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

Discriminating multi-species populations in biofilms with peptide nucleic acid fluorescence in situ hybridization (PNA FISH)

Background: ur current understanding of biofilms indicates that these structures are typically composed of many different microbial species. However, the lack of reliable techniques for the discrimination of each population has meant that studies focusing on multi-species biofilms are scarce and typically generate qualitative rather than quantitative data.Methodology/principal findings: we employ peptide nucleic acid fluorescence in situ hybridization (PNA FISH) methods to quantify and visualize mixed biofilm populations. As a case study, we present the characterization of Salmonella enterica/Listeria monocytogenes/Escherichia coli single, dual and tri-species biofilms in seven different support materials. Ex-situ, we were able to monitor quantitatively the populations of ~56 mixed species biofilms up to 48 h, regardless of the support material. In situ, a correct quantification remained more elusive, but a qualitative understanding of biofilm structure and composition is clearly possible by confocal laser scanning microscopy (CLSM) at least up to 192 h. Combining the data obtained from PNA FISH/CLSM with data from other established techniques and from calculated microbial parameters, we were able to develop a model for this tri-species biofilm. The higher growth rate and exopolymer production ability of E. coli probably led this microorganism to outcompete the other two [average cell numbers (cells/cm2) for 48 h biofilm: E. coli 2,1×108 (±2,4×107); L. monocytogenes 6,8×107 (±9,4×106); and S. enterica 1,4×106 (±4,1×105)]. This overgrowth was confirmed by CSLM, with two well-defined layers being easily identified: the top one with E. coli, and the bottom one with mixed regions of L. monocytogenes and S. enterica.Significance: while PNA FISH has been described previously for the qualitative study of biofilm populations, the present investigation demonstrates that it can also be used for the accurate quantification and spatial distribution of species in polymicrobial communities. Thus, it facilitates the understanding of interspecies interactions and how these are affected by changes in the surrounding environmen

PTPN11 mutations in childhood acute lymphoblastic leukemia occur as a secondary event associated with high hyperdiploidy

Letter to the Editor Leukemia (2010) 24, 232\u2013235; doi:10.1038/leu.2009.200; published online 24 September 2009 PTPN11 mutations in childhood acute lymphoblastic leukemia occur as a secondary event associated with high hyperdiploidy C G Molteni1, G te Kronnie2, S Bicciato3, T Villa1, M Tartaglia4, G Basso2, A Biondi1,5 and G Cazzaniga1,5 1Centro Ricerca Tettamanti, Clinica Pediatrica Universit\ue0 Milano-Bicocca, Ospedale San Gerardo, Monza, Italy 2Laboratorio di Onco-Ematologia, Clinica Pediatrica, Universit\ue0 di Padova, Padua, Italy 3Dipartimento di Scienze Biomediche, Universit\ue0 di Modena e Reggio Emilia, Modena, Italy 4Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanit\ue0, Rome, Italy Correspondence: G Cazzaniga, E-mail: [email protected] 5AB and GC share the seniorship of this paper. The protein tyrosine phosphatase, non-receptor type 11 (PTPN11) gene encodes SHP-2, a phosphatase involved in many signaling pathways, with a key role in development and hematopoiesis. Somatic PTPN11 mutations were found with variable prevalences in pediatric leukemia, most frequently associated with juvenile myelomonocytic leukemia (JMML).1, 2 In vitro and in vivo studies, mainly in a myeloid context, demonstrated a crucial involvement of PTPN11 mutations in the hyperactivation of the RAS/ERK pathway.3 The oligoclonality of transgene integration sites, and the long latency before overt leukemia in mice transduced with mutant PTPN11,3 suggested that additional molecular lesions are needed to cooperate with PTPN11 mutations in leukemogenesis. This observation is in line with the \u2018two hit model\u2019 proposed by Greaves4 for B-cell precursor childhood acute lymphoblastic leukemia (ALL), in which an initiating alteration, often occurring prenatally, gives rise to a preleukemic clone, which eventually becomes fully malignant by subsequent acquisition of other molecular alterations

Clinical manifestations and socio-economic impact of influenza among healthy children in the community.

Objectives: To evaluate the total burden of influenza among healthy children in the community in order to analyse the cost of influenza in paediatric age. Methods: This prospective study involved a total community population of 21,986 children, 6988 of whom experienced an influenza-like illness (ILI) between 1 November 2008 and 30 April 2009. An electronic chart was completed, a nasopharyngeal swab was obtained, and information was recorded concerning the clinical outcomes and household impact of the ILI episodes. Influenza A and B viruses were detected in all the swabs by means of polymerase chain reaction, and costs of the disease were calculated. Results: Influenza viruses were detected in 2143 cases (30.7%), an incidence of 96.4 per 1000 children. Influenza A and B viruses were found in respectively 1751 (81.7%) and 392 cases (18.3%). The mean cost of influenza was no less than \u20ac130, 32% higher than the cost of influenza-negative ILIs (p 5 years (p < 0.05). The differences were mainly related to the indirect costs of the parents' lost working days. Conclusions: The findings of this study confirm that influenza among healthy children is important because of its frequency and its indirect consequences on the households of infected children, and support the use of influenza vaccination in healthy children aged between 6 months and 5 years

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