An Outbreak of COVID-19 among mRNA-Vaccinated Nursing Home Residents.

An outbreak was described among the guests of a Long-Term Care Facility in the North of Italy. Among 23 guests, 20 of whom were fully vaccinated with BNT162b2 vaccine, the outbreak led to a final count of 11 positive guests, 9 of whom were vaccinated, and 4 positive healthcare workers, of whom only 1 was vaccinated. Eight of the positive guests (six vaccinated and two unvaccinated) had symptoms that in five cases (three vaccinated and two unvaccinated) led to death. The risk of infection and the risk of death appeared not to be correlated with the health status neither with the serological titer, but only with age.

[Seroprevalence of anti-SARS-CoV-2 IgG/IgM antibodies in Borgosesia (Piedmont Region, Northern Italy) population: a surveillance strategy in post-lockdown period?] / La prevalenza della risposta immunitaria a SARS-CoV-2 nella popolazione di Borgosesia (VC): una strategia di sorveglianza in fase post-lockdown?

BACKGROUND: to avoid a new spread of the SARS-CoV-2 infection, the post lockdown period requires the implementation of effective strategies for the case finding and contact tracing. The presence of asymptomatic subjects in the population, that are responsible for about 30% of the new infections, may complicate this phase. Serological tests for the measurement of immune response could represent an effective tool for the rapid monitoring of the population with asymptomatic infections and for estimating the proportion of immune in a territory, too. OBJECTIVES: to describe the distribution of the immune response to SARS-CoV-2 infection in the population of the Municipality of Borgosesia (Piedmont Region, Northern Italy) and to estimate the efficacy of this strategy for the identification of asymptomatic cases. DESIGN: Cross-sectional study with administration of a rapid test to assess the seroprevalence of anti-SARS-CoV-2 IgG/IgM antibodies. SETTING AND PARTICIPANTS: all subjects resident in Borgosesia over the age of 18, where invited to participate. A rapid serological test was administered to enrolled participants to detect the presence of SARS-CoV-2 IgG and IgM antibodies on peripheral blood. Subjects with IgG or IgM positivity were offered to perform a swab test for viral RNA research. MAIN OUTCOME MEASURES: the prevalence of IgM and IgG, and the relative risks of having positive swab test and of having symptoms similar to those of COVID-19 in the recent past has been estimated. RESULTS: 4,987 subjects participated to study, 44.5% of the adult population of Borgosesia. The average age was 55 years. There was a greater participation of women (54.4%), of people with a higher education level (37.3%) and of people without specific previous symptoms (95.1%). 245 people had a positive test for IgM or IgG, and the estimated prevalence was of 4.9%. 209 out of 245 subjects who were positive to the rapid test underwent to the RT-PCR test and this allowed to isolate 24 positive subjects. CONCLUSIONS: the seroprevalence values ​​estimated for subjects residing in the city of Borgosesia which underwent the rapid test for the detection of type M and type G antibodies on peripheral blood, confirmed the population-based estimates reported in literature, in particular with the results of the Italian survey of seroprevalence. Furthermore, the implementation of this test allowed the identification and isolation of completely asymptomatic subjects, that could have been identified only through screening with tests for viral RNA.

Vaccines for women for preventing neonatal tetanus.

BACKGROUND: Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium tetani. It occurs in newborn infants born to mothers who do not have sufficient circulating antibodies to protect the infant passively, by transplacental transfer. Prevention may be possible by the vaccination of pregnant or non-pregnant women, or both, with tetanus toxoid, and the provision of clean delivery services. Tetanus toxoid consists of a formaldehyde-treated toxin that stimulates the production of antitoxin. OBJECTIVES: To assess the effectiveness of tetanus toxoid, administered to women of reproductive age or pregnant women, to prevent cases of, and deaths from, neonatal tetanus. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2015), CENTRAL (The Cochrane Library 2015, Issue 1), PubMed (1966 to 28 January 2015), EMBASE (1974 to 28 January 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised or quasi-randomised trials evaluating the effects of tetanus toxoid in pregnant women or women of reproductive age on numbers of neonatal tetanus cases and deaths. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: Two effectiveness trials (9823 infants) and one safety trial (48 mothers) were included. The main outcomes were measured on infants born to a subset of those randomised women who became pregnant during the course of the studies. For our primary outcomes, there was no high-quality evidence according to GRADE assessments.One study (1182 infants) assessed the effectiveness of tetanus toxoid in comparison with influenza vaccine in preventing neonatal tetanus deaths. A single dose did not provide significant protection against neonatal tetanus deaths, (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.26 to 1.24; 494 infants; GRADE: low-quality evidence). However, a two- or three-dose course did provide protection against neonatal deaths, (RR 0.02, 95% CI 0.00 to 0.30; 688 infants; GRADE: moderate-quality evidence). Administration of a two- or three-dose course resulted in significant protection when all causes of death are considered as an outcome (RR 0.31, 95% CI 0.17 to 0.55; 688 infants; GRADE: moderate-quality evidence). No effect was detected on causes of death other than tetanus. Cases of neonatal tetanus after at least one dose of tetanus toxoid were reduced in the tetanus toxoid group, (RR 0.20, 95% CI 0.10 to 0.40; 1182 infants; GRADE: moderate-quality evidence).Another study, involving 8641 children, assessed the effectiveness of tetanus-diphtheria toxoid in comparison with cholera toxoid in preventing neonatal mortality after one or two doses. Neonatal mortality was reduced in the tetanus-diphtheria toxoid group (RR 0.68, 95% CI 0.56 to 0.82). In preventing deaths at four to 14 days, neonatal mortality was reduced again in the tetanus-diphtheria toxoid group (RR 0.38, 95% CI 0.27 to 0.55). The quality of evidence as assessed using GRADE was found to be low.The third small trial assessed that pain at injection site was reported more frequently among pregnant women who received tetanus diphtheria acellular pertussis than placebo (RR 5.68, 95% CI 1.54 to 20.94; GRADE: moderate-quality evidence). AUTHORS' CONCLUSIONS: Available evidence supports the implementation of immunisation practices on women of reproductive age or pregnant women in communities with similar, or higher, levels of risk of neonatal tetanus, to the two study sites.

Vaccines for women to prevent neonatal tetanus.

BACKGROUND: Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium tetani. It occurs in newborn infants born to mothers who do not have sufficient circulating antibodies to protect the infant passively, by transplacental transfer. Prevention may be possible by the vaccination of pregnant or non-pregnant women, or both, with tetanus toxoid, and the provision of clean delivery services. Tetanus toxoid consists of a formaldehyde-treated toxin which stimulates the production of antitoxin. OBJECTIVES: To assess the effectiveness of tetanus toxoid, administered to women of childbearing age or pregnant women, to prevent cases of, and deaths from, neonatal tetanus. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2012), The Cochrane Library (2012, Issue 10), PubMed (1966 to 31 October 2012), EMBASE (1974 to 31 October 2012). We also used the results from handsearching and consultations with manufacturers and authors. SELECTION CRITERIA: Randomised or quasi-randomised trials evaluating the effects of tetanus toxoid in pregnant women or women of childbearing age on numbers of neonatal tetanus cases and deaths. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials for inclusion and trial quality, and extracted data. MAIN RESULTS: Two trials (10,560 infants) were included. It should be noted that these trials are very old,1966 and 1980 respectively, and one trial randomised exclusively non-pregnant women. The main outcomes were measured on infants born to a subset of those randomised women who became pregnant during the course of the studies. One study (1919 infants) assessed the effectiveness of tetanus toxoid in comparison with influenza vaccine in preventing neonatal tetanus deaths. After a single dose, the risk ratio (RR) was 0.57 (95% confidence interval (CI) 0.26 to 1.24), and the vaccine effectiveness was 43%. With a two- or three-dose course, the RR was 0.02 (95% CI 0.00 to 0.30); vaccine effectiveness was 98%. No effect was detected on causes of death other than tetanus. The RR of cases of neonatal tetanus after at least one dose of tetanus toxoid was 0.20 (95% CI 0.10 to 0.40); vaccine effectiveness was 80%. Another study, involving 8641 children, assessed the effectiveness of tetanus-diptheria toxoid in comparison with cholera toxoid in preventing neonatal mortality after one or two doses. The RR was 0.68 (95% CI 0.56 to 0.82); vaccine effectiveness was 32%. In preventing deaths at four to 14 days, the RR was 0.38 (95% CI 0.27 to 0.55), and vaccine effectiveness 62% (95% CI 45% to 73%). AUTHORS' CONCLUSIONS: Available evidence supports the implementation of immunisation practices on women of childbearing age or pregnant women in communities with similar, or higher, levels of risk of neonatal tetanus, to the two study sites. More information is needed on possible interference of vaccination by malaria chemoprophylaxis on the roles of malnutrition and vitamin A deficiency, and on the quality of tetanus toxoid production and storage.

Hepatitis B immune memory in children primed with hexavalent vaccines and given monovalent booster vaccines: an open-label, randomised, controlled, multicentre study.

BACKGROUND: In 2000, hexavac and infanrix hexa were licensed in Europe for primary immunisation of children against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, and invasive infections caused by Haemophilus influenzae b. In 2005, hexavac was suspended because of concerns about the long-term immunogenicity of its hepatitis B component. We aimed to assess the duration of immunity and need for booster injections in children primed with these vaccines. METHODS: In an open-label, randomised, controlled, multicentre study in six local health units and at the Bambino Gesù Paediatric Research Hospital in Italy, antibody concentrations were measured 5 years after immunisation of infants with hexavac or infanrix hexa. Children with concentrations of antibodies to hepatitis B surface antigen (anti-HBs) lower than 10 mIU/mL were randomly assigned by simple randomisation to receive a booster of HBVaxPro or engerix B monovalent hepatitis B vaccine and tested 2 weeks later. Primary endpoints were the proportion of children with anti-HBs concentrations of at least 10 mIU/mL, geometric mean concentrations (GMCs) of antibody 5 years after vaccination, and the proportion of children with anti-HBs concentrations lower than 10 mIU/mL who had anamnestic response to booster. The study is registered with Agenzia Italiana del Farmaco, code FARM67NFPN. FINDINGS: 1543 children were enrolled, 833 had received hexavac and 710 infanrix hexa. 831 children who received hexavac and 709 who received infanrix hexa were included in the analysis. 319 children who received hexavac (38.4%, 95% CI 35.1-41.7) had anti-HBs concentrations of at least 10 mIU/mL compared with 590 who received infanrix hexa (83.2%, 80.5-86.0; p<0.0001). GMCs before booster were 4.5 mIU/mL in the hexavac group compared with 61.3 mIU/mL in the infanrix hexa group (p<0.0001). After booster 409 (92.1%, 89.6-94.6) of 444 children primed with hexavac and 99 (94.3%, 89.8-98.7) of 105 primed with infanrix hexa had anti-HBs concentrations of at least 10 mIU/mL (p=0.4); GMCs were 448.7 mIU/mL and 484.9 mIU/mL (p=0·6). The two booster vaccine groups did not differ in number of side-effects; no serious adverse events were reported. INTERPRETATION: 5 years after immunisation with hexavalent vaccines, immunological memory seems to persist in children with anti-HBs concentrations lower than 10 mIU/mL, suggesting that booster doses are not needed. Additional follow-up is needed. FUNDING: Agenzia Italiana del Farmaco.

A cohort study to evaluate persistence of hepatitis B immunogenicity after administration of hexavalent vaccines.

BACKGROUND: In 2001, two hexavalent vaccines were licensed in Italy (Hexavac, Infanrix Hexa), and since 2002 were extensively used for primary immunization in the first year of life (at 3, 5, 11/12 months of age). In 2005, the market authorization of Hexavac was precautionary suspended by EMEA, because of doubts on long-term protection against hepatitis B virus. The objectives of this study were to evaluate the persistence of antibodies to anti-HBs, in children in the third year of life, and to investigate the response to a booster dose of hepatitis B vaccine. METHODS: Participant children were enrolled concomitantly with the offering of anti-polio booster dose, in the third year of life. Anti-HBs titers were determined on capillary blood samples. A booster dose of hepatitis B vaccine was administered to children with anti-HBs titers < 10 mIU/ml, with the monovalent precursor product of the previously received hexavalent vaccine. HBsAb titers were tested again one month after the booster. RESULTS: Sera from 113 children previously vaccinated with Hexavac, and from 124 vaccinated with Infanrix Hexa were tested for anti-HBs. Titers were > or = 10 mIU/ml in 69% and 96% (p < 0,0001) respectively. The proportion of children with titers > or = 100 mIU/ml did also significantly differ among groups (27% and 78%; p < 0,0001).Post-booster, 93% of children achieved titers > or = 10 mIU/ml, with no significant difference by vaccine group. DISCUSSION: Fifteen months after third dose administration, a significant difference in anti-HBs titers was noted in the two vaccine groups considered. Monovalent hepatitis B vaccine administration in 3-year old children induced a proper booster response, confirming that immunologic memory persists in children with anti-HBs titers < 10 mIU/ml. However, long-term persistence of HBV protection after hexavalent vaccines administration should be further evaluated over time.

Incidence of vaccine preventable pneumococcal invasive infections and blood culture practices in Italy.

In order to estimate the incidence of invasive pneumococcal diseases (IPD) and the amount of vaccine preventable serious infections, a 1-year population-based surveillance was undertaken in two comparable Italian regions (Piemonte and Puglia, representing 14% of the Italian population) prospectively collecting data and strains from all the hospital microbiological laboratories. A retrospective analysis of hospital discharge records, matched with the laboratory database, was also undertaken in nine hospitals in these two regions to determine the frequency of use of blood cultures and its impact on IPD incidence estimate. For children under 2 years of age, the incidence rates of IPD were 11.3 per 100,000 and 5.9 per 100,000 in Piemonte and in Puglia, respectively; for subjects 65 years of age and over the incidence rates were 5.7 per 100,000 and 0.2 per 100,000, in the two regions, respectively. The number of blood cultures performed was six times higher in Piemonte than that in Puglia. About 96% of isolates from IPD patients, aged 65 years and over, belonged to serogroups included in the 23-valent polysaccharide vaccine, whereas about 79% of strains isolated from patients under 5 years of age were related to serotypes included in the 7-valent conjugate vaccine. The estimate of the incidence of IPD is affected greatly by the different attitudes in performing blood cultures, especially in older patients. In Italy, bacteriological culture procedures should be undertaken more frequently to provide decision-makers with reliable estimates of serious vaccine preventable conditions.

The Cochrane Vaccines Field.

The Cochrane Vaccines Field (CVF) is a Cochrane Collaboration entity. The CVF was founded to facilitate the gathering of evidence on vaccines and their effects (ability to prevent the target disease, short and long term safety and efficiency) finalised to the production of systematic reviews. The CVF formulate criteria for population-based quality assessment of vaccines. The Cochrane Vaccines Field was registered in 1996 and is now based in Alessandria, Italy since 2000. The specific contribution of the Cochrane Vaccines Field is to promote the preparations and maintenance of systematic reviews on the effects of vaccines facilitating the coverage of the knowledge gaps in vaccinology and thus forming a methodological focus for a population based assessment of vaccines and systematic gathering and dissemination of information on vaccines. The targets reached until now are: the handsearch of Vaccine and The Journal of Medical Virology, the updating of an overview on the current status of knowledge on vaccines, the preparation and maintenance of systematic reviews. The next Key objective of the Cochrane Vaccines Field is to develop "The Vaccines Register" a register comprising all relevant studies on the effectiveness, the safety and the economical aspects of vaccines. This Register aims to be an extensive and up to date reference to enable those making decisions on the use of human vaccines to make best use of available evidence assessed by its reliability.