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1.  Biopsy-proven autoimmune myocarditis in HIV-associated dilated cardiomyopathy 
BMC Infectious Diseases  2014;14:729.
Dilated cardiomyopathy occurring in HIV-infected patients raises both diagnostic and therapeutic challenging problems. Indeed myocardial involvement in HIV infection has been variously attributed to several causes, including viral, toxic, nutritional and autoimmune, but no specific treatment capable to substantially improve patients’ prognosis has been recognized so far.
Case Presentation
Hereby we describe the case of an autoimmune myocarditis manifesting with heart failure in a3 9-year-old man with HIV infection.
Left ventricular endomyocardial biopsy showed a lymphocytic myocarditis characterized by over-expression of HLA-DR and negative polymerase chain reaction for cardiotropic viruses. Steroid treatment was followed by recovery of cardiac dimension and function.
Presence of auto-reactive myocarditis should be considered in patients with HIV-associated dilated cardiomyopathy. Its recognition by endomyocardial biopsy followed by steroid administration may result in a complete resolution of cardiac disease.
PMCID: PMC4325940
HIV (Human immunodeficiency virus); Biopsy (Heart); Myocarditis; Heart failure; Recovery of function
2.  The potential impact of routine testing of individuals with HIV indicator diseases in order to prevent late HIV diagnosis 
BMC Infectious Diseases  2013;13:473.
The aim of our work was to evaluate the potential impact of the European policy of testing for HIV all individuals presenting with an indicator disease, to prevent late diagnosis of HIV. We report on a retrospective analysis among individuals diagnosed with HIV to assess whether a history of certain diseases prior to HIV diagnosis was associated with the chance of presenting late for care, and to estimate the proportion of individuals presenting late who could have been diagnosed earlier if tested when the indicator disease was diagnosed.
We studied a large cohort of individuals newly diagnosed with HIV infection in 13 counselling and testing sites in the Lazio Region, Italy (01/01/2004-30/04/2009). Considered indicator diseases were: viral hepatitis infection (HBV/HCV), sexually transmitted infections, seborrhoeic dermatitis and tuberculosis. Logistic regression analysis was performed to estimate association of occurrence of at least one indicator disease with late HIV diagnosis.
In our analysis, the prevalence of late HIV diagnosis was 51.3% (890/1735). Individuals reporting at least one indicator disease before HIV diagnosis (29% of the study population) had a lower risk of late diagnosis (OR = 0.7; 95%CI: 0.5-0.8) compared to those who did not report a previous indicator disease. 52/890 (5.8%) late presenters were probably already infected at the time the indicator disease was diagnosed, a median of 22.6 months before HIV diagnosis.
Our data suggest that testing for HIV following diagnosis of an indicator disease significantly decreases the probability of late HIV diagnosis. Moreover, for 5.5% of late HIV presenters, diagnosis could have been anticipated if they had been tested when an HIV indicator disease was diagnosed.
However, this strategy for enhancing early HIV diagnosis needs to be complemented by client-centred interventions that aim to increase awareness in people who do not perceive themselves as being at risk for HIV.
PMCID: PMC3852490  PMID: 24112129
HIV testing; Indicator diseases; Sexually transmitted infections; Late diagnosis
3.  HIV-1 drug resistance in recently HIV-infected pregnant mother’s naïve to antiretroviral therapy in Dodoma urban, Tanzania 
BMC Infectious Diseases  2013;13:439.
HIV resistance affects virological response to therapy and efficacy of prophylaxis in mother-to-child-transmission. The study aims to assess the prevalence of HIV primary resistance in pregnant women naïve to antiretrovirals.
Cross sectional baseline analysis of a cohort of HIV + pregnant women (HPW) enrolled in the study entitled Antiretroviral Management of Antenatal and Natal HIV Infection (AMANI, peace in Kiswahili language). The AMANI study began in May 2010 in Dodoma, Tanzania. In this observational cohort, antiretroviral treatment was provided to all women from the 28th week of gestation until the end of the breastfeeding period. Baseline CD4 cell count, viral load and HIV drug-resistance genotype were collected.
Drug-resistance analysis was performed on 97 naïve infected-mothers. The prevalence of all primary drug resistance and primary non-nucleoside reverse-transcriptase inhibitors resistance was 11.9% and 7.5%, respectively. K103S was found in two women with no M184V detection. HIV-1 subtype A was the most commonly identified, with a high prevalence of subtype A1, followed by C, D, C/D recombinant, A/C recombinant and A/D recombinant. HIV drug- resistance mutations were detected in A1 and C subtypes.
Our study reports an 11.9% prevalence rate of primary drug resistance in naïve HIV-infected pregnant women from a remote area of Tanzania. Considering that the non-nucleoside reverse-transcriptase inhibitors are part of the first-line antiretroviral regimen in Tanzania and all of Africa, resistance surveys should be prioritized in settings where antiretroviral therapy programs are scaled up.
PMCID: PMC3849050  PMID: 24053581
HIV-drug resistance; MTCT; HIV-genotype; Low-resources countries
4.  Infections in patients taking Rituximab for hematologic malignancies: two-year cohort study 
BMC Infectious Diseases  2013;13:317.
Rituximab (R) is a chimeric human-murine anti-CD20 monoclonal antibody used to treat B-cell lymphomas. Despite R remarkable activity against malignant cells, there are concerns that R may facilitate the occurrence of infections. This study is aimed to define risk factors for infections, and the potential interaction with time since therapy, in patients undergoing R containing regimens.
The study has been designed as a multiple failure events historical cohort including all patients who received a R contain regimen at London Royal Free Hospital between May 2007 and April 2009.
One-hundred-eighty-one infections occurred among the 113 enrolled patients (overall incidence rate 3.30 per 1000 person-days). Multivariate analysis showed that lymphocyte counts at nadir, graft versus host disease, HIV sero-status and the type of malignancy were all independently associated with the risk of infection. In addition the analysis of the interaction with the time since the start of therapy provided evidence that different risk factors may increase risk of infections in different times.
This study provides preliminary data to describe the association between several patients’ baseline characteristics and infections during therapy with R.
PMCID: PMC3716624  PMID: 23849292
5.  Attitude towards antiretroviral pre-exposure prophylaxis (PrEP) prescription among HIV specialists 
BMC Infectious Diseases  2013;13:217.
To investigate perceptions and attitude to prescribe Pre-Exposure Prophylaxis (PrEP) among HIV specialists.
A questionnaire developed through a Focus Group and literature review was administered to a convenience sample of HIV specialists during educational courses in two Regions and an online survey in February-May 2012. Participants were classified as having a positive or negative attitude according to their willingness to prescribe PrEP. Demographic and working information, experience with HIV-infected patients, information and provision of antiretrovirals to uninfected persons, self-reported knowledge, perceptions and concerns regarding PrEP were assessed. The association between a different attitude towards PrEP prescription and selected characteristics was assessed through univariate and multivariate regression analysis.
Of 311 specialists, 70% would prescribe PrEP, mainly to serodiscordant partners (64%) but also to people at ongoing, high risk of HIV infection (56%); 66% advocated public support of costs. A negative attitude towards PrEP was significantly associated with lack of provision of information on, and prescription of, antiretroviral post-exposure prophylaxis; specialists with a negative attitude believed behavioural interventions to be more effective than PrEP and were more concerned about toxicity. Overall, 90% of specialists disagreed regarding a lack of time for engaging in prevention counselling and PrEP monitoring; 79% would welcome formal guidelines, while those with a negative attitude did not consider this advisable.
Although conflicting attitudes appear evident, most specialists seem to be willing, with guidance from normative bodies, to promote PrEP within multiple prevention strategies among vulnerable populations. More scientific evidence regarding effectiveness could overcome resistance.
PMCID: PMC3658955  PMID: 23672424
HIV pre-exposure prophylaxis; Antiretroviral drugs; HIV prevention; HIV healthcare providers; Health knowledge, Attitudes, Practice
6.  HIV incidence estimate combining HIV/AIDS surveillance, testing history information and HIV test to identify recent infections in Lazio, Italy 
The application of serological methods in HIV/AIDS routine surveillance systems to identify persons with recently acquired HIV infection has been proposed as a tool which may provide an accurate description of the current transmission patterns of HIV. Using the information about recent infection it is possible to estimate HIV incidence, according to the model proposed by Karon et al. in 2008, that accounts for the effect of testing practices on the number of persons detected as recently infected.
We used data from HIV/AIDS surveillance in the period 2004-2008 to identify newly diagnosed persons. These were classified with recent/non-recent infection on the basis of an avidity index result, or laboratory evidence of recently acquired infection (i.e., previous documented negative HIV test within 6 months; or presence of HIV RNA or p24 antigen with simultaneous negative/indeterminate HIV antibody test). Multiple imputation was used to impute missing information. The incidence estimate was obtained as the number of persons detected as recently infected divided by the estimated probability of detection. Estimates were stratified by calendar year, transmission category, gender and nationality.
During the period considered 3,633 new HIV diagnoses were reported to the regional surveillance system. Applying the model, we estimated that in 2004-2008 there were 5,465 new infections (95%CI: 4,538-6,461); stratifying by transmission category, the estimated number of infections was 2,599 among heterosexual contacts, 2,208 among men-who-have-sex-with-men, and 763 among injecting-drug-users. In 2008 there were 952 (625-1,229) new HIV infections (incidence of 19.9 per 100,000 person-years). In 2008, for men-who-have-sex-with-men (691 per 100,000 person-years) and injecting drug users (577 per 100,000 person-years) the incidence remained comparatively high with respect to the general population, although a decreasing pattern during 2004-2008 was observed for injecting-drug-users.
These estimates suggest that the transmission of HIV infection in Lazio remains frequent and men-who-have-sex-with men and injecting-drug-users are still greatly affected although the majority of new infections occurs among heterosexual individuals.
PMCID: PMC3359282  PMID: 22433313
HIV incidence; Test for recent infection; Testing history; Avidity index
7.  Infection control management of patients with suspected highly infectious diseases in emergency departments: data from a survey in 41 facilities in 14 European countries 
In Emergency and Medical Admission Departments (EDs and MADs), prompt recognition and appropriate infection control management of patients with Highly Infectious Diseases (HIDs, e.g. Viral Hemorrhagic Fevers and SARS) are fundamental for avoiding nosocomial outbreaks.
The EuroNHID (European Network for Highly Infectious Diseases) project collected data from 41 EDs and MADs in 14 European countries, located in the same facility as a national/regional referral centre for HIDs, using specifically developed checklists, during on-site visits from February to November 2009.
Isolation rooms were available in 34 facilities (82,9%): these rooms had anteroom in 19, dedicated entrance in 15, negative pressure in 17, and HEPA filtration of exhausting air in 12. Only 6 centres (14,6%) had isolation rooms with all characteristics. Personnel trained for the recognition of HIDs was available in 24 facilities; management protocols for HIDs were available in 35.
Preparedness level for the safe and appropriate management of HIDs is partially adequate in the surveyed EDs and MADs.
PMCID: PMC3292988  PMID: 22284435
8.  Duration of viral shedding in hospitalized patients infected with pandemic H1N1 
BMC Infectious Diseases  2011;11:140.
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.
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.
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.
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.
PMCID: PMC3123568  PMID: 21605362
9.  IP-10 response to RD1 antigens might be a useful biomarker for monitoring tuberculosis therapy 
BMC Infectious Diseases  2011;11:135.
There is an urgent need of prognosis markers for tuberculosis (TB) to improve treatment strategies. The results of several studies show that the Interferon (IFN)-γ-specific response to the TB antigens of the QuantiFERON TB Gold (QFT-IT antigens) decreases after successful TB therapy. The objective of this study was to evaluate whether there are factors other than IFN-γ [such as IFN-γ inducible protein (IP)-10 which has also been associated with TB] in response to QFT-IT antigens that can be used as biomarkers for monitoring TB treatment.
In this exploratory study we assessed the changes in IP-10 secretion in response to QFT-IT antigens and RD1 peptides selected by computational analysis in 17 patients with active TB at the time of diagnosis and after 6 months of treatment. The IFN-γ response to QFT-IT antigens and RD1 selected peptides was evaluated as a control. A non-parametric Wilcoxon signed-rank test for paired comparisons was used to compare the continuous variables at the time of diagnosis and at therapy completion. A Chi-square test was used to compare proportions.
We did not observe significant IP-10 changes in whole blood from either NIL or QFT-IT antigen tubes, after 1-day stimulation, between baseline and therapy completion (p = 0.08 and p = 0.7 respectively). Conversely, the level of IP-10 release to RD1 selected peptides was significantly different (p = 0.006). Similar results were obtained when we detected the IFN-γ in response to the QFT-IT antigens (p = 0.06) and RD1 selected peptides (p = 0.0003). The proportion of the IP-10 responders to the QFT-IT antigens did not significantly change between baseline and therapy completion (p = 0.6), whereas it significantly changed in response to RD1 selected peptides (p = 0.002). The proportion of IFN-γ responders between baseline and therapy completion was not significant for QFT-IT antigens (p = 0.2), whereas it was significant for the RD1 selected peptides (p = 0.002), confirming previous observations.
Our preliminary study provides an interesting hypothesis: IP-10 response to RD1 selected peptides (similar to IFN-γ) might be a useful biomarker for monitoring therapy efficacy in patients with active TB. However, further studies in larger cohorts are needed to confirm the consistency of these study results.
PMCID: PMC3120672  PMID: 21595874
10.  Molecular epidemiology of a hepatitis C virus epidemic in a haemodialysis unit: outbreak investigation and infection outcome 
BMC Infectious Diseases  2010;10:257.
HCV is a leading cause of liver chronic diseases all over the world. In developed countries the highest prevalence of infection is reported among intravenous drug users and haemodialysis (HD) patients. The present report is to identify the pathway of HCV transmission during an outbreak of HCV infection in a privately run haemodialysis (HD) unit in Italy in 2005.
Dynamics of the outbreak and infection clinical outcomes were defined through an ambi-directional cohort study. Molecular epidemiology techniques were used to define the relationships between the viral variants infecting the patients and confirm the outbreak. Risk analysis and auditing procedures were carried out to define the transmission pathway(s).
Of the 50 patients treated in the HD unit 5 were already anti-HCV positive and 13 became positive during the study period (AR = 28.9%). Phylogenic analysis identified that, all the molecularly characterized incident cases (10 out of 13), were infected with the same viral variant of one of the prevalent cases. The multivariate analysis and the auditing procedure disclosed a single event of multi-dose vials heparin contamination as the cause of transmission of the infection in 11 out of the 13 incident cases; 2 additional incident cases occurred possibly as a result of inappropriate risk management.
More than 30% of all HCV infections in developed countries results from poor application of standard precautions during percutaneous procedures. Comprehensive strategy which included: educational programmes, periodical auditing on standard precaution, use of single-dose vials whenever possible, prospective surveillance for blood-borne infections (including a system of prompt notification) and risk assessment/management dedicated staff are the cornerstone to contain and prevent outbreaks in HD
The outbreak described should serve as a reminder to HD providers that patients undergoing dialysis are at risk for HCV infection and that HCV may be easily transmitted whenever standard precautions are not strictly applied.
PMCID: PMC2940904  PMID: 20799943
11.  Surgical site infections in Italian Hospitals: a prospective multicenter study 
Surgical site infections (SSI) remain a major clinical problem in terms of morbidity, mortality, and hospital costs. Nearly 60% of SSI diagnosis occur in the postdischarge period. However, literature provides little information on risk factors associated to in-hospital and postdischarge SSI occurrence. A national prospective multicenter study was conducted with the aim of assessing the incidence of both in-hospital and postdisharge SSI, and the associated risk factors.
In 2002, a one-month, prospective national multicenter surveillance study was conducted in General and Gynecological units of 48 Italian hospitals. Case ascertainment of SSI was carried out using standardized surveillance methodology. To assess potential risk factors for SSI we used a conditional logistic regression model. We also reported the odds ratios of in-hospital and postdischarge SSI.
SSI occurred in 241 (5.2%) of 4,665 patients, of which 148 (61.4%) during in-hospital, and 93 (38.6%) during postdischarge period. Of 93 postdischarge SSI, sixty-two (66.7%) and 31 (33.3%) were detected through telephone interview and questionnaire survey, respectively. Higher SSI incidence rates were observed in colon surgery (18.9%), gastric surgery (13.6%), and appendectomy (8.6%). If considering risk factors for SSI, at multivariate analysis we found that emergency interventions, NNIS risk score, pre-operative hospital stay, and use of drains were significantly associated with SSI occurrence. Moreover, risk factors for total SSI were also associated to in-hospital SSI. Additionally, only NNIS, pre-operative hospital stay, use of drains, and antibiotic prophylaxis were associated with postdischarge SSI.
Our study provided information on risk factors for SSI in a large population in general surgery setting in Italy. Standardized postdischarge surveillance detected 38.6% of all SSI. We also compared risk factors for in-hospital and postdischarge SSI, thus providing additional information to that of the current available literature. Finally, a large amount of postdischarge SSI were detected through telephone interview. The evaluation of the cost-effectiveness of the telephone interview as a postdischarge surveillance method could be an issue for further research.
PMCID: PMC2311314  PMID: 18328101

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