Congenital cytomegalovirus (CMV) infection is the leading cause of sensoneurinal disability due to infectious congenital disease. The diagnosis of congenital CMV infection is based on the search of ...CMV in the urine within the first two weeks of life. Viral culture of urine is the gold standard. However, the PCR is highly sensitive and faster. It is becoming an alternative choice. The objective of this study is the validation of real-time PCR by Abbott RealTime CMV with m2000 for the detection of cytomegalovirus in urine. Repeatability, reproducibility, detection limit and inter-sample contamination were evaluated. Urine samples from patients (n=141) were collected and analyzed simultaneously in culture and PCR in order to assess the correlation of these two methods. The sensitivity and specificity of PCR were also calculated. The Abbott RealTime CMV PCR in urine is an automated and sensitive method (detection limit 200 UI/mL). Fidelity is very good (standard deviation of repeatability: 0.08 to 0.15 LogUI/mL and reproducibility 0.18 LogUI/mL). We can note a good correlation between culture and Abbott RealTime CMV PCR (kappa 96%). When considering rapid culture as reference, real-time PCR was highly sensitive (100%) and specific (98.2%). The real-time PCR by Abbott RealTime CMV with m2000 is optimal for CMV detection in urine.
Hepatitis C virus (HCV) infection in children is mainly acquired via maternal transmission. Our aim was to identify mother-to-child-transmission (MTC) risk factors, namely those associated with ...maternal virological characteristics and mode of delivery.
Women were included between October 1998 and September 2002 in six hospitals in Southern France on the basis of positive HCV serological status. Recorded data included maternal characteristics, circumstances of delivery and laboratory data concerning mother and child. Paediatric follow-up lasted 1 year, and 2 years for children with circulating HCV RNA.
A total of 214 mother-and-child pairs were analysed; 55 (26%) were HCV/HIV co-infected. The probability of HCV transmission was three-fold higher for HCV/HIV-co-infected women (P = 0.05). Twelve children were HCV RNA positive at 1 year of age (MTC = 5.6%); three became HCV RNA negative between 12 (M12) and 18 months of age (M18) and recovered normal alanine aminotransferase levels. Circulating HCV RNA was found in 137 (69%) mothers. Mothers of infected children all displayed HCV viraemia (MTC = 8.8%): six children were born of HCV/HIV-co-infected HCV RNA positive women (MTC = 13.6%) and six from HCV monoinfected women with positive HCV RNA (MTC = 6.5%). When maternal HCV RNA levels were below 6 log-IU/ml, the rate of transmission was significantly higher in the case of HCV/HIV co-infection (odds ratio = 8.3, 95% confidence interval, 1.4-47.5) P = 0.01. This association did not, however, exist for HCV RNA-positive mothers with levels of at least 6 log-IU/ml. Rate of transmission did not differ significantly between children born by vaginal delivery or caesarean section after membrane rupture and those born by elective caesarean section independently of HIV status.
Routine use of the automated chemiluminescent microparticle immunoassay Abbott ARCHITECT
® anti-HBc for diagnosis of hepatitis B is limited in case of borderline reactive sera with low signal close ...to the cut-off index. In order to determine the significance of anti-HBc detection when borderline reactivity occurs using the ARCHITECT
® anti-HBc assay, a comparative study was designed. 3540 serum samples collected over a 2-month period in the hospital of Nice were examined for markers of HBV infection (HBsAg, anti-HBs and anti-HBc). One hundred seven samples with sufficient volume and with borderline reactivity by the ARCHITECT
® assay were tested by two other anti-HBc assays, a microparticle enzyme immunoassay (MEIA, AxSYM
® Core™, Abbott Laboratories, IL, USA) and an enzyme linked fluorescent assay (ELFA, VIDAS
® Anti-HBc Total II, bioMérieux, Lyon, France). Only 46 samples were confirmed by the AxSYM
® and the VIDAS
® assays. Additional serological information linked to patient history showed that the remaining samples (61) were false positives (11), had low titer of anti-HBc antibodies (13), or were inconclusive (37). This comparative study highlighted the existence of a grey zone around the cut-off index. Confirmative results through a different immunoassay are needed to confirm the diagnosis of HBV on borderline reactive sera using the ARCHITECT
® anti-HBc assay.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We previously isolated human papillomavirus 83 (HPV83m) from a cervical smear. Sequence analysis of E6 and E7 proteins highlighted five mutations located in the second putative zinc-finger region of ...E6 (E6m), an important domain for protein-protein or protein-DNA interactions. Here, we show that E6m of HPV83m can trigger human primary cell proliferation and anchorage-independent growth properties, similarly to E6 of HPV16, a high-risk HPV (HR-HPV). Interestingly, we demonstrate that, in contrast to E6 of HPV16, E6m corrupts neither p53 stability nor telomerase activity, but acts as a specific modulator of the transcriptional machinery. By studying E6m reversion mutants, we confirmed the importance of the second zinc-finger domain in triggering the observed upregulation of cell growth and of the transcriptional machinery. Reversion of these mutations in E6m (to yield strain E6r) fully abolished the oncogenic potential of E6m, transforming the phenotype of E6 from a high-risk to a low-risk phenotype. Importantly, our data define the importance of a cluster of mutations in the second zinc finger of E6m in increasing the oncogenic potential of HPV83.
AIM: To evaluate virological response to telaprevir or boceprevir in combination with pegylated interferon and ribavirin and resistance mutations to NS3/4A inhibitors in hepatitis C virus-human ...immunodeficiency virus(HCV-HIV) coinfected patients in a real life setting. METHODS: Patients with HCV genotype 1-HIV coinfection followed in Nice University Hospital internal medicine and infectious diseases departments who initiated treatment including pegylated interferon and ribavirin(Peg IFN/RBV) + telaprevir or boceprevir, according to standard treatment protocols, between August 2011 and October 2013 entered this observational study. Patient data were extracted from an electronic database(Nadis?). Liver fibrosis was measured by elastometry(Fibroscan?) with the following cut-off values: F0-F1: < 7.1 k Pa, F2: 7.1-9.5 k Pa, F3: 9.5-14.5 k Pa, F4: ≥ 14.5 k Pa. The proportion of patients with sustained virological response(SVR) twelve weeks after completing treatment, frequency and type of adverse events, and NS3/4A protease inhibitor mutations were described. RESULTS: Forty-one patients were included: 13(31.7%) patients were HCV-treatment na?ve, 22(53.7%) had advanced liver fibrosis or cirrhosis(Fibroscan stage F3 and F4); none had decompensated cirrhosis or hepatocellular carcinoma; all were receiving antiretroviral treatment, consisting for most them(83%) in either a nucleoside reverse-transcriptase inhibitor/protease inhibitor or/integrase inhibitor combination; all patients had undetectable HIV-RNA. One patient was lost to follow-up. SVR was achieved by 52.5% of patients. Five patients experienced virological failure during treatment and four relapsed. Seven discontinued treatment due to adverse events. Main adverse events included severe anemia(88%) and rash(25%). NS3/4A protease mutations were analyzed at baseline and at the time of virological failure in the 9 patients experiencing non-response, breakthrough or relapse. No baseline resistance mutation could predict resistance to HCV protease inhibitor-based treatment. CONCLUSION: Telaprevir and boceprevir retain their place among potential treatment strategies in HIVHCV coinfected patients including those with advanced compensated liver disease and who failed previous Peg IFN/RBV therapy.
Background
A notable increase in severe cases of COVID-19, with significant hospitalizations due to the emergence and spread of JN.1 was observed worldwide in late 2023 and early 2024. However, no ...clinical data are available regarding critically-ill JN.1 COVID-19 infected patients.
Methods
The current study is a substudy of the SEVARVIR prospective multicenter observational cohort study. Patients admitted to any of the 40 participating ICUs between November 17, 2022, and January 22, 2024, were eligible for inclusion in the SEVARVIR cohort study (NCT05162508) if they met the following inclusion criteria: age ≥ 18 years, SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR) in nasopharyngeal swab samples, ICU admission for acute respiratory failure. The primary clinical endpoint of the study was day-28 mortality. Evaluation of the association between day-28 mortality and sublineage group was conducted by performing an exploratory multivariable logistic regression model, after systematically adjusting for predefined prognostic factors previously shown to be important confounders (i.e. obesity, immunosuppression, age and SOFA score) computing odds ratios (OR) along with their corresponding 95% confidence intervals (95% CI).
Results
During the study period (November 2022–January 2024) 56 JN.1- and 126 XBB-infected patients were prospectively enrolled in 40 French intensive care units. JN.1-infected patients were more likely to be obese (35.7% vs 20.8%; p = 0.033) and less frequently immunosuppressed than others (20.4% vs 41.4%; p = 0.010). JN.1-infected patients required invasive mechanical ventilation support in 29.1%, 87.5% of them received dexamethasone, 14.5% tocilizumab and none received monoclonal antibodies. Only one JN-1 infected patient (1.8%) required extracorporeal membrane oxygenation support during ICU stay (vs 0/126 in the XBB group; p = 0.30). Day-28 mortality of JN.1-infected patients was 14.6%, not significantly different from that of XBB-infected patients (22.0%; p = 0.28). In univariable logistic regression analysis and in multivariable analysis adjusting for confounders defined a priori, we found no statistically significant association between JN.1 infection and day-28 mortality (adjusted OR 1.06 95% CI (0.17;1.42); p = 0.19). There was no significant between group difference regarding duration of stay in the ICU (6.0 3.5;11.0 vs 7.0 4.0;14.0 days; p = 0.21).
Conclusions
Critically-ill patients with Omicron JN.1 infection showed a different clinical phenotype than patients infected with the earlier XBB sublineage, including more frequent obesity and less immunosuppression. Compared with XBB, JN.1 infection was not associated with higher day-28 mortality.
Background
During the first COVID-19 pandemic wave, COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in up to 11–28% of critically ill COVID-19 patients and associated with ...increased mortality. As new SARS-CoV-2 variants emerged, the characteristics of critically ill COVID-19 patients have evolved, particularly in the era of Omicron. The purpose of this study is to investigate the characteristics of CAPA in the era of new variants.
Methods
This is a prospective multicenter observational cohort study conducted in France in 36 participating intensive care units (ICU), between December 7th, 2021 and April 26th 2023. Diagnosis criteria of CAPA relied on European Confederation of Medical Mycology (ECMM)/International Society for Human & Animal Mycology (ISHAM) consensus criteria.
Results
566 patients were included over the study period. The prevalence of CAPA was 5.1% 95% CI 3.4–7.3, and rose to 9.1% among patients who required invasive mechanical ventilation (IMV). Univariable analysis showed that CAPA patients were more frequently immunosuppressed and required more frequently IMV support, vasopressors and renal replacement therapy during ICU stay than non-CAPA patients. SAPS II score at ICU admission, immunosuppression, and a SARS-CoV-2 Delta variant were independently associated with CAPA in multivariable logistic regression analysis. Although CAPA was not significantly associated with day-28 mortality, patients with CAPA experienced a longer duration of mechanical ventilation and ICU stay.
Conclusion
This study contributes valuable insights into the prevalence, characteristics, and outcomes of CAPA in the era of Delta and Omicron variants. We report a lower prevalence of CAPA (5.1%) among critically-ill COVID-19 patients than previously reported, mainly affecting intubated-patients. Duration of mechanical ventilation and ICU stay were significantly longer in CAPA patients.
Persistent cervical high-risk human papillomavirus (HPV) infection is correlated with an increased risk of developing a high-grade cervical intraepithelial lesion. A two-step method was developed for ...detection and genotyping of high-risk HPV. DNA was firstly amplified by asymmetrical PCR in the presence of Cy3-labelled primers and dUTP. Labelled DNA was then genotyped using DNA microarray hybridization. The current study evaluated the technical efficacy of laboratory-designed HPV DNA microarrays for high-risk HPV genotyping on 57 malignant and non-malignant cervical smears. The approach was evaluated for a broad range of cytological samples: high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL) and atypical squamous cells of high-grade (ASC-H). High-risk HPV was also detected in six atypical squamous cells of undetermined significance (ASC-US) samples; among them only one cervical specimen was found uninfected, associated with no histological lesion. The HPV oligonucleotide DNA microarray genotyping detected 36 infections with a single high-risk HPV type and 5 multiple infections with several high-risk types.Taken together, these results demonstrate the sensitivity and specificity of the HPV DNA microarray approach. This approach could improve clinical management of patients with cervical cytological abnormalities.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Sialylated glycoconjugates mediate several key lymphocyte functions. We previously reported that hyposialylation occurred in latently HIV‐1‐infected CEM T cells, despite the fully preserved catalytic ...activity of several sialyltransferases. We show now that these cells are affected by a down‐regulation of UDP‐N‐acetylglucosamine 2‐epimerase/N‐acetylmannosamine kinase (GNE), which leads to a dramatic decrease in the synthesis of CMP‐sialic acid, the donor substrate of all sialyltransferases. The GNE gene promoter was found to be located in a CpG island with several regulatory motifs CREB, SP1, and AP‐2. De novo hypermethylation of this promoter was observed in HIV‐1‐infected CEM cells. This phenomenon might explain some immunological disorders that persist in infected individuals despite long‐term therapeutically controlled viral replication. Indeed, an overall decrease in sialic acid engraftment can affect glycoproteins, notably those in which the sialylation status is crucial to ensure homing, recirculation, and survival of lymphocytes.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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