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Background: The first influenza pandemic of the 21th century was ignited by a new strain of influenza A virus (A/H1N1pdm). Specific patient groups, including those with comorbidities, pregnant women, young children, older and immunocompromised patients, are at increased risk for serious influenza-related disease. This study was aimed at investigating the influence of clinical presentation, antiviral treatment and possible drug resistance-associated mutations, on the extent and duration of viral shedding in patients infected with A/H1N1pdm., Methods: An observational study was performed, based on retrospective review of clinical and laboratory records of patients who were hospitalized for A/H1N1pdm infection at the National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy, between April 24 and December 31, 2009. Among 119 hospitalized patients, 39 were selected for a post hoc analysis, based on the availability of serial nasopharyngeal swabs samples and related information., Results: Eleven out of the 39 study patients (28.2%) presented with pneumonia; 29 (74.4%) received antiviral treatment. Patients with pneumonia were significantly older than patients without pneumonia. The mean values of viral RNA concentration were not significantly increased in patients with pneumonia, but a significant increase in the duration of viral shedding was observed as compared to patients without pneumonia. In patients receiving antivirals, the viral RNA concentration was significantly reduced in comparison to untreated patients at days 4-5 after symptom onset, while the overall duration of viral shedding was only marginally affected. A significant correlation between duration of viral shedding and time elapsed between symptom onset and therapy start was observed, with a significant reduction of days of viral shedding when therapy was initiated within 2 days of symptoms appearance. No known drug resistance mutations were detected in patients with prolonged viral shedding., Conclusions: Our results show that severe respiratory illness is associated with delayed virus clearance in patients with A/H1N1pdm infection. Antivirals caused an early reduction of viral load, but only marginally affected the overall duration of shedding. Prolonged shedding was not associated with the emergence of strains carrying known drug-resistance mutations.

Background: Five thematic working groups composed of Italian infectious disease experts and a group coordinator, supported by a scientific secretary, identified controversial issues in the field of severe healthcare-associated infections caused by multidrug-resistant organisms. The five group coordinators received training courses on data sources and electronic databases, literature search strategies, the scientific revision methods of quality assessment, and the construction of an evidence matrix., Working Plan and Methods: The working plan identified the following step: definition of the controversial issues and identification of documents for a systematic literature review. A specific methodology to classify the selected evidence was used that required the evaluation of the quality of review documents and statement documents and evaluation of the quality of original research. An original method to assess review documents and statement documents was proposed. A matrix model to extract and evaluate the evidence from original studies was designed using the CONSORT method to evaluate randomized clinical trials and the Newcastle-Ottawa Quality Assessment Scale for case-control studies, cohorts, and retrospective studies., Quality of Evidence: A modified GRADE working group method was applied for grading quality of evidence and strength of recommendations. The working groups reviewed the available studies and formulated recommendations to be voted on at the national consensus conference held in Rome in June 2009., (Copyright © 2010. Published by Elsevier Ltd.)

In October 2009, a traveller returning from Africa to Italy was hospitalised with symptoms suggestive of a haemorrhagic fever of unknown origin. The patient was immediately placed in a special biocontainment unit until laboratory investigations confirmed the infection to be caused by a dengue serotype 3 virus. This case reasserts the importance of returning travellers as sentinels of unknown outbreaks occurring in other countries, and highlights how the initial symptoms of dengue fever resemble those of other haemorrhagic fevers, hence the importance of prompt isolation of patients until a final diagnosis is reached.

Background: Five known human coronaviruses infect the human respiratory tract: HCoV-OC43, HCoV-229E, SARS-CoV, HCoV-NL63 and HCoV-HKU1., Objectives: To evaluate the prevalence of HCoV-NL63 in hospitalized adult patients and to perform molecular characterization of Italian strains., Study Design: HCoV-NL63 was sought by RT-PCR in 510 consecutive lower respiratory tract (LRT) samples, collected from 433 Central-Southern Italy patients over a 1-year period. Phylogenetic analysis was performed by partial sequencing of S and ORF1a. Additional S sequences from Northern Italy were included in the phylogenetic trees., Results: HCoV-NL63 was detected in 10 patients (2.0%) with symptomatic respiratory diseases, mainly during winter. Phylogenetic analysis indicated a certain degree of heterogeneity in Italian isolates. The ORF1a gene clustering in phylogenetic trees did not match with that of the S gene., Conclusions: As observed by others, HCoV-NL63 is often associated with another virus. Phylogenetic characterization of HCoV-NL63 circulating in Italy indicates that this virus circulates as a mixture of variant strains, as observed in other countries.

No information is currently available on the influence of injectable second-line drugs on treatment outcomes of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) patients. To investigate this issue, a large series of MDR- and XDR-TB cases diagnosed in Estonia, Germany, Italy and the Russian Federation (Archangels Oblast) between 1999 and 2006 were analysed. All study sites performed drug susceptibility testing for first- and second-line anti-TB drugs, laboratory quality assurance and treatment delivery according to World Health Organization recommendations. Out of 4,583 culture-confirmed cases, 240 MDR- and 48 XDR-TB cases had a definitive outcome recorded (treatment success, death, failure). Among MDR- and XDR-TB cases, capreomycin resistance yielded a higher proportion of failure and death than capreomycin-susceptible cases. Resistance to capreomycin was independently associated with unfavourable outcome (logistic regression analysis: odds ratio 3.51). In the treatment of patients with multidrug-resistant and extensively drug-resistant tuberculosis, resistance to the injectable drug capreomycin was an independent predictor for therapy failure in this cohort. As Mycobacterium tuberculosis drug resistance is increasing worldwide, there is an urgent need for novel interventions in the fight against tuberculosis.

Background: Respiratory infections are the most common infections in humans. The prevalence of respiratory viruses in adults is largely underestimated, and relevant data mostly concern infants and children., Objectives: To evaluate the prevalence of respiratory viruses in adults hospitalized in Italy., Study Design: During April 2004--May 2005, 510 consecutive lower respiratory tract samples were prospectively collected. These were evaluated with a molecular panel that detected 12 respiratory viruses., Results: Two hundred and fifteen samples were positive for at least one viral pathogen, with an overall sample prevalence of 42.2%. Human rhinoviruses (HRVs) were the most commonly detected viruses (32.9%), followed by influenza virus (FLU)-A (9.0%); the other viruses were 2% or less. Multiple agents were detected in 30 samples from 29 patients, resulting in a co-infection rate of 6.7%., Conclusions: This study shows a high prevalence of viruses in the lower respiratory tract samples of hospitalized adults, mostly HRV and FLU-A. It is not possible to establish the role of viruses detected at low frequency, but our findings suggest the necessity to consider them as potential causes or precursors of lower respiratory tract infections (LRTIs).

Highly Pathogenic Avian Influenza Virus H5N1 has so far caused more than 250 human cases. This virus is not transmitted efficaciously from person to person, but the capacity of human-to-human transmission could be acquired in the future. Consequently, the epidemiological and virological evolution of H5N1 is strictly monitored, insofar as the virus is a potential agent of an influenza pandemic. During such a pandemic, health care facilities would have to cope with many cases of severe respiratory illnesses, often requiring intensive care and mechanical pulmonary ventilation. In this article, the impact of the pandemic on health care facilities in Lazio, Italy, is evaluated using a statistical model, Flu-Surge. Moreover, some aspects of hospital preparedness for a pandemic, in particular in emergency departments, are discussed.

RT-PCR is the most sensitive assay for diagnosis of influenza, due to enhanced rapidity and sensitivity as compared to classical methods. Hemi-nested RT-PCR was developed, targeting NP gene for influenza A and NS gene for influenza B, based on a previous single round RT-PCR method. The new method was compared with the previous technique for analytical sensitivity and specificity, and was applied to clinical samples from the lower and upper respiratory tract. The analytical sensitivity of hemi-nested RT-PCR was 10 (influenza A) and 4 times (influenza B) higher than the previous method. A high specificity of the new hemi-nested RT-PCR assay was observed by using whole respiratory viruses. When applied to lower respiratory tract specimens, the new method showed an increased rate of positivity as compared to the previous technique (9.3% versus 0.7% for influenza A, and 0.9% versus 0.2% for influenza B). Screening of upper respiratory tract samples collected during the seasonal 2005-2006 outbreak indicated 26.4% and 5.8% positivity for influenza A and B, respectively. The results were confirmed by sequence analysis: apart from influenza B, both influenza A subtypes H3N2 and H1N1, associated with the seasonal outbreak, were detected.

Human immunodeficiency virus (HIV)-infected patients failing highly active antiretroviral therapy (HAART) have a substantially lower chance of clinical success than naive patients given their first antiretroviral therapy. This suggests that HAART failure is a determinant for an increase in the cost of treatment. A review of the literature regarding cost and impact of antiretroviral drug-resistance testing was performed. Examination of existing methods to execute a cost-effectiveness analysis on the use of these tests in clinical practice was also undertaken. The cost of treatment failure in HIV-infected patients has been quantified in several retrospective studies. The cost of care for patients with virological suppression was significantly lower than those with a single virological failure. Moreover, the latter group had lower costs than patients with multiple failures. The result of the cost-effective analysis based on a specific model application using genotypic resistance assays to guide the choice of a subsequent therapy in HIV disease, is cost-effective under a wide range of assumptions regarding effectiveness and costs. The available studies on the cost-effective evaluation of genotypic tests are limited, and the respective studies supply important indications on cost-effective evaluations. Despite its demonstrated benefits, antiretroviral drug resistance testing presents features and limitations that also restrict the cost-effectiveness analysis.

Objective: To comparise three methods for assessing the productivity of radiological services: a) simple count of radiological examinations, b) method proposed by SNR-SAGO-SIRM, c) method used by Regione Emilia Romagna (RER) to evalutate the characteristics of these methods and to find a common method of estimate., Material and Methods: On the radiological examinations performed at our unit over a period of 12 months were recorded. The different types of examinations were clustered into five homogenous groups (general radiology, ultrasound, barium examinations, CT, MRI). The data were assessed by a) number of examinations/hour per radiologist, b) score/hour according to the SNR-SAGO-SIRM method and c) score/hour according to the RER method, and then compared for the percentage of the single aggregates., Results: a) The total number of examinations was 26,776 with 40% being accounted for by general radiology; mean numbers of examinations our ranged from 2.43 (August) to 4.20 (March). b) The total score according to the SNR-SAGO-SIRM method was 67,054. The radiologist weight per hour ranged from 6.37 (August) to 9.67 (May). Ultrasound was the most relevant examination in the unit accounting for 43% of total weight. c) The total score according to the RER method was 1,850,780. The radiologist weight per hour ranged from 159 (August) to 316 (April). CT was the most relevant examination (51% of total weight)., Conclusion: According to the simple count of examinations, general radiology and ultrasound were the most relevant examinations together accounting for 75% of examinations, i.e. 40% and 35% respectively, whereas by SNR-SAGO-SIRM standards the two techniques represent 19% and 45% respectively. The simple count method therefore fails to give adequate weight to technologically advanced imaging technique. The SNR-SAGO-SIRM method adequately takes into account the combination of patient-number and patient weight. The RER method gives excessive weight costly technology as it considers the total weight of the examination and not only the radiologist's activity.

The aim of this study was to assess the degree of implementation of national guidelines for isoniazid preventive therapy (IPT) among human immunodeficiency virus (HIV)-infected individuals and factors affecting the impact of the programme. Twenty-eight infectious disease hospital units in Italy participated in this observational, multicentre, prospective cohort study. A number of HIV-infected subjects, (n=1,705) seen for the first time as outpatients, were included in this analysis. Of the subjects considered, 1,215 out of the 1,705 completed purified protein derivative (PPD) screening. Variables independently associated with offering and completion of PPD screening included having acquired immune deficiency syndrome (AIDS), higher educational levels and currently receiving therapy. Overall, 103 subjects were identified as candidates for IPT. Of these subjects, five had tuberculosis and 15 had contraindications to IPT. Forty subjects agreed to start IPT, and 29 completed a full-course regimen. The incidence of tuberculosis among IPT candidates who either did not begin or discontinued IPT was 6.1 per 100 person-yrs, while no cases of tuberculosis were observed in subjects completing IPT. Several factors may limit the implementation of an isoniazid preventive therapy programme for human immunodeficiency virus-infected persons. Physicians fail to offer purified protein derivative screening to patients with high degrees of immunodeficiency, and those with a more intense workload seem to pay less attention to this test. The high number of contraindications among patients and their low level of acceptance further affects the impact of isoniazid preventive therapy.