Depression of early phase of HTLV-I infection in vitro mediated by human beta-interferon.

Natural human interferon beta (beta-IFN) was tested during the early phase of in vitro infection with HTLV-I virus of human cord blood mononuclear cells (CBL), to evaluate whether its antiviral and immunomodulating effects might prevent spreading of infection in the host. beta-IFN was found to reduce HTLV-I transmission and integration in CBL cultures. Moreover, beta-IFN had no effect in preventing virus transmission and integration in K562 and a very limited effect in HL60 and Molt-4 human tumour lines, suggesting a cell-type specific mode of action. beta-IFN induced a 'priming' response on CBL, since overnight pretreatment of recipient cells or one single treatment at the onset of the coculture were almost equally effective in protecting against HTLV-I infection. During the early days post infection (p.i.), IFN-treated CBL showed a pattern of phenotypic markers that was closer to that of non-infected CBL. In contrast, untreated CBL exposed to HTLV-I showed a percent increase of Tac+, M3+ and Leu 11+ subpopulations. Cell-mediated immune responses of CBL were depressed after coculturing with HTLV-I producer MT-2 cells. beta-IFN was able to boost the cell-mediated cytotoxicity of fresh and infected CBL against both K562 and MT-2 target cells. Leukocyte blastogenesis in mixed lymphocyte/tumour cell cultures, evaluated in terms of 3H-thymidine incorporation during the first week p.i., was also enhanced by IFN when macrophages and lymphocytes were reconstituted at an optimal 1:20 ratio. It is conceivable that this overall enhancement of the immune response induced by beta-IFN could contribute to reduce HTLV-I infection in vitro

Antibiotic susceptibility of vancomyin and nitrofurantoin in Staphylococcus aureus isolated from burnt patients in Sulaimaniyah, Iraqi Kurdistan

Burns remain a significant public health problem in terms of morbidity and mortality throughout the world, especially in low and middle-income countries. Burning raptures the skin barriers that normally prevent invasion by microorganisms and infection is a major complication in burn patients. Methicillin resistant Staphylococcus aureus (MRSA) is the most important nosocomial pathogen. This retrospective analysis was conducted in the burn unit of the Department of Microbiology in the Sulamaini Plastic Surgery and Burns Hospital. The analysis is based on data collected from the medical records of 2938 burn patients, hospitalized between May 2008 and December 2011. The clinical samples were taken from various body sources for microbiological tests. Patients with a high percentage of total body surface area burnt (P<0.001) and a longer hospital stay (P<0.001) were more likely to have infection compared to other patients. In addition, among all tested antibiotics, vancomycin and nitrofurantion seem to be the most effective antibiotics for MR- SA. Furthermore there was a significant association between age and antibiotic resistance for all antibiotics except for vancomycin and nitrofurantoin. Resistance to antibiotics increased with advancing age. The wide use of antibiotics in the treatment of bacterial infections has probably led to the emergence and spread of resistant strains. Routine microbiological surveillance and careful in vitro testing prior to antibiotic use and strict adherence to hospital antibiotic policy may help in the prevention and treatment of antibiotic resistant pathogens in burn infections

Highlights on HIV eradication in 2013

Almost 20 years after the introduction of HAART, scientific community, doctors and patients are still struggling with the absence of effective strategies aimed at eradicating HIV infection, or at preventing it through a vaccin

The multifactorial pathways towards resistance to the cytosine analogues emtricitabine and lamivudine: Evidences from literature

The article by Bulteel et al.,1 published in the September issue of the journal, has investigated the rate of M184V emergence in patients receiving HAART combinations containing efavirenz (EFV), tenofovir (TDF) and lamivudine (3 TC) or emtricitabine (FTC) within the UK Collaborative HIV Cohort. By analyzing 304 genotypic resistance tests, the authors asserted that, although patients receiving 3 TC-based regimens were more likely to develop M184V than those receiving FTC-based regimens (event rate: 0.55 [95%CI: 0.28–0.96] for 3 TC versus 0.34 [95%CI: 0.21–0.46] for FTC), this association was not statistically significant in both univariable and multivariable models. These results are different from those reported in previous studies from our and other groups2, 3 and 4 showing a significant decrease in M184V emergence in patients failing FTC + TDF-based compared to 3 TC + TDF-based HAART (Table 1). The lower prevalence of M184V in FTC-containing regimen was also supported by a recently published letter showing a strong trend (P = 0.051) towards higher rates of resistance to the 3 TC containing regimen 5.5 (1.8–12.8) per 1000 patient years when compared with the FTC containing regimens 1.7 (0.8–3.2) per 1000 patient year

Screening of respiratory pathogens by Respiratory Multi Well System (MWS) r-gene™ assay in hospitalized patients

Novel respiratory viruses have been identified as possible agents of upper and lower respiratory tract infections. Multiplex real-time PCRs have been developed to identify clinically relevant respiratory pathogens. In this study, 178 respiratory samples already screened for influenza virus types A and B by Flu A/B ASR real-time PCR kit were retrospectively analyzed with the Respiratory Multi Well System (MWS) r-gene™ real-time PCR kit which detects a wide spectrum of respiratory pathogens. The goal was to demonstrate the importance of a wide spectrum screening compared to a single diagnostic request. The Flu A/B ASR kit detected influenza B virus in 1.7% of the samples (3/178) and no influenza A virus. The MWS r-gene™ kit detected influenza virus in 6.7% (12/178) of samples (0.6% influenza A, and 6.2% influenza B), while the overall detection rate for respiratory pathogens was 54% (96/178). Co-infections were detected in 8/178 (4.5%) samples. Adenovirus was the infectious agent detected most frequently, followed by respiratory syncytial virus. The risk of being infected by respiratory syncytial virus is almost threefold higher in patients older than 65 years compared to the younger age group (OR:2.7, 95% CI: 1.2-6.2). Wide spectrum screening of respiratory pathogens by real-time PCR is an effective means of detecting clinically relevant viral pathogens

Comparative antiviral activity of integrase inhibitors in human monocyte-derived macrophages and lymphocytes

The activity of raltegravir and 4 other integrase inhibitors (MK-2048, L870,810, IN2, and IN5) was investigated in primary human macrophages, PBMC and C8166-lymphocytic T cells, in order to determine their relative potency and efficacy in different cellular systems of HIV infection. Raltegravir showed better protective efficacy in all cell types; MK-2048, L870,810 and IN5 showed a potent anti-HIV-1 activity in macrophages, while in lymphocytes only MK-2048 and L870,810 showed an inhibitory effect comparable to raltegravir. IN2 was a poorly effective anti-HIV-1 compound in all cellular systems. All effective integrase inhibitors exhibited a potent antiviral activity against both X4 and R5 HIV-1 strains. In general, raltegravir, MK-2048, L870,810 and IN5 showed anti HIV activity similar or slightly higher in macrophages compared to PBMC and C8166 T cells: for MK-2048, the EC(50) was 0.4, 0.9, 11.5nM in macrophages, in PBMCs and T cells, respectively; for L870,810, the EC(50) was 1.5, 14.3, and 10.6nM, respectively; for IN5 the EC(50) was 0.5, 13.7, and 5.7nM, respectively

Selected amino acid changes in HIV-1 subtype-C gp41 are associated with specific gp120(V3) signatures in the regulation of co-receptor usage

The majority of studies have characterized the tropism of HIV-1 subtype-B isolates, but little is known about the determinants of tropism in other subtypes. So, the goal of the present study was to genetically characterize the envelope of viral proteins in terms of co-receptor usage by analyzing 356 full-length env sequences derived from HIV-1 subtype-C infected individuals. The co-receptor usage of V3 sequences was inferred by using the Geno2Pheno and PSSM algorithms, and also analyzed to the "11/25 rule". All reported env sequences were also analyzed with regard to N-linked glycosylation sites, net charge and hydrophilicity, as well as the binomial correlation phi coefficient to assess covariation among gp120(V3) and gp41 signatures and the average linkage hierarchical agglomerative clustering were also performed. Among env sequences present in Los Alamos Database, 255 and 101 sequences predicted as CCR5 and CXCR4 were selected, respectively. The classical V3 signatures at positions 11 and 25, and other specific V3 and gp41 amino acid changes were found statistically associated with different co-receptor usage. Furthermore, several statistically significant associations between V3 and gp41 signatures were also observed. The dendrogram topology showed a cluster associated with CCR5-usage composed by five gp41 mutated positions, A22V, R133M, E136G, N140L, and N166Q that clustered with T2V(V3) and G24T(V3) (bootstrap=1). Conversely, a heterogeneous cluster with CXCR4-usage, involving S11GR(V3), 13-14insIG/LG(V3), P16RQ(V3), Q18KR(V3), F20ILV(V3), D25KRQ(V3), Q32KR(V3) along with A30T(gp41), S107N(gp41), D148E(gp41), A189S(gp41) was identified (bootstrap=0.86). Our results show that as observed for HIV-1 subtype-B, also in subtype-C specific and different gp41 and gp120V3 amino acid changes are associated individually or together with CXCR4 and/or CCR5 usage. These findings strengthen previous observations that determinants of tropism may also reside in the gp41 protein

Non-B HIV type 1 subtypes among men who have sex with men in Rome, Italy

An increase in the circulation of HIV-1 non-B subtypes has been observed in recent years in Western European countries. Due to the lack of data on the circulation of HIV-1 non-B subtypes among European HIV-1-infected men who have sex with men (MSM), a biomolecular study was conducted in Rome, Italy. HIV-1 partial pol gene sequences from 111 MSM individuals (76 drug naive and 35 drug experienced) were collected during the years 2004-2006. All these sequences were analyzed using the REGA HIV-1 Subtyping Tool, and aligned using CLUSTAL X followed by manual editing using the Bioedit software. A BLAST search for non-B subtype sequences was also performed. Twenty-six (23.4%) MSM were not Italians. Eight individuals (7.2%) were diagnosed as HIV infected before 1991, 20 (18.0%) between 1991 and 1999, and 83 (74.8%) from 2000 to 2006. Fifteen (15/111, 13.5%) individuals were infected with the non-B subtype. The percentage of infection with HIV-1 non-B subtypes was 8.2% (7/85) among Italian MSM and 30.8% (8/26) among the non-Italians (OR = 4.95 95% IC: 1.40-17.87). Individuals infected with the non-B subtype were significantly younger than those infected with the HIV-1 B subtype (28 years vs. 34 years, p = 0.003). The CRFs were more prevalent (8.1%) than pure subtypes (5.4%), which were distributed as follows: subtype C (2.6%), subtype A1 (1.7%), and subtype F1 (0.9%). Major mutations conferring resistance to antiretroviral drugs (ARV) were not found among HIV-1 non-B subtype drug-naive patients but were found in two ARV-experienced individuals. The data show that viral diversity is likely increasing in a population group that had been previously characterized by the circulation of HIV-1 subtype B. © Copyright 2009, Mary Ann Liebert, Inc

In vivo acquisition and risk of inter-species spread of blaKPC-3-plasmid from Klebsiella pneumoniae to Serratia marcescens in the lower respiratory tract

In recent years, Serratia marcescens has emerged as an important agent of hospital-acquired infections, such as pneumonia, urinary tract infection, septicaemia and meningitis, particularly in vulnerable patients. Compared to Klebsiella pneumoniae and Escherichia coli, S. marcescens is less commonly associated with blaKPC genes, yet few cases of plasmid transmission at the gastrointestinal level from K. pneumoniae carbapenemase (KPC)-producing Enterobacterales to S. marcescens have been described. Here we report a case of in vivo acquisition, during a 3-month period of hospitalization in the intensive care unit, of a blaKPC-3 gene carried by a pKpQIL-IT plasmid, and its probable transmission at the bronchial level among different species of Enterobacterales, including K. pneumoniae and S. marcescens. By using whole genome sequence analyses we were able provide insight into the dynamics of carbapenem-resistance determinants acquisition in the lower respiratory tract, a novel anatomical region for such plasmid transmission events, that usually involve the gastrointestinal tract. The co-presence at the same time of both wild-type and resistant Enterobacterales could have been the critical factor leading to the spread of plasmids harbouring carbapenem-resistance genes, of particular importance during surveillance screenings. The possibility of such an event may have significant consequences in terms of antimicrobial treatment, with a potential limitation of therapeutic options, thereby further complicating the clinical management of high-risk critically ill patients

Successful switch to tenofovir after suboptimal response to entecavir in an immunocompromised patient with chronic hepatitis B and without genotypic hepatitis B virus resistance

We report a case of an immunocompromised patient affected by chronic hepatitis B virus (HBV) with high basal HBV viremia (>8 log(10) IU/ml) who failed an entecavir regimen, despite the absence of primary or secondary drug resistance mutations. The patient achieved sustained virological success (serum HBV DNA <12 IU/ml) when tenofovir was added to the treatment. This case highlights the difficulty in choosing an optimal therapy in such specific conditions and supports the concept of tailoring therapy (including combination regimens) on the basis of the particular conditions of each individual patient