A case of dengue type 3 virus infection imported from Africa to Italy, October 2009.

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.

Response to Rv2628 latency antigen associates with cured tuberculosis and remote infection.

Interferon-gamma release assays based on region of difference 1 antigens have improved diagnosis of latent tuberculosis infection (LTBI). However, these tests cannot discriminate between recently acquired infection (higher risk of progression to active tuberculosis) and remote LTBI. The objective of the present study was to evaluate the T-cell interferon-gamma responses to Mycobacterium tuberculosis DosR-regulon-encoded antigens (latency antigens) compared with QuantiFERON TB-Gold In-Tube (QFT-GIT) in subjects at different stages of tuberculosis. A total of 16 individuals with remote LTBI and 23 with recent infection were studied; 15 controls unexposed to M. tuberculosis and 50 patients with active tuberculosis and 45 with cured tuberculosis were also analysed. The results indicated that subjects with remote LTBI showed significantly higher whole-blood interferon-gamma responses to M. tuberculosis latency antigen Rv2628 than did individuals with recent infection, active tuberculosis and controls (p<0.003), whereas no significant differences between these groups were found for other latency antigens tested (Rv2626c, Rv2627c, Rv2031c and Rv2032). The proportion of responders to Rv2628 was five-fold higher among QFT-GIT-positive-individuals with remote infection than among those with recently acquired infection. These data suggest that responses to M. tuberculosis latency antigen Rv2628 may associate with immune-mediated protection against tuberculosis. In contact-tracing investigations, these preliminary data may differentiate recent (positive QFT-GIT results without responses to Rv2628) from remote infection (positive to both tests).

Phylogenetic analysis of human coronavirus NL63 circulating in Italy.

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.

Resistance to second-line injectables and treatment outcomes in multidrug-resistant and extensively drug-resistant tuberculosis cases.

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.

Frequency of detection of respiratory viruses in the lower respiratory tract of hospitalized adults.

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).

Mycobacterium tuberculosis DNA detection in soluble fraction of urine from pulmonary tuberculosis patients.

SETTING: A tertiary care and research institution in Italy. BACKGROUND: Small DNA fragments from cells dying throughout the body have been detected in urine (transrenal DNA [Tr-DNA]). OBJECTIVE: To test the hypothesis that Mycobacterium tuberculosis Tr-DNA could be detected in the urine of pulmonary tuberculosis (TB) patients. DESIGN: We studied 43 patients with culture-confirmed pulmonary TB with no evidence of extra-pulmonary involvement, 10 patients with pulmonary diseases other than TB and 13 healthy controls. DNA was extracted from urine and analysed by semi-nested polymerase chain reaction (PCR). RESULTS: M. tuberculosis-specific sequences were found in the urine of 34 of 43 (79%) TB patients studied, whereas all controls were negative. The transrenal nature of M. tuberculosis DNA was demonstrated by two lines of evidence: first, separate analysis of supernatants and sediments from eight of the study patients found seven positive supernatants but only two matched positive sediments. Second, M. tuberculosis-specific sequences were amplified by semi-nested PCR with primers designed for short but not large amplicons. CONCLUSION: Small M. tuberculosis DNA fragments may be detected in the urine of a significant proportion of patients with pulmonary TB. If these observations are confirmed by larger studies, Tr-DNA technology could represent a new approach for detecting pulmonary M. tuberculosis infection.

Comparison of Versant HBV DNA 3.0 and COBAS AmpliPrep-COBAS TaqMan assays for hepatitis B DNA quantitation: Possible clinical implications.

We compared two commercial assays for HBV DNA quantitation, Versant HBV 3.0, System 340 (bDNA; Bayer Diagnostics) and COBAS AmpliPrep-COBAS TaqMan HBV Test (TaqMan; Roche Diagnostics). Analytical sensitivity, calculated on WHO International Standard, predicted 95% detection rate at 11.4 and 520.2IU/ml for TaqMan and bDNA, respectively. Specificity, established on 50 blood donor samples, was 100% and 84% for TaqMan and bDNA, respectively. When using clinical samples, HBV DNA was detected by TaqMan in 21/55 samples negative to bDNA. Mean values of HBV DNA obtained with bDNA were higher than those obtained with TaqMan (4.09log(10)+/-1.90 versus 3.39log(10)+/-2.41, p<0.001), and 24.4% of samples showed differences in viral load values >0.5log(10), without association with HBV genotype. There was a good correlation for HBV DNA concentrations measured by the two assays (r=0.94; p<0.001) within the overlapping range, and the distribution of results with respect to relevant clinical threshold recently confirmed (20,000 and 2000IU/ml) was similar. Approximately 50% of samples with low HBV DNA, appreciated by TaqMan but not by bDNA, were successfully sequenced in pol region, where drug resistance mutations are located.

[Guidelines for the management of HCV infection in HIV-infected patients. Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani]. / Linee-guida per la gestione clinica della infezione/malattia da HCV nei pazienti con infezione da HIV.

It is crucial to ensure an optimal clinical management of HCV infection in HIV-co-infected persons. The reasons for the development of guidelines on HCV-infection treatment in HIV-infected persons arise from the need for a standardised management of HIV/HCV coinfection in our Institute. The aim of these guidelines are: to clarify principles of clinical management of HCV infection in HIV-infected patients to care-providers; to improve the awareness of HIV-infected patients cared for our Institute on current management of HCV infection; to improve the quality of care on this topic. These guidelines, based on Evidence based Medicine principles, have been developed by a panel of experts, who conducted a systematic review of the literature, mainly taking into account current international recommendations. In the present document, the most frequent clinical presentation occurring in the management of HIV/HCV co-infected patients at our Institution are discussed. The adherence to present guidelines and their effectiveness at our Institution, outcome indicators will be evaluated. The present guidelines cannot entirely substitute the judgement of an expert clinician. However, adherence to these guidelines will contribute to the improvement of the standard of care of HIV/HCV-co-infected persons.

The impact of nosocomial infections on hospital care costs.

Estimating costs due to nosocomial infection (NI) requires the incremental costs associated with NI diagnosis and treatment must be distinguished from those attributable to the management of the original healthcare problems. We carried out a review of the analyses of additional costs resulting from NIs and the evaluation of the methods used to estimate these costs, in order to perform a cost benefit analysis of NI prevention activities. Characteristics of additional costs for main NIs were initially considered. Secondly, a review of methods for estimating the incremental costs was performed. Finally, a cost effectiveness analysis of NI prevention activities was performed. Few studies estimated the incidence of NLs and assessed the economic burden they cause. Investigators generally estimated only direct additional costs. Implicit physician assessment, unmatched group comparison, matched control and appropriateness evaluation protocol (AEP)-based methods are the methodologies used to estimate incremental days of stay due to NIs. Different studies show possible benefits, in terms of health and cost savings, when hospital-acquired infections are prevented. However, there is a need for further studies to evaluate in greater detail the variables related to costs attributable to these infections and to enhance the control strategies. Moreover, a structured surveillance and control program of NI is the single most effective tool for prevention.

The model of response to viral haemorrhagic fevers of the National Institute for Infectious Diseases "Lazzaro Spallanzani".

Viral haemorrhagic fevers (VHF) are severe and life-threatening diseases caused by a range of viruses. However, only four agents of VHF are known to be readily capable of person-to-person spread: Lassa virus, Crimean/Congo haemorrhagic fever virus, Ebola and Marburg viruses. Diseases caused by these viruses are endemic only in few areas in the world, most notably Africa and some rural parts of the Middle East and Eastern Europe. Nonetheless, the increasing volume of international travel presents a greater likelihood for the importation of these infections or of suspected cases in non endemic countries. Four conditions can lead to the importation and to the subsequent recognition of VHF within Europe: 1) patients arriving as a result of a planned medical evacuation; 2) persons who became sick on route to their destination; 3) persons discovered ill when entering a country, for example during routine clinical examination at the airport; 4) persons becoming sick after their arrival. Public health implications and the risk of secondary spread of pathogens in the above reported circumstances are very different. Similarly, preparedness and response should vary. This paper summarizes the present knowledge on the four VHF capable of person-to-person spread, describes the high isolation area constructed at the Italian National Institute for Infectious Diseases Lazzaro Spallanzani in Rome to respond to the occurrence of VHF. A brief overview of procedures and equipment adopted is provided.

Hospital care for patients with AIDS at "Lazzaro Spallanzani" Institute in the last decade.

We reviewed data on hospital care of HIV/AIDS patients at Lazzaro Spallazani Institute between 1991 and 1999. The number of newly diagnosed AIDS cases increased until 1995 and decreased constantly thereafter. The proportion of AIDS cases diagnosed at our institution over the total number of cases reported in our region and in our country increased from 31.2 to 59.8% and from 3.9 to 8.7% respectively (p<0.001). In the entire study period, 10044 out of 18,434 (54.5%) of patients admitted to acute care wards were diagnosed with HIV related pathologies. The number of admission of HIV/AIDS patients to acute-care wards increased until 1995 and remained constant thereafter. Our data suggest that a consistent need for inpatient hospital care remains even in the era of HAART.

Guidelines of tuberculosis preventive therapy for HIV-infected persons: a prospective, multicentre study. GISTA (Gruppo Italiano di Studio Tubercolosi e AIDS).

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.

Sexual behaviour of heterosexual individuals with HIV infection naive for antiretroviral therapy in Italy.

BACKGROUND: Specific information about determinants of sexual behaviour of HIV infected heterosexuals, like injecting drug use (IDU), are essential to design interventions aimed at promoting safer sex practices. METHODS: We analysed data on sexual behaviour collected, between March 1997 and March 1999, through a self administered questionnaire among 1050 IDUs and 642 non-IDU heterosexuals enrolled in a prospective multicentre cohort study on the natural history of HIV infection. RESULTS: Among non-IDU heterosexuals, more women (48.5%) than men (25.1%) (p<0.001) reported that they were infected by HIV positive regular partners whose HIV status they were not aware of. Among the 1119 heterosexual males, one fifth reported having had more than 25 sexual partners during their lifetime. Condom use in the last sexual intercourse was more common among heterosexual IDUs (64.9%) than among non-IDU heterosexual males (58.3%) (p=0.05). Heterosexual IDU males were more likely (66.7%) than non-IDU heterosexuals (50.6%) to have an HIV negative partner (p<0.001). Of the 573 heterosexual females studied, 10.2% reported having had more than 25 lifetime sex partners. This proportion was higher among heterosexual IDUs (18.8%) than among non-IDU heterosexuals (4.3%) (p<0.001). Nearly 50% of the women in both groups reported having used a condom in the last intercourse. Almost 57% of heterosexual IDUs had a current HIV negative partner, compared with 34.9% non-IDU heterosexuals (p<0.001). In both sexes, the findings from univariate analysis were confirmed by multiple logistic regression analysis. CONCLUSIONS: This study identified some important differences, in both males and females, in sexual lifestyles according to injecting drug use (for example, in terms of HIV negative partners). This observation indicates the need to tailor HIV prevention messages according to history of injecting drug use.

[Comparison between estimates of radiological workload]. / Esperienza di confronto tra indicatori per misurare i volumi di attività in radiologia.

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.

Role of guidelines in clinical practice for the management of HIV-related diseases.

Several guidelines have been developed for the diagnosis, treatment and prevention of infectious diseases. Actually, evidence-based clinical practice guidelines provide physicians and other health care professionals with scientific information about the most appropriate strategy for the management of these patients, in order to avoid unnecessary or inappropriate interventions. As medical technology rapidly increases and becomes more complex, clinical guidelines can help health care providers to assess current practices and integrate new technological advances. Since AIDS was first recognized nearly 20 years ago, remarkable progress has been made in improving the quality and duration of life for HIV+ patients. In this area, clinical guidelines have been developed to manage patient care, focusing on: antiretroviral therapy, prevention of opportunistic infections, and treatment of tuberculosis. The quality of the guideline is notable when appropriate methodologies are applied. Different methods for developing guidelines are evaluated here: Agency for Health Care Policy and Research (AHPCR) methodology is designed to produce evidence-based guidelines that are valid, clinically applicable, and flexible. Finally, the problems associated with the implementation of guidelines for HIV-related diseases and other infectious diseases are examined.

Sexual behaviour of women living with HIV/AIDS naïve for antiretroviral therapy: the ICONA-BEHEPI Study.

This study describes the sexual behaviours of women living with HIV, and assesses differences by history of drug use. Its general aim is to contribute in the design of programmes to help people with HIV/AIDS (PWH/A) adopt and maintain safe sexual behaviours. A self-administered questionnaire on sexual and drug use behaviours was distributed to study participants. Between 1997 and 1999, 573 women with HIV infection naive to antiretroviral therapies completed the questionnaire (of whom 234 reported a history of injection drug use (IDU) and were enrolled in the study. Non-IDU women reported fewer sexual partners, both in their lifetime and in the preceding month, than IDU women: 19% of IDU and 4% of non-IDU women reported more than 25 lifetime sexual partners (p < 0.001). Interestingly, 83% of non-IDU women were infected by their regular partners: these women reported the lowest number of sexual partners. No difference emerged between IDU and non-IDU women in terms of number of sexual intercourse in the two weeks preceding the interview or in terms of condom use in the last intercourse (reported, overall, by 54% of these 573 women). Among women who had sex partners at the time of interview, more non-IDU (65%) than IDU (43%) women reported HIV-positive partners (p < 0.001). Overall, these findings stress a marked heterogeneity in the levels of past and recent sexual promiscuity according to history of drug use. It suggests the need to differentiate and individualize messages about self-protection and behaviours that may prevent further spread of HIV infection.