Massimo Rittà

Evaluation of CMV-specific cellular immune response by EliSPOT assay in kidney transplant patients.

BACKGROUND Immunological monitoring for CMV can be useful in transplant patients; however, few centers perform it on a routine basis. OBJECTIVES In this study, CMV-specific cellular response was evaluated in a population of kidney transplant recipients and related to viral infection/reactivation and other demographic and clinical features. STUDY DESIGN Three hundred and twenty-eight patients were studied by EliSPOT assay: 201 prospectively monitored in the first year posttransplantation, 127 with a single determination at >1 year. Clinical features, including occurrence of CMV-DNAemia, CMV serostatus, anti-viral strategies and immunosuppressive protocols, were evaluated. RESULTS Overall, 66.5% of patients were CMV-responders at EliSPOT assay. No episode of infection occurred at follow-up (mean 24.5 months) in 73.4% responders versus 55.5% non-responders (p<0.005); CMV-free period was significantly longer in responders (p<0.001). Although no significant difference of peak viral load was found, prevalence of CMV-DNAemia values >10(5)copies/mL was significantly higher in non-responders versus responders (8.2% and 2.3%, p<0.05). Non-responder status was significantly associated to CMV-seronegativity (p<0.0001), anti-viral prophylaxis use (p<0.0001), and immunosuppression induction with basiliximab (p<0.005). No significant association was found for other clinical features and immunosuppressive protocols. CONCLUSIONS Immunological data for CMV could be used in the clinical evaluation and decision-making process, in combination with virological monitoring, in kidney transplant recipients.

Everolimus-based immunosuppressive regimens in lung transplant recipients: Impact on CMV infection

UNLABELLED Cytomegalovirus (CMV) is one of the most important viral pathogen in solid organ transplant (SOT) recipients, with heart and lung transplant patients being at considerably high risk for CMV direct and indirect effects. Prevention strategies have resulted in significant reduction in disease and CMV related morbidity and mortality. Few studies reported a lower incidence of CMV infections in solid organ transplant recipients treated with immunosuppressive protocols including the mTOR inhibitor everolimus (EVR). PURPOSE The aim of the current study was to evaluate the impact of EVR-based immunosuppressive regimens on the occurrence and kinetics of CMV infection in a population of lung transplant recipients, at both systemic and pulmonary level. Thirty-two lung transplants (LT) were investigated; eighteen were on EVR-based immunosuppressive regimens. CMV events occurring in the first two years post-transplantation at both systemic and pulmonary levels were reported. PRINCIPAL RESULTS No differences were reported in CMV viraemia occurrence at both one- and two-year follow up between patients undergoing EVR-based and EVR-free immunosuppressive regimens. Considering CMV episodes at pulmonary levels, as determined by routinely performed broncho-alveolar lavages (BALs), during EVR-administration the patients experienced significantly fewer episodes of high-load CMV (as defined by viral loads⩾10(5) copies/mL) than during EVR-free immunosuppressive regimens. MAJOR CONCLUSION EVR-based immunosuppressive regimens in lung transplantation settings appear to be associated to lower incidence of clinically relevant CMV episodes at pulmonary levels, striking the possibility of extending the use of EVR to such a group of transplant recipients.

Prevalence of HPV infection in racial-ethnic subgroups of head and neck cancer patients

The landscape of HPV infection in racial/ethnic subgroups of head and neck cancer (HNC) patients has not been evaluated carefully. In this study, a meta-analysis examined the prevalence of HPV in HNC patients of African ancestry. Additionally, a pooled analysis of subject-level data was also performed to investigate HPV prevalence and patterns of p16 (CDNK2A) expression amongst different racial groups. Eighteen publications (N = 798 Black HNC patients) were examined in the meta-analysis, and the pooled analysis included 29 datasets comprised of 3,129 HNC patients of diverse racial/ethnic background. The meta-analysis revealed that the prevalence of HPV16 was higher among Blacks with oropharyngeal cancer than Blacks with non-oropharyngeal cancer. However, there was great heterogeneity observed among studies (Q test P<0.0001). In the pooled analysis, after adjusting for each study, year of diagnosis, age, gender and smoking status, the prevalence of HPV16/18 in oropharyngeal cancer patients was highest in Whites (61.1%), followed by 58.0% in Blacks and 25.2% in Asians (P<0.0001). There was no statistically significant difference in HPV16/18 prevalence in non-oropharyngeal cancer by race (P=0.682). With regard to the pattern of HPV16/18 status and p16 expression, White patients had the highest proportion of HPV16/18+/p16+ oropharyngeal cancer (52.3%), while Asians and Blacks had significantly lower proportions (23.0% and 22.6%, respectively) [P <0.0001]. Our findings suggest that the pattern of HPV16/18 status and p16 expression in oropharyngeal cancer appears to differ by race and this may contribute to survival disparities. at Freie U nivrsitaet B erlin on D ecem er 8, 2016 http://carcfordjournals.org/ D ow nladed fromThe landscape of HPV infection in racial/ethnic subgroups of head and neck cancer (HNC) patients has not been evaluated carefully. In this study, a meta-analysis examined the prevalence of HPV in HNC patients of African ancestry. Additionally, a pooled analysis of subject-level data was also performed to investigate HPV prevalence and patterns of p16 (CDNK2A) expression amongst different racial groups. Eighteen publications (N = 798 Black HNC patients) were examined in the meta-analysis, and the pooled analysis included 29 datasets comprised of 3,129 HNC patients of diverse racial/ethnic background. The meta-analysis revealed that the prevalence of HPV16 was higher among Blacks with oropharyngeal cancer than Blacks with non-oropharyngeal cancer. However, there was great heterogeneity observed among studies (Q test P<0.0001). In the pooled analysis, after adjusting for each study, year of diagnosis, age, gender and smoking status, the prevalence of HPV16/18 in oropharyngeal cancer patients was highest in Whites (61.1%), followed by 58.0% in Blacks and 25.2% in Asians (P<0.0001). There was no statistically significant difference in HPV16/18 prevalence in non-oropharyngeal cancer by race (P=0.682). With regard to the pattern of HPV16/18 status and p16 expression, White patients had the highest proportion of HPV16/18+/p16+ oropharyngeal cancer (52.3%), while Asians and Blacks had significantly lower proportions (23.0% and 22.6%, respectively) [P <0.0001]. Our findings suggest that the pattern of HPV16/18 status and p16 expression in oropharyngeal cancer appears to differ by race and this may contribute to survival disparities.

Diagnosis of viral gastroenteritis: limits and potential of currently available procedures.

The diagnostic approaches to viral gastroenteritis have evolved substantially over the past decades because of the advances in detection methods, the emergence of new pathogens, and the increase in diarrhea hospitalizations attributed to viruses, especially in young children in non-industrialized countries. Overall, these factors have lead to a relevant improvement of types and operating characteristics of diagnostic methods (including sensitivity and specificity), as well as turnaround time. In this review, clinical and laboratory approaches to the diagnosis of viruses causing gastroenteritis are presented; in particular, specimen collection and detection methods are reviewed and discussed, taking into account performance and limitations.

Ficus religiosa L. bark extracts inhibit infection by herpes simplex virus type 2 in vitro

Ficus religiosa extracts have been used in traditional Indian medicine to treat sexually transmitted infections such as gonorrhea and genital ulcers. The aim of this study was to investigate the antiviral activity of F. religiosa extracts against herpes simplex virus type 2 (HSV-2), the main causative agent of genital ulcers and sores. Water and chloroform bark extracts were the most active against HSV-2, and also against an acyclovir-resistant strain. We demonstrate that the water extract has a direct virus-inactivating activity. By contrast, the chloroform extract inhibits viral attachment and entry and limits the production of viral progeny.

Inhibition of HSV-2 infection by pure compounds from Thymus capitatus extract in vitro : Anti-HSV-2 compounds from Thymus capitatus extract

Thymus capitatus represents 1 of the 5 Tunisian species of the genus Thymus, which has long‐standing use for flavouring and preserving several food products. Its constituents have been reported to endow antimicrobial properties, but little is known about their antiviral activities. The aim of this study was to examine the antiviral activity of pure compounds from the most bioactive inhibitory T. capitatus extract in vitro against herpes simplex virus Type 2 (HSV‐2) infection and to identify their mechanism of action. Either the extracts or the essential oil exert inhibitory activity against HSV‐2 infection, with the ethanolic extract showing the lowest EC50 value (2.3 μg/ml). Three pure compounds were then isolated from the ethanolic extract and investigated for their antiviral activity. β‐sitosterol showed the most favourable selectivity index and both cinnamaldehyde and carvacrol exerted moderate antiviral effect. Investigation of the mechanism of action revealed that all three compounds directly inactivated the infectivity of the virus particles. These findings suggest the use of T. capitatus ethanolic extract as source of anti‐HSV‐2 pure compounds and warrant further studies to evaluate their therapeutic potential.

The traditional use of Vachellia nilotica for sexually transmitted diseases is substantiated by the antiviral activity of its bark extract against sexually transmitted viruses

ETHNOPHARMACOLOGICAL RELEVANCE Vachellia (Acacia) nilotica and other plants of this genus have been used in traditional medicine of Asian and African countries to treat many disorders, including sexually transmitted diseases, but few studies were performed to validate their anti-microbial and anti-viral activity against sexually transmitted infections. AIM OF THE STUDY The present study was undertaken to explore whether the ethnomedical use of V.nilotica to treat genital lesions is substantiated by its antiviral activity against the human immunodeficiency virus (HIV), the herpes simplex virus (HSV) and the human papillomavirus (HPV). MATERIALS AND METHODS The antiviral activity of V.nilotica was tested in vitro by virus-specific inhibition assays using HSV-2 strains, sensible or resistant to acyclovir, HIV-1IIIb strain and HPV-16 pseudovirion (PsV). The potential mode of action of extract against HSV-2 and HPV-16 was further investigated by virus inactivation and time-of-addition assays on cell cultures. RESULTS V.nilotica chloroform, methanolic and water bark extracts exerted antiviral activity against HSV-2 and HPV-16 PsV infections; among these, methanolic extract showed the best EC50s with values of 4.71 and 1.80µg/ml against HSV-2 and HPV-16, respectively, and it was also active against an acyclovir-resistant HSV-2 strain with an EC50 of 6.71µg/ml. By contrast, no suppression of HIV infection was observed. Investigation of the mechanism of action revealed that the methanolic extract directly inactivated the infectivity of the HPV-16 particles, whereas a partial virus inactivation and interference with virus attachment (EC50 of 2.74µg/ml) were both found to contribute to the anti-HSV-2 activity. CONCLUSIONS These results support the traditional use of V.nilotica applied externally for the treatment of genital lesions. Further work remains to be done in order to identify the bioactive components.