Enteroviruses are the most frequent cause of acute meningitis and are seen increasingly in sepsis-like disease and fever without source in the paediatric population. Detection of enterovirus in ...cerebrospinal fluid (CSF) specimens by PCR is the gold standard diagnostic test. Our aim was to assess a method of detecting enterovirus in blood specimens by PCR.
We did a prospective, multicentre, observational study at 35 French paediatric and emergency departments in 16 hospitals. We recruited newborn babies (aged ≤28 days) and infants (aged >28 days to ≤2 years) with fever without source, sepsis-like disease, or suspected meningitis, and children (aged >2 years to ≤16 years) with suspected meningitis, who were admitted to a participating hospital. We used a standardised form to obtain demographic, clinical, and laboratory data, which were anonymised. Enterovirus PCR testing was done in blood and CSF specimens.
Between June 1, 2015, and Oct 31, 2015, and between June 1, 2016, and Oct 31, 2016, we enrolled 822 patients, of whom 672 had enterovirus PCR testing done in blood and CSF specimens. Enterovirus was detected in 317 (47%) patients in either blood or CSF, or both (71 newborn babies, 83 infants, and 163 children). Detection of enterovirus was more frequent in blood samples than in CSF specimens of newborn babies (70 99% of 71 vs 62 87% of 71; p=0·011) and infants (76 92% of 83 vs 62 75% of 83; p=0·008), and was less frequent in blood samples than in CSF specimens of children (90 55% of 163 vs 148 91% of 163; p<0·0001). Detection of enterovirus was more frequent in blood samples than in CSF specimens of infants aged 2 years or younger with fever without source (55 100% of 55 vs 41 75% of 55; p=0·0002) or with sepsis-like disease (16 100% of 16 vs nine 56% of 16; p=0·008). Detection of enterovirus was less frequent in blood than in CSF of patients with suspected meningitis (165 67% of 246 vs 222 90% of 246; p<0·0001).
Testing for enterovirus in blood by PCR should be an integral part of clinical practice guidelines for infants aged 2 years or younger. This testing could decrease the length of hospital stay and reduce exposure to antibiotics for low-risk patients admitted to the emergency department with febrile illness.
University Hospital Clermont-Ferrand.
After 1 year, among 236 hospital staff members (HSMs) tested positive for SARS-CoV-2, we observed five cases of suspected reinfection in our teaching hospital in France. No probable reinfection was ...retained considering PCR Cycle Threshold and clinical context. Focus should concern COVID-free HSMs still not vaccinated rather than the ones previously infected.
Human respiratory syncytial virus (RSV) is a globally prevalent negative-stranded RNA virus, which can cause life-threatening respiratory infections in young children, elderly people and ...immunocompromised patients. Its transcription termination factor M2-1 plays an essential role in viral transcription, but the mechanisms underpinning its function are still unclear. We investigated the cellular interactome of M2-1 using green fluorescent protein (GFP)-trap immunoprecipitation on RSV infected cells coupled with mass spectrometry analysis. We identified 137 potential cellular partners of M2-1, among which many proteins associated with mRNA metabolism, and particularly mRNA maturation, translation and stabilization. Among these, the cytoplasmic polyA-binding protein 1 (PABPC1), a candidate with a major role in both translation and mRNA stabilization, was confirmed to interact with M2-1 using protein complementation assay and specific immunoprecipitation. PABPC1 was also shown to colocalize with M2-1 from its accumulation in inclusion bodies associated granules (IBAGs) to its liberation in the cytoplasm. Altogether, these results strongly suggest that M2-1 interacts with viral mRNA and mRNA metabolism factors from transcription to translation, and imply that M2-1 may have an additional role in the fate of viral mRNA downstream of transcription.
After one year, among 236 hospital staff members (HSMs) tested positive for SARS-CoV-2, we observed 5 cases of suspected reinfection in our teaching hospital in France. No probable reinfection was ...retained considering PCR Cycle Threshold and clinical context. Focus should concern COVID-free HSMs still not vaccinated rather than the ones previously infected.
Background. Little is known about the epidemiology and the prognostic factors of Guillain—Barré syndrome (GBS) following primary infection with cytomegalovirus (CMV-GBS). Methods. We prospectively ...followed up 506 patients with cases of GBS who were admitted to our center from 1996 through 2006. We diagnosed 63 (12.4%) CMV-GBS cases by immunoglobulin (Ig) M detection and IgG avidity. Plasma CMV DNA was detected at hospital admission. Patient subgroups were compared using Fisher's exact test and the Wilcoxon rank-sum test. Temporal variations were analyzed with time series methods. Results. Patients with CMV-GBS were mostly young (median age, 32 years; sex ratio, 0.85), but we also identified a subpopulation of patients consisting of women aged >50 years. Sensory defects (in 72% of cases) and facial palsy (49%) were frequent, and test results positive for CMV DNA in plasma at hospital admission (found in 62% of cases) tended to be associated with objective sensory defect (P = .052). The main factors associated with long-term neurological sequelae (21%) were older age (P <.001) and assisted ventilation during hospitalization (P = .005). The number of CMV-GBS cases decreased between 1996 and 2006 (P = .019) and displayed an annual periodicity between the months of July and October. The incidence of CMV-GBS was estimated to be between 0.6 and 2.2 cases per 1000 cases of primary CMV infection (versus 0.25 to 0.65 cases per 1000 cases of Campylobacter jejuni infection). Conclusions. This study provides new insights about the epidemiology of CMV-GBS and shows that the risk of developing GBS is similar following primary CMV infection or C. jejuni infection. Our results also suggest a direct or indirect involvement of viral replication in the neuropathological processes of CMV-GBS.
The impact of the COVID-19 pandemic on bloodstream infections (BSIs) due to Streptococcus pneumoniae and Streptococcus pyogenes was assessed in 25 university hospitals of Paris. Monthly BSIs ...incidence rates that appeared stable in 2018 and 2019, decreased for the 2 pathogens during the 2 COVID-19 lockdown periods of 2020. Containment policies, including social distancing, masking and hand hygiene strengthening in both community and hospital settings are likely to reduce BSIs due to these pathogens.
Indicators for comparing and understanding differences in antimicrobial resistance (AMR) and healthcare-associated infections (HAIs) for benchmarking are essential to identify priorities for ...hospitals.
This study measured the incidence of hospital-acquired or resistant Gram-negative bacilli bloodstream infections (GNB-BSIs) in a large public healthcare consortium in the Parisian region of France.
Within each hospital, there was a strong positive correlation between the incidence of GNB-BSIs due to resistant GNB and the incidence of hospital-acquired GNB-BSIs. Two scores measuring AMR and HAI rates by combining different GNB-BSI incidence rates were developed as indicators. These scores were highly variable within the hospital consortium. On multi-variate analysis, AMR and HAI scores were significantly associated with the proportion of surgical beds, staff absenteeism and the consumption of alcohol-based hand rub, with the latter two characteristics being amenable to interventions. Carbapenem use was also linked to AMR, but this may be because carbapenems are the preferred drug for treating resistant infections.
These results shed light on the incidence of HAIs and AMR in the study hospitals, and suggest possibilities for targeted interventions at healthcare facility level.
Objective
To develop a population pharmacokinetic model for lopinavir boosted by ritonavir in coronavirus disease 2019 (Covid-19) patients.
Methods
Concentrations of lopinavir/ritonavir were assayed ...by an accredited LC-MS/MS method. The population pharmacokinetics of lopinavir was described using non-linear mixed-effects modeling (NONMEM version 7.4). After determination of the base model that better described the data set, the influence of covariates (age, body weight, height, body mass index (BMI), gender, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), C reactive protein (CRP), and trough ritonavir concentrations) was tested on the model.
Results
From 13 hospitalized patients (4 females, 9 males, age = 64 ± 16 years), 70 lopinavir/ritonavir plasma concentrations were available for analysis. The data were best described by a one-compartment model with a first-order input (KA). Among the covariates tested on the PK parameters, only the ritonavir trough concentrations had a significant effect on CL/F and improved the fit. Model-based simulations with the final parameter estimates under a regimen lopinavir/ritonavir 400/100 mg b.i.d. showed a high variability with median concentration between 20 and 30 mg/L (
C
min
/
C
max
) and the 90% prediction intervals within the range 1–100 mg/L.
Conclusion
According to the estimated 50% effective concentration of lopinavir against SARS-CoV-2 virus in Vero E6 cells (16.7 mg/L), our model showed that at steady state, a dose of 400 mg b.i.d. led to 40% of patients below the minimum effective concentration while a dose of 1200 mg b.i.d. will reduce this proportion to 22%.
Background. In Western countries, the cause of 60% of all Guillain-Barré syndrome (GBS) cases remains unidentified. The number of cases of unidentified cause peaks in winter, and these cases are ...commonly preceded by respiratory tract infection or influenza-like illness. We investigated the triggering role of influenza virus infection. Methods. Of 405 patients with GBS who were admitted to a French reference center during 1996–2004, 234 had cases caused by an unidentified agent. We used time-series methods to study the correlation between the monthly incidence of such cases and influenza-like illnesses reported by the Sentinelles surveillance network. We analyzed anti-influenza antibodies using complement fixation testing and hemagglutination-inhibition assays. We studied etiological subgroups using Wilcoxon and Fisher's exact tests. Results. We found a positive association between the monthly incidence of GBS caused by an unidentified agent and reported influenza-like illnesses. Of 73 patients whose cases occurred during periods in which there was a possible link to influenza, 10 (13.7%) had serological evidence of recent influenza A, and 4 (5.5%) had serological evidence of influenza B. Eight of 10 influenza A—related cases occurred during “major” influenza seasons, and antibodies specific to the current epidemic strain were found in 9 cases. Most patients with influenza A—related cases were aged <65 years, and none had antiganglioside antibodies. Influenza-related cases differed both from Campylobacter jejuni—related cases, with regard to the lack of need for mechanical ventilation (P=.014), and from the cases caused by an unidentified agent, with regard to the presence of preceding influenza-like illness or respiratory tract infection (P=.015) and longer time from the infectious event to GBS onset (P=.04). Conclusions. Influenza viruses are infrequent triggering agents of GBS but may play a significant role during major influenza outbreaks. Influenza-related GBS displays specific features and is not associated with antiganglioside antibody response, which suggests the presence of underlying immune mechanisms.
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