Prevalence and risk factors for gonococcal infection in Reunion Island.

OBJECTIVE: To determine the prevalence and risk factors for gonococcal infection, and the resistance profile of Neisseria gonorrhoeae (NG) in Reunion Island. PATIENTS AND METHODS: All patients who visited the four sexually transmitted infection (STI) clinics of Reunion Island between January 2017 and December 2018 were screened by multiplex polymerase chain reaction. Data on patient characteristics were collected using a self-administered questionnaire (reason for screening, marital status, risk-taking behaviors, place of birth, employment status, type of health care coverage, sexual orientation, number of sexual partners, occurrence of extra-marital relationships, history of STIs, and symptomatology. Precarity was defined as being unemployed and/or receiving universal health insurance). RESULTS: The prevalence of NG (n=4289) in the screened population was 2.8% (95% CI [2.3-3.3]). Minors were especially at-risk (4.4% (95% CI [2.6-7])) and especially girls (5.6% (95% CI [3.2-8.9])). The prevalence observed in the homosexual population was 4.0% [2.6-5.9]. Gonococcal infection was asymptomatic in 56 (69%) patients. For all infection sites, the main risk factors were male minors (P=0.019), individuals living in conditions of precarity (P=0.023), individuals co-infected with chlamydia (P<0.001) or syphilis (P<0.001), and individuals of foreign origin (P=0.006). No NG strain was resistant to ceftriaxone. Strains were resistant to penicillin G, ciprofloxacin, and azithromycin in 22% (20/91), 38% (35/91), and 1% (1/91) of cases, respectively. CONCLUSION: The prevalence of NG in patients visiting STI clinics in Reunion Island is particularly high among minors. Prevention programs targeting this population should be reinforced and screening should be facilitated in school settings.

[COV IMPACT: Stress exposure analysis among hospital staff in 2 hospitals in France during the COVID-19 pandemic]. / COV IMPACT : analyse des différents facteurs de stress du personnel hospitalier dans 2 centres hospitaliers en France lors de la pandémie COVID-19.

The COVID-19 pandemic has swept through our hospitals which have had to adapt as a matter of urgency. We are aware that a health crisis of this magnitude is likely to generate mental disorders particularly affecting exposed healthcare workers. Being so brutal and global, this one-of the kind pandemic has been impacting the staff in their professional sphere but also within their private circle. The COV IMPACT study is an early assessment survey conducted for 2 weeks in May 2020, of the perception by all hospital workers of the changes induced in their professional activity by the pandemic. The study was carried out by a survey sent to the hospital staff of Béziers and Montfermeil. The readjusted working conditions were source of increased physical fatigue for 62 % of the respondents. Moral exhaustion was reported by 36 %. It was related to the stress of contracting the infection (72 %) but above all of transmitting it to relatives (89 %) with a broad perception of a vital risk (41 %). This stress affected all socio-professional categories (CSP) and was independent of exposure to COVID. Change in organisation, lack of information and protective gear and equipment were major factors of insecurity at the start of the epidemic. Work on supportive measures is necessary. It should focus on the spread of information, particularly towards the youngest, as well as bringing more psychological support and a larger amount of medical equipment, beyond healthcare workers and the COVID sectors.

Fluoroscopic versus laparoscopic implantation of peritoneal dialysis catheters: a retrospective cohort study.

PURPOSE: A previous clinical trial showed that radiologic insertion of first peritoneal dialysis (PD) catheters by modified Seldinger technique is noninferior to laparoscopic surgery in patients at low risk in a clinical trial setting. The present cohort study was performed to confirm clinical effectiveness of radiologic insertion in everyday practice, including insertion in patients with expanded eligibility criteria and by fellows in training. MATERIALS AND METHODS: Between 2004 and 2009, 286 PD catheters were inserted in 249 patients, 133 with fluoroscopic guidance in the radiology department and 153 by laparoscopic surgery. Survival analyses were performed with the primary outcome of complication-free catheter survival and secondary outcomes of overall catheter survival and patient survival. Outcomes were assessed at last follow-up, as long as 365 days after PD catheter insertion. RESULTS: In the radiologic group, unadjusted 365-day complication-free catheter, overall catheter, and patient survival rates were 22.6%, 81.2%, and 82.7%, respectively, compared with 22.9% (P = .52), 76.5% (P = .4), and 92.8% (P = .01), respectively, in the laparoscopic group. Frequencies of individual complications were similar between groups. Adjusting for patient age, comorbidity, and previous PD catheter, the hazard ratio (HR) for catheter complications by radiologic versus laparoscopic insertion is 0.90 (95% confidence interval [CI], 0.62-1.31); the HR for overall catheter survival is 1.25 (95% CI, 0.59-2.65); and that for death is 2.47 (95% CI, 0.84-7.3). CONCLUSIONS: Radiologic PD catheter insertion is a clinically effective alternative to laparoscopic surgery, although there was poorer long-term survival with radiologic catheter placement, possibly because of preferential selection of radiologic insertion for more frail patients.

Association between antimicrobial locks for hemodialysis central venous catheters and antibiotic resistance.

Antimicrobial locks (AMLs) are effective in preventing catheter-associated bloodstream infections (CABSI) in hemodialysis (HD) patients, but may increase antibiotic resistance. In our center, gentamicin-heparin locks have been used for all HD central venous catheters since July 1, 2004. We previously reported a significant reduction in CABSI rates, but a short-term trend to increased gentamicin resistance among coagulase-negative staphylococci (CNS). We present a further 3-year follow-up study of bacterial resistance in our dialysis center. We examined the susceptibility of bacterial isolates from CABSI from July 1, 2006 to July 31, 2009, restricting analyses to CNS, gram-negative bacilli, and Staphylococcus aureus. We compared the frequency of gentamicin resistance in these isolates between four groups: CABSI in HD patients, non-CABSI in HD patients, peritonitis in peritoneal dialysis (PD) patients, and bloodstream infection in the non-end-stage kidney failure general population. For CNS isolates, the frequency of gentamicin resistance was similar between the CABSI and PD peritonitis groups, but higher in both groups than the general population. The pattern was similar for S. aureus although the differences were of borderline statistical significance. The frequency of gentamicin resistance among gram-negative bacilli isolates did not differ between groups. Gentamicin resistance was more common than expected in CNS and possibly S. aureus isolates from CABSI, although this resistance may be part of a generally higher frequency of antibiotic resistance in the dialysis population, rather than a direct result of AML use. AMLs remain a valuable clinical tool although surveillance is needed to ensure that benefits continue to outweigh risks.

Effect of antimicrobial locks for tunneled hemodialysis catheters on bloodstream infection and bacterial resistance: a quality improvement report.

BACKGROUND: Catheter-restricted antimicrobial lock (AML) use reduces catheter-associated bloodstream infection (CA-BSI) in clinical trial settings, but may not be as effective in clinical settings and may increase bacterial resistance. DESIGN: Quality improvement report analyzed using a cross-sectional time series (unbalanced panel) design. SETTING & PARTICIPANTS: The study cohort comprised all prevalent adults treated with hemodialysis through a tunneled catheter for any, but not necessarily all, of the time from January 1, 2003, to June 30, 2006, in Manukau City, New Zealand (135,346 catheter-days, 404 tunneled catheters, 320 patients). QUALITY IMPROVEMENT PLAN: Catheter-restricted AMLs (heparin plus gentamicin) for all tunneled catheters from July 1, 2004. MEASURES: Repeated observations of CA-BSI, hospitalization, tunneled catheter removal, and death from CA-BSI analyzed by using generalized estimating equations with a single level of clustering for each tunneled catheter and patterns of bacterial resistance analyzed by using simple descriptive statistics. RESULTS: AML use was associated with reductions in rates of CA-BSI and hospitalization for CA-BSI by 52% and 69% for patients with tunneled catheters locked continuously with AMLs since their insertion compared with those with tunneled catheters that were not, respectively. AML exposure also was associated with a trend to increased gentamicin resistance amongst coagulase-negative staphylococci isolates, a pattern similar to that observed for BSIs in our general hemodialysis population in which tunneled catheters were not the source of BSI, but different from that in the general non-end-stage renal disease population in the region. LIMITATIONS: This is an uncontrolled observational study and cannot prove causality. The follow-up period of 18 months is longer than for other studies, but still too short to definitely answer whether AML use drives bacterial resistance. CONCLUSIONS: A change to use of AMLs may improve clinical outcomes; however, additional study of associated bacterial resistance is needed before AML use becomes standard care.

Ubiquitylated Tax targets and binds the IKK signalosome at the centrosome.

Constitutive activation of the NF-kappaB pathway by the Tax oncoprotein plays a crucial role in the proliferation and transformation of HTLV-I infected T lymphocytes. We have previously shown that Tax ubiquitylation on C-terminal lysines is critical for binding of Tax to IkappaB kinase (IKK) and its subsequent activation. Here, we report that ubiquitylated Tax is not associated with active cytosolic IKK subunits, but binds endogenous IKK-alpha, -beta, -gamma, targeting them to the centrosome. K63-ubiquitylated Tax colocalizes at the centrosome with IKK-gamma, while K48-ubiquitylated Tax is stabilized upon proteasome inhibition. Altogether, these results support a model in which K63-ubiquitylated Tax activates IKK in a centrosome-associated signalosome, leading to the production of Tax-free active cytoplasmic IKK. These observations highlight an unsuspected link between Tax-induced IKK activation and the centrosome.

In situ surface oxidation study of a planar Co/SiO2/Si(100) model catalyst with nanosized cobalt crystallites under model Fischer-Tropsch synthesis conditions.

The oxidation of nanosized metallic cobalt to cobalt oxide during Fischer-Tropsch synthesis (FTS) has long been postulated as a major deactivation mechanism. In this study a planar Co/SiO(2)/Si(100) model catalyst with well-defined cobalt crystallites, close to the threshold value reported for oxidation in the literature (4-10 nm), was prepared by the spin coating method. The planar Co/SiO(2)/Si(100) model catalyst was characterized with atomic force microscopy, X-ray photoelectron spectroscopy, and Rutherford backscattering. The surface oxidation behavior of the nanosized metallic cobalt crystallites of 4-5 nm was studied using in situ near-edge X-ray absorption fine structure under model FTS conditions, i.e., H(2)/H(2)O = 1, P(Total) = 0.4 mbar, and 150-450 degrees C. No surface oxidation of metallic cobalt was observed under these model FTS conditions over a wide temperature range, i.e., 150-400 degrees C.

[Foamy virus, an original retroviral model]. / Les virus foamy, un modèle rétroviral original.

Foamy viruses (FVs) or spumaviruses are complex retroviruses isolated in several mammal species like cats, cattle and horses. Highly prevalent in non-human primates they are not naturally present in humans, although several cases of simian-to-human transmissions have been described. Interestingly, the replication strategy of FVs differs in many aspects from that of other retroviruses, presenting features that are closely related to pararetroviruses, exemplified by the hepatitis B virus (HBV), but also characteristics that are closely related to yeast retrotransposons leding to the creation of the distinct Spumaretrovirina subfamily.

[Insights into a new weapon against cancer: oncolytic viruses]. / Une nouvelle arme contre le cancer : bilan sur les virus oncolytiques.

Within the framework of the fight against cancer, oncolytic viruses inducing the specific death of represent tumour cells, a new therapeutic approach. If some viruses such as the reovirus, the parvovirus or the vesicular stomatitis virus are naturally oncotropic, most of viruses assessed for their property to specifically lyse cancer cells are genetically modified. Mostly, these modifications consist in deleting genes which are necessary for replication in normal cells but dispensable in a neoplasic context. Thus, the adenovirus Onyx-015 or the herpes virus G207 are already prone to clinical studies. However, efficiency of these modified viruses is limited by the host's immune system. Moreover, these modified agents derived from their disease-induced wild-type counterparts could potentially evolved in vivo and cause unexpected adverse effects. Therefore, future research will focus on generating safer and tolerated viral tools. In that context, a better knowledge of the biology and the bio-distribution of these viruses is required.

Non-primate foamy viruses.

Foamy viruses (PFVs), also called spumaviruses, are complex retroviruses inducing a characteristic cytopathic effect in cell culture, leading rapidly to cell lysis. These viruses have been isolated mostly in non-human primates, but three non primate PFVs were characterized, namely the bovine foamy virus, the feline foamy virus and more recently the equine foamy virus. In their hosts, PFVs seem to be apathogenic, mirroring an efficient control of virus replication in vivo. Comparing the biology of the different virus isolates will certainly help to unravel the biology of these retroviruses.

PML mediates the interferon-induced antiviral state against a complex retrovirus via its association with the viral transactivator.

The promyelocytic leukaemia (PML) protein localizes in the nucleus both in the nucleoplasm and in matrix-associated multiprotein complexes known as nuclear bodies (NBs). The number and the intensity of PML NBs increase in response to interferon (IFN). Overexpression of PML affects the replication of vesicular stomatitis virus and influenza virus. However, PML has a less powerful antiviral activity against these viruses than the IFN mediator MxA. Here, we show that overexpression of PML, but not that of Mx1 or MxA, leads to a drastic decrease of a complex retrovirus, the human foamy virus (HFV), gene expression. PML represses HFV transcription by complexing the HFV transactivator, Tas, preventing its direct binding to viral DNA. This physical interaction requires the N-terminal region of Tas and the RING finger of PML, but does not necessitate PML localization in NBs. Finally, we show that IFN treatment inhibits HFV replication in wild-type but not in PML-/- cells. These findings point to a role for PML in transcriptional repression and suggest that PML could play a key role in mediating an IFN-induced antiviral state against a complex retrovirus.

Human foamy virus capsid formation requires an interaction domain in the N terminus of Gag.

Retroviral Gag expression is sufficient for capsid assembly, which occurs through interaction between distinct Gag domains. Human foamy virus (HFV) capsids assemble within the cytoplasm, although their budding, which mainly occurs in the endoplasmic reticulum, requires the presence of homologous Env. Yet little is known about the molecular basis of HFV Gag precursor assembly. Using fusions between HFV Gag and a nuclear reporter protein, we have identified a strong interaction domain in the N terminus of HFV Gag which is predicted to contain a conserved coiled-coil motif. Deletion within this region in an HFV provirus abolishes viral production through inhibition of capsid assembly.

Isolation and characterization of an equine foamy virus.

Foamy viruses (FVs) are complex retroviruses which have been isolated from different animal species including nonhuman primates, cattle, and cats. Here, we report the isolation and characterization of a new FV isolated from blood samples of horses. Similar to other FVs, the equine foamy virus (EFV) exhibits a highly characteristic ultrastructure and induces syncytium formation and subsequent cell lysis on a large number of cell lines. Molecular cloning of EFV reveals that the general organization is that of other known FVs, whereas sequence similarity with its bovine FV counterpart is only 40%. Interestingly, EFV buds exclusively from the plasma membrane and not from the endoplasmic reticulum (ER), as previously shown for other FVs. The absence of the ER retrieval dilysine motif in EFV Env is likely responsible for this unexpected sorting pathway.

[The retroviral spumaviruses: new data in retrovirology]. / Les rétrovirus spumeux ou spumavirus: nouvelles données en rétrovirologie.

Spumaviruses or foamy viruses belong to the Retroviridae family. Their genomic structure enables to classify them among the complex retroviruses like lentiviruses and the T leukemia viruses. These viruses, discovered 40 years ago, present a large cellular tropism and although highly lytic in vitro, they seem to be innocuous in vivo. However, recent fascinating findings on foamy viruses bring new important biological aspects of general interest for the field of retrovirology and show that these viruses are at the crossroads between retroviruses and pararetroviruses.

An evolutionarily conserved splice generates a secreted env-Bet fusion protein during human foamy virus infection.

Foamy viruses (spumaretroviruses) represent a retroviral genus which exhibits unusual features relating it to pararetroviruses. Previously, we reported the existence of a protein species harboring Env, Bel, and Bet epitopes in human foamy virus (HFV)-infected cells (M. L. Giron, F. Rozain, M. C. Debons-Guillemin, M. Canivet, J. Périès, and R. Emanoil-Ravier, J. Virol. 67:3596-3600, 1993). Here, we identify this protein as a 160-kDa Env-Bet fusion glycoprotein (gp160) translated from an mRNA species harboring a highly conserved splice site which deletes the membrane anchor domain of Env and fuses the env open reading frame with that of bel1/bet. While gp160 and Bet proteins were both secreted into the supernatant, only Bet was taken up by recipient cells. Since Bet plays a key role in the switch from lytic to chronic infection, secretion of Bet and gp160, together with cellular uptake of Bet, could be highly relevant for both immune response and development of HFV infection in vivo.

Study of human foamy virus proviral integration in chronically infected murine cells.

This report describes integration sites of human foamy virus (HFV) in chronically infected BALB/c murine cells that we isolated by inverse PCR and characterized. We show that integration of HFV proviral genome mainly occurs in highly repetitive and/or transcriptionally active regions and leads to the formation of a 4-bp cellular direct repeat sequence at each provirus extremity. As non-random deletions were previously described in the HFV be/1 transactivator gene as well as in the long terminal repeats (LTRs), these regions were verified in integrated HFV. The analysis reveals that, in the studied chronic state, the defective interfering virus (delta HFV) is the main integrated proviral form and is always associated with a small LTR. Our results show that HFV can use a classic retroviral integration process to enter the host cell genome and stress the importance of delta HFV and the short LTRs in the establishment of the chronic state of infection.

The 3' untranslated region of the B19 parvovirus capsid protein mRNAs inhibits its own mRNA translation in nonpermissive cells.

Although parvoviruses are found throughout the animal kingdom, only the human pathogenic B19 virus has so far been shown to possess a limited host range, with erythroid progenitor cells as the main target cells supporting B19 propagation. The underlying mechanism of such erythroid tropism is still unexplained. Synthesis of the NS1 nonstructural protein occurs in permissive and nonpermissive cells, such as megakaryocytes, whereas synthesis of the VP1 and VP2 capsid proteins seems to be restricted to burst-forming units and CFU of erythroid cells. In nonpermissive cells, the NS1 protein is overexpressed and the NS1 RNAs are the predominant RNA species. However, the VP1 and VP2 proteins are not detectable, although the corresponding mRNAs are synthesized. Since all transcripts have part of the 5' untranslated region (5' UTR) in common but distinct 3' UTRs characterizing the nonstructural- and structural-protein mRNAs, we investigated, in transient transfection assays, the possible involvement of the 3' UTR of the capsid protein mRNAs in VP1 and VP2 protein synthesis in nonpermissive Cos cells. The results showed that (i) the 3' UTR of mRNAs coding for the capsid proteins repressed VP1 and VP2 protein synthesis, (ii) the 3' UTR did not affect nuclear export or mRNA stability, and (iii) mRNAs bearing the 3' UTR of the capsid protein mRNAs did not associate with ribosomes at all. Taken together, these results indicate that in nonpermissive cells, the 3' UTR of the capsid protein mRNAs represses capsid protein synthesis at the translational level by inhibiting ribosome loading.

Long-term persistent infection of domestic rabbits by the human foamy virus.

Human foamy virus (HFV) belongs to the spumaretrovirus group of the Retroviridae taxonomic family. Attempts to associate HFV or other foamy viruses to a specific pathology still remain unsuccessful. However, viral gene expression as well as tissue-specific tropism in an in vivo context remain poorly analyzed. To address this issue, we have infected domestic rabbits with a single dose of HFV and followed them at the biological and molecular levels for 5 years. No apparent pathology was detectable in the infected animals which have developed a strong immunological response against major viral proteins. We found that HFV provirus in blood cells and several organs persisted predominantly in its defective form, delta HFV, suggesting that in vivo viral persistence could be related to homologous interference as was recently shown in vitro. This animal model might be useful for studying the in vivo targets of HFV and should also be convenient for testing therapeutic effects of antiretroviral drugs.