Galactomannan and Real-Time PCR in the diagnosis of invasive Aspergillosis: preliminary data

The diagnosis of invasive aspergillosis is notoriously difficult. The standard culture-based methods have shown considerable limitations in performance. For this reason, non-culture methods have been increasingly employed for the diagnosis of invasive aspergillosis, and, among them, the methods based on Real-Time polymerase chain reaction (RT-PCR). In this study we assess the contribution in lowering diagnosis errors provided by the RT-PCR method when run alongside other methods. We analyzed 23 biological samples, 14 serum samples, and 9 bronchoalveolar lavage samples (BAL) from 10 immunocompromised patients who were selected according to EORTC/MSG criteria (European Organization for Research and Treatment of Cancer/Mycoses Study Group). On the serum sample we searched the galactomannan (GM) (Platelia Aspergillus®) and the fungal genome (MycAssayTMAspergillus); the BAL samples were subjected also to the culture tests. In 11 serum samples the results showed concordance between GM and RT–PCR tests, while in 3 samples we report discordance: 2 results were GM positive and RT-PCR negative, and 1 results GM negative and RT-PCR indeterminate. In 5 BAL samples the results showed concordance between the two methods, while 4 were GM positive and RT-PCR negative. The data, although still preliminary, suggest an increased accuracy in the diagnosis of suspected invasive aspergillosis when employing both RT-PCR and GM tests given that the RT-PCR test eliminates the false positive results of the GM test. The PCR methods require, however, further applications of this type of diagnostic because of the severe limit given by the lack of standardization

Anti-rods/rings autoantibody seropositivity does not affect response to telaprevir treatment for chronic hepatitis C infection

Autoantibodies to intracellular 'rods and rings' structures (anti-rods/rings or anti-RR) are strongly associated with hepatitis C (HCV) patients treated with interferon-α/ribavirin (IFN/RBV) and are linked with non-responsiveness to IFN/RBV or relapse, especially in Italian patients. This is the first study to determine whether there is any correlation of anti-RR with non-responsiveness to IFN/RBV treatment in patients also treated with telaprevir (TPV), one of several new therapies for chronic HCV recently implemented. METHODS: From 2013 to 2014, 52 HCV-infected patients were treated with IFN/RBV and TPV at five Italian clinics. Patient sera were collected and analyzed by indirect immunofluorescence for the presence of anti-RR antibodies. Patients were classified as anti-RR positive or anti-RR negative, and then various biological and clinical variables were analyzed to compare the two groups, including gender, age, HCV genotype, previous IFN/RBV treatment, and IFN/RBV/TPV treatment outcome. RESULTS: Of these 52 HCV patients treated with IFN/RBV/TPV, 10/32 (31%) who previously received IFN/RBV were anti-RR positive, compared to 0 of 20 treatment-naïve patients. Anti-RR-positive patients relapsed more than anti-RR-negative patients (3/10, 30% vs. 2/42, 5%; p < 0.05). However, zero anti-RR-positive patients were non-responsive, and frequencies of sustained virological response were similar (anti-RR positive: 7/10, 70% vs. anti-RR negative: 33/42, 79%). CONCLUSIONS: Overall, the data suggest that anti-RR seropositivity is not associated with resistance to TPV treatment in this patient cohort, but monitoring anti-RR-positive patients for relapse within the first 6 months after treatment may be useful

Tick-borne encephalitis in North-East Italy: A 14-year retrospective study, January 2000 to December 2013

Italy is considered at low incidence of tick-borne encephalitis (TBE), and the occurrence of human cases of TBE appears to be geographically restricted to the north east of the country. However, most information to date derives from case series, with no systematic data collection. To estimate incidence rates (IR) and spatial distribution of TBE cases, we conducted a retrospective study in north-eastern Italy. Data were collected through the infectious disease units and public health districts of three regions (Friuli Venezia Giulia, Trentino Alto Adige and Veneto) between 2000 and 2013. Overall, 367 cases were identified (IR: 0.38/100,000). The cases\u2019 median age was 56 years and 257 (70%) were male. Central nervous system involvement was reported in 307 cases (84%). Annual fluctuations in case numbers occurred, with peaks in 2006 and in 2013, when 44 and 42 cases were respectively observed. A strong seasonality effect was noted, with the highest number of cases in July. In terms of geographical location, three main endemic foci with high TBE IR (> 10/100,000) were identified in three provinces, namely Belluno (Veneto region), Udine (Friuli Venezia Giulia) and Trento (Trentino Alto- Adige). When investigating the whole study area in terms of altitude, the IR between 400 and 600 m was greater (2.41/100,000) than at other altitudes (p< 0.01). In conclusion, the incidence of TBE in Italy is relatively low, even considering only the three known affected regions. However, three endemic foci at high risk were identified. In these areas, where the risk of TBEV infection is likely high, more active offer of TBE vaccination could be considere

The ANA-reflex test as a model for improving clinical appropriateness in autoimmune diagnostics.

Reflex tests are widely used in clinical laboratories, for example, to diagnose thyroid disorders or in the follow-up of prostate cancer. Reflex tests for antinuclear antibodies (ANA) have recently gained attention as a way to improve appropriateness in the immunological diagnosis of autoimmune rheumatic diseases and avoid waste of resources. However, the ANA-reflex test is not as simple as other consolidated reflex tests (the TSH-reflex tests or the PSA-reflex tests) because of the intrinsic complexity of the ANA test performed by the indirect immunofluorescence method on cellular substrates. The wide heterogeneity of the ANA patterns, which need correct interpretation, and the subsequent choice of the most appropriate confirmatory test (ANA subserology), which depend on the pattern feature and on clinical information, hinder any informatics automation, and require the pathologist's intervention. In this review, the Study Group on Autoimmune Diseases of the Italian Society of Clinical Pathology and Laboratory Medicine provides some indications on the configuration of the ANA-reflex test, using two different approaches depending on whether clinical information is available or not. We further give some suggestions on how to report results of the ANA-reflex test

Has VZV epidemiology changed in Italy? Results of a seroprevalence study

The aim of the study was to evaluate if and how varicella prevalence has changed in Italy. In particular a seroprevalence study was performed, comparing it to similar surveys conducted in pre-immunization era. During 2013–2014, sera obtained from blood samples taken for diagnostic purposes or routine investigations were collected in collaboration with at least one laboratory/center for each region, following the approval of the Ethics Committee. Data were stratified by sex and age. All samples were processed in a national reference laboratory by an immunoassay with high sensitivity and specificity. Statutory notifications, national hospital discharge database and mortality data related to VZV infection were analyzed as well. A total of 3707 sera were collected and tested. In the studied period both incidence and hospitalization rates decreased and about 5 deaths per year have been registered. The seroprevalence decreased in the first year of life in subjects passively protected by their mother, followed by an increase in the following age classes. The overall antibody prevalence was 84%. The comparison with surveys conducted with the same methodology in 1996–1997 and 2003–2004 showed significant differences in age groups 1–19 y. The study confirms that in Italy VZV infection typically occurs in children. The impact of varicella on Italian population is changing. The comparison between studies performed in different periods shows a significant increase of seropositivity in age class 1–4 years, expression of vaccine interventions already adopted in some regions

People living with undiagnosed HIV infection and a low CD4 count: Estimates from surveillance data, Italy, 2012 to 2014

Background and aims: Late HIV diagnosis is associated with onward HIV transmission, higher morbidity, mortality and healthcare costs. In Italy, more than half of people living with HIV were diagnosed late during the last decade, with a CD4 count < 350 cells/mm3 at diagnosis. We aimed to determine the number and characteristics of people living with undiagnosed HIV infection and low CD4 counts in Italy. Methods: Data on newly reported HIV diagnoses from 2012 \u20132014 were obtained from the national HIV surveillance system. We used the European Centre for Disease Prevention and Control HIV modelling tool to calculate the undiagnosed prevalence and yearly diagnosed fraction (YDF) in people with low CD4 count. Results: The estimated annual number undiagnosed HIV infections with low CD4 count was on average 6,028 (95% confidence interval (CI): 4,954\u20138,043) from 2012\u20132014. In 2014, most of the undiagnosed people with low CD4 count were men (82.8%), a third acquired HIV through sex between men (MSM) (35.0%), and heterosexual transmission (33.4%), respectively. The prevalence of undiagnosed HIV infection was 11.3 (95% CI: 9.3\u201314.9) per 100,000 residents ranging from 0.7 to 20.8 between Italian regions. Nationally the prevalence rate was 280.4 (95% CI: 173.3\u2013450.2) per 100,000 MSM, 8.3 (95% CI: 4.9\u201313.6) per 100,000 heterosexual men, and 3.0 (95% CI: 1.4\u20135.6) per 100,000 women. The YDF was highest among heterosexual women (27.1%; 95% CI: 16.9\u201345.2%). Conclusions: These findings highlight the importance of improving efforts to identify undiagnosed HIV infections primarily among men, both MSM and heterosexual men

Global guideline for the diagnosis and management of rare mould infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiology

With increasing numbers of patients needing intensive care or who are immunosuppressed, infections caused by moulds other than Aspergillus spp or Mucorales are increasing. Although antifungal prophylaxis has shown effectiveness in preventing many invasive fungal infections, selective pressure has caused an increase of breakthrough infections caused by Fusarium, Lomentospora, and Scedosporium species, as well as by dematiaceous moulds, Rasamsonia, Schizophyllum, Scopulariopsis, Paecilomyces, Penicillium, Talaromyces and Purpureocillium species. Guidance on the complex multidisciplinary management of infections caused by these pathogens has the potential to improve prognosis. Management routes depend on the availability of diagnostic and therapeutic options. The present recommendations are part of the One World—One Guideline initiative to incorporate regional differences in the epidemiology and management of rare mould infections. Experts from 24 countries contributed their knowledge and analysed published evidence on the diagnosis and treatment of rare mould infections. This consensus document intends to provide practical guidance in clinical decision making by engaging physicians and scientists involved in various aspects of clinical management. Moreover, we identify areas of uncertainty and constraints in optimising this management