In Chronic Hepatitis C Infection, Myeloid-Derived Suppressor Cell Accumulation and T Cell Dysfunctions Revert Partially and Late After Successful Direct-Acting Antiviral Treatment.

Chronic HCV infection is characterized by several immunological alterations, such as the accumulation of suppressor cells and of hyperactivated T lymphocytes. However, it is unclear whether direct-acting antiviral (DAA)-mediated HCV clearance restores immune dysfunctions. We performed a phenotypic characterization by flow cytometry of different immune cell subsets, including monocytic myeloid-derived suppressor cells (M-MDSCs) and T lymphocytes in 168 patients with persistent HCV infection not treated, under DAA therapies and sustained virological responders. Chronic HCV infection prompted the accumulation of M-MDSCs independently of patient and clinical characteristics, and altered their metabolic properties. HCV RNA was undetectable in the majority of patients just after few weeks of DAA therapy, whereas M-MDSC levels normalized only 6 months after therapy. In addition, HCV infection deeply perturbed the T cell compartment since a re-distribution of memory CD4+ and CD8+ T cells was observed at the expenses of naïve cells, and memory T lymphocytes displayed increased activation. Notably, these features were only partially restored by DAA therapies in the CD4, but not in the CD8, compartment as high immune activation levels persisted in the terminally differentiated memory CD8+ T cells even more than 1 year after sustained virological response. Together, these results suggest that successful DAA therapies do not lead to full immunological reconstitution as fast as viral clearance.

Oral and anal high-risk human papilloma virus infection in HIV-positive men who have sex with men over a 24-month longitudinal study: complexity and vaccine implications.

BACKGROUND: Few studies focused on longitudinal modifications over time of high-risk HPV (HR-HPV) at anal and oral sites in HIV+ men who have sex with men (MSM). METHODS: We described patterns and longitudinal changes of HR-HPV detection and the prevalence of HR-HPV covered by the nonavalent HPV vaccine (vax-HPV) at oral and anal sites in 165 HIV+ MSM followed in an Italian hospital. The samples were collected at baseline and after 24 months (follow-up). The presence of HPV was investigated with Inno-LiPA HPV Genotyping Extra II. RESULTS: Median age was 44 years (IQR 36-53), median CD4+ cell count at nadir was 312 cells/mm3 (IQR 187-450). A total of 120 subjects (72.7%) were receiving successful antiretroviral therapy (ART). At baseline and follow-up, the frequency of HR-HPV was significantly higher in the anal site (65.4% vs 9.4 and 62.4% vs 6.8%, respectively). Only 2.9% of subjects were persistently HR-HPV negative at both sites. All oral HR-HPV were single at baseline vs 54.6% at baseline at the anal site (p = 0.005), and all oral HR-HPV were single at follow-up vs 54.4% at anal site at follow-up (p = 0.002). The lowest rate of concordance between the oral and anal results was found for HR-HPV detection; almost all HR-HPV positive results at both anal and oral sites had different HR-HPV.The most frequent HR-HPV in anal swabs at baseline and follow-up were HPV-16 and HPV-52.At follow-up at anal site, 37.5% of patients had different HR-HPV genotypes respect to baseline, 28.8% of subjects with 1 HR-HPV at baseline had an increased number of HR-HPV, and patients on ART showed a lower frequency of confirmed anal HR-HPV detection than untreated patients (p = 0.03) over time. Additionally,54.6 and 50.5% of patients had only HR-vax-HPV at anal site at baseline and follow-up, respectively; 15.2% had only HR-vax-HPV at baseline and follow-up. CONCLUSIONS: We believe that it is important testing multiple sites over time in HIV-positive MSM. ART seems to protect men from anal HR-HPV confirmed detection. Vaccination programmes could reduce the number of HR-HPV genotypes at anal site and the risk of the first HR-HPV acquisition at the oral site.

Soluble CD163 and soluble CD14 plasma levels but not cellular HIV-DNA decrease during successful interferon-free anti-HCV therapy in HIV-1-HCV co-infected patients on effective combined anti-HIV treatment.

Soluble CD163, soluble CD14 and cellular HIV-1-DNA levels reflect two different aspects of HIV infection: immune activation and the reservoir of infected cells. The aim of this study was to describe their relationships in a cohort of HIV-HCV co-infected patients successfully treated for both HCV and HIV infections. Fifty-five patients were recruited and studied prior to the start of direct-acting antivirals (DAAs) (T0), at week 12 of DAA treatment (T1) and 24 weeks after T0 (T2). The subjects were classified as having undetectable plasma HIV viraemia (UV) or low-level viraemia (LLV) in the 18 months before T2. Plasma levels of sCD163 and of sCD14 were comparable in patients with UV and in subjects with LVL at T0, T1 and T2. The HIV DNA level was positively correlated with LLV but not with sCD163 and sCD14 levels; these two markers of inflammation were positively correlated (p = 0.017). Soluble CD163 and sCD14 decreased over time from T0 to T2 (p = 0.000 and p = 0.034, respectively). In conclusion, the significant decrease in sCD163 and sCD14 levels in patients cured of HCV infection, regardless of the presence of LLV, suggests a main role for HCV in immune activation in HIV-HCV co-infected patients.

Plasmodium knowlesi malaria in a traveller returning from the Philippines to Italy, 2016.

Plasmodium knowlesi is a simian parasite responsible for most human cases of malaria in Malaysian Borneo. A timely recognition of infection is crucial because of the risk of severe disease due to the rapid increase in parasitemia. We report a case of P. knowlesi infection in a traveller who developed fever and thrombocytopenia after returning from the Philippines in 2016. Rapid antigen test was negative, microscopy examination showed parasites similar to Plasmodium malariae, with a parasite count of 10,000 parasites per µL blood, while molecular testing identified P. knowlesi infection. Treatment with atovaquone-proguanil led to resolution of fever and restoration of platelet count in two days. P. knowlesi infection should be suspected in febrile travellers returning from South East Asia. Due to the low sensitivity of rapid antigen tests and the low specificity of microscopy, confirmation by molecular tests is recommended.

Prevalence, molecular epidemiology and intra-hospital acquisition of Klebsiella pneumoniae strains producing carbapenemases in an Italian teaching hospital from January 2015 to September 2016.

OBJECTIVES: We described Klebsiella pneumoniae producing carbapenemase (CPKP) spread from 01/01/2015 to 13/09/16 in a tertiary level hospital. METHODS: The first positive surveillance rectal swab (SRS) or clinical sample (CS) collected in the medical department (MD), surgical department (SD) and intensive care department (ICD) were included in the study. A validated in-house Real-Time PCR method was used to detect carbapenemases; multilocus sequence typing (MLST) was used for further characterization of the strains. RESULTS: 21535 patients were included: 213 CPKP strains from surveillance rectal swab (SRS) and 98 from clinical samples (CS) were collected. The percentage of CPKP detected in SRS with respect to CS increased in the medical MD from 2015 to 2016 (p=0.01) and in ICD from 2012 to 2015 (p=0.0001), while it decreased in SD from 2014 to 2016 (p=0.003); 68.5% of the positive SRS had a previous negative SRS; CPKP was more frequently identified in CS than in SRS in MD. Twelve strains harboured more than one carbapenemase gene. Many other species harbouring a carbapenemase gene were collected. CONCLUSIONS: MDs need more inclusive surveillance criteria. The late detection of positive SRS underlined the risk of colonization during hospitalization.

Prevalence of Klebsiella pneumoniae strains producing carbapenemases and increase of resistance to colistin in an Italian teaching hospital from January 2012 To December 2014.

BACKGROUND: The aim of this study was to characterize the spread of carbapenemase-producing Klebsiella pneumoniae (CPKP) in a tertiary level hospital using ongoing active surveillance with rectal swab cultures. Furthermore, this study analyzed the presence of CPKP in the clinical samples (CS) of a single patient as well as the evolution of Colistin-sensitive strains (CoS) to Colistin-resistant strains (CoR). METHODS: This study was performed from January 1, 2012 to December 31, 2014. In 2012, a survey was conducted in the Intensive Care Department. In autumn 2013, active monitoring was extended to the Surgery Department, and since mid-2014, the surveillance has included the Medical Department as well. Only the first isolated strain from each patient was included. Antimicrobial susceptibility testing was performed on CPKP isolates: Klebsiella pneumoniae carbapenemase, oxacillinase-48, Verona integron-encoded metallo-ß-lactamase and New Delhi metallo-ß-lactamase were detected using a validated in-house PCR method, and multilocus sequence typing (MLST) was used to investigate the clonal transmission of strains. RESULTS: A total of 15,104 patients were included in the study, and 496 consecutive non-replicated strains of CPKP were collected: 149 strains were collected in 2012 (39 [26.2 %] from surveillance rectal swabs [SRS]), 133 strains were collected in 2013 (70 [52.6 %] from SRS) and 214 strains were collected in 2014 (164 [76.6 %] from SRS). We observed a significant increase in the percentage of positive SRS cases in 2014 relative to 2013 and 2012 (p = 0.0001 and p = 0.0172, respectively) and in the proportion of CPKP first isolated by SRS relative to those identified by CS (p < 0.0001). Among all available samples, the number of CoR isolated from SRS was higher in 2013 and 2014 compared with 2012 (p = 0.0019 and p = 0.008, respectively). ST-258 and ST-512 were more prevalent in the tested specimens, and a new single locus variant (SLV) of ST-512 (ST-745) was isolated. CONCLUSIONS: The results of this 3-year study of 15,104 patients highlight the clinical relevance of antimicrobial resistance as well as the drug-selection pressure of colistin therapy. The active surveillance in the three different departments increased the level of CPKP cases isolated by SRS.

Sustained virological response and baseline predictors in HIV-HCV coinfected patients retreated with pegylated interferon and ribavirin after failing a previous interferon-based therapy: systematic review and meta-analysis.

BACKGROUND: Published data on retreatment with pegylated interferon and ribavirin of previously failing HIV-HCV coinfected patients are sparse and limited to observational study. We aimed to evaluate efficacy and pretreatment predictors. METHODS: Systematic review and meta-analysis of observational studies. The overall and genotype-related success rate was investigated. A direct comparison was performed between genotypes 1/4 and 2/3 by evaluating the sustained virological response (SVR) rate ratio (RR). The effect of study level variables on the effect size was investigated by meta-regression. Variables that were analyzed included age, gender, advanced hepatic fibrosis, pretreatment of HCV RNA and CD4, and successful antiretroviral treatment (ART). RESULTS: The available evidence was from 5 open-label, cohort studies (275 patients). The overall SVR rate was 0.280 (95% CI,0.171-0.425). The SVR rate in genotype 1/4 infections was 0.174 (95% CI, 0.129-0.230), and in genotype 2/3 infections it was 0.474 (95% CI, 0.286-0.670). The pooled RR comparing the SVR of genotype 1/4 to 2/3 was 0.369 (95% CI, 0.239-0.568), with a decreased probability of response for genotype 1/4 (P < .001). HIV RNA suppression had a significant effect on SVR (P = .005). The other covariates had no effect on the overall SVR rate. CONCLUSIONS: The overall SVR rate was 28%, consistent with the rate reported in the retreatment of mono-infected patients with the same schedule. A substantial relative reduction in the SVR rate of about one-third, when treating genotypes 1/4, was found, with a low SVR rate of 17%. Successful HIV suppression by ART predicted a higher rate of treatment success.