The clinical and economic costs associated with regional disparities in varicella vaccine coverage in Italy over 50 years (2020-2070).

Italy implemented two-dose universal varicella vaccination (UVV) regionally from 2003 to 2013 and nationally from 2017 onwards. Our objective was to analyze regional disparities in varicella outcomes resulting from disparities in vaccine coverage rates (VCRs) projected over a 50-year time-horizon (2020-2070). A previously published dynamic transmission model was updated to quantify the potential public health impact of the UVV program in Italy at the national and regional levels. Four 2-dose vaccine strategies utilizing monovalent (V) and quadrivalent (MMRV) vaccines were evaluated for each region: (A) MMRV-MSD/MMRV-MSD, (B) MMRV-GSK/MMRV-GSK, (C) V-MSD/MMRV-MSD, and (D) V-GSK/MMRV-GSK. Costs were reported in 2022 Euros. Costs and quality-adjusted life-years (QALYs) were discounted 3% annually. Under strategy A, the three regions with the lowest first-dose VCR reported increased varicella cases (+ 34.3%), hospitalizations (+ 20.0%), QALYs lost (+ 5.9%), payer costs (+ 22.2%), and societal costs (+ 14.6%) over the 50-year time-horizon compared to the three regions with highest first-dose VCR. Regions with low first-dose VCR were more sensitive to changes in VCR than high first-dose VCR regions. Results with respect to second-dose VCR were qualitatively similar, although smaller in magnitude. Results were similar across all vaccine strategies.

Unique combined penA/mtrR/porB mutations and NG-MAST strain types associated with ceftriaxone and cefixime MIC increases in a 'susceptible' Neisseria gonorrhoeae population.

OBJECTIVES: To determine which mutations in penA, mtrR and porB are implicated in increasing minimum MICs of ceftriaxone and cefixime in a susceptible gonococcal population and to ascertain associations with gonococcal strain types (STs). METHODS: One hundred and forty-six Neisseria gonorrhoeae isolates formed two extended-spectrum cephalosporin susceptibility groups: group 1 isolates with cefixime and ceftriaxone MICs of 0.0005-0.016 mg/L; and group 2 isolates with cefixime MICs of 0.03-0.125 mg/L (n = 24) and ceftriaxone MICs of 0.03-0.06 mg/L (n = 23). Mutation patterns in penicillin-binding protein 2 (PBP2; penA), multiple transfer resistance repressor (MtrR; mtrR) and porin B (PorB; porB) were ascertained by DNA sequence and bioinformatic analysis. STs were determined using N. gonorrhoeae multiantigen sequence typing (NG-MAST). RESULTS: Most isolates carried PBP2 mutation pattern IX (D345a, F504L, A510V, A516G and P551L; 50/146, 34.2%), a G45D substitution in MtrR (37.7%) and a wild-type (WT) sequence for PorB (43.2%). Group 2 gonococcal isolates were significantly associated with: penA pattern IX; dual mutations in the promoter (A-) and DNA dimerization domain (H105Y) of MtrR; and G120K;A121D substitutions in PorB. There were 50 combined penA/mtrR/porB mutation patterns, with corresponding patterns I/WT/WT and IX/G45D/G120K;A121D predominating. Gonococci susceptible to ceftriaxone and cefixime were significantly associated with NG-MAST ST 25 (33/36; 92%) and the combined penA/mtrR/porB mutation pattern I/WT/WT. No combined mutation pattern or specific ST was associated with elevated ceftriaxone MICs. NG-MAST ST 3654 was significantly associated with the pattern IX/G45D/G120K;A121D and cefixime group 2 isolates. CONCLUSIONS: Specific single or combined mutation patterns in penA, mtrR and porB and specific STs were associated with differences in susceptibility to ceftriaxone and cefixime.

Azithromycin-resistant Neisseria gonorrhoeae strains recently isolated in Italy.

OBJECTIVES: The aim of this study was to characterize 22 azithromycin-resistant Neisseria gonorrhoeae isolates, collected in Italy from January 2007 through June 2008, during a study of the prevalence of antibiotic resistance. METHODS: MICs of azithromycin, ciprofloxacin, ceftriaxone, penicillin and tetracycline were determined by the Etest method. Azithromycin-resistant strains (MIC > or = 1 mg/L) were genetically analysed by N. gonorrhoeae multi-antigen sequence typing (NG-MAST) and PFGE. RESULTS: A total of 22 azithromycin-resistant isolates were found among the 219 collected. Five of the 22 isolates showed high-level azithromycin resistance (MICs of 128 or 256 mg/L). Sixteen of the 22 were isolated from men who have sex with men. Among the 14 sequence types (STs) found by NG-MAST, 5 STs, containing clusters of two, three or four strains, were homogeneous with respect to epidemiology and/or antibiotic susceptibility. PFGE divided the 22 strains into two main groups that were possibly related. CONCLUSIONS: This is the first report of gonococci with high-level resistance to azithromycin circulating in Italy. Correlation between NG-MAST results and epidemiological data for some of the analysed strains and patients could be established. This study represents a reference point for future surveillance in Italy and suggests the need to add azithromycin to the antibiotic susceptibility panel for gonococci.

Phenotypic and genotypic characterization of Neisseria gonorrhoeae in parts of Italy: detection of a multiresistant cluster circulating in a heterosexual network.

Data concerning Neisseria gonorrhoeae infections in Italy are scarce, and there is little information on the phenotypic and genotypic characteristics of the circulating strains. In this study, 326 isolates collected from 397 patients, with or without concurrent human immunodeficiency virus (HIV) infection, were cultured and characterized by serovar and antimicrobial susceptibility to five antimicrobials. N. gonorrhoeae multi-antigen sequence typing (NG-MAST) was also performed for strain characterization and to identify a transmission network. Gonococcal infection was diagnosed in 364 males and 33 females, 296 of whom were Italian and 96 of whom were foreigners (nationality was unknown in five cases). Among the 364 males, 197 were heterosexual, and the median age was 31 years. Approximately 8.3% of all the investigated patients were HIV-1-positive. The isolates were assigned to three different serovars (IA, IB, IA/IB), IB being the most frequently encountered. A significant rate of resistant gonococci was also observed; 34%, 25.5% and 19.1% of ciprofloxacin-resistant, penicillin-resistant and tetracycline-resistant phenotypes, respectively, were detected, and 10.2% of strains were multidrug-resistant. Together with the presence of different sequence types (STs), identified by NG-MAST, a multidrug-resistant cluster, ST661, was detected in a heterosexual network in a precise geographical area of the country. In particular, all strains belonging to ST661 showed identical profiles according to pulsed-field gel electrophoresis (PFGE), all were serotype IB, and all were resistant to penicillin, ciprofloxacin and tetracycline.

Impairment of recent thymic emigrants in HCV infection.

Hepatitis C Virus (HCV) often has a more favorable course in younger patients. Considering the involution of the thymic function with age, we investigated the output of recent thymic emigrants (RTE) in HCV patients. To evaluate RTE, we used a competitive quantitative PCR in order to determine the percentages of cells with cj-T cell receptor excision circles (TREC). This study was performed in 14 HCV patients at diagnosis and before any anti-HCV treatment. The results obtained in this group were compared to those obtained in a group of age-matched controls. We found that in the 14 HCV patients naive for anti-HCV treatment the mean percentage of cj-TREC was 3%. We could not detect a correlation between the percentages of cj-TREC and age or patients' viremia. In contrast, in the 26 age-matched controls mean percentage of cj-TREC was 5.6% (P=0.01). Our study describes a novel immune defect in HCV patients. Additional studies are needed to get further insight in the possible role of TREC defect in the pathogenesis and prognosis of the disease.

Increased frequency of the immunoglobulin enhancer HS1,2 allele 2 in coeliac disease.

BACKGROUND: Coeliac disease (CD) is characterized by increased immunological responsiveness to ingested gliadin in genetically predisposed individuals. This genetic predisposition is not completely defined. A dysregulation of immunoglobulins (Ig) is present in CD: since antiendomysium antibodies (anti-EMA) are of the IgA class. One polymorphic enhancer within the locus control region (LCR) of the immunoglobulin heavy chain cluster at the 3' of the C alpha-1 gene was investigated. The correlation of the penetrance of the four different alleles of the HS1,2-A enhancer of the LCR-1 3' to C alpha-1 in CD patients compared to a control population was analysed. METHODS: A total of 115 consecutive CD outpatients, on a gluten-free diet, and 248 healthy donors, age- and sex-matched, from the same geographical area were enrolled in the study. HS1,2-A allele frequencies were investigated by nested polymerase chain reaction (PCR). RESULTS: The frequency of allele 2 of the enhancer HS1,2-A gene was increased by 30.8% as compared to the control frequency. The frequency of homozygosity for allele 2 was significantly increased in CD patients. Crude odds ratio (OR) showed that those with 2/2 and 2/4 (OR 2.63, P < 0.001 and OR 2.01, P = 0.03) have a significantly higher risk of developing the disease. In contrast, allele 1/2 may represent a protective genetic factor against CD (OR 0.52, P = 0.01). CONCLUSIONS: These data provide further evidence of a genetic predisposition in CD. Because of the Ig dysregulation in CD, the enhancer HS1,2-A may be involved in the pathogenesis.