Clinical importance and impact on the households of oseltamivir-resistant seasonal A/H1N1 influenza virus in healthy children in Italy

A resistance of A/H1N1 influenza viruses to oseltamivir has recently emerged in a number of countries. However, the clinical and socioeconomic importance of this resistance has not been precisely defined. As children have the highest incidence of influenza infection and are at high risk of severe disease, the aim of this study was to evaluate the clinical importance and the impact on the households of oseltamivir-resistant seasonal A/H1N1 influenza virus in an otherwise healthy pediatric population. A total of 4,726 healthy children younger than 15 years with influenza-like illness were tested for influenza viruses by real-time polymerase chain reaction in the winters of 2007-2008 and 2008-2009 in Italy. The influenza A virus-positive samples underwent neuraminidase gene analysis using pyrosequencing to identify mutations H275Y and N294 S in A/H1N1, and E119V, R292K, and N294 S in A/H3N2. Among the A/H1N1 subtypes, the H275Y mutation was found in 2/126 samples taken in 2007-2008 (1.6%) and in all 17 samples (100%; p < 0.0001) taken in 2008-2009. No other mutation was identified in any of the A/H1N1 or A/H3N2 influenza viruses. No significant differences were found in terms of clinical importance or impact on the households between the children with oseltamivir-resistant seasonal A/H1N1 influenza virus and those with the wild-type. The spread of H275Y-mutated A/H1N1 seasonal influenza virus is a common phenomenon and the clinical importance and impact on the households of the mutated virus is similar to that of the wild-type in an otherwise healthy pediatric population

Preventing transmission of infectious agents in the pediatric in-patients hematology-oncology setting: what is the role for non-pharmacological prophylaxis?

The most intensive chemotherapy regimens were used in the past for leukemia patients who were the main focus of trials on infections; today there are increasing numbers of children with solid cancer and considerable risk of infection who do receive intensive standard-dose chemotherapy. Despite a continuous will to protect the immune-compromised child from infections, evidence-based indications for intervention by non-pharmacological tools is still lacking in the pediatric hematology-oncology literature. Guidelines on standard precautions as well as precautions to avoid transmission of specific infectious agents are available. As a result of a consensus discussion, the Italian Association for Pediatric Hematology-Oncology (AIEOP) Cooperative Group centers agree that for children treated with chemotherapy both of these approaches should be implemented and vigorously enforced, while additional policies, including strict environmental isolation, should be restricted to patients with selected clinical conditions or complications. We present here a study by the working group on infectious diseases of AIEOP

Clinical and socioeconomic impact of different types and subtypes of seasonal influenza viruses in children during influenza seasons 2007/2008 and 2008/2009

<p>Abstract</p> <p>Background</p> <p>There are few and debated data regarding possible differences in the clinical presentations of influenza A/H1N1, A/H3N2 and B viruses in children. This study evaluates the clinical presentation and socio-economic impact of laboratory-confirmed influenza A/H1N1, A/H3N2 or B infection in children attending an Emergency Room because of influenza-like illness.</p> <p>Methods</p> <p>Among the 4,726 children involved, 662 had influenza A (143 A/H1N1 and 519 A/H3N2) and 239 influenza B infection detected by means of real-time polymerase chain reaction. Upon enrolment, systematic recordings were made of the patients' demographic characteristics and medical history using standardised written questionnaires. The medical history of the children was re-evaluated 5-7 days after enrolment and until the resolution of their illness by means of interviews and a clinical examination by trained investigators using standardised questionnaires. During this evaluation, information was also obtained regarding illnesses and related morbidity among households.</p> <p>Results</p> <p>Children infected with influenza A/H1N1 were significantly younger (mean age, 2.3 yrs) than children infected with influenza A/H3N2 (mean age, 4.7 yrs; p < 0.05)) or with influenza B (mean age, 5.2 yrs; p < 0.05). Adjusted for age and sex, children with influenza A/H3N2 in comparison with those infected by either A/H1N1 or with B influenza virus were more frequently affected by fever (p < 0.05) and lower respiratory tract involvement (p < 0.05), showed a worse clinical outcome (p < 0.05), required greater drug use (p < 0.05), and suffered a worse socio-economic impact (p < 0.05). Adjusted for age and sex, children with influenza B in comparison with those infected by A/H1N1 influenza virus had significantly higher hospitalization rates (p < 0.05), the households with a disease similar to that of the infected child (p < 0.05) and the need for additional household medical visits (p < 0.05).</p> <p>Conclusions</p> <p>Disease due to influenza A/H3N2 viral subtype is significantly more severe than that due to influenza A/H1N1 subtype and influenza B virus, which indicates that the characteristics of the different viral types and subtypes should be adequately considered by health authorities when planning preventive and therapeutic measures.</p

The Third Fermi Large Area Telescope Catalog of Gamma-ray Pulsars

We present 294 pulsars found in GeV data from the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope. Another 33 millisecond pulsars (MSPs) discovered in deep radio searches of LAT sources will likely reveal pulsations once phase-connected rotation ephemerides are achieved. A further dozen optical and/or X-ray binary systems co-located with LAT sources also likely harbor gamma-ray MSPs. This catalog thus reports roughly 340 gamma-ray pulsars and candidates, 10% of all known pulsars, compared to $\leq 11$ known before Fermi. Half of the gamma-ray pulsars are young. Of these, the half that are undetected in radio have a broader Galactic latitude distribution than the young radio-loud pulsars. The others are MSPs, with 6 undetected in radio. Overall, >235 are bright enough above 50 MeV to fit the pulse profile, the energy spectrum, or both. For the common two-peaked profiles, the gamma-ray peak closest to the magnetic pole crossing generally has a softer spectrum. The spectral energy distributions tend to narrow as the spindown power $\dot E$ decreases to its observed minimum near $10^{33}$ erg s$^{-1}$, approaching the shape for synchrotron radiation from monoenergetic electrons. We calculate gamma-ray luminosities when distances are available. Our all-sky gamma-ray sensitivity map is useful for population syntheses. The electronic catalog version provides gamma-ray pulsar ephemerides, properties and fit results to guide and be compared with modeling results.Comment: 142 pages. Accepted by the Astrophysical Journal Supplemen

Management of chronic hepatitis C in childhood: The impact of therapy in the clinical practice during the first 2 decades

Background and aim: Treatment of chronic hepatitis C in children is controversial and its role in the clinical practice is unknown. We retrospectively investigated the impact of treatment in a large cohort of children with chronic hepatitis C over the past 20years. Methods: 376 hepatitis C virus RNApositive children were recruited consecutively in five Italian centres since 1990and followed for1–17years. Results: 86 (23%)subjects were treated: 73 with recombinant interferon alone and 13 with pegylated-interferon and ribavirin. Sustained clearance of hepatitis C virus RNA was observed in 25%of the former, in 92%of the latter and in 9% of untreated cases(p &lt; 0.001). Loss of viraemia was recorded in all children with genotype2–3 and in 6of7 with hepatitis C virus genotype 1 treated with combination therapy.At last evaluation 45% of patients were young adults and 15%had cleared viraemia. Overall, 152 (40%)were putative candidates to therapy. Conclusions: Few Italian children with chronic hepatitis C have been treated in the past 20years.The poor propensity to spontaneous clearance of viraemia and the efficacy of ombination therapy should encourage to consider treatment in attempt to shorten the duration of viral replication

Chronic hepatitis C virus infection in childhood: clinical patterns and evolution in 224 white children.

The characteristics and evolution of hepatitis C virus (HCV) infection were retrospectively investigated in a study of 224 HCV RNA-seropositive white children who were consecutively recruited at 7 European centers in 1980-1998. At presentation, all patients were positive for antibodies to hepatitis C virus, 87% were asymptomatic, and 48% had alanine aminotransferase (ALT) levels that were or =15 years of age (range, 0-6 years; P<.01). Pediatric HCV infection is usually mild, but few patients, especially those who are perinatally infected, clear viremia in the medium-term follow-up. Conversely, the higher rates of fibrosis observed in older patients suggest the possibility of an insidious progression of HCV-associated liver disease

Guidelines on Vaccinations in Paediatric Haematology and Oncology Patients

Objective. Vaccinations are the most important tool to prevent infectious diseases. Chemotherapy-induced immune depression may impact the efficacy of vaccinations in children. Patients and Methods. A panel of experts of the supportive care working group of the Italian Association Paediatric Haematology Oncology (AIEOP) addressed this issue by guidelines on vaccinations in paediatric cancer patients. The literature published between 1980 and 2013 was reviewed. Results and Conclusion. During intensive chemotherapy, vaccination turned out to be effective for hepatitis A and B, whilst vaccinations with toxoid, protein subunits, or bacterial antigens should be postponed to the less intensive phases, to achieve an adequate immune response. Apart from varicella, the administration of live-attenuated-virus vaccines is not recommended during this phase. Family members should remain on recommended vaccination schedules, including toxoid, inactivated vaccine (also poliomyelitis), and live-attenuated vaccines (varicella, measles, mumps, and rubella). By the time of completion of chemotherapy, insufficient serum antibody levels for vaccine-preventable diseases have been reported, while immunological memory appears to be preserved. Once immunological recovery is completed, usually after 6 months, response to booster or vaccination is generally good and allows patients to be protected and also to contribute to herd immunity