Fabio Tramuto

Can the serological status of anti-HBc alone be considered a sentinel marker for detection of occult HBV infection?

Some individuals have “occult” infection with hepatitis B virus (HBV), defined as presence of HBV genome in the serum or liver tissue without HBV surface antigen (HBsAg) in the serum. The aim of this study was to investigate whether serum antibodies against HBV core antigen in isolation (“anti‐HBc alone”) are a useful marker of “occult” HBV in patients with or without hepatitis C virus (HCV) infection. “Anti‐HBc alone” was detected in the sera of 119/6,544 (1.8%) asymptomatic outpatients referred to the diagnostic laboratory for routine testing for viral hepatitis, 62/607 (10.2%) drug users, and 42/195 (21.5%) patients with hepatocellular carcinoma. Using three in‐house nested‐PCR amplification assays to detect HBV preS‐S (S), precore‐core (C), and Pol viral regions, respectively, “occult” HBV sequences were found in 9 of the 223 sera (4.0%) with “anti‐HBc alone.” The highest prevalence of “occult” HBV sequences (5.9%) was detected in “anti‐HBV alone” sera of individuals referred to the diagnostic laboratory without HCV antibodies. Direct sequencing of all PCR products confirmed the specificity of the PCR reactions and revealed the predominance of HBV genotype D. The data presented in this study suggest that detection of “anti‐HBc alone” could reflect unrecognized “occult” HBV infection and that physicians should consider investigating such patients with HBV molecular tests. J. Med. Virol. 80:577–582, 2008.

Urban air pollution and emergency room admissions for respiratory symptoms: a case-crossover study in Palermo, Italy

BackgroundAir pollution from vehicular traffic has been associated with respiratory diseases. In Palermo, the largest metropolitan area in Sicily, urban air pollution is mainly addressed to traffic-related pollution because of lack of industrial settlements, and the presence of a temperate climate that contribute to the limited use of domestic heating plants. This study aimed to investigate the association between traffic-related air pollution and emergency room admissions for acute respiratory symptoms.MethodsFrom January 2004 through December 2007, air pollutant concentrations and emergency room visits were collected for a case-crossover study conducted in Palermo, Sicily. Risk estimates of short-term exposures to particulate matter and gaseous ambient pollutants including carbon monoxide, nitrogen dioxide, and sulfur dioxide were calculated by using a conditional logistic regression analysis.ResultsEmergency departments provided data on 48,519 visits for respiratory symptoms. Adjusted case-crossover analyses revealed stronger effects in the warm season for the most part of the pollutants considered, with a positive association for PM10 (odds ratio = 1.039, 95% confidence interval: 1.020 - 1.059), SO2 (OR = 1.068, 95% CI: 1.014 - 1.126), nitrogen dioxide (NO2: OR = 1.043, 95% CI: 1.021 - 1.065), and CO (OR = 1.128, 95% CI: 1.074 - 1.184), especially among females (according to an increase of 10 μg/m3 in PM10, NO2, SO2, and 1 mg/m3 in CO exposure). A positive association was observed either in warm or in cold season only for PM10.ConclusionsOur findings suggest that, in our setting, exposure to ambient levels of air pollution is an important determinant of emergency room (ER) visits for acute respiratory symptoms, particularly during the warm season. ER admittance may be considered a good proxy to evaluate the adverse effects of air pollution on respiratory health.

Can influenza vaccination coverage among healthcare workers influence the risk of nosocomial influenza-like illness in hospitalized patients?

BACKGROUND Approximately 20% of healthcare workers are infected with influenza each year, causing nosocomial outbreaks and staff shortages. Despite influenza vaccination of healthcare workers representing the most effective preventive strategy, coverage remains low. AIM To analyse the risk of nosocomial influenza-like illness (NILI) among patients admitted to an acute care hospital in relation to influenza vaccination coverage among healthcare workers. METHODS Data collected over seven consecutive influenza seasons (2005-2012) in an Italian acute care hospital were analysed retrospectively. Three different sources of data were used: hospital discharge records; influenza vaccination coverage among healthcare workers; and incidence of ILI in the general population. Clinical modification codes from the International Classification of Diseases, 9(th) Revision were used to define NILI. FINDINGS Overall, 62,343 hospitalized patients were included in the study, 185 (0.03%) of whom were identified as NILI cases. Over the study period, influenza vaccination coverage among healthcare workers decreased from 13.2% to 3.1% (P < 0.001), whereas the frequency of NILI in hospitalized patients increased from 1.1‰ to 5.7‰ (P < 0.001). A significant inverse association was observed between influenza vaccination coverage among healthcare workers and rate of NILI among patients (adjusted odds ratio 0.97, 95% confidence interval 0.94-0.99). CONCLUSION Increasing influenza vaccination coverage among healthcare workers could reduce the risk of NILI in patients hospitalized in acute hospitals. This study offers a reliable and cost-saving methodology that could help hospital management to assess and make known the benefits of influenza vaccination among healthcare workers.

Pneumococcal colonization in the familial context and implications for anti-pneumococcal immunization in adults: Results from the BINOCOLO project in sicily

The spread of Streptococcus pneumoniae within families has been scarcely investigated so far. This feasibility study aimed to estimate the prevalence of pneumococcal carriage in school-aged children and co-habiting relatives and to explore the potential link between the family environment and the sharing of pneumococcal serotypes covered by the vaccine. Oropharyngeal samples of 146 subjects belonging to 36 different family groups were molecularly tested for pneumococcal detection and serotyping. The overall prevalence of pneumococcal carriage was 65.8% (n = 96/146), whereas it was higher among schoolchildren (77.8%, n = 28/36); subjects of seven years of age had the highest odds of being colonized (odds ratio, OR = 5.176; p = 0.145). Pneumococcal serotypes included in the 13-valent conjugate vaccine formulation were largely detected in the study population and multiple serotypes colonization was considerable. Factors relating to a close proximity among people at the family level were statistically associated with pneumococcal carriage (OR = 2.121; p = 0.049), as well as active smoking habit with a clear dose-response effect (ORs = 1.017–3.326). About half of family clusters evidenced similar patterns of carried pneumococcal serotypes and the odds of sustaining a high level of intrafamilial sharing increased with household size (ORs = 1.083–5.000). This study highlighted the potential role played by the family environment in sustaining both the circulation and horizontal transmission of pneumococcus.

Variable phenotypic expression of chylomicron retention disease in a kindred carrying a mutation of the Sara2 gene

Chylomicron retention disease is a recessive inherited disorder characterized by fat malabsorption and steatorrhea and is associated with failure to thrive in infancy. We describe a kindred carrying a mutation of Sara2 gene causing a chylomicron retention phenotype. The proband was a 5-month-old baby, born of consanguineous, apparently healthy parents from Morocco, with failure to thrive. There was a large quantity of fats in feces and malabsorption of fat-soluble vitamins. Intestinal biopsies showed a diffused enterocyte vacuolization with large cytosolic lipid droplets. Chylomicron retention disease or Anderson disease was hypothesized, and the Sara2 gene was analyzed by direct sequencing. Analysis of the Sara2 gene in the proband identified a 2-nucleotide homozygous deletion in exon 3 leading to a premature stop codon (c.75-76 del TG-L28fsX34). The father was heterozygous for the same mutation, whereas the probands mother was homozygous, suggesting a variable phenotypic expression of the molecular defect. More studies are needed to understand the reasons of the phenotypic variability of the same molecular defect in the same family.

Transmission of Drug-Resistant HIV Type 1 Strains in HAART-Naive Patients: A 5-Year Retrospective Study in Sicily, Italy

The transmission of drug-resistant HIV-1 strains might compromise the efficacy of current first-line antiretroviral (ARV) regimens. Between 2004 and 2008, HIV-1 reverse transcriptase (RT) and protease (PR) genes of 108 ARV-naive Sicilian patients were amplified and sequenced to describe the prevalence of ARV resistance mutations among HAART-naive HIV-1-infected individuals. The frequency of transmitted drug resistance mutations (DRAMs) was determined by using genotypic interpretation algorithms. The proportion of HAART-naive HIV-1-infected patients in Sicily increased from 18.4% to 23.5% during 2004-2008. Among naive patients, the overall prevalence of DRAMs was 15.7% [17/108; 95% CI: 9.4-24.0]. DRAMs to nonnucleoside reverse transcriptase inhibitors (nNRTI) were detected most frequently [11/108 (10.2%)], of which K103N was the most prevalent (4.6%), whereas the prevalence of DRAMs was lowest for protease inhibitors (PI) [3/108 (2.8%)]. Drug resistance substitutions associated with two or three drug classes were rarely observed. The prevalence of HIV-1 DRAMs in Sicily was relatively higher than that observed in Italy and other European geographic areas and much higher than in resource-limited countries. However, the possible clinical role played by DRAMs in HAART-naive HIV-1-infected individuals will require further assessment.

Dairy calcium intake and lifestyle risk factors for bone loss in hiv-infected and uninfected mediterranean subjects

BackgroundDespite the reported high prevalence of osteoporosis in the human immunodeficiency virus (HIV)-population, there have been no previous studies examining dairy calcium intake and bone mineral density (BMD) in HIV-subjects.We assessed the prevalence of low BMD in HIV-infected and uninfected subjects and analyzed the effects of calcium intake, lifestyle and HIV-related risk factors on BMD.MethodsOne hundred and twelve HIV-infected subjects were consecutively enrolled. Seventy- six HIV-uninfected subjects matched for age and sex were enrolled as the control group. The HIV-subjects were interviewed about lifestyle habits and completed a weekly food-frequency questionnaire to estimate calcium intake. HIV-RNA, CD4+ T-cell count and data on antiretroviral therapy were also recorded. Both biochemical bone turnover markers and BMD, assessed by dual-energy radiographic absorptiometry (DXA) were recorded in the HIV-cases and controls. We also calculated the 10-year fracture risks using the WHO FRAX equation.ResultsOsteoporosis prevalence was significantly higher in the HIV-cases than controls (p < 0.05). BMI values were positively correlated with BMD (p < 0.05). Vitamin D levels were lower in the HIV-subjects (p < 0.02). No correlation was found with daily calcium intake.BMI values were significantly correlated with dairy intake quartiles (p < 0.003). In HIV-subjects, the mean of FRAX score was 1.2 % for hip and 4.7 % for major osteoporotic fractures. On multivariate analysis of the lumbar spine DXA T-score, age (p < 0.005) and HIV/hepatitis C virus co-infection (p < 0.0001) were negatively correlated with BMD, while yogurt intake was a protective predictor of BMD (p < 0.05). In the femur DXA T-score, age (p < 0.01), nadir CD4 + T-cell count < 200 cells/μL (p < 0.05) and drug addiction ( p < 0.0001) were negatively correlated with BMD.ConclusionsAmong the foods rich in calcium, yogurt was a protective predictor of BMD in HIV-subjects. HIV/HCV co-infection, nadir CD4 + T-cell count < 200 cells/μL and drug addiction were independent predictors of severe BMD. Promoting behavioral changes in food intake and lifestyle, aimed at the primary prevention of bone disease in the chronically-infected subjects seems to be essential for implementing medical intervention in these cases.

Detection of HIV type 1 non-B subtypes in Sicily, Italy

To evaluate the presence of HIV-1 non-B subtypes in Sicily, we sequenced and genotyped HIV-1 PR and RT regions of the pol gene using plasma from 169 HIV-1-infected adult patients. All samples were obtained from a study of antiretroviral-associated resistance mutations resulting in virological failure during highly active antiretroviral therapy (HAART). Eight (4.7%) patients had the non-B HIV-1 subtype including some circulating recombinant forms (CRFs). All of these individuals acquired the infection by heterosexual transmission. The detection of HIV-1 non-B strains was significantly associated with younger age of HIV-1 acquisition. Our findings indicate, for the first time, the presence of HIV-1 non-B subtypes in Sicily in patients who experienced virological failure during HAART, and highlight the need for implementing a network for the epidemiological surveillance of HIV-1 subtypes in Southern Europe.

The Molecular Epidemiology and Evolutionary Dynamics of Influenza B Virus in Two Italian Regions during 2010–2015: The Experience of Sicily and Liguria

Molecular epidemiology of influenza B virus remained poorly studied in Italy, despite representing a major contributor to seasonal epidemics. This study aimed to reconstruct the phylogenetic relationships and genetic diversity of the hemagglutinin gene sequences of 197 influenza B strains circulating in both Southern (Sicily) and Northern (Liguria) Italy between 2010 and 2015. Upper respiratory tract specimens of patients displaying symptoms of influenza-like illness were screened by real-time RT-PCR assay for the presence of influenza B virus. PCR-positive influenza B samples were further analyzed by sequencing. Neighbor-joining phylogenetic trees were constructed and the amino-acid alignments were analyzed. Phylogenetic analysis showed clusters in B/Victoria clade 1A/1B (n = 29, 14.7%), and B/Yamagata clades 2 (n = 112, 56.8%) and 3 (n = 56, 28.4%). Both influenza B lineages were found to co-circulate during the study period, although a lineage swap from B/Victoria to B/Yamagata occurred in Italy between January 2011 and January 2013. The most represented amino-acid substitutions were N116K in the 120-loop (83.9% of B/Yamagata clade 3 strains) and I146V in the 150-loop (89.6% of B/Victoria clade 1 strains). D197N in 190-helix was found in almost all viruses collected. Our findings provide further evidence to support the adoption of quadrivalent influenza vaccines in our country.

Prevalence of occult hepatitis B virus infection in a cohort of HIV-positive patients resident in Sicily, Italy.

Occult hepatitis B virus (OBI) in HIV-infected groups is still debated, as well as the associated risk-factors and clinical significance. In this paper, we examined a total of 405 HBsAg-negative/HIV-infected patients enrolled from January 2007 to December 2009. Overall, the prevalence of OBI was 5.9% (95% confidence interval (CI95%): 3.8–8.7%); it was more frequently associated with “anti-HBc alone” serological marker (11.3%; adjusted odds ratio = 3.7, CI95%: 1.4–9.8), although it was also detected in the absence of any HBV serological marker (4.9%; CI95%: 2.3–9.1%). A low prevalence of anti-HCV-positive patients with OBI was found (3.1%; CI95%: 0.6–8.7%). HIV RNA plasma levels or other immunological/clinical characteristics were not significantly associated with OBI. All but one occult HBV infections were sustained by genotype D viral strains. OBI is relatively frequent in HIV-infected patients, although it does not seem to exert a relevant clinical impact. Viral genotypes in occult HBV infections reflect those circulating in the Mediterranean area.