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Background: Human metapneumovirus (hMPV) is one of the leading respiratory viruses. This prospective observational study aimed to describe the clinical features and the outcomes of hMPV-associated lower respiratory tract infections in adult inpatients., Methods: Consecutive adult patients admitted to one of the 31 participating centers with an acute lower respiratory tract infection and a respiratory multiplex PCR positive for hMPV were included. A primary composite end point of complicated course (hospital death and/or the need for invasive mechanical ventilation) was used., Results: Between March 2018 and May 2019, 208 patients were included. The median age was 74 [62-84] years. Ninety-seven (47 %) patients were men, 187 (90 %) had at least one coexisting illness, and 67 (31 %) were immunocompromised. Median time between first symptoms and hospital admission was 3 [2-7] days. The two most frequent symptoms were dyspnea (86 %) and cough (85 %). The three most frequent clinical diagnoses were pneumonia (42 %), acute bronchitis (20 %) and acute exacerbation of chronic obstructive pulmonary disease (16 %). Among the 52 (25 %) patients who had a lung CT-scan, the most frequent abnormality was ground glass opacity (41 %). While over four-fifths of patients (81 %) received empirical antibiotic therapy, a bacterial coinfection was diagnosed in 61 (29 %) patients. Mixed flora (16 %) and enterobacteria (5 %) were the predominant documentations. The composite criterion of complicated course was assessable in 202 (97 %) patients, and present in 37 (18 %) of them. In the subpopulation of pneumonia patients (42 %), we observed a more complicated course in those with a bacterial coinfection (8/24, 33 %) as compared to those without (5/60, 8 %) (p = 0.02). Sixty (29 %) patients were admitted to the intensive care unit. Among them, 23 (38 %) patients required invasive mechanical ventilation. In multivariable analysis, tachycardia and alteration of consciousness were identified as risk factors for complicated course., Conclusion: hMPV-associated lower respiratory tract infections in adult inpatients mostly involved elderly people with pre-existing conditions. Bacterial coinfection was present in nearly 30 % of the patients. The need for mechanical ventilation and/or the hospital death were observed in almost 20 % of the patients., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Astrid VABRET disclosed payment or honoraria for lectures, presentations and support for attending meetings and/or travel from ANOFI, 10.13039/501100003103ASTRA ZENECA, MODERNA, and participation on a Data Safety Monitoring Board from SANOFI, 10.13039/100030732MSD, MODERNA and GSK. Frederic Schlemmer disclosed consulting fees from 10.13039/100004319Pfizer, payment or honoraria for lectures, presentations from 10.13039/100005564Gilead, and participation on a Data Safety Monitoring Board from Boerhinger Ingelheim, 10.13039/100019719Chiesi, Elivie, 10.13039/100005564Gilead, 10.13039/100004330GlaxoSmithKline and Oxyvie. Anne Bergeron disclosed payment or honoraria for lectures, presentations and support for attending meetings and/or travel from Astra Zeneca and 10.13039/100004336Novartis, and participation on a Data Safety Monitoring Board from Enanta. Anahita Rouzé disclosed payment or honoraria for lectures, presentations and support for attending meetings and/or travel from 10.13039/100030732MSD, 10.13039/100005564Gilead, Mundipharma. Blandine RAMMAERT disclosed payment or honoraria for lectures, presentations from Gilead. Cedric Daubin disclosed support for attending meetings and/or travel from 10.13039/100005564Gilead. Nicolas Terzi disclosed payment or honoraria for lectures, presentations from 10.13039/100004319Pfizer and Boehringher Inghelheim, and support for attending meetings and/or travel from 10.13039/100005564Gilead. Quentin Philippot disclosed payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from 10.13039/100005564Gilead and Elsevier, and grants or contracts from APHP, 10.13039/501100017007ARS Ile de France and 10.13039/501100001677Inserm 10.13039/501100007492Fondation Bettencourt Schueller, and support for the present manuscript from SOS Oxygen. Other authors did not disclose competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Introduction: Acute respiratory infections (ARI) are the most common infections in the general population and are mainly caused by respiratory viruses. Detecting several viruses in a respiratory sample is common. To better understand these viral codetections and potential interferences, we tested for the presence of viruses and developed quantitative PCR (Polymerase Chain Reaction) for the viruses most prevalent in coinfections: human rhinovirus (HRV) and respiratory syncytial virus (RSV), and quantified their viral loads according to coinfections and health status, age, cellular abundance and other variables., Materials and Methods: Samples from two different cohorts were analyzed: one included hospitalized infants under 12 months of age with acute bronchiolitis (n=719) and the other primary care patients of all ages with symptoms of ARI (n=685). We performed Multiplex PCR on nasopharyngeal swabs, and quantitative PCR on samples positive for HRV or/and RSV to determine viral loads (VL). Cellular abundance (CA) was also estimated by qPCR targeting the GAPDH gene. Genotyping was performed either directly from first-line molecular panel or by PCR and sequencing for HRV., Results: The risks of viral codetection were 4.1 (IC 95 [1.8; 10.0]) and 93.9 1 (IC 95 [48.7; 190.7]) higher in infants hospitalized for bronchiolitis than in infants in primary care for RSV and HRV respectively (p<0.001). CA was higher in samples positive for multiple viruses than in mono-infected or negative samples (p<0.001), and higher in samples positive for RSV (p<0.001) and HRV (p<0.001) than in negative samples. We found a positive correlation between CA and VL for both RSV and HRV. HRV VL was higher in children than in the elderly (p<0.05), but not RSV VL. HRV VL was higher when detected alone than in samples coinfected with RSV-A and with RSV-B. There was a significant increase of RSV-A VL when codetecting with HRV (p=0.001) and when co-detecting with RSV-B+HRV versus RSV-A+ RSV-B (p=0.02)., Conclusions: Many parameters influence the natural history of respiratory viral infections, and quantifying respiratory viral loads can help disentangle their contributions to viral outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Petat, Corbet, Leterrier, Vabret and Ar Gouilh.)

Background: Immunization against the Yellow fever virus (YFV) with the 17D live-attenuated vaccine is the most effective way to prevent the disease. However, unexpected severe adverse events can occur. They consist in a neurological impairment - neurological disease (YEL-AND), a YF-like illness - viscerotropic disease (YEL-AVD) or anaphylaxis. In this article, we describe the epidemiology, clinical and biological features of YEL-AND and YEL-AVD cases reported to the French National Reference Center for Arboviruses (NRCA) in the past 10 years., Methods: We conducted a national, retrospective study using the database of the NRCA from June 2012 to June 2022. All patients whose biological samples were sent to the NRCA for detection of YFV by serology and/or RT-qPCR for a suspected vaccine-associated adverse event were included. We collected data by reading medical records and conducted complementary neuro-immunological analysis, followed by a search for autoimmunity against type-1-interferon when samples were available at the NRCA., Results: There were 10 cases of YEL-AND and 2 cases of YEL-AVD reported to the NRCA in the past 10 years, which represented an overall incidence of 0.6 for 100 000 doses. A total of 6/12 cases were previously healthy patients (50%, mean age 31 years), and 4/12 cases had cardiovascular co-morbidities (42%, mean age 56 years). The majority of YEL-AND had a favourable outcome at 6 months of follow up. One YEL-AVD patient passed. In secondary analyses, we evidenced a significant blood cerebrospinal fluid (CSF) barrier dysfunction, without intrathecal synthesis of immunoglobulin and without argument for a neuron damage. We further detected a significant rate of anti-type-1alpha interferon antibodies in 3/10 tested patients (2 YEL-AND and 1 YEL-AVD)., Conclusion: YEL-AND and YEL-AVD are rare events that can underlie defect in the innate immunity of apparently healthy or mild co-morbid subjects. Outcome was generally favourable in the YEL-AND cases of our series, but still life-threatening or even fatal in the YEL-AVD cases., (© International Society of Travel Medicine 2023. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). Although respiratory pathogens are frequently detected in children with ACS, their respective role in triggering the disease is still unclear. We hypothesized that the incidence of ACS followed the unprecedented population-level changes in respiratory pathogen dynamics after COVID-19-related nonpharmaceutical interventions (NPIs)., Research Question: What is the respective role of respiratory pathogens in ACS epidemiology?, Study Design and Methods: This study was an interrupted time series analysis of patient records from a national hospital-based surveillance system. All children aged < 18 years with SCD hospitalized for ACS in France between January 2015 and May 2022 were included. The monthly incidence of ACS per 1,000 children with SCD over time was analyzed by using a quasi-Poisson regression model. The circulation of 12 respiratory pathogens in the general pediatric population over the same period was included in the model to assess the fraction of ACS potentially attributable to each respiratory pathogen., Results: Among the 55,941 hospitalizations of children with SCD, 2,306 episodes of ACS were included (median [interquartile range] age, 9 [5-13] years). A significant decrease was observed in ACS incidence after NPI implementation in March 2020 (-29.5%; 95% CI, -46.8 to -12.2; P = .001) and a significant increase after lifting of the NPIs in April 2021 (24.4%; 95% CI, 7.2 to 41.6; P = .007). Using population-level incidence of several respiratory pathogens, Streptococcus pneumoniae accounted for 30.9% (95% CI, 4.9 to 56.9; P = .02) of ACS incidence over the study period and influenza 6.8% (95% CI, 2.3 to 11.3; P = .004); other respiratory pathogens had only a minor role., Interpretation: NPIs were associated with significant changes in ACS incidence concomitantly with major changes in the circulation of several respiratory pathogens in the general population. This unique epidemiologic situation allowed determination of the contribution of these respiratory pathogens, in particular S pneumoniae and influenza, to the burden of childhood ACS, highlighting the potential benefit of vaccine prevention in this vulnerable population., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: N. O. reports travel grants from GlaxoSmithKline, Pfizer, and Sanofi. A. R. reports travel grants from Pfizer and AstraZeneca and personal fees from MSD outside the submitted work. A. V. reports personal fees from Sanofi, Moderna, GlaxoSmithKline, and MSD. R. C. reports speaking and lecture fees from Pfizer, Sanofi, GlaxoSmithKline, and MSD; and funding and travel grants from Pfizer. E. V. reports grants from Santé Publique France, Pfizer, and MSD. F. A. reports honoraria from Pfizer, GlaxoSmithKline, MSD, and Sanofi outside the submitted work. None declared (Z. A., Z. V., F. K., A. L., L.-L. P., L. L., A. F., M. C., C. L., F. G., B. K.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Introduction: Acute respiratory infections (ARIs) are the most common viral infections encountered in primary care settings. The identification of causal viruses is still not available in routine practice. Although new strategies of prevention are being identified, knowledge of the relationships between respiratory viruses remains limited., Materials and Methods: ECOVIR was a multicentric prospective study in primary care, which took place during two pre-pandemic seasons (2018-2019 and 2019-2020). Patients presenting to their General practitioner (GP) with ARIs were included, without selecting for age or clinical conditions. Viruses were detected on nasal swab samples using a multiplex Polymerase Chain Reaction test focused on 17 viruses [Respiratory Syncytial Virus-A (RSV-A), RSV-B, Rhinovirus/Enterovirus (HRV), human Metapneumovirus (hMPV), Adenovirus (ADV), Coronaviruses (CoV) HKU1, NL63, 229E, OC43, Influenza virus (H1 and H3 subtypes), Influenza virus B, Para-Influenza viruses (PIVs) 1-4, and Bocavirus (BoV)]., Results: Among the 668 analyzed samples, 66% were positive for at least one virus, of which 7.9% were viral codetections. The viral detection was negatively associated with the age of patients. BoV, ADV, and HRV occurred more significantly in younger patients than the other viruses ( p  < 0.05). Codetections were significantly associated with RSV, HRV, BoV, hMPV, and ADV and not associated with influenza viruses, CoV, and PIVs. HRV and influenza viruses were negatively associated with all the viruses. Conversely, a positive association was found between ADV and BoV and between PIVs and BoV., Conclusion: Our study provides additional information on the relationships between respiratory viruses, which remains limited in primary care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Petat, Schuers, Marguet, Humbert, Le Bas, Rabiaza, Corbet, Leterrier, Vabret and Ar Gouilh.)

The highly contagious respiratory syncytial virus (RSV) is responsible for up to approximately 50,000 hospitalisations during each RSV season in children aged under 5 years in France, with the burden greatest in infants younger than 1 year who were born at term. There is a need for a strategy to universally protect young children from RSV infection, and thereby reduce the pressure that RSV places every year on RSV-infected children, their parents, and French healthcare systems. Potential strategies currently undergoing clinical investigation include passive immunisation via maternal vaccination or administration of long-acting monoclonal antibodies at or soon after birth, followed by vaccination later in infancy or childhood. An ongoing partnership and collaboration between parents, public health authorities, and frontline primary healthcare will need to be reinforced once these new RSV prevention strategies are available, to facilitate their use and ensure that all children receive adequate protection from the start of their first RSV season., (© 2022. The Author(s).)

Acute respiratory infections (ARIs) need to be better understood and treated, as they are critical to public health, especially during crises such as the SARS-CoV2 pandemic. These are the most abundant infections in the general population and are seen primarily in primary care by general practitioners (GPs). Many different viruses are involved, according to epidemic variations. Viral co-detections account for a significant proportion of ARIs in hospital cohorts. The objective of the ECOVIR cohort was to study viral co-detections by setting up a biobank of respiratory tract samples from patients consulting their general practitioner for ARI symptoms. We report here on the course of the study: the design, the conduct, and the difficulties encountered. ECOVIR (Etude des CO-detections VIrales dans les prélèvements Respiratoires) was a prospective, multicenter cohort conducted in France during two epidemic seasons (2018-2019 and 2019-2020). We recruited GPs. Each GP investigator (GPI) saw patients weekly for examination, clinical data collection, and nasopharyngeal swabbing. Each sample was sent to the virology unit for biobanking and molecular analysis. Clinical and sociodemographic data were collected 7 days after inclusion. ECOVIR involved 36 GPIs. Patients with symptoms of an ARI were included ( n = 685). The median number of inclusions was 16 patients per GPI over both seasons (IC 25-75% [4.75; 27]). Patients aged 18 to 64 years were the most numerous (57%), followed by children (30%), and the elderly (13% over 65 years). This age distribution emphasizes the young adult and middle-aged population. Residents participated in the project and called patients on day 7 to obtain clinical and sociodemographic data. Our study triggered the creation of an original network, which plans to establish a functional link between research and primary health care. Primary care is unfortunately poorly represented in research protocols, particularly in respiratory infections, even though it is a cornerstone of our French health care system, as demonstrated every day in this period of crisis., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Rapid and accurate diagnosis of SARS-CoV-2 infection is essential for the management of the COVID-19 outbreak. RT-LAMP LoopDeetect COVID-19 (LoopDeescience, France) is a rapid molecular diagnostic tool which operates with the LoopDeelab (LoopDeescience, France) device. RAPID COVID is a prospective double-blind research protocol which was conducted to evaluate the concordance between Loopdeetect COVID-19 and RT-PCR Allplex 2019 n-Cov (Seegene, Korea). Between 11 May 2020 and 14 June 2021, a total of 1122 nasopharyngeal swab specimens were collected, of which 741 were finally analysed. There were 32 "positive" and "indeterminate" RT-PCR results. The intrinsic performances of Loopdeetect COVID-19 are equivalent to other commercial RT-LAMP PCR COVID-19 kits, with a sensitivity and specificity of 69.23% [CI 95%: 48.21-85.67] and 100% [CI 95%: 99.58-100.00], respectively. To the best of our knowledge, LoopDeelab is the only LAMP PCR diagnostic device allowing such a fast and reliable analysis with low-cost equipment; this makes it a new and innovative technology, designed for field use. This device being portable, the development of other detection kits will be useful for the management of epidemics with a high attack rate and would facilitate the rapid application of health measures.

Introduction: Bronchiolitis is the leading cause of hospitalization for infants but its economic burden is not well documented. Our objective was to describe the clinical evolution and to assess the 1-month cost of a first episode of acute bronchiolitis presenting to the emergency department (ED)., Methods: Our study was an epidemiologic analysis and a cost study of the cohort drawn from the clinical trial GUERANDE, conducted in 24 French pediatric EDs. Infants of 6 weeks to 12 months of age presenting at pediatric EDs with a first episode of bronchiolitis were eligible. The costs considered were collected from a societal viewpoint, according to the recommendations of the French National Health Authority., Results: A total of 777 infants were included with a median age of 4 months. A total of 57% were hospitalized during the month following the first consultation in the ED, including 28 (3.6%) in an intensive care unit. The mean length of stay was 4.2 days (SD = 3.7). The average time to relief of all symptoms was 13 days (SD = 7). Average total cost per patient was €1919 (95% confidence interval: 1756-2138) from a societal perspective, mostly due to hospitalization cost. The estimated annual cost of bronchiolitis in infants was evaluated to be between €160 and €273 million in France., Discussion: Bronchiolitis represent a high cost for the health care system and broadly for society, with hospitalizations costs being the main cost driver. Thus significant investments should be made to develop innovative therapies, to reduce the number of hospitalizations and length of stay., (© 2021 Wiley Periodicals LLC.)

A prospective study was conducted among different intra and extra-hospital populations of French Guiana to evaluate the performance of saliva testing compared to nasopharyngeal swabs. Persons aged 3 years and older with mild symptoms suggestive of COVID-19 and asymptomatic persons with a testing indication were prospectively enrolled. Nasopharyngeal and salivary samples were stored at 4°C before analysis. Both samples were analyzed with the same Real-time PCR amplification of E gene, N gene, and RdRp gene. Between July 22th and October 28th, 1159 persons were included, of which 1028 were analyzed. When only considering as positives those with 2 target genes with Ct values <35, the sensitivity of RT-PCR on saliva samples was 100% relative to nasopharyngeal samples. Specificity positive and negative predictive values were above 90%. Across a variety of cultures and socioeconomic conditions, saliva tests were generally much preferred to nasopharyngeal tests and persons seemed largely confident that they could self-sample. For positive patients defined as those with the amplification of 2 specific target genes with Ct values below 35, the sensitivity and specificity of RT-PCR on saliva samples was similar to nasopharyngeal samples despite the broad range of challenging circumstances in a tropical environment., Competing Interests: The authors have declared that no competing interests exist.

Background: Acute respiratory infections (ARI) are associated with a huge morbidity and mortality worldwide. Rhinoviruses (RVs) and Enteroviruses (EVs) are recognized as leading causes of ARI., Objectives: The present study describes the molecular epidemiology of RVs and EVs in Cameroon over a 3-year surveillance period., Methods: From September 2011 to October 2014, nasopharyngeal swabs were collected from patients with influenza-like illness (ILI) and severe acute respiratory infections (SARI). Two sub-genomic regions of the EVs and RVs were targeted for molecular characterization. These included the most conserved 5'-untranslated region (5'UTR) and the viral protein 4/viral protein 2 transition region (VP4/VP2)., Results: A total of 974 samples were collected. Children ≤5 years accounted for 85.7% (835/974) of all participants. Among them, 160 (16.4%) were positive for RVs and/or EVs. RVs and/or EVs were significantly more identified in ILI compared to SARI patients (P = .015). Both viruses co-circulated all year long with a marked increase of occurrence during rainy and cold season. All RV species were found to circulate in Cameroon, with 6, 10 and 6 virus types belonging to the RV-A, RV-B and RV-C, respectively. EV species identified comprised EV-A (1 Coxsackie virus A5), EV-B (1 Coxsackie virus A9 and 2 Coxsackie virus B1) and EV-C (1 EV-C117)., Conclusions: This study indicates a strong year-round occurrence of EV and RV associated respiratory infections in Cameroon. Molecular characterization identified a wide variety of RVs and EVs in patients with ARI in Cameroon., (© 2021 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: Tenofovir and emtricitabine interfere with the SARS CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). Several cohorts reported that people treated by tenofovir disoproxil fumarate and emtricitabine are less likely to develop SARS CoV-2 infection and related severe COVID-19., Methods: We conducted a pilot randomized, open-label, controlled, phase 2 trial at two hospitals in France. Eligible patients were consecutive outpatients (aged ≥18 years) with RT-PCR-confirmed SARS-CoV-2 infection and an interval from symptom onset to enrolment of 7 days or less. Patients were randomly assigned in a 1:1 ratio to receive oral tenofovir disoproxil fumarate and emtricitabine (2 pills on day 1 followed by 1 pill per day on days 2-7) or the standard of care. The primary and secondary endpoints were SARS-CoV-2 viral clearance from baseline assessed by cycle threshold (Ct) RT-PCR on nasopharyngeal swab collected at day 4 and day 7, respectively. A higher Ct corresponds to a lower SARS CoV-2 viral burden. Other endpoints were the time to recovery and the number of adverse events. This trial is registered with ClinicalTrials.gov, NCT04685512., Findings: From November, 20 th 2020 to March, 19 th 2021, 60 patients were enrolled and randomly assigned to a treatment group (30 to tenofovir disoproxil fumarate and emtricitabine and 30 to standard of care). The median number of days from symptom onset to inclusion was 4 days (IQR 3-5) in both groups. Amongst patients who received tenofovir disoproxil fumarate, the difference from standard of care in the increase in Ct RT-PCR from baseline was 2.3 (95% confidence interval [-0.6 to 5.2], p  = 0.13) at day 4 and 2.9 (95% CI [0.1 to 5.2], p  = 0.044) at day 7. At day 7, 6/30 in the tenofovir disoproxil fumarate and emtricitabine group and 3/30 in the standard of care group reported no COVID-related symptoms. Adverse events included 11 cases of gastrointestinal side effects (grade ≤ 2), three of which leaded to drug discontinuation. Three patients had COVID-19 related hospitalisation, no participant died., Interpretation: In this pilot study of outpatients adult with recent non-severe COVID-19, tenofovir disoproxil fumarate plus emtricitabine appeared to accelerate the natural clearance of nasopharyngeal SARS-CoV-2 viral burden. These findings support the conduct of larger trials of tenofovir-based therapies for the prevention and early treatment of COVID-19., Funding: No external funding., Competing Interests: J.-JP reports personal fees and grant support from Gilead Sciences, Merck Sharp & Dohme and ViiV Healthcare outside the submitted work. L.H. reports personal fees and non-financial support from Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme and ViiV Healthcare outside the submitted work. Other authors declare no competing interests., (© 2021 The Author(s).)

Over two years (2012-2014), 719 nasopharyngeal samples were collected from 6-week- to 12-month-old infants presenting at the emergency department with moderate to severe acute bronchiolitis. Viral testing was performed, and we found that 98% of samples were positive, including 90% for respiratory syncytial virus, 34% for human rhino virus, and 55% for viral co-detections, with a predominance of RSV/HRV co-infections (30%). Interestingly, we found that the risk of being infected by HRV is higher in the absence of RSV, suggesting interferences or exclusion mechanisms between these two viruses. Conversely, coronavirus infection had no impact on the likelihood of co-infection involving HRV and RSV. Bronchiolitis is the leading cause of hospitalizations in infants before 12 months of age, and many questions about its role in later chronic respiratory diseases (asthma and chronic obstructive pulmonary disease) exist. The role of virus detection and the burden of viral codetections need to be further explored, in order to understand the physiopathology of chronic respiratory diseases, a major public health issue.

Prolonged measles virus detection in maternal saliva and blood was evidenced in 6 pregnant women. Maternal-fetal transmission was evidenced in 2 of 4 infants who were asymptomatic at birth, 21-24 weeks after maternal infection. Whereas peripartum congenital measles is severe, asymptomatic measles virus vertical transmission can occur earlier in pregnancy., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Current testing for COVID-19 relies on reverse-transcriptase polymerase chain reaction from a nasopharyngeal swab specimen. Saliva samples have advantages regarding ease and painlessness of collection, which does not require trained staff and may allow self-sampling. We enrolled 776 persons at various field-testing sites and collected nasopharyngeal and pooled saliva samples. One hundred sixty two had a positive COVID-19 RT-PCR, 61% were mildly symptomatic and 39% asymptomatic. The sensitivity of RT-PCR on saliva samples vs. nasopharygeal swabs varied depending on the patient groups considered or on Ct thresholds. There were 10 (6.2%) patients with a positive saliva sample and a negative nasopharyngeal swab, all of whom had Ct values <25 for three genes. For symptomatic patients for whom the interval between symptoms onset and sampling was <10 days sensitivity was 77% but when excluding persons with isolated N gene positivity (54/162), sensitivity was 90%. In asymptomatic patients, the sensitivity was only 24%. When we looked at patients with Cts <30, sensitivity was 83 or 88.9% when considering two genes. The relatively good performance for patients with low Cts suggests that Saliva testing could be a useful and acceptable tool to identify infectious persons in mass screening contexts, a strategically important task for contact tracing and isolation in the community., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nacher, Mergeay-Fabre, Blanchet, Benoit, Pozl, Mesphoule, Sainte-Rose, Vialette, Toulet, Moua, Saout, Simon, Guidarelli, Galindo, Biche, Faurous, Chaizemartin, Fahrasmane, Rochemont, Vignier, Vabret and Demar.)

We report a fatal case of measles inclusion-body encephalitis occurring in a woman from Romania with AIDS. After an extensive but unsuccessful diagnostic evaluation, a pan-pathogen shotgun metagenomic approach revealed a measles virus infection. We identified no mutations previously associated with neurovirulence.

Background: Despite high overall population vaccine coverage, identified clusters of persons refraining from vaccination interfere with pursued measles elimination. Clinical diagnosis of measles is often obvious due to its typical rash. Yet, febrile rashes may occur during many viral infections. Misdiagnosis of a specific primary viral infection may have severe consequences, particularly in immunocompromised subjects or pregnant women. To our knowledge, this case presentation is the first description of a measles and parvovirus B19 coinfection outbreak. Analysis of this outbreak underlines rash diagnosis difficulties and potential serology interpretation pitfalls. This case report is helpful for the clinicians in the context of measles re-emergence and proposes several methods to improve the diagnosis approach., Case Presentation: We investigated an outbreak of rash in 6 out of 8 Traveler family members presenting to Rennes University Hospital (West of France). Anti-B19V and measles IgM/IgG antibodies were measured and detection of Parvovirus B19 and measles virus genomes were done on blood and/or respiratory samples. Virological investigations finally documented 6 cases of parvovirus B19 infections, including 4 associated with measles. Interestingly, in the four coinfection cases, the rash was typical of B19V primary infection for the two children but typical of measles for the two adults. Clinical diagnosis of rash may be misleading and thorough virological investigations may be required to avoid misdiagnosis., Conclusions: This investigation first reports an intra-familial outbreak of MeV/B19V coinfections highlighting the high transmissibility of both viruses and the diagnostic challenges of dual rash-associated infections. This report also underlines the potential deleterious consequences of failure to identify measles cases, especially in a community with low vaccination coverage.

Background: Identified in 2001, Human Metapneumovirus (HMPV) is a Pneumovirus associated with acute lower and upper respiratory infections in all age groups and especially in newborns, elderly and immunocompromised subjects. Data are still limited in sub-Saharan African countries genetic characterization of this respiratory virus. This study reports the genetic variability of HMPV strains in Cameroonian children for 3 consecutive epidemic seasons (September 2011-October 2014)., Methods: A prospective surveillance was conducted to identify inpatient and outpatient children less than 15 years with respiratory symptoms ≤5 days. The nasopharyngeal samples were tested for HMPV using a multiplex polymerase chain reaction. Viral distribution and demographic data were analyzed statistically. Positive samples for HMPV were amplified by semi-nested polymerize chain reaction and then partially sequenced at the G gene. Phylogenetic analyzes were performed on the partial nucleotide and protein sequences of the G gene., Results: From September 2011 to October 2014, 822 children under 15 years were enrolled in the study. HMPV was identified in each of 3.9% (32/822) of children. HMPV were detected throughout the year. HMPV-A (73.3%; 11/15) was predominant compared to HMPV-B (26.7; 4/15). Cameroonian HMPV strains are grouped among the members of genotype A2b (for HMPV-A), B1 and B2 (for HMPV-B)., Conclusion: This study suggests that about 4% of ARI recorded in children in Cameroon are caused by HMPV. The present study is also the first report on the genetic variability of the G gene of HMPV strains in the region. Although this work partially fills gaps for some information, additional studies are required to clarify the molecular epidemiology and evolutionary pattern of HMPV in sub-Saharan Africa in general and more particularly in Cameroon., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In this study, we report a complete (clinical, radiological, and virological) sustained (1 year) response after nivolumab salvage therapy in a progressive multifocal leukoencephalopathy patient. Analyses of the cells infiltrate in a pretreatment brain biopsy suggest that parenchymal programmed cell death-L1 + macrophages could be the T-cells partnership in immune exhaustion and virus escape., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We described nosocomially clustered cases of measles secondary to a nonvaccinated index case occurring in a teenage psychiatric unit despite optimum vaccine coverage. Surveillance of this fully vaccinated closed cohort showed a 7% attack rate. Vaccination limited the risk of complicated measles and the onset of a large outbreak.

Human Parainfluenza viruses (HPIV) type 1 and 3 are important causes of respiratory tract infections in young children globally. HPIV infections do not confer complete protective immunity so reinfections occur throughout life. Since no effective vaccine is available for the two virus subtypes, comprehensive understanding of HPIV-1 and HPIV-3 genetic and epidemic features is important for diagnosis, prevention, and treatment of HPIV-1 and HPIV-3 infections. Relatively few whole genome sequences are available for both HPIV-1 and HPIV-3 viruses, so our study sought to provide whole genome sequences from multiple countries to further the understanding of the global diversity of HPIV at a whole-genome level. We collected HPIV-1 and HPIV-3 samples and isolates from Argentina, Australia, France, Mexico, South Africa, Switzerland, and USA from the years 2003-2011 and sequenced the genomes of 40 HPIV-1 and 75 HPIV-3 viruses with Sanger and next-generation sequencing with the Ion Torrent, Illumina, and 454 platforms. Phylogenetic analysis showed that the HPIV-1 genome is evolving at an estimated rate of 4.97 × 10-4 mutations/site/year (95% highest posterior density 4.55 × 10-4 to 5.38 × 10-4) and the HPIV-3 genome is evolving at a similar rate (3.59 × 10-4 mutations/site/year, 95% highest posterior density 3.26 × 10-4 to 3.94 × 10-4). There were multiple genetically distinct lineages of both HPIV-1 and 3 circulating on a global scale. Further surveillance and whole-genome sequencing are greatly needed to better understand the spatial dynamics of these important respiratory viruses in humans., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Daniel E. Noyola has participated as a member of the speakers' bureau of AbbVie and speakers' bureau and advisory board for Sanofi Pasteur. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Seasonal influenza has a major individual and collective impact, especially among the elderly living in nursing homes. To prevent infection by influenza viruses, vaccination of residents and professionals is an essential measure. However, while the vaccination rates of residents are generally high (>85%), rates among professionals are generally approximately 20%. To evaluate the effectiveness of an intervention campaign on the improvement of the influenza vaccination rate of professionals, a regional intervention study was proposed for nursing homes during the 2014-15 season., Methods: Cluster-randomized controlled trial (with a nursing home representing a cluster). In the intervention group, a campaign on influenza vaccination was offered to staff, combining different teaching aids in a multimodal approach. In the control group, no intervention was proposed. The primary endpoint was the rate of influenza vaccination among staff. Before and after the study, professionals were asked to complete short questionnaires on their perceptions of influenza vaccination. A multilevel analysis was carried out to compare the vaccination rates between the 2 groups and their evolution before/after the winter period., Results: A total of 32 nursing homes were randomized, and 6 were excluded. Initial vaccination rates were 27.6% in the intervention group and 24.2% in the control group (p = 0.16). After the study, these rates increased to 33.7% and 22.9%, respectively, which was a relative difference of +22.1% in the intervention group compared to -5.4% in the control group, p = 0.0025., Conclusions: Despite professionals' reluctance to be vaccinate, participation in a promotional campaign with a pragmatic approach has increased the rate of influenza vaccination. The approach will be offered to all nursing homes in the region after revision of the tools to enhance their ease of use and pedagogical messages focused on the direct benefits to professionals., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

In this study, we assessed the sensitivity of myeloma cells to the oncolytic measles virus (MV) in relation to p53 using 37 cell lines and 23 primary samples. We showed that infection and cell death were correlated with CD46 expression, which was associated with TP53 status; TP53 abn cell lines highly expressed CD46 and were preferentially infected by MV when compared with the TP53 wt cell lines ( P = .046 and P = .045, respectively). Infection of myeloma cells was fully dependent on CD46 expression in both cell lines and primary cells. In the TP53 wt cell lines, but not the TP53 abn cell lines, activation of the p53 pathway with nutlin3a inhibited both CD46 expression and MV infection, while TP53 silencing reciprocally increased CD46 expression and MV infection. We showed using a p53 chromatin immunoprecipitation assay and microRNA assessment that CD46 gene expression was directly and indirectly regulated by p53. Primary myeloma cells overexpressed CD46 as compared with normal cells and were highly infected and killed by MV. CD46 expression and MV infection were inhibited by nutlin3a in primary p53-competent myeloma cells, but not in p53-deficient myeloma cells, and the latter were highly sensitive to MV infection. In summary, myeloma cells were highly sensitive to MV and infection inhibition by the p53 pathway was abrogated in p53-deficient myeloma cells. These results argue for an MV-based clinical trial for patients with p53 deficiency., (© 2018 by The American Society of Hematology.)

Aim: The epidemiology of human respiratory syncytial virus (HRSV) infection has not yet been systematically investigated in Africa. This systematic review and meta-analysis are to estimate the prevalence of HRSV infections in people with acute respiratory tract infections (ARTI) in Africa., Method: We searched PubMed, EMBASE, Africa Journal Online, and Global Index Medicus to identify observational studies published from January 1, 2000, to August 1, 2017. We used a random-effects model to estimate the prevalence across studies. Heterogeneity (I 2 ) was assessed via the chi-square test on Cochran's Q statistic. Review registration: PROSPERO CRD42017076352., Results: A total of 67 studies (154 000 participants) were included. Sixty (90%), seven (10%), and no studies had low, moderate, and high risk of bias, respectively. The prevalence of HRSV infection varied widely (range 0.4%-60.4%). The pooled prevalence was 14.6% (95% CI 13.0-16.4, I 2  = 98.8%). The prevalence was higher in children (18.5%; 95% CI 15.8-21.5) compared to adults (4.0%; 95% CI 2.2-6.1) and in people with severe respiratory tract infections (17.9%; 95% CI 15.8-20.1) compared to those with benign forms (9.4%; 95% CI 7.4-11.5); P-values <0.0001. The HRSV prevalence was not associated with sex, subregion in Africa, setting, altitude, latitude, longitude, and seasonality., Conclusion: This study suggests a high prevalence of HRSV in people with ARTI in Africa, particularly among children and people with severe clinical form. All innovative strategies to curb the burden should first focus on children which present the highest HRSV-related burden., (© 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Background: Human adenoviruses (HAdVs) cause a wide range of diseases worldwide, including respiratory infections. Studies on HAdV molecular epidemiology are limited in Cameroon. The purpose of this study is to document the different types HAdV circulating in Cameroon in children with acute respiratory infections., Methods: Nasopharyngeal swabs were collected from 811 children under 15 years from 2011 to 2014. The HAdV detection was assessed by semi-quantitative generic PCR r-gene®. The HAdV-positive samples were typed by amplification and sequencing of partial hexon gene and a real-time PCR. Demographic data were collected and analyzed. The infection and hospitalization risk factors were assessed thought the Chi-square test., Results: A total of 137/220 HAdV-positive samples were amplified successfully. Six species of HAdV (Mastadenovirus A to F) were detected with B (108/220) and C (47/220) being the predominant strains. Hospitalization and age were significantly associated to HAdV-B and HAdV-C respectively. Phylogenetic analysis of HAdV-B3 virus (18) and B7 (5) shows a conserved and a significant temporal stability in relation to the reference sequence (99.1 to 100% of similarity)., Conclusion: This study reported HAdV species and types detected in children with acute respiratory infections in Cameroon between September 2011 and July 2014. These results support further evaluation of the spatio-temporal circulation pattern of HAdV species and types in Cameroon.

Availability of accurate data on the burden of the Human Respiratory Syncytial Virus (HRSV) can help to implement better strategies to curb this burden in Africa continent among people with acute respiratory tract infections (ARTI). We summarize here available contemporaneous data published from January 1, 2000 to August 31, 2017 on the prevalence of HSRV infection among people with ARTI in the continent.

Background: Prodromal symptoms are frequently reported in the atypical form of Hemolytic uremic syndrome (aHUS) suggesting implication of infectious triggers. Some pathogens may also play a role in the mechanisms of production of autoantibody directed against Factor H (FH), a complement regulator, leading to aHUS., Methods: The presence of 15 gastrointestinal (GI) pathogens was investigated by using xTAG-based multiplex PCR techniques on stools collected at the acute phase in a cohort of Indian HUS children classified according to the presence or absence of anti-FH autoantibodies., Results: Prevalence of pathogens in patients with anti-FH antibody (62.5%) was twice that in those without (31.5%). Different pathogens were detected, the most frequent being Clostridium difficile, Giardia intestinalis, Salmonella, Shigella, Rotavirus, Norovirus and Entamoeba histolytica. No stool was positive for Shigatoxin., Conclusion: This study reveals a higher prevalence of GI pathogens in anti-FH positive than in negative patients. No single pathogen was implicated exclusively in one form of HUS. These pathogens may play a role in the disease initiation by inducing complement activation or an autoimmune response.

Background: Human respiratory syncytial virus (HRSV) is the main viral cause of severe lower respiratory tract disease in infants and young children. The aim of this study was to describe for the first time the genetic variability of HRSV in Cameroonian patients living in Yaounde for three consecutive epidemic seasons., Methods: HRSV-positive nasopharyngeal samples detected in children less than 15 years in Yaounde were collected from September 2011 to December 2013. Semi-nested RT-PCR, sequencing, and phylogenetic analyses of the second hypervariable region of the G gene were performed., Results: A total of 57 HRSV-positive samples were collected during the study period. Among these, 46 (80.7%) could be amplified in the G gene. HRSV group A (HRSV-A) and group B (HRSV-B) co-circulated in this population at 17.4 and 82.6%, respectively. HRSV-A strains clustered in the NA-1 genotype while HRSV-B strains clustered in the BA-9 genotype. HRSV-A strains accounted for 33.3% (2/6), 4.3% (1/23), and 29.4% (5/17) of the viruses isolated in 2011, 2012, and 2013, respectively., Conclusions: This study reports molecular epidemiology data of HRSV in Cameroon for the first time. Additional studies are required to clarify evolutionary patterns of HRSV throughout sub-Saharan Africa to support antiviral and vaccine development., Competing Interests: Samples were submitted to the “Centre Pasteur du Cameroon” as part of influenza surveillance in Cameroon and the IMMI (Institut de Microbiologie et de Maladies Infectieuses) project. Written informed consent was obtained from the parents or guardians of all children enrolled in the study. The procedures of the original study were evaluated and approved by the National Ethics Committee and the Ministry of Public Health of Cameroon.Not applicableThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The emergence of SARS-CoV and MERS-CoV, triggered the discovery of a high diversity of coronaviruses in bats. Studies from Europe have shown that coronaviruses circulate in bats in France but this reflects only a fraction of the whole diversity. In the current study the diversity of coronaviruses circulating in western Europe was extensively explored. Ten alphacoronaviruses in eleven bat species belonging to the Miniopteridae, Vespertilionidae and Rhinolophidae families and, a SARS-CoV-related Betacoronavirus in Rhinolophus ferrumequinum were identified. The diversity and prevalence of bat coronaviruses presently reported from western Europe is much higher than previously described and includes a SARS-CoV sister group. This diversity demonstrates the dynamic evolution and circulation of coronaviruses in this species. That said, the identified coronaviruses were consistently associated with a particular bat species or genus, and these relationships were maintained no matter the geographic location. The observed phylogenetic grouping of coronaviruses from the same species in Europe and Asia, emphasizes the role of host/pathogen coevolution in this group., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Importance: Acute bronchiolitis is the leading cause of hospitalization among infants. Previous studies, underpowered to examine hospital admission, have found a limited benefit of nebulized hypertonic saline (HS) treatment in the pediatric emergency department (ED)., Objective: To examine whether HS nebulization treatment would decrease the hospital admission rate among infants with a first episode of acute bronchiolitis., Design, Setting, and Participants: The Efficacy of 3% Hypertonic Saline in Acute Viral Bronchiolitis (GUERANDE) study was a multicenter, double-blind randomized clinical trial on 2 parallel groups conducted during 2 bronchiolitis seasons (October through March) from October 15, 2012, through April 15, 2014, at 24 French pediatric EDs. Among the 2445 infants (6 weeks to 12 months of age) assessed for inclusion, 777 with a first episode of acute bronchiolitis with respiratory distress and no chronic medical condition were included., Interventions: Two 20-minute nebulization treatments of 4 mL of HS, 3%, or 4 mL of normal saline (NS), 0.9%, given 20 minutes apart., Main Outcomes and Measures: Hospital admission rate in the 24 hours after enrollment., Results: Of the 777 infants included in the study (median age, 3 months; interquartile range, 2-5 months; 468 [60.2%] male), 385 (49.5%) were randomized to the HS group and 387 (49.8%) to the NS group (5 patients did not receive treatment). By 24 hours, 185 of 385 infants (48.1%) in the HS group were admitted compared with 202 of 387 infants (52.2%) in the NS group. The risk difference for hospitalizations was not significant according to the mixed-effects regression model (adjusted risk difference, -3.2%; 95% CI, -8.7% to 2.2%; P = .25). The mean (SD) Respiratory Distress Assessment Instrument score improvement was greater in the HS group (-3.1 [3.2]) than in the NS group (-2.4 [3.3]) (adjusted difference, -0.7; 95% CI, -1.2 to -0.2; P = .006) and similarly for the Respiratory Assessment Change Score. Mild adverse events, such as worsening of cough, occurred more frequently among children in the HS group (35 of 392 [8.9%]) than among those in the NS group (15 of 384 [3.9%]) (risk difference, 5.0%; 95% CI, 1.6%-8.4%; P = .005), with no serious adverse events., Conclusions and Relevance: Nebulized HS treatment did not significantly reduce the rate of hospital admissions among infants with a first episode of acute moderate to severe bronchiolitis who were admitted to the pediatric ED relative to NS, but mild adverse events were more frequent in the HS group., Trial Registration: clinicaltrials.gov Identifier: NCT01777347.

Objective: Human Bocavirus (HBoV) was first identified in 2005 and has been shown to be a common cause of respiratory infections and gastroenteritis in children. In a recent study, we found that 10.7% of children with acute respiratory infections (ARI) were infected by HBoV. Genetic characterization of this virus remains unknown in Central Africa, particularly in Cameroon Leeding us to evaluate the molecular characteristics of HBoV strains in Cameroonian children with ARI., Results: Phylogenetic analysis of partial HBoV VP1/2 sequences showed a low level of nucleotide variation and the circulation of HBoV genotype 1 (HBoV-1) only. Three clades were obtained, two clustering with each of the reference strains ST1 and ST2, and a third group consisting of only Cameroon strains. By comparing with the Swedish reference sequences, ST1 and ST2, Cameroon sequences showed nucleotide and amino acid similarities of respectively 97.36-100% and 98.35-100%. These results could help improve strategies for monitoring and control of respiratory infections in Cameroon.

Background: Respiratory syncytial virus (RSV) is responsible for severe respiratory infections and higher costs in medical care. The two aims of this work were to assess the performances of SOFIA ® RSV tests in "real-life-laboratory" conditions (study 1) and implemented at point-of-care testing in a pediatric emergency department (ED, study 2), during two consecutive winter seasons., Methods: In study 1, fresh nasopharyngeal swabs from patients of all ages were sampled in 1.5 ml of Universal virological Transport Medium (UTM) and prospectively tested using SOFIA ® RSV tests. In study 2, conducted in a pediatric ED, nasopharyngeal swabs were placed in 3 ml of UTM. All SOFIA ® RSV tests were confirmed by molecular testing, considered as reference method. The epidemiological and clinical features of tested patients, as well as the care of these patients after obtaining quick results were evaluated., Results: The sensitivities of SOFIA ® RSV in infants (aged under 24 months) performed in the laboratory and in the pediatric ED were respectively 95% (95% CI: 86.8-98.1) and 74.8% (95% CI: 68.0-80.9) compared to PCR. In study 1, the sensitivity among children (from 2 to 15 years old) and adults (above 15 years old) dropped to 45% (95% CI: 23.1-68.5) and 59% (95% CI: 32.9-81.6), respectively. In study 2, there were some differences in bed-management of SOFIA ® RSV positive compared to SOFIA ® RSV negative infants., Conclusions: SOFIA ® RSV tests performed in the laboratory and in the pediatric ED show high and satisfactory sensitivities among young children under 24 months, which supports its robustness and reliability. However, the impact of these tests on patient care at point-of-care cannot be clearly assessed when considering the limits of the study 2 design.

We sequenced the first Bovine coronavirus (BCoV) complete genome sequence from France. This BCoV was directly sequenced from a fecal sample collected from a calf in Normandy in 2014., (Copyright © 2017 Kin et al.)

International case definitions recommended by the Centers for Disease Control and Prevention (CDC), the European Centre for Disease Prevention and Control (ECDC), and the World Health Organization (WHO) are commonly used for influenza surveillance. We evaluated clinical factors associated with the laboratory-confirmed diagnosis of influenza and the performance of these influenza case definitions by using a complete dataset of 14,994 patients with acute respiratory infection (ARI) from whom a specimen was collected between August 2009 and April 2014 by the Groupes Régionaux d'Observation de la Grippe (GROG), a French national influenza surveillance network. Cough and fever ≥ 39 °C most accurately predicted an influenza infection in all age groups. Several other symptoms were associated with an increased risk of influenza (headache, weakness, myalgia, coryza) or decreased risk (adenopathy, pharyngitis, shortness of breath, otitis/otalgia, bronchitis/ bronchiolitis), but not throughout all age groups. The WHO case definition for influenza-like illness (ILI) had the highest specificity with 21.4%, while the ECDC ILI case definition had the highest sensitivity with 96.1%. The diagnosis among children younger than 5 years remains challenging. The study compared the performance of clinical influenza definitions based on outpatient surveillance and will contribute to improving the comparability of data shared at international level., (This article is copyright of The Authors, 2017.)

Measles outbreaks are regularly reported in European countries despite efforts to improve vaccination coverage. In January 2016, an outbreak occurred in a refugee settlement in Calais, France. We report here the complete genome sequence of a wild-type measles virus isolated from a health care worker (MVi/Calais. FRA/01.16) infected during this outbreak., (Copyright © 2017 Dina et al.)

Human coronaviruses (HCoV) are single strand RNA viruses. To date, there are four so-called « classical » or « novel » HCoVs, characterized by a winter circulation. These coronaviruses are responsible for mild respiratory infection in general population. However, HCoVs are associated to more severe respiratory tract infection among susceptible population. Indeed, HCoVs account for 2 to 7% of hospitalizations due to a respiratory infection, particularly among children, immunocompromised or elderly people. Thereby, HCoVs are included in the panel of respiratory viruses detected in routine using molecular biology tools. These four circulating HCoVs have to be distinguished from the two emerging HCoVs: SARS-CoV and MERS-CoV. These later are associated to a more severe respiratory infection and differ from other HCoVs by their increased epidemic potential, their more important health impact, and their atypical circulation. Such as paramyxoviruses and Influenza viruses, coronaviruses have to be monitored due to their associated risk of emergence in human population from animal reservoirs., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Bronchiolitis epidemiology. Respiratory syncytial virus is the most important viral pathogen causing acute lower respiratory infection and infants hospitalizations. Other viruses are also identified (métapneumovirus, rhino/enterovirus, coronavirus, influenza, parainfluenza, adenovirus …). The research develops on new therapies and prevention., Competing Interests: J. Brouard déclare des interventions ponctuelles pour Novartis ( board « Asthme grave et mucoviscidose ») et Astra-Zeneca ( board « Grippe enfant »), Pasteur-Merrieux, MSD et ALK ; et avoir été pris en charge lors de congrès par ALK, Astra-Zeneca, Nestlé et Novartis. L. Tran, A. Flammang et A. Vabret déclarent n’avoir aucun lien d’intérêts.

Competing Interests: J. Brouard déclare des interventions ponctuelles pour Novartis ( board « Asthme grave et mucoviscidose ») et AstraZeneca ( board « Grippe enfant »), Pasteur/Merrieux, MSD et ALK ; et avoir été pris en charge lors de congrès par ALK, AstraZeneca, Nestlé et Novartis. L. Tran, A. Flammang et A. Vabret déclarent n’avoir aucun lien d’intérêts.

Background: Severe acute respiratory illness (SARI) is recognized as an important cause of morbidity, mortality, and hospitalization among children in developing countries. Little is known, however, in tropical countries like Cameroon about the cause and seasonality of respiratory infections, especially in hospitalized settings., Objectives: Our study investigates the viral etiology and seasonality of SARI in hospitalized children in Yaounde, Cameroon., Methods: Prospective clinic surveillance was conducted to identify hospitalized children aged ≤15 years presenting with respiratory symptoms ≤5-day duration. Demographic and clinical data, and respiratory specimens were collected. Nasopharyngeal samples were tested for 17 respiratory viruses using a multiplex polymerase chain reaction. The viral distribution and demographic data were statistically analyzed., Results: From September 2011 through September 2013, 347 children aged ≤15 years were enrolled. At least one virus was identified in each of 65·4% children, of which 29·5% were coinfections; 27·3% were positive for human adenovirus (hAdV), 13·2% for human respiratory syncytial virus (hRSV), 11·5% for rhinovirus/enterovirus (RV/EV), 10·6% for human bocavirus (hBoV), 9·8% for influenza virus (Inf), 6·6% for human parainfluenza virus (hPIV), 5·7% for human coronavirus (hCoV), and 2·3% for human metapneumovirus (hMPV). While hRSV showed seasonal patterns, hAdV and RV/EV were detected throughout the year and no evident temporal patterns were observed for the remaining viruses., Conclusion: Respiratory viruses were associated with a high burden of hospitalizations among children in Cameroon. Nevertheless, additional studies evaluating asymptomatic Cameroonian children will be important in understanding the relationship between viral carriage and disease., (© 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

The objective of this study is primarily to compare the performance of the VIDAS(®) Measles immunoglobulin (Ig)G assay to that of two other serological assays using an immunoassay technique, Enzygnost(®) Anti-measles Virus/IgG (Siemens) and Measles IgG CAPTURE EIA(®) (Microimmune). The sensitivity and the agreement of the VIDAS(®) Measles IgG assay compared to the Enzygnost(®) Anti-measles Virus/IgG assay and the Measles IgG CAPTURE EIA(®) assay are 100%, 97.2% and 99.0%, 98.4%, respectively. The very low number of negative sera for IgG antibodies does not allow calculation of specificity. As a secondary objective, we have evaluated the ability of the VIDAS(®) Measles IgG assay to measure anti-measles virus IgG antibody avidity with the help of the VIDAS(®) CMV IgG Avidity reagent, using 76 sera from subjects with measles and 238 other sera. Different groups of populations were analyzed. In the primary infection measles group, the mean IgG avidity index was 0.16 (range of 0.07 to 0.93) compared to 0.79 (range of 0.25 to 1) in the serum group positive for IgG antibodies and negative for IgM. These data allow to define a weak anti-measles virus IgG antibody avidity as an avidity index (AI) < 0.3 and a strong avidity as an AI > 0.6. The VIDAS(®) Measles IgG assay has a performance equivalent to that of other available products. Its use, individual and quick, is well adapted to testing for anti-measles immunity in exposed subjects.

Background: Respiratory viral diagnosis of upper respiratory tract infections has largely developed through multiplex molecular techniques. Although the sensitivity of different types of upper respiratory tract samples seems to be correlated to the number of sampled cells, this link remains largely unexplored., Methods: Our study included 800 upper respiratory tract specimens of which 400 negative and 400 positive for viral detection in multiplex PCR. All samples were selected and matched for age in these 2 groups. For the positive group, samples were selected for the detected viral species., Results: Among the factors influencing the cellularity were the type of sample (p < 0.0001); patient age (p < 0.001); viral positive or negative nature of the sample (p = 0.002); and, for the positive samples, the number of viral targets detected (0.004 < p < 0.049) and viral species., Conclusion: The cellular load of upper respiratory samples is multifactorial and occurs for many in the sensitivity of molecular detection. However it was not possible to determine a minimum cellularity threshold allowing molecular viral detection. The differences according to the type of virus remain to be studied on a larger scale.

Bovine coronaviruses (BCoVs) are widespread around the world and cause enteric or respiratory infections among cattle. The current study includes 13 samples from BCoVs collected in Normandy during an 11-year period (from 2003 to 2014), 16 French HCoV-OC43s, and 113 BCoVs or BCoVs-like sequence data derived from partial or complete genome sequences available on GenBank. According to a genotyping method developed previously for HCoV-OC43, BCoVs and BCoVs-like are distributed on three main sub-clusters named C1, C2, and C3. Sub-cluster C1 includes BCoVs and BCoVs-like from America and Asia. Sub-cluster C2 includes BCoVs from Europe. Sub-cluster C3 includes prototype, vaccine, or attenuated BCoV strains. The phylogenetic analyses revealed the monophyletic status of the BCoVs from France reported here for the first time. Moreover, BCoV exhibits a relative genetic stability when compared to HCoV-OC43 we previously described from the same region. The numerous recombination detected between HCoV-OC43 were much less frequent for BCoV. The analysis points thus to the influence of different evolutive constraints in these two close groups., (Copyright © 2016 Elsevier B.V. All rights reserved.)

There is imperious need for efficient therapies against ubiquitous and life-threatening respiratory viruses, foremost among them being the human respiratory syncytial virus (hRSV). Several research groups who performed functional screens for broad-spectrum antivirals identified compounds targeting the de novo pyrimidine biosynthesis pathway. Despite their strong antiviral activity in vitro, whether such antimetabolites are effective in vivo remains highly controversial. Here, we evaluated two potent pyrimidine biosynthesis inhibitors developed in our laboratory, IPPA17-A04 and GAC50, in a model of mild hRSV-infection in cynomolgus macaques. In this model, hRSV replication is restricted to the epithelium of the upper respiratory tract, and is compatible with a topical treatment by intranasal sprays. The local administration of palivizumab, a neutralizing anti-hRSV antibody used in clinics, significantly reduced virus replication. In contrast, pyrimidine biosynthesis inhibitors did not show any inhibitory effect on hRSV growth when delivered topically as experimented in our model. Our results should help to better define the potential applications of this class of antimetabolites in the treatment of viral infections., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Acute Respiratory Infections (ARIs) are responsible for considerable morbidity and mortality worldwide. Documentation of respiratory specimens can help for an appropriate clinical management with a significant effect on the disease progress in patient, the antimicrobial therapy used and the risk of secondary spread of infection. Here, we compared the performances of four commercial multiplex kits used in French University Hospital diagnostic microbiology laboratories for the detection of ARI pathogens (i.e., the xTAG Respiratory Viral Panel Fast, RespiFinder SMART 22, CLART PneumoVir and Fast Track Diagnostics Respiratory Pathogen 33 kits). We used a standardised nucleic acids extraction protocol and a comprehensive comparative approach that mixed reference to well established real-time PCR detection techniques and analysis of convergent positive results. We tested 166 respiratory clinical samples and identified a global high degree of correlation for at least three of the techniques (xTAG, RespiFinder and FTD33). For these techniques, the highest Youden's index (YI), positive predictive (PPV) and specificity (Sp) values were observed for Core tests (e.g., influenza A [YI:0.86-1.00; PPV:78.95-100.00; Sp:97.32-100.00] & B [YI:0.44-1.00; PPV:100.00; Sp:100.00], hRSV [YI:0.50-0.99; PPV:85.71-100.00; Sp:99.38-100.00], hMPV [YI:0.71-1.00; PPV:83.33-100.00; Sp:99.37-100.00], EV/hRV [YI:0.62-0.82; PPV:93.33-100.00; Sp:94.48-100.00], AdV [YI:1.00; PPV:100.00; Sp:100.00] and hBoV [YI:0.20-0.80; PPV:57.14-100.00; Sp:98.14-100.00]). The present study completed an overview of the multiplex techniques available for the diagnosis of acute respiratory infections.