Maria Giovanna Cappelli

Towards the 13-valent pneumococcal conjugate universal vaccination: effectiveness in the transition era between PCV7 and PCV13 in Italy, 2010-2013.

Pneumococcal disease epidemiology has changed after introduction of pneumococcal conjugate vaccines. Seven-valent vaccine (PCV7) has been effective in reducing invasive pneumococcal disease (IPD). In Europe, PCV13 effectiveness was estimated at 78% (95% CI: −18–96%) for 2-priming doses. In Italy, PCV7 was introduced in 2006 in the childhood immunization schedule and replaced with PCV13 in 2010. In Apulia, vaccination coverage has reached 95.1% (birth-cohort 2010). We estimated PCV program effectiveness and its impact on S. pneumoniae diseases. PCV Effectiveness: We used the screening method. We calculated the Proportion of Population Vaccinated from immunization registries and detected cases through a laboratory-confirmed surveillance among hospitalized children ≤60 months. A confirmed IPD case was a child with PCR positive for S. pneumoniae. Differences among children were assessed with the Chi-square or the Fisher exact test (P value < 0.05). PCV Impact: We constructed time series using outcome-specific Poisson regression models: hospitalization rate in pre-PCV era and hospitalization risk ratios (RRs) with 95% CIs for both PCV7 and PCV7/PCV13 shifting era. We calculated hospitalization RR with 95% CIs comparing pre-PCV years with vaccination period. The PCV effectiveness was 84.3% (95% CI: 84.0–84.6%). In May 2010-January 2013, we enrolled 159 suspected IPD of whom 4 were confirmed. Two (fully vaccinated) were caused by serotype 9V, 1 (not vaccinated) by serotype 3, 1 (vaccinated with 2 PCV13 doses) by 15B/C. The most important reduction was for pneumococcal pneumonia (RR: 0.43, 95% CI: 0.21–0.90). The PCV program show promising results in terms of both PCV13 effectiveness and its impact in reducing IPD in children <5 years.

Effectiveness of vaccination against varicella in children under 5 years in Puglia, Italy 2006–2012

In Italy, between 2003 and 2010, 8/21 Regions recommended varicella routine vaccination (URV). The National Immunization Plan (PNPV) 2012–2014 scheduled the introduction of URV nationwide in 2015, following the results achieved by the eight Regions. Puglia adopted varicella URV in 2006. This study describes epidemiology and costs of varicella in Puglia between 2003 and 2012. One-dose Vaccine Effectiveness (VE) against varicella of any severity and severe hospitalized cases in children was also evaluated. Vaccination coverage (VC) was estimated from the regional immunization registry. Incidence and hospitalization rates were calculated from computerised surveillance system for communicable diseases and hospital discharge registry (ICD9-CM codes: 052.x), respectively. URV impact was assessed by Incidence Rate Ratios (IIRs) and Hospitalization Risk Ratios (HRRs). Hospitalization costs were also evaluated. VE was estimated using the screening method, where PPV was VC in children aged <72 months and PCV was the proportion of cases vaccinated among notified or hospitalized cases, respectively. One-dose VC in children aged ≤ 24 months increased from 49% in the birth cohort 2006 to 91.1% in the cohort 2010; 2-dose VC was 64.8% and 28.8% in the 2005 and 1997 cohort, respectively. Comparing pre and post-vaccination era, incidence declined from 122.5 ×100 000 in 2003–2005 to 13.7 in 2009–2012 (IRR = 0.11, 95% CI = 0.10–0.12), hospitalization rate from 3.9 ×100 000 to 1.1 (HRR = 0.29, 95% CI = 0.21–0.4), hospitalization costs from 319 000 Euros/year to 106 000. One-dose VE against varicella of any severity and severe hospitalized disease was 98.8% and 99%, respectively. Our findings strongly support varicella URV introduction into the Italian Essential Health Interventions, as scheduled by 2015.

Impact of Pneumococcal Conjugate Universal Routine Vaccination on Pneumococcal Disease in Italian Children.

In Italy, the effectiveness of pneumococcal universal vaccination in preventing vaccine-type invasive pneumococcal disease (IPD) in the PCV7/PCV13 shifting period was estimated to be 84.3% (95% CI: 84.0–84.6%) in children <5 years. This study aims at corroborating the estimation of both the effectiveness (VE) of PCVs and its impact in reducing pneumococcal diseases. A 1 : 3 matched-case-control study was conducted among children <5 years old hospitalized for IPD or pneumococcal pneumonia (PP) between 2006 and 2012 in the Puglia region. Moreover, hospitalizations for pneumococcal outcomes in the pre- and postvaccination period and the hospitalization risk ratios (HRRs) with 95% CIs were computed in Italy and in the first eight regions that introduced PCVs in 2006. The overall effectiveness of PCVs was 75% (95% CI: 61%–84%); it was 69% (95% CI: 30%–88%) against IPD and 77% (95% CI: 61%–87%) against PP. PCVs showed a significant impact on IPD and acute otitis media either at a national level or in those regions with a longer vaccination history, with a nearly 40% reduction of hospitalizations for both outcomes. Our findings provide further evidence of the effectiveness of PCVs against pneumococcal diseases and its impact on nasopharyngeal carriage in children <5 years, indicating the importance of maintaining high immunization coverage.

Further efforts in the achievement of congenital rubella syndrome/rubella elimination

The Italian National Plan of Measles and Rubella Elimination 2010–2015 has deferred the objective to reduce congenital rubella syndrome (CRS) to <1 case per 100 000 live births to 2015 and has highlighted the need to reduce to <5% susceptibility to rubella among women in childbearing-age. In Puglia region, MMR vaccine coverage is 93% in newborns (cohort 2010; one dose), 85% in children 5–6 years old and 77% in adolescents (cohort 2005 and 1997, respectively; two doses). Combining available seroepidemiological data and results of a survey on the attitude towards rubella vaccination and rubella testing before pregnancy, we could estimate that 5.7% of Apulian women in childbearing-age are currently susceptible to rubella infection. The regional infectious disease routine notification system reported no cases of CRS and rubella in pregnancy in 2001–2010 period. The inconsistency among the mentioned data triggered the evaluation of the reliability of disease reporting. We performed a retrospective case-finding for the years 2003–2011. We scanned the regional hospital discharge registry to identify hospitalizations for rubella in pregnancy and CRS and retrieve individual records. We also searched for clinical history of CRS mothers in the delivery assistance certificate registry. We identified one CRS, two confirmed and four suspected congenital infections, and seven cases of rubella in pregnancy. Passive surveillance of CRS and rubella in pregnancy appears not to be reliable in the light of strengthening rubella elimination strategies.

Incidence of Type 1 Diabetes among Children and Adolescents in Italy between 2009 and 2013: The Role of a Regional Childhood Diabetes Registry

Background. Surveillance represents a key strategy to control type 1 diabetes mellitus (T1DM). In Italy, national data are missing. This study aimed at evaluating the incidence of T1DM in subjects <18 year olds in Apulia (a large southeastern region, about 4,000,000 inhabitants) and assessing the sensitivity of the regional Registry of Childhood-Onset Diabetes (RCOD) in the 2009–2013 period. Methods. We performed a retrospective study matching records from regional Hospital Discharge Registry (HDR), User Fee Exempt Registry (UFER), and Drugs Prescription Registry (DPR) and calculated T1DM incidence; completeness of each data source was also estimated. In order to assess the RCOD sensitivity we compared cases from the registry to those extracted from HDR-UFER-DPR matching. Results. During 2009–2013, a total of 917 cases (about 184/year) in at least one of the three sources and an annual incidence of 25.2 per 100,000 were recorded, lower in infant, increasing with age and peaked in 5- to 9-year-olds. The completeness of DPR was 78.7%, higher than that of UFER (64.3%) and of HDR (59.6%). The RCODs sensitivity was 39.05% (360/922; 95% CI: 34.01%–44.09%). Conclusions. Apulia appeared as a high-incidence region. A full, active involvement of physicians working in paediatric diabetes clinics would be desirable to improve the RCOD performance.

A seroprevalence survey on varicella among adults in the vaccination era in Apulia (Italy)

In 2006, the Apulia Region (Italy) introduced universal routine vaccination (URV) against varicella disease. The coverage for one dose of varicella vaccine at 24 month of age reached 91.1% in 2010 birth-cohort. Vaccination coverage for the second dose at 5-6 years was 64.8% for the cohort 2005, and 28.8% for adolescents born in 1997. The aim of the present study is to evaluate the pattern of immunity/susceptibility to varicella in Apulian adults by a seroprevalence survey carried out 6 years after the introduction of URV. The study was carried out from May 2011 to June 2012 among blood donors of the Department of Transfusion Medicine of Policlinico General Hospital in Bari. Subjects were enrolled by a convenience sample. For each enrolled patient we collected a sample of serum of 5 ml. Anti-VZV IgG in collected sera were analyzed by chemiluminescence (CLIA). We enrolled 1769 subject; 1365 (77.2%) were male with a mean age of 38.4 ± 11.7 years. 93% (95% CI=91.7-94.1) of enrolled subject presented a titre of anti-VZV IgG >164 mIU/mL. GMT of anti-VZV IgG titre was 1063.4 mIU/ml and no difference was observed between different age group. According to our data, URV did not seem to have any impact on susceptibility among adults and in particular we did not note any cluster of susceptible subjects among young adults. Also in the vaccination era, we did not note that the average age of infection shifts among adults and then we could exclude an increase of case of complicated varicella related to the URV.

Trichinellosis outbreak due to wild boar meat consumption in southern Italy

We report a Trichinella britovi outbreak investigated during February-March 2016 in southern Italy. The source of infection was meat from infected wild boars that were illegally hunted and, hence, not submitted to post-mortem veterinary inspection. Thirty persons reported having eaten raw dried homemade sausages; five cases of trichinellosis were confirmed. Wild game meat consumers need to be educated about the risk for trichinellosis.

Estimation of the Impact of Meningococcal Serogroup C Universal Vaccination in Italy and Suggestions for the Multicomponent Serogroup B Vaccine Introduction

In Italy, the meningococcal C conjugate vaccine (MenC) has been offered in most regions since 2009-2010. The incidence of Invasive Meningococcal Disease (IMD) was 0.25 confirmed cases per 100,000 in 2011, but this may be considerably underestimated due to underdetection and underreporting. This study estimates the impact of the MenC universal vaccination (URV) in the Puglia region by assessing the completeness of three registration sources (notifications, hospitalizations, and laboratory surveillance). Capture-recapture analysis was performed on meningococcal meningitis collected within 2001–2013. The impact of URV among ≤18-year-olds was assessed by attributable benefit, preventable fraction, and prevented fraction. Missed opportunities for vaccination were evaluated from surveillance of IMD. The proportion of detected serogroups was applied to the number of IMD in the postvaccination period to compute the cases still preventable. The sensitivity of the three sources was 36.7% (95% CI: 17.5%–57.9%) and registrations lost nearly 28 cases/year in the period. Attributable benefit of URV was −0.5 cases per 100,000, preventable fraction 19.6%, and prevented fraction 31.3%. Three adolescent cases missed the opportunity to be vaccinated. The multicomponent serogroup B meningococcal vaccine has the potential to further prevent at least three other cases/year. Vaccination strategy against serogroup B together with existing programmes makes IMD a 100% vaccine-preventable disease.

Determinants of varicella breakthrough: Results of a 2012 case control study

This study aims to evaluate the determinants of breakthrough infection after one dose of varicella vaccine. We designed a retrospective case-control study. Breakthrough cases were children, aged 1–15, who presented varicella symptoms ≥42 days after the first dose of varicella vaccine (breakthrough). Controls were children, aged 1–15 years, who attended the same class (in a school or in a kindergarten) than the cases in the year of the breakthrough onset; they received a dose of varicella vaccine ≥42 days before the case rash onset and they did not develop varicella symptoms. We enrolled 45 cases and 135 controls. 40% of cases (n = 18; 95% CI = 25.4–54.6) presented at least one risk factor; this proportion was 39.2% (95% CI = 30.9–47.6) among the controls (chi-square = 0.0078; P = 0.93). Time between vaccination and virus exposure was longer among cases. Logistic regression showed that breakthrough disease was associated with duration of time from vaccination.

Cervical cancer prevention: An Italian scenario between organised screening and human papillomaviruses vaccination

Abstract We aimed to assess the cervical cancer burden and performance of screening programme over the last decade in Apulia, Italy. Data from Hospital Discharge, Causes of Death and of Outpatient Services registries were analysed to estimate the disease burden, and data collected by the screening information system were used to evaluate the performance of the programme. We computed annual hospitalisation, incidence and mortality rates and number of outpatient services prescriptions for the follow‐up of preneoplastic/neoplastic lesions. Indicators as proposed by the National Centre for Screening Monitoring were computed to describe the screening performance. Hospitalisation rates declined from 47 in 2001 to 28 per 100,000 in 2014, incidence from 10.3 in 2004 to 6.0 per 100,000 in 2014 and mortality from 1.4 in 2001 to 1.0 per 100,000 in 2010. Prescriptions increased from 3,333 in 2006 to 4,968 in 2010, then decreased to 3,634/year in 2012–2014. Actual extension of screening increased from 10.8% in 2007 to 62% in 2014; compliance with the invitation was 32%/year. In the last decade, we observed a reduction in the cervical cancer burden as early effect of screening implementation.