Maria Chironna

Long-term immunogenicity of hepatitis B vaccination and policy for booster: an Italian multicentre study

BACKGROUND Universal anti-hepatitis-B vaccination of infants and adolescents was implemented in Italy in 1991. We undertook a multicentre study in previously vaccinated individuals to assess the duration of immunity and need for booster, over 10 years after vaccination. METHODS In 1212 children and 446 Italian Air Force recruits vaccinated as infants and adolescents, respectively, we measured the concentrations of antibodies to hepatitis-B surface antigen (anti-HBs) and the presence of antibodies to hepatitis-B core antigen (anti-HBc) at enrollment; postimmunisation values were not available. Individuals positive for anti-HBc were tested for hepatitis B surface antigen (HBsAg) and hepatitis B viral DNA. Individuals with anti-HBs concentrations at 10 IU/L or more were regarded as protected; those with antibody less than 10 IU/L were given a booster dose and retested 2 weeks later. Individuals showing postbooster anti-HBs concentrations of less than 10 IU/L were offered two additional vaccine doses and retested 1 month after the third dose. FINDINGS Protective anti-HBs concentrations were retained in 779 (64%, 95% CI 61.6-67) children and 398 (89%, 86.4-92.1) recruits. We recorded antibody amounts of less than 10 IU/L in 433 children (36%, 33-38.4) and 48 (11%, 7.9-13.6) recruits. One child and four recruits were positive for anti-HBc, but negative for HBsAg and hepatitis B viral DNA. Antibody concentrations were higher in recruits than in children (geometric mean titre 234.8 IU/L vs 32.1 IU/L, p=0.0001). 332 (97%) of 342 children and 46 (96%) of 48 recruits who received a booster showed an anamnestic response, whereas ten (3%) children and two (4%) recruits remained negative for anti-HBs or had antibody concentrations of less than 10 IU/L. Prebooster and postbooster antibody titres were strongly correlated with each other in both groups. All individuals given two additional vaccine doses (eight children and two recruits) showed anti-HBs amounts of more than 10 IU/L at 1 month after vaccination. INTERPRETATION Strong immunological memory persists more than 10 years after immunisation of infants and adolescents with a primary course of vaccination. Booster doses of vaccine do not seem necessary to ensure long-term protection.

Pegylated interferon-α, ribavirin, and rituximab combined therapy of hepatitis C virus–related mixed cryoglobulinemia: a long-term study

This study illustrates the use and efficacy of a combination of pegylated interferon-alpha (Peg-IFN-alpha) and ribavirin (RBV), with or without rituximab (RTX), in hepatitis C virus (HCV)-related mixed cryoglobulinemia (MC). Twenty-two patients with HCV-related MC received Peg-IFN-alpha (2a: 180 mug or 2b: 1.5 mug/kg) weekly plus RBV (1000 or 1200 mg) daily for 48 weeks, and RTX (375 mg/m(2)) once a week for 1 month followed by two 5-monthly infusions (termed PIRR). Fifteen additional patients received Peg-IFN-alpha/RBV with the same modalities as the PIRR schedule. Complete response was achieved in 54.5% (12/22) and in 33.3% (5/15) of patients who received PIRR and Peg-IFN-alpha/RBV, respectively (P < .05). Clearance of HCV RNA and conversion of B-cell populations from oligoclonal to polyclonal in liver, bone marrow, and peripheral blood was maintained for up to 3 years in 10 of 12 (83.3%) and in 2 of 5 (40%) patients receiving PIRR and Peg-IFN-alpha/RBV, respectively (P < .01). Cryoproteins in 22.7% (5/22) of patients with PIRR and in 33.3% (5/15) with Peg-IFN-alpha/RBV persisted despite sustained HCV RNA clearance. No response occurred in remaining 5 patients of both groups. PIRR therapy is well tolerated and more effective than Peg-IFN-alpha/RBV combination in HCV-related MC. Its effect may last for more than 3 years.

Emergence of macrolide-resistant strains during an outbreak of Mycoplasma pneumoniae infections in children

OBJECTIVES Mycoplasma pneumoniae is a frequent cause of human lower respiratory tract infections (LRTIs) for which macrolides are the treatment of choice. The aim of this study was to determine the rate of macrolide resistance and to subtype M. pneumoniae strains in Italy. PATIENTS AND METHODS During an outbreak of M. pneumoniae infections in southern Italy in 2010, 48 clinical specimens from 43 paediatric patients hospitalized for LRTIs were analysed for macrolide resistance. The mutations associated with resistance (A2063G and A2064G) and M. pneumoniae subtypes were detected by sequencing the targeted domain V region of the 23S rRNA gene and a region in the MPN528a gene, respectively. RESULTS Macrolide resistance genotypes were detected in 11 (26%) of the 43 M. pneumoniae-positive children. The A2063G mutation was identified in seven patients and the A2064G mutation was identified in the remaining four. Upon admission, the isolates from three patients showed a susceptible genotype but subsequently acquired the A2063G mutation. Genotyping revealed M. pneumoniae subtype 1 in 33 of 40 sequenced strains and subtype 2 in the remaining 7. There was no association between macrolide resistance or susceptibility and the M. pneumoniae subtypes. CONCLUSIONS This is the first report of macrolide resistance among M. pneumoniae strains in Italy. Our findings indicate an unexpected high prevalence of macrolide resistance genotypes in children, and so macrolide resistance should be carefully considered in patients who do not respond appropriately to antibiotic treatment. The epidemiological monitoring of macrolide resistance has become necessary in Italy and in the rest of Europe.

Detection of hepatitis A virus in mussels from different sources marketed in Puglia region (South Italy).

Hepatitis A virus (HAV) infection is endemic in Puglia (South Italy). Epidemiological studies indicate that shellfish consumption, particularly mussels, is a major risk factor for HAV infection, since these products are eaten raw or slightly cooked. Nested reverse transcriptase-polymerase chain reaction (RT-PCR) has been shown to be a sensitive technique for the detection of HAV in mussels. The aim of the present study was to detect the presence of HAV in a large sample of mussels by nested RT-PCR and to confirm the presence of infectious viral particles in positive samples by cell culture infection and RT-PCR confirmation. Two hundred and ninety samples of mussels from different sources were collected between December 1999 and January 2000. One hundred samples were collected before being subjected to depuration, 90 after depuration, and 100 were sampled in different seafood markets. HAV-RNA was detected in 20 (20.0%) of non-depurated mussels, in 10 (11.1%) of depurated samples, and in 23 (23.0%) of samples collected in the shellfish markets, without any significant difference in the prevalence of positive samples by collection sources (chi2 = 4.79, p = 0.09). Of the 53 samples found positive by nested RT-PCR, 18 (34.0%) resulted positive by cell culture assay. No relationship between viral contamination and bacterial contamination was found (p = 0.41). This study confirms the usefulness of molecular techniques in detecting HAV in shellfish and, thus, for the screening of a large sample of naturally contaminated mussels. Improved shellfish depuration methods are needed to obtain virus-safe shellfish and reduce the risk for public human health.

Outbreak of Infection with Hepatitis A Virus (HAV) Associated with a Foodhandler and Confirmed by Sequence Analysis Reveals a New HAV Genotype IB Variant

ABSTRACT An outbreak of infection with hepatitis A virus associated with a foodhandler and involving 26 subjects occurred in Southern Italy. Sequence analysis of the VP3-VP1 and VP1-P2A junctions confirmed that the outbreak was due to a point source and allowed the identification of a new genotype IB variant. This report confirms the usefulness of sequence-based molecular fingerprinting during outbreaks.

PREVALENCE RATES OF VIRAL HEPATITIS INFECTIONS IN REFUGEE KURDS FROM IRAQ AND TURKEY

Abstract.Background: Since little is known about the burden of viral hepatitis in Kurds, the prevalence of infection with hepatitis A virus (HAV), hepatitis E virus (HEV), hepatitis B virus (HBV) and hepatitis C virus (HCV) was investigated in a sample of refugee Kurds from Iraq and Turkey. Patients and Methods: A cross-sectional study was carried out. Serological markers to hepatitis viruses were determined for 1,005 subjects from all age-groups of which 36.6% were from Turkey and 63.4% from Iraq. Results: Overall seroprevalence for anti-HAV was 94.4% and 14.8% for anti-HEV. A significantly higher prevalence for anti-HEV was found among Iraqis (17.5%) compared to Turkish immigrants (10.0%). The prevalence of hepatitis B surface antigen (HBsAg) and total anti-HBc (core) was 6.8% and 35.6% in Turkish Kurds and 2.2% and 12.7% in Iraqis, respectively. Only 10% of children aged up to 10 years and 2.8% of subjects aged 11–20 years had been vaccinated against HBV, the majority of them coming from Iraq. One subject was confirmed as positive for anti-HCV (0.1%) and HCV-RNA and analysis showed a 4c/4d genotype. Conclusion: This survey shows a high prevalence of enterically transmitted viral hepatitis in Kurds. HBV infection is moderately endemic, while the prevalence of HCV infection is low. There is a need for a universal immunization strategy for HBV in the Kurd population.

Determinants of acquiring hepatitis A virus disease in a large Italian region in endemic and epidemic periods

Summary.  Viral hepatitis A is endemic in Puglia region (southeast Italy). Over the last 13 years, annual incidence rates have ranged from 4 to 138 per 100 000 inhabitants and periodical regional epidemics have been described. Between 1 January 1996 and 31 December 1997 over 11 000 cases of hepatitis A were reported accounting for an annual incidence rate over 130/100 000. To identify exposures during the epidemics, a case–control study was performed in two different rounds and since 1997, an enhanced surveillance system has permitted the monitoring of exposures of subsequent cases. Raw seafood consumption was identified as the major risk factor for hepatitis A. Adjusted odds ratio and 95% confidence intervals for this exposure from the first round of the case–control study was 38.6 (12.2–122.4) and for the second round for consumption of raw mussels it was 30.7 (16.0–52.0). Hepatitis A epidemiology in Puglia is consistent with an endemic situation sustained by locally contaminated seafood consumed raw and by the recurrence of large epidemics, where size is influenced by the accumulation of susceptible subjects in the population.

Identification of the novel Kawasaki 2014 GII.17 human norovirus strain in Italy, 2015

Surveillance of noroviruses in Italy identified the novel GII.17 human norovirus strain, Kawasaki 2014, in February 2015. This novel strain emerged as a major cause of gastroenteritis in Asia during 2014/15, replacing the pandemic GII.4 norovirus strain Sydney 2012, but being reported only sporadically elsewhere. This novel strain is undergoing fast diversification and continuous monitoring is important to understand the evolution of noroviruses and to implement the future strategies on norovirus vaccines.

HBV, HCV and HDV infections in Albanian refugees in Southern Italy (Apulia region)

The seroprevalence of hepatitis B, C and D markers was assessed in a sample of 670 Albanian refugees in Southern Italy in 1997. The mean age was 25 years (S.D. = 12.3). Of study subjects 62.1% (95% CI: 58.4-65.7) were positive for anti-HBc antibodies and 13.6% (95% CI: 10.9-16.1) for HBsAg. The prevalence of anti-HBs was 47.6% (95% CI: 43.8-51.3). Among HBsAg carriers the prevalence of HBeAg was 7.7% (95% CI: 2.2-13.1). The highest carrier rate for HBsAg (25.5%; 95% CI: 16.7-34.3) was found in the age group 21-25 years. A relevant finding was a prevalence of HBsAg of 8.1% in children 10 years and under. The prevalence of anti-HCV antibodies was 0.3% (95% CI: 0.0-0.7) while only one of the HBsAg carriers was positive for anti-HDV (1.1%, 95% CI: 0-3.2). In Albania, hepatitis B infection represents a public health priority that should be addressed by a universal vaccination campaign.

Macrolide-resistant Mycoplasma pneumoniae in paediatric pneumonia

To the Editors: Mycoplasma pneumoniae is one of the most common causes of bacterial community-acquired pneumonia (CAP) in paediatrics, and can lead to severe and long-lasting disease [1]. Macrolides are usually considered the first-choice antimicrobials for M. pneumoniae CAP in children because the alternatives ( i.e. fluoroquinolones and tetracyclines) are not approved for use in the first years of life [2]. Recent studies from Japan and China have shown macrolide resistance in up to 80% of M. pneumoniae strains [3, 4], but it has been detected in relatively few cases in the USA, France and Germany, and not at all in other European countries [5–7]. The mechanism of M. pneumoniae macrolide resistance is related to point mutations in domain V of the 23S rRNA gene of M. pneumoniae and macrolide resistance is usually detected at disease onset [4]. We here describe the first case of macrolide-resistant M. pneumoniae detected during treatment with clarithromycin in an otherwise healthy child with CAP. An otherwise healthy 6-yr-old girl with an unremarkable medical history who had never travelled abroad was admitted in Bari, Italy, after suffering from a dry cough for 3 days with fever up to 40.5°C, accompanied by increasing malaise and dyspnoea. Upon admission, she was severely ill, with a high temperature, lethargy, an increased respiratory rate (60 breaths·min−1), tachycardia and normal blood pressure. Room air oximetry revealed 85% oxygen saturation, whereas arterial gas sampling showed severe hypoxaemia (50 mmHg) with hypocapnia and a normal pH. Other routine blood examinations revealed neutrophilia with increased C-reactive protein levels and a high erythrocyte sedimentation rate. A physical examination revealed diffuse crackles with reduced vesicular sounds on both lungs, and chest radiography showed an interstitial pattern with multiple “ground-glass” infiltrates. Blood, nasopharyngeal …