In 2014, the United States (US) experienced a nationwide outbreak of enterovirus D68 (EV-D68) infection with 1,152 cases reported mainly in hospitalised children with severe asthma or bronchiolitis. ...Following the US alert, 11 laboratories of the French enterovirus (EV) surveillance network participated in an EV-D68 survey. A total of 6,229 respiratory samples, collected from 1 July to 31 December 2014, were screened for EV-D68 resulting in 212 EV-D68-positive samples. These 212 samples corresponded to 200 EV-D68 cases. The overall EV-D68 positivity rates among respiratory samples were of 5% (184/3,645) and 1.1% (28/2,584) in hospitalised children and adults respectively. The maximum weekly EV-D68 positivity rates were of 16.1% for children (n = 24/149; week 43) and 2.6% for adults (n = 3/115; week 42). Of 173 children with EV-D68 infection alone, the main symptoms were asthma (n = 83; 48.0%) and bronchiolitis (n = 37; 21.4%). One child developed acute flaccid paralysis (AFP) following EV-D68-associated pneumonia. Although there was no significant increase in severe respiratory tract infections reported to the French public health authorities, 10.7% (19/177) of the EV-D68 infected children and 14.3% (3/21) of the EV-D68 infected adults were hospitalised in intensive care units. Phylogenetic analysis of the viral protein 1 (VP1) sequences of 179 EV-D68 cases, revealed that 117 sequences (65.4%), including that of the case of AFP, belonged to the B2 variant of clade B viruses. Continuous surveillance of EV-D68 infections is warranted and could benefit from existing influenza-like illness and EV surveillance networks.
Abstract
Background
Successful 2-drug regimens (2DRs) for HIV were made possible by the availability of drugs combining potency and tolerability with a high genetic barrier to resistance. How these ...deal with resistance development/re-emergence, compared with 3DRs, is thus of paramount importance.
Materials and methods
A national survey including patients who were either naive or experienced with any 2DR or 3DR but failing integrase strand transfer inhibitor (INSTI)-containing regimens two consecutive plasma viral load (VL) values >50 copies/mL was conducted between 2014 and 2019. Genotypic resistance tests were interpreted with the v28 ANRS algorithm.
Results
Overall, 1104 patients failing any INSTI-containing regimen (2DRs, n = 207; 3DRs, n = 897) were analysed. Five hundred and seventy-seven (52.3%) patients were infected with a B subtype and 527 (47.3%) with non-B subtypes. Overall, 644 (58%) patients showed no known integrase resistance mutations at failure. In multivariate analysis, factors associated with the emergence of at least one integrase mutation were: high VL at failure (OR = 1.24 per 1 log10 copies/mL increase); non-B versus B subtype (OR = 1.75); low genotypic sensitivity score (GSS) (OR = 0.10 for GSS = 2 versus GSS = 0–0.5); and dolutegravir versus raltegravir (OR = 0.46). Although 3DRs versus 2DRs reached statistical significance in univariate analysis (OR = 0.59, P = 0.007), the variable is not retained in the final model.
Conclusions
This study is one of the largest studies characterizing integrase resistance in patients failing any INSTI-containing 2DR or 3DR in routine clinical care and reveals factors associated with emergence of integrase resistance that should be taken into consideration in clinical management. No difference was evidenced between patients receiving a 2DR or a 3DR.
BackgroundEnding the HIV pandemic must involve new tools to rapidly identify and control local outbreaks and prevent the emergence of recombinant strains with epidemiological advantages.AimThis ...observational study aimed to investigate in France a cluster of HIV-1 cases related to a new circulating recombinant form (CRF). The confirmation this CRF's novelty as well as measures to control its spread are presented.MethodsPhylogenetic analyses of HIV sequences routinely generated for drug resistance genotyping before 2018 in French laboratories were employed to detect the transmission chain. The CRF involved was characterised by almost full-length viral sequencing for six cases. Cases' clinical data were reviewed. Where possible, epidemiological information was collected with a questionnaire.ResultsThe transmission cluster comprised 49 cases, mostly diagnosed in 2016-2017 (n = 37). All were infected with a new CRF, CRF94_cpx. The molecular proximity of this CRF to X4 strains and the high median viraemia, exceeding 5.0 log
copies/mL, at diagnosis, even in chronic infection, raise concerns of enhanced virulence. Overall, 41 cases were diagnosed in the Ile-de-France region and 45 were men who have sex with men. Among 24 cases with available information, 20 reported finding partners through a geosocial networking app. Prevention activities in the area and population affected were undertaken.ConclusionWe advocate the systematic use of routinely generated HIV molecular data by a dedicated reactive network, to improve and accelerate targeted prevention interventions. Geosocial networking apps can play a role in the spread of outbreaks, but could also deliver local targeted preventive alerts.
From Service dhématologie – Greffe (MR, PdL, CF, VR, AD, EG, PR, GS); Laboratoire de virologie (SMJ, CS); Service de maladies infectieuses (JMM); Service de pneumologie (AB); INSERM U728 (GS), ...Paris, France
Correspondence: Prof. Gérard Socié, Hôpital Saint Louis, Service dHématologie, Greffe, 1 avenue Claude Vellefaux, 75475 Paris Cedex 10, France. E-mail: gerard.socie{at}paris7.jussieu.fr
We analyzed the factors and outcome of patients with disseminated adenovirus infection (dAdV) after allogeneic hematopoeitic stem cell transplantation (HSCT). Thirty patients with dAdV were identified among 620 allogeneic HSCT recipients. Primary diseases were leukemia (n=17), Fanconi anemia (n=12) or others (n=1). Source of stem cells was unrelated in 28 and related in 2 patients. The graft consisted of peripheral blood (n=3), bone marrow (n=12) and unrelated cord-blood (UCB, n=15). Risk factors for dAdV in unrelated HSCT recipients were previous Fanconi disease ( p =0.03) and GVHD ( p =0.02) in children, and cord blood source of stem cells ( p =0.029) and GVHD (0.024) in adults.
Key words: adenovirus infection, allogeneic hemetopoietic stem cell transplantation, risk factors.
Varicella-zoster virus (VZV) is, like other alphaherpes viruses, neurotropic. Of the admissions to hospital for varicella, 7.6-25% are due to neurologic manifestations. Most of the time, the ...concomitant skin lesions facilitate the diagnosis. The justification of qualitative PCR (polymerase chain reaction) for VZV DNA in cerebrospinal fluid in the management of these patients is not clear. The aim of this study was to evaluate the prognostic value of qualitative PCR for VZV DNA in cerebrospinal fluid and to assess its impact on patient management. We conducted a retrospective monocentric study in Versailles Hospital (France). It included every child admitted for neurologic manifestations associated with varicella and compared the patients with positive PCR for VZV DNA to those with a negative PCR in the cerebrospinal fluid. Seven patients with positive PCR and 16 patients with negative PCR were included. The median age of the children included was 3 years (range, 1.6-12 years) and 2 years (range, 0.6-5 years), respectively. In the positive PCR group, 86% of the children had fever on first examination and the average time between the onset of skin lesions and neurological signs was +1.28 days (range, -2 to +5 days). In comparison, in the negative PCR group, 81% of the children had fever and the average time delay was +1.75 days (-2 to +7 days). There was no significant difference in terms of length of hospitalization; 3 days (range, 0-6 days) and 3 days (range, 2-7 days), respectively. All patients discharged from our department went home. In addition, there was no significant difference between the two groups in terms of treatment with acyclovir; two children (28.5%) were treated in the positive PCR group versus four (25%) in the negative PCR group. Our study showed no prognostic value for qualitative PCR for VZV DNA in the cerebrospinal fluid of patients with neurologic manifestations of varicella. Therefore, its relevance can be questioned in clinical practice. However, in case of encephalitis and meningitis during primary infection with VZV, quantitative PCR for VZV DNA might have a prognostic value and therefore requires further study.
Human parechoviruses (HPeV), like their counterpart enteroviruses (EV), are associated with clinical manifestations ranging from asymptomatic disease to infections of the central nervous system. ...Newborn and young infants are particularly at risk for severe infection. In the last 5 years, the molecular diagnosis of HPeV infection in cerebrospinal fluid (CSF) and the identification of the associated HPeV type revealed the specific association between HPeV3 and meningitis or sepsis-like illness in neonates and infants. HPeV infection is not yet routinely diagnosed in clinical virology laboratories.
To determine the clinical, biological, and epidemiological characteristics of HPeV infections of patients hospitalized at the Centre Hospitalier de Versailles, France.
A total of 380 CSF samples originally referred to our laboratory for enterovirus testing between January 1st, 2007 and August 31st, 2011, were selected and retrospectively screened for the genome detection of HPeV. All HPeV detected were identified by amplification and sequencing of the complete 1D sequence encoding the VP1 protein.
The HPeV genome was detected in CSF samples from nine (2.8%) patients. All were young infants under 18 months of age (median, 30 days; age range, 8 days to 18 months). Fever was observed for all children and eight out of nine (89%) presented with irritability. No pleiocytosis and normal glucose and protein levels were observed. The mean duration of the hospital stay was 4 days (range, 2-7 days) and antibiotics were administered to five patients (55.6%). Yearly frequency of genome detection varied remarkably: 1.1% in 2007, 0% in 2008 and 2011, 2.9% in 2009 and 7.1% in 2010. All genotyped viruses were HPeV3.
This study confirmed the importance of the HPeV genome detection in CSF samples from patients presenting with sepsis-like illness or suspected infection of the central nervous system, particularly in children under 2 years of age. The introduction of the molecular diagnosis of HPeV infection broadens the panel of diagnosis of neonatal sepsis and central nervous system symptoms in young children. Rapid identification of HPeV by PCR could also contribute to shorter duration of both antibiotic use and hospital stay.
Febrile infants under 3 months of age are often treated with broad-spectrum intravenous antibiotics while awaiting culture results, to prevent mother-to-child bacterial infections. Human ...parechoviruses (HPeV) have recently been described as etiologic agents of meningitis and severe sepsis in neonates and young infants. They are rarely investigated and are therefore probably underestimated. They cause acute clinical symptoms that can incorrectly suggest a bacterial infection. In the present case, a 6-week-old infant infected with HPeV developed severe sepsis, complicated by hepatic cytolysis, meningitis, acute renal failure, and mild hemophagocytic lymphohistiocytosis. HPeV type 3 was found by routine specific RT-PCR in cerebrospinal fluid, stools, and plasma. The outcome was spontaneously favorable after 4 days. Early diagnosis of the HPeV infection by routine specific RT-PCR reduces unnecessary antibiotic use and extended hospitalization in febrile young infants.
Enteroviruses (EV) are a common cause of aseptic meningitis in children. Virological diagnosis of EV meningitis is currently based on the detection of the viral genome in the cerebrospinal fluid ...(CSF). This study attempted to determine the correlation and the temporality of the polymerase chain reaction (PCR) assay in serum and CSF and to evaluate the possibility of diagnosing EV infection only on the serum PCR. The EV genome was sought by RT real-time PCR (Smart Cycler EV Primer and Probe Set(®), Cepheid) in CSF and serum, collected at the same time, for all children who underwent a lumbar puncture for suspected meningitis, between 1 June and 31 July 2010 at the Versailles Hospital. Forty-four patients were included in the study. EV infection was documented for 22 of them. In 10 patients, the EV genome was detected in CSF only; in 3 patients in serum only, and in 9 patients in both. Among patients with acute EV neurological infection, viremic children were significantly younger (1.6 months versus 5.8 years; P<0.001). Viremia was detected when the serum was sampled within 30 h after the beginning of symptoms. These results confirm previous reports of early and transient viremia in young children. This preliminary study shows the limits and added value of EV PCR in serum. It suggests that in some children and under certain conditions (age >3 months, clinical and biological compatibility with a viral infection, no previous antibiotic therapy, time from symptom onset to blood sampling <30 h, PCR in serum analyzed within 3h), PCR in serum, when positive, is a possible alternative. Therefore, it may be possible to diagnose EV infection without performing a lumbar puncture in a limited number of young children (11.4% of our suspected cases). This study needs to be reinforced by a multicenter study with a broader panel of patients.
Le diagnostic des méningites à entérovirus (EV) repose actuellement sur la réaction de polymérisation en chaîne (PCR) dans le liquide céphalorachidien (LCR). L’objectif de cette étude était d’étudier ...la corrélation entre les PCR EV dans le sérum et le LCR. La PCR EV a été réalisée dans le LCR et le sérum, prélevés au même moment, chez tous les enfants ayant eu une ponction lombaire (PL) pour suspicion de méningite entre le 1er juin et le 31 juillet 2010. Quarante-quatre enfants ont été inclus et une infection à EV a été documentée chez 22 d’entre eux. Le génome a été détecté uniquement dans le LCR chez 10 enfants, dans le sérum chez 3 et dans les deux chez 9. Les enfants virémiques étaient significativement plus jeunes (1,6 mois versus 5,8ans, p<0,001). Cette virémie était précoce et transitoire, détectée uniquement lorsque le sérum avait été prélevé moins de 30h après le début des symptômes. Si elle avait été connue en temps réel, elle aurait pu permettre d’éviter la PL chez 5 enfants parmi les 44 suspects (11,4 %). Cette étude préliminaire souligne l’intérêt et les limites de la PCR EV dans le sérum. Positive, elle ne permettrait d’éviter qu’un nombre limité de PL sous certaines conditions : âge supérieur à 3 mois, signes cliniques et biologiques compatibles avec une infection virale, délai entre le début des symptômes et le prélèvement sanguin inférieur à 30h, absence d’antibiothérapie préalable, résultat rendu en 3h.
Enteroviruses (EV) are a common cause of aseptic meningitis in children. Virological diagnosis of EV meningitis is currently based on the detection of the viral genome in the cerebrospinal fluid (CSF). This study attempted to determine the correlation and the temporality of the polymerase chain reaction (PCR) assay in serum and CSF and to evaluate the possibility of diagnosing EV infection only on the serum PCR. The EV genome was sought by RT real-time PCR (Smart Cycler EV Primer and Probe Set®, Cepheid) in CSF and serum, collected at the same time, for all children who underwent a lumbar puncture for suspected meningitis, between 1 June and 31 July 2010 at the Versailles Hospital. Forty-four patients were included in the study. EV infection was documented for 22 of them. In 10 patients, the EV genome was detected in CSF only; in 3 patients in serum only, and in 9 patients in both. Among patients with acute EV neurological infection, viremic children were significantly younger (1.6months versus 5.8years; P<0.001). Viremia was detected when the serum was sampled within 30h after the beginning of symptoms. These results confirm previous reports of early and transient viremia in young children. This preliminary study shows the limits and added value of EV PCR in serum. It suggests that in some children and under certain conditions (age >3months, clinical and biological compatibility with a viral infection, no previous antibiotic therapy, time from symptom onset to blood sampling <30h, PCR in serum analyzed within 3h), PCR in serum, when positive, is a possible alternative. Therefore, it may be possible to diagnose EV infection without performing a lumbar puncture in a limited number of young children (11.4% of our suspected cases). This study needs to be reinforced by a multicenter study with a broader panel of patients.
Les parechovirus (HPeV), comme les entérovirus (HEV), peuvent être responsables de manifestations cliniques allant d’une fièvre non spécifique à des infections du système nerveux central, les ...nouveau-nés étant les plus à risque d’infections graves. Pourtant, la recherche du génome des HPeV n’est pas encore réalisée de façon courante dans les laboratoires de virologie clinique.
Préciser les caractéristiques cliniques et épidémiologiques des infections à HPeV au centre hospitalier de Versailles.
La recherche du génome des HPeV a été réalisée rétrospectivement par reverse transcription polymerase chain reaction (RT-PCR) dans 380 liquides céphalorachidiens (LCR) de patients, dont 256 enfants, ayant présenté une suspicion d’infection neuroméningée entre le 1er janvier 2007 et le 31 août 2011. L’identification des HPeV a été réalisée par génotypage.
Le génome des HPeV a été détecté dans le LCR de 9 (2,4 %) enfants âgés de moins de 2ans (médiane=30j, extrêmes : 8 j – 18 mois). Les signes cliniques les plus fréquemment observés étaient la fièvre (100 %) et une irritabilité (8/9, 89 %). Les analyses cytologiques et biochimiques du LCR étaient normales. Il s’agissait du type 3 pour les 6 enfants pour lesquels le génotypage a été possible.
Cette étude montre l’intérêt de la recherche du génome des HPeV dans le LCR des enfants de moins de 2ans présentant une suspicion d’infection neuroméningée. L’introduction du diagnostic rapide des infections à HPeV permet d’augmenter le champ diagnostique des causes d’infections neuroméningées chez le jeune enfant et d’améliorer ainsi leur prise en charge.
Human parechoviruses (HPeV), like their counterpart enteroviruses (EV), are associated with clinical manifestations ranging from asymptomatic disease to infections of the central nervous system. Newborn and young infants are particularly at risk for severe infection. In the last 5 years, the molecular diagnosis of HPeV infection in cerebrospinal fluid (CSF) and the identification of the associated HPeV type revealed the specific association between HPeV3 and meningitis or sepsis-like illness in neonates and infants. HPeV infection is not yet routinely diagnosed in clinical virology laboratories.
To determine the clinical, biological, and epidemiological characteristics of HPeV infections of patients hospitalized at the Centre Hospitalier de Versailles, France.
A total of 380 CSF samples originally referred to our laboratory for enterovirus testing between January 1st, 2007 and August 31st, 2011, were selected and retrospectively screened for the genome detection of HPeV. All HPeV detected were identified by amplification and sequencing of the complete 1D sequence encoding the VP1 protein.
The HPeV genome was detected in CSF samples from nine (2.8%) patients. All were young infants under 18 months of age (median, 30 days; age range, 8 days to 18 months). Fever was observed for all children and eight out of nine (89%) presented with irritability. No pleiocytosis and normal glucose and protein levels were observed. The mean duration of the hospital stay was 4 days (range, 2–7 days) and antibiotics were administered to five patients (55.6%). Yearly frequency of genome detection varied remarkably: 1.1% in 2007, 0% in 2008 and 2011, 2.9% in 2009 and 7.1% in 2010. All genotyped viruses were HPeV3.
This study confirmed the importance of the HPeV genome detection in CSF samples from patients presenting with sepsis-like illness or suspected infection of the central nervous system, particularly in children under 2 years of age. The introduction of the molecular diagnosis of HPeV infection broadens the panel of diagnosis of neonatal sepsis and central nervous system symptoms in young children. Rapid identification of HPeV by PCR could also contribute to shorter duration of both antibiotic use and hospital stay.
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