptance, and recent experiences seem to show a high efficacy of the vaccination offer during hospitalization. This model could be helpful to improve influenza and pneumococcal vaccination offers to patient with underlying chronic conditions.

Medical students' attitude toward influenza vaccination: Results of a survey in the University of Bari (Italy).

Influenza vaccination is strongly recommended for Italian healthcare professionals, but vaccine coverage is low. Since 2012, vaccination is also offered to medical students as part of the National Immunization Plan; however, few Medical Schools has implemented the plan so far. To study determinants of vaccination compliance, we conducted a survey among medical students at the University of Bari, where influenza vaccination has been actively offered since 2013. Information was obtained by means of an online anonymous questionnaire administered in April 2014. We enrolled 669 students, 383 (57%) vaccinated; 54% were female and the average age was 23.9 ± 4.9 y. Determinants of getting vaccinated were analyzed in a multivariate logistic model. Receiving invitation from the University (aOR = 3.8; 95%CI = 1.2-12.3; p = 0.026), the opinion that vaccine is safe (aOR = 2.8; 95%CI = 1.5-5.0; p = 0.001) and useful (aOR = 3.4; 95%CI = 1.7-6.7; p<0.0001), a specific training about influenza vaccination during the course (aOR = 1.5; 95%CI = 1.1-2.1; p = 0.043), and considering himself as at a major risk of influenza complication (aOR = 1.8; 95% CI = 1.1-2.9; p = 0.001) were significantly associated with vaccine acceptance. Active invitation and training are confirmed as key actions (as in children vaccination strategies) and, according to our results, they could be routinely used to promote vaccination in hard-to-reach groups such as healthcare workers.

Active offer of vaccinations during hospitalization improves coverage among splenectomized patients: An Italian experience.

In 2014, an Italian hospital implemented a protocol for pneumococcal, meningococcal, and Haemophilus influenzae type b vaccines offer to splenectomized patients during their hospitalization. After 1 year, coverage for recommended vaccinations increased from 5.7%-66.7% and the average time between splenectomy and vaccines administration decreased from 84.7-7.5 days.

Lack of immunity against rubella among Italian young adults.

BACKGROUND: To support the evaluation of the 2010-15 National Plan for Measles and Congenital Rubella Elimination, the authors designed and performed a serosurveillance survey to verify the immunity/susceptibility rate against rubella among Apulian young adults. METHODS: The study was carried out from May 2011 to June 2012 in the Department of Transfusion Medicine/Blood Bank of Policlinico General Hospital in Bari. Subjects were enrolled by a convenience sampling. For each enrolled patient a 5 ml serum sample was collected and tested for anti-rubella IgG. The geometrical means (GMT) of anti-rubella IgG was calculated. T student test or ANOVA test, when appropriate, was used to compare the means of age per gender and GMT of anti-rubella IgG titres per age classes. Chi-square test was used to compare the proportion of anti-rubella IgG positive subjects per gender and per age classes. For all tests, a p value <0.05 was considered as significant. RESULTS: At the end of the study 1764 subjects were enrolled, 1362 (77.2%) of which were male. The mean age was 38.4 ± 11.7 years (range: 17-65). 86.7% (95% CI = 85.0-88.2) had a positive titre of anti-rubella IgG. GMT of anti-rubella IgG titre was 4.3. The proportion of positive subjects was of 76.8% (n = 279/363; 95% CI = 72.2-81.1) in persons aged 18-26 years; 88.1% (n = 310/352; 95% CI = 84.2-91.3) in 27-35 year-old people; 88.5% (n = 464/524; 95% CI = 85.5-91.1) in 36-45 year-old people; 90.7% (n = 350/386; 95% CI = 87.3-93.4) among people aged 46-55 years and 90.6% (n = 126/139; 95% CI = 84.5-94.9) in 55-65 year-old people (Chi-square = 39.7; p < 0.0001). GMT of anti-rubella IgG titre was 4.3 (4.3 in male and 4.2 in female, t = 2.2; p = 0.03) and seems to differ dividing the enrolled subjects by age group (F = 14.3; p < 0.0001). CONCLUSIONS: According to our data, too many women of child-bearing age are still unprotected from rubella in the elimination era and in this scenario the public health efforts should be oriented to catch-up activities.

Serosurveillance of hepatitis A in a region which adopted the universal mass vaccination.

Hepatitis A is a common infectious disease worldwide that was endemic in many regions of Southern Italy, such as Apulia region. After a large hepatitis A outbreak occurred between 1996 and 1997, in Apulia an active-free immunization program that was targeted to new-borns and adolescents was started. The aim of this study is to investigate the hepatitis A seroprevalence in the adult Apulian population 18 years after the immunization program introduction, in order to evaluate the risk of new epidemics onset.The study was carried out from May 2011 to June 2012 among blood donors from Department of Transfusion Medicine and Blood Bank of Policlinico General Hospital in Bari. Participants signed a written consent and filled out a questionnaire including items on demographic characteristics, risk factors, disease memory, and raw food consumption. Serum samples, collected from each patient, were tested for anti-HAV using the chemiluminescent microparticle immunoassay. Vaccination status against hepatitis A was checked on Regional Digital Immunization Registry (GIAVA).In total 1827 donors agreed to participate (77.7% male) with a mean age of 38.4 ±â€Š11.7 years. However, 1172 (64.1%) donors were seropositive with no difference by sex. The highest proportion of seronegative subjects was in the 27 to 35 years age group. 91.8% of 1-dose vaccinated subjects (n = 190/207; 95%CI = 87.2-95.1) and 96.1% (n = 171/178; 95%CI = 92.1-98.1) of 2-doses vaccinated subjects were immune to the disease. Sensitivity of disease memory in unvaccinated subjects was 14.4% (95%CI = 12.2-16.7), specificity was 97.8% (95%CI = 96.3-98.8), positive predictive value was 91% (95%CI = 85.3-95), and negative predictive value was 42.6% (95%CI = 40-45.2). Raw seafood consumption in unvaccinated subjects was associated with the anti-HAV IgG positivity (OR = 2.1; 95%CI = 1.7-2.7; z = 7.4; P < 0.0001).The vaccination program seems to have changed the virus circulation pattern, with a higher seronegativity rate among subjects not included in the vaccination strategy: 67% of susceptible subjects were among younger people aged 27 to 35 years. Immunization program implementation with a catch-up strategy may be needed to avoid a possible increase of hepatitis A incidence and outbreaks in Apulia. Epidemiological surveillance should be continued and vaccination should actively be offer for free to all the cases contacts, in order to prevent new outbreaks onset.

Long time immunogenicity of measles vaccine in the vaccination era: An open question.

After WHO European Region determined the 2005 - 2010 Strategic Plan for measles elimination, the number of reported measles cases in Europe fell dramatically. This decrease is related to the vaccination strategy carried out by European countries. This extensive immunization strategy changes the epidemiological patter and could influence the effectiveness and the long-time immunogenicity of the vaccine. To evaluate the long-time immunogenicity of the measles vaccine in the vaccination era, a pilot study among vaccinated blood donors in Apulia was designed. Of 174 enrolled patients, 93.7% presented an anti-measles IgG titer positive. GMT seems to increase by age (p = 0.001). The GMT seems to increase by age and this could be related to the exposition to natural boosters, that was more probable before the beginning of universal mass vaccination against measles. Future studies have to focus the correlation between GMT and age.

Community-wide outbreak of haemolytic uraemic syndrome associated with Shiga toxin 2-producing Escherichia coli O26:H11 in southern Italy, summer 2013.

In summer 2013, an excess of paediatric cases of haemolytic uraemic syndrome (HUS) in a southern region of Italy prompted the investigation of a community-wide outbreak of Shiga toxin 2-producing Escherichia coli (STEC) O26:H11 infections. Case finding was based on testing patients with HUS or bloody diarrhoea for STEC infection by microbiological and serological methods. A case-control study was conducted to identify the source of the outbreak. STEC O26 infection was identified in 20 children (median age 17 months) with HUS, two of whom reported severe neurological sequelae. No cases in adults were detected. Molecular typing showed that two distinct STEC O26:H11 strains were involved. The case-control study showed an association between STEC O26 infection and consumption of dairy products from two local plants, but not with specific ready-to-eat products. E.coli O26:H11 strains lacking the stx genes were isolated from bulk milk and curd samples, but their PFGE profiles did not match those of the outbreak isolates. This outbreak supports the view that infections with Stx2-producing E. coli O26 in children have a high probability of progressing to HUS and represent an emerging public health problem in Europe.

How will the MMR universal mass vaccination change the epidemiologic pattern of mumps? A 2012 Italian serosurvey.

To investigate the changes in the epidemiologic pattern of mumps, we carried out a serosurvey among young adults from Apulia, Italy. A convenience sample of 1,764 blood donors were enrolled in 2012: 93.4% (95% confidence interval, 92.1-94.5) showed a positive antimumps immunoglobulin G titre, geometric mean titer was 2.05. Results were consistent with previously published data on the immunogenicity of mumps vaccine but showed a lack of immunity (10% of people aged 18-26 years susceptible for mumps). Future research must be focused on the long-time immunogenicity of the mumps vaccine.

Immunization coverage among splenectomized patients: Results of an ad hoc survey in Puglia Region (South of Italy).

Patients with anatomic or functional asplenia have a 10-50 times higher risk than general population to develop Overwhelming Post-Splenectomy Infection. Evidences are unanimous in recommending splenectomised patients to receive meningococcal, antipneumococcal and Haemophilus influenzae type B vaccinations according to a specific timing. In Italy there are no current data on the immunisation coverage in these patients. This study aims to investigate immunisation coverage in patients undergoing elective or urgent splenectomy for 2012-2013 in the 3 Apulian hospitals. The patients discharged with the code ICD-9-CM 41.5 - "Total splenectomy" were enrolled. The administration of vaccines was verified through consultation of medical records, archives of general practitioners and vaccination offices. In the study period, 166 subjects underwent splenectomy and none of them received vaccinations during hospitalization. 25 splenectomised patients (15.1%) received at least one of the recommended vaccinations. 21 patients (12.6%) received vaccine against Streptococcus pneumonia, 13 (7.8%) meningococcal vaccine, 10 patients (6%) Haemophilus influenzae type B vaccine. The low vaccination coverage could be due both to poor perception of the risk of infection and to a lack of knowledge on vaccinations by surgeons. For this reason it is necessary to draw up and share operational protocols that establish the administration of vaccines.

Migrant health: the Apulian model.

INTRODUCTION: Since the 1990s Puglia has been totally involved in the reception and assistance of refugees. The prevention of infectious diseases among migrants, especially those residing in communities, is an important concern for public health authorities, since infectious diseases eliminated in Europe may still be widespread in the migrants' countries of origin, and other diseases may have a higher incidence than in European countries. Thus immigrants may contribute to the burden and spread of infectious diseases. OBJECTIVE: We describe the Apulian model of management and prevention of infectious disease among the population of Asylum Seeker Centres (CARA). It consists of a number of activities: surveillance of Poliovirus circulation, tuberculosis screening, seroprevalence studies of viral hepatitis and HIV, an immunization program for children, and syndromic surveillance. All the activities are organized and carried out by the Regional Observatory for Epidemiology among refugees hosted in the Bari Palese CARA. RESULTS: Surveillance of Poliovirus circulation has been carried out periodically since 2008 by assessing the presence of wild poliovirus or Sabin-like poliovirus in stool samples and seroprevalence studies. Data did not show circulation of poliovirus and indicated a good level of immunization against polio among refugees. Seroprevalence studies of viral hepatitis and HIV were carried out in 2008 and involved 529 refugees; 44 individuals (8.3%) were HBsAg positive, 24 (4.5%) were anti-HCV positive, 8 (1.5%) were HIV positive. Tuberculosis screening started in 2009 after a refugee's death due to tuberculosis and has been ongoing since then. The Mantoux tuberculin skin test is used and cutipositive migrants are examined by chest X-ray. Around 50% of migrants have been found to be cutipositive and 10% showed TB sequelae. Syndromic surveillance and an immunization program began in 2011 because of the significant increase in migration flow following civil unrest in North Africa; respiratory tract infection and diarrhoea were the most frequent notified syndromes. The immunization program involved 129 children coming from 23 countries: all received the appropriate vaccinations. The program also includes an annual special session to vaccinate all refugees against flu. CONCLUSIONS: The results confirmed some traditional concerns about migrant health and especially about the control of infectious diseases among these populations and the need, from our point of view, to strengthen screening to aid the development of trust between migrants and resident population.

Clinical benefits of routine varicella vaccination for adults.

Varicella is a highly contagious disease caused by varicella zoster virus. In children, it is generally a mild to moderate illness while it is often more severe in adults, with serious complications as dehydration, pneumonia, bleeding problems, infection or inflammation of the brain, secondary bacterial infections, sepsis, toxic shock syndrome, bone infections, joint infections and deaths. Some groups of adults are at major risk of complications, in particular immunocompromised persons as subjects with impaired humoral immunity and who is receiving systemic steroids, persons who live or work in environments in which transmission of varicella is likely, health-care personnel and pregnant women. After the introduction of Universal Mass Vaccination (UMV), the first mathematical models suggested that vaccination will lead to a shift in the average age at infection from children to adults with an increasing numbers of complicated forms, nevertheless new models predicted that, although an upward shift in the age at infection may occur, the overall morbidity due to varicella is likely to decrease. Current literature seems to suggest that for public health authorities the key action to prevent an increase of varicella incidence among adults is to achieve high vaccination coverage among babies and adolescents in countries who adopted UMV.