Characteristics of respiratory viruses' circulation through a six-year period (2016-2022) in a pediatric population in Normandy, France, and the impact of COVID-19 pandemic.

IMPORTANCE: The report highlights an epidemiological change in the circulation of respiratory viruses in pediatric populations due to strategies adopted against COVID-19 pandemic. COVID-19 has resulted in a significant increase in requests for multiplex respiratory research to identify the virus responsible for the symptoms. The diagnostic needs have increased, and the number of samples analyzed in 2021-2022 is equal to the samples analyzed over the four epidemic periods preceding the pandemic. The report suggests the importance of active surveillance of respiratory viruses' circulation and new recommendations for respiratory virus detection in pediatric patients.

[ECOVIR: Study of a primary care cohort in of patients with Acute Respiratory Infections in Normandy, an example of pluri-professional hospital-primary care coordination]. / ECOVIR : mise en place d'une cohorte en soins primaires, un exemple de coopération pluri-professionnelle ville-hôpital.

Acute Respiratory Infections (ARI) need be better understood and more effectively treated, especially insofar as they are of pivotal importance in public health, particularly during a crisis such as the SARS-CoV2 pandemic. The prospective, multicentric cohort study of viral codetections in respiratory samples study known as ECOVIR was conducted in Normandy, France during two winters (2018-2019, 2019-2020). The objective of the project was to create a biobank of respiratory tract samples from patients consulting their general practitioner (GP) for ARI symptoms. ECOVIR involved 36 GP investigators (GPI), from 8 health care centers throughout Normandy. Six hundred and eighty-five patients with ARI symptoms were included; naso-pharyngeal samples were taken by the GPIs and subsequently analyzed in virology laboratories for the purposes of viral codetection. The median of inclusions was 16 patients for each of the 31 actively participating GPIs over the two winters (CI25-75% [4.75; 27]). By D7, 92% of the patients contacted had responded to our call for participation, enabling us to obtain clinical, environmental and socio-demographic data. Through this study, we created an original functional network, thereby establishing a viable link between research and primary care, which is generally underrepresented in research protocols, even though it constitutes the cornerstone of the French health care system, especially during this prolonged period of sanitary crisis.

[Virological diagnosis of lower respiratory tract infections]. / Diagnostic virologique des infections respiratoires basses.

INTRODUCTION: The etiological diagnosis of bronchopulmonary infections cannot be assessed with clinical, radiological and epidemiological data alone. Viruses have been demonstrated to cause a large proportion of these infections, both in children and adults. BACKGROUND: The diagnosis of viral bronchopulmonary infections is based on the analysis of secretions, collected from the lower respiratory tract when possible, by techniques that detect either influenza and respiratory syncytial viruses, or a large panel of viruses that can be responsible for respiratory disease. The latter, called multiplex PCR assays, allow a syndromic approach to respiratory infection. Their high cost for the laboratory raises the question of their place in the management of patients in terms of antibiotic economy and isolation. In the absence of clear recommendations, the strategy and equipment are very unevenly distributed in France. OUTLOOK: Medico-economic analyses need to be performed in France to evaluate the place of these tests in the management of patients. The evaluation of the role of the different viruses often detected in co-infection, especially in children, also deserves the attention of virologists and clinicians. CONCLUSIONS: The availability of new diagnostic technologies, the recent emergence of SARS-CoV-2, together with the availability of new antiviral drugs are likely to impact future recommendations for the management of viral bronchopulmonary infections.

[State of immunization against measles among health professionals in at-risk units of the Caen University Hospital]. / État d'immunisation contre la rougeole chez les professionnels de santé au sein des services à risques du centre hospitalier universitaire de Caen.

BACKGROUND: France is facing a new resurgence of measles. Since November 2017, the number of cases has been increasing sharply. Immunization coverage in the general population, all ages combined, is below the threshold required for a rapid decline of the virus propagation. Regarding health professionals, the rate of immunization against this disease is insufficiently documented. In this context, the Occupational Health Service of the University Hospital of Caen has carried out an inventory of health personnel knowledge of immunization against measles in the units the most exposed to risk. METHODS: Knowledge of immunization against measles was studied in pediatric, imaging, and pediatric and adult emergencies departments of the University Hospital of Caen, and the Hematology Institute of Lower Normandy (IHBN). The analysis included all health professionals present within these units during the study period: March and April 2018. Data collection was carried out by consulting the medical files of the occupational health unit and considering the set of responses to postal inquiries sent to staff. RESULTS: Measured immunization status data refer to 1017 health professionals. Based on the criteria specific to the recommendations, 234 (50.6%) of the 462 professionals born before 1980 and 437 (78.7%) of the 555 professionals born in or after 1980 could be considered as immune. Of the total sample, 115 (11.3%) had positive measles serology. Among these 1017 professionals, information on the state of immunization against measles was lacking for 174 (17.1%). CONCLUSION: The state of immunization of the nursing staff remains insufficient to prevent the occurrence of measles cases and the staff is also insufficiently informed. It is essential to have knowledge of the immunization status of this population, to organize the vaccination of non-immunized personnel within the occupational health unit, to prevent the emergence of new cases of measles and to reinforce the information regarding the importance of precautions related to airborne transmission in case of measles.

[Virus and Atypical Pathogens Detected in Community-Acquired Lower Respiratory Tract Infection in Infants and Children of Sfax Region, Tunisia]. / Virus et bactéries atypiques détectés dans les infections respiratoires basses communautaires de l'enfant dans la région de Sfax en Tunisie.

Little is known about viral and atypical bacteria pathogen spectra of community-acquired lower respiratory tract infection in children in Tunisia. Thus, a prospective study was carried out between January 2009 and March 2010 in Sfax. Nasopharyngeal aspirates collected from 368 patients (78 with pneumonia and 290 with acute bronchiolitis) were analyzed by indirect immunofluorescence assay and PCR to detect influenza viruses, parainfluenza viruses, respiratory syncytial virus (RSV), human metapneumovirus, human rhinovirus, human enterovirus, adenovirus, coronavirus, Mycoplasma pneumonia (Mpn) and Chlamydia pneumonia (Cpn). One or more etiology was documented in 319 cases (86.7%). The most detected viruses were RSV (42.7%), rhinovirus (32.9%) and adenovirus (28.5%). Co-detection of two or three pathogens was found in 40% of positive samples. This study highlights the importance of respiratory viruses in lower respiratory tract infection in children of Sfax region as well as the high rate of co-detection of multiple viruses, resulting in challenges in clinical interpretation.

Le profil étiologique microbien des infections respiratoires basses (IRB) communautaires de l'enfant a été peu étudié en Tunisie. Une étude prospective a été menée à Sfax entre janvier 2009 et mars 2010 sur 368 enfants hospitalisés pour pneumonie (n = 78) ou bronchiolite aiguë (n = 290). Les aspirations nasopharyngées ont été analysées par immunofluorescence et par PCR à la recherche des virus influenza, virus para-influenza, virus respiratoire syncytial (VRS), métapneumovirus, rhinovirus, entérovirus, adénovirus, coronavirus, Mycoplasma pneumoniae (Mpn) et Chlamydia pneumoniae (Cpn). Une étiologie ou plus a été retrouvée dans 319 cas (86,7 %) : principalement le VRS (42,7 %), des rhinovirus (32,9 %) et des adénovirus (28,5 %). Dans 40 % des prélèvements positifs, deux ou trois agents pathogènes ont été codétectés. Cette étude a permis de montrer la prévalence élevée des virus dans les IRB de l'enfant dans la région de Sfax et leur détection fréquente en co-infection posant la question sur leur rôle pathogène réel.

Single reaction, real time RT-PCR detection of all known avian and human metapneumoviruses.

Current molecular methods for the detection of avian and human metapneumovirus (AMPV, HMPV) are specifically targeted towards each virus species or individual subgroups of these. Here a broad range SYBR Green I real time RT-PCR was developed which amplified a highly conserved fragment of sequence in the N open reading frame. This method was sufficiently efficient and specific in detecting all MPVs. Its validation according to the NF U47-600 norm for the four AMPV subgroups estimated low limits of detection between 1000 and 10copies/µL, similar with detection levels described previously for real time RT-PCRs targeting specific subgroups. RNA viruses present a challenge for the design of durable molecular diagnostic test due to the rate of change in their genome sequences which can vary substantially in different areas and over time. The fact that the regions of sequence for primer hybridization in the described method have remained sufficiently conserved since the AMPV and HMPV diverged, should give the best chance of continued detection of current subgroups and of potential unknown or future emerging MPV strains.

Predominance of G9P[8] rotavirus strains throughout France, 2014-2017.

OBJECTIVES: Group A rotavirus is a major cause of acute gastroenteritis in young children worldwide. A prospective surveillance network has been set up in France to investigate rotavirus infections and to detect the emergence of potentially epidemic strains. METHODS: From 2014 to 2017, rotavirus-positive stool samples were collected from 2394 children under 5 years old attending the paediatric emergency units of 13 large hospitals. Rotaviruses were genotyped by RT-PCR with regard to their outer capsid proteins VP4 and VP7. RESULTS: Genotyping of 2421 rotaviruses showed that after a marked increase in G9P[8] (32.1%) during the 2014-2015 season, G9P[8] became the predominant genotype during the 2015-2016 and 2016-2017 seasons with detection rates of 64.1% and 77.3%, respectively, whereas G1P[8] were detected at low rates of 16.8% and 6.6%, respectively. Phylogenetic analysis of the partial rotavirus VP7 and VP4 coding genes revealed that all of these G9P [8] strains belonged to the lineage III and the P [8]-3 lineage, respectively, and shared the same genetic background (G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1) as did most of previously detected G9P[8] strains and particularly the emerging G9P[8] strains from the 2004-2005 season in France. CONCLUSIONS: G9P[8] rotaviruses have become the predominant circulating genotype for the first time since their emergence a decade ago. In the absence of rotavirus immunization programmes in France, our data give an insight into the natural fluctuation of rotavirus genotypes in a non-vaccinated population and provide a base line for a better interpretation of data in European countries with routine rotavirus vaccination.

[Rhinovirus: Underestimated pathogens in patients during the neonatal period]. / Rhinovirus : des pathogènes sous-estimés chez les patients en période néonatale.

INTRODUCTION: In recent years, developments in virological tools have led to the easy detection of rhinoviruses and enteroviruses (E/RV). Their detection is very frequent in cases of airway involvement in children and their demonstrated causality. But the morbidity of E/RV in the neonatal period is unknown due to lack of epidemiological data. The objective of this study was to evaluate the incidence and clinical characteristics of these infections in hospitalized neonates. MATERIALS AND METHODS: We retrospectively analyzed the virology specimens of all neonates hospitalized at the Caen University Hospital between 2006 and 2011. Clinical characteristics were obtained from the charts. RESULTS: During the study period, 4544 infants aged less than 28 days were hospitalized: 4159 in the neonatal ward and 385 in the pediatric ward. Among these, 711 virology specimens were available, 31 % of which identified at least one virus. An E/RV was identified in 87 patients (1.9 % of the neonates admitted during the study period): 52 in the pediatric ward (13.5 % of 385), and 35 in the neonatal ward (0.8 % of 4159). The mean gestational age was 39 weeks in the pediatric cohort and 35 weeks in the neonatal cohort. The main indication for virological analysis was persistent drowsiness (28 %), temperature above 38°C (25 %), an apparently life-threatening event (23 %), bradycardia (20.5 %), and pallor (20.5 %). Respiratory symptoms associated with E/RV infection were coryza (74 %), cough (35 %), hypoxemia (32 %), accessory muscle use, and recession (31 %). Digestive symptoms were poor feeding (59 %), regurgitation (38 %), abdominal distension (24 %), and projectile vomiting (17 %). Twenty-three percent of the patients required admission to the neonatal ICU or pediatric ICU. Respiratory treatments included oxygen (24 % of 87 patients), continuous positive airway pressure (11 %), and ventilation (5 %). Antibiotics were prescribed in 41 % of the patients (46), but only 10 % (9) had an identified concomitant bacterial infection. In the neonatal department, nosocomial acquisition was suspected in 50 % of E/RV infections. CONCLUSION: E/RV infections have a significant morbidity in neonates, and nosocomial transmission of the virus is underestimated. We recommend that respiratory viruses, including E/RV, be tested for in any unexplained signs in a neonate. Better identification of viruses might shorten the duration of unnecessary antibiotics.

[The interactions between microorganisms and the small airways. A paediatric focus]. / Interactions micro-organismes et voies aériennes distales : spécificités pédiatriques.

The spectrum of respiratory viruses is expanding and emerging diseases have been described regularly over the last fifteen years. The origin of these emerging respiratory viruses may be zoonotic (by crossing species barrier, after changes to RNA viruses such as avian influenza virus type A or coronaviruses), or related to the use of new identification techniques (metapneumovirus, bocavirus). The relationship between bronchiolitis and asthma is now better understood thanks to prospective follow up of birth cohorts. The role of rhinovirus has become predominant with respect to respiratory syncytial virus. The identification of predisposing factors immunological, functional, atopic and genetic, for the onset of asthma after rhinovirus infection suggests that viral infection reveals a predisposition rather than itself being a cause of asthma. The role of bacteria in the natural history of asthma is also beginning to be better understood. The results of the COPSAC Danish cohort have shown the frequency of bacterial identification during wheezy episodes before 3 years, and the impact of bacterial colonization at the age of one month on the onset of asthma by age 5 years. The role of bacterial infections in severe asthma in young children is also discussed.

Prevalence of HIV-1 drug resistance in treated patients with viral load >50 copies/mL: a 2014 French nationwide study.

Background: Surveillance of HIV-1 resistance in treated patients with a detectable viral load (VL) is important to monitor, in order to assess the risk of spread of resistant viruses and to determine the proportion of patients who need new antiretroviral drugs with minimal cross-resistance. Methods: The HIV-1 protease and reverse transcriptase (RT) and integrase genes were sequenced in plasma samples from 782 consecutive patients on failing antiretroviral regimens, seen in 37 specialized centres in 2014. The genotyping results were interpreted using the ANRS v24 algorithm. Prevalence rates were compared with those obtained during a similar survey conducted in 2009. Results: The protease and RT sequences were obtained in 566 patients, and the integrase sequence in 382 patients. Sequencing was successful in 60%, 78%, 78% and 87% of patients with VLs of 51-200, 201-500, 501-1000 and >1000 copies/mL, respectively. Resistance to at least one antiretroviral drug was detected in 56.3% of samples. Respectively, 3.9%, 8.7%, 1.5% and 3.4% of patients harboured viruses that were resistant to any NRTI, NNRTI, PI and integrase inhibitor (INI). Resistance rates were lower in 2014 than in 2009. Resistance was detected in 48.5% of samples from patients with a VL between 51 and 200 copies/mL. Conclusion: In France in 2014, 90.0% of patients in AIDS care centres were receiving antiretroviral drugs and 12.0% of them had VLs >50 copies/mL. Therefore, this study suggests that 6.7% of treated patients in France might transmit resistant strains. Resistance testing may be warranted in all treated patients with VL > 50 copies/mL.

Clinical severity and molecular characteristics of circulating and emerging rotaviruses in young children attending hospital emergency departments in France.

Group A rotavirus (RVA) is the leading cause of acute gastroenteritis in young children worldwide. A prospective surveillance network has been set up to investigate the virological and clinical features of RVA infections and to detect the emergence of potentially epidemic strains in France. From 2009 to 2014, RVA-positive stool samples were collected from 4800 children <5 years old attending the paediatric emergency units of 16 large hospitals. Rotaviruses were then genotyped by RT-PCR with regard to their outer capsid proteins VP4 and VP7. Genotyping of 4708 RVA showed that G1P[8] strains (62.2%) were predominant. The incidence of G9P[8] (11.5%), G3P[8] (10.4%) and G2P[4] (6.6%) strains varied considerably, whereas G4P[8] (2.7%) strains were circulating mostly locally. Of note, G12P[8] (1.6%) strains emerged during the seasons 2011-12 and 2012-13 with 4.1% and 3.0% prevalence, respectively. Overall, 40 possible zoonotic reassortants, such as G6 (33.3%) and G8 (15.4%) strains, were detected, and were mostly associated with P[6] (67.5%). Analysis of clinical records of 624 hospitalized children and severity scores from 282 of them showed no difference in clinical manifestations or severity in relation to the genotype. The relative stability of RVA genotypes currently co-circulating and the large predominance of P[8] type strains may ensure vaccine effectiveness in France. The surveillance will continue to monitor the emergence of new reassortants that might not respond to current vaccines, all the more so as all genotypes can cause severe infections in infants.

[Respiratory syncytial virus (RSV) infections in the pediatric teaching hospital Charles de Gaulle of Ouagadougou, Burkina Faso]. / Infections à virus respiratoire syncytial (VRS) au CHU pédiatrique Charles de Gaulle de Ouagadougou, Burkina Faso.

Human respiratory syncytial virus (RSV) infections are little known in Burkina Faso. The objective of our work is to study the epidemiological and clinical aspects of RSV infections in infants in the Pediatric Teaching Hospital Charles de Gaulle of Ouagadougou. Between July 1(st) 2010 and June 30(th) 2011, we analyzed by direct immunofluorescence and PCR nasopharyngeal swabs from children from 0 to 36 months old. All in all, 210 patients among whom 74 from the external consultation (35.2%) and 136 hospitalized (64.7%) benefited from a nasopharyngeal aspiration. The motives for consultation were cough (91.7%), rhinitis (79.2%), fever (79.2%) and respiratory distress syndrome (66.7%). The evoked diagnoses were predominantly the acute bronchiolitis in 14 cases (58.3%) followed by the acute pulmonary disease in 7 patients (26.2%) then flue in 1 patient (16.7%). We detected by direct immunofluorescence the antigens of the respiratory viruses in 21 nasopharyngeal aspirations with 10 cases of respiratory syncytial virus (RSV) infections (47.6%). The PCR realized on 208 samples allowed to identify 153 positive samples (73.2%) with 24 RSV, i.e. a global prevalence of 16.1% with a peak of 18 cases (75%). In October, all the patients benefited from an often multiple antibiotic treatment of at least 10 days which was not still necessary. The evolution was favorable for all patients. This study confirms the important place of the viruses which are detected in 70% of the cases. The PCR multiplex, certainly expensive but effective and successful, deserves to be used in our developing countries to avoid the irrational prescription of antibiotic.

[Winter viral ecology in a pediatric intensive care unit: a prospective study]. / Étude prospective de l'écologie virale hivernale dans un service de réanimation pédiatrique.

INTRODUCTION: Viral respiratory infections are common in children, most of which are due to a virus. They can lead to serious infections, and these children may require treatment in a pediatric intensive care unit (PICU). This prospective study evaluated the epidemiology of respiratory viruses and associated illnesses among children hospitalized in a PICU during the three winter months of 2012-2013. METHODS: All the children admitted to the PICU, University Hospital of Caen, France, were included. Nasal swabs were collected and specimens were tested using a single real-time PCR (polymerase chain reaction). RESULTS: Of the 105 patients admitted to the PICU during the study period, 84 fulfilled the inclusion criteria. The "respiratory group" included 37 patients with respiratory symptoms at admission while the "nonrespiratory group" included 47 patients with no respiratory symptoms. The 84 nasal swabs collected included 54 that were considered positive (64.3%) and 70 viruses were detected. The most commonly detected virus was RSV (n=28; 40.0% positive samples), followed by HRV (n=24; 34.3%). Viruses were more frequently detected in the respiratory (86.5%) than in the nonrespiratory (42.6%) group (P<0.001). Statistical analysis by subgroups revealed that RSV infections were significantly more frequent in the respiratory group (54.1%) than in the nonrespiratory group (6.4%) (P<0.001). There was no difference for HRV (32.4% and 27.7%) or for the other viruses. No difference in duration of hospitalization or duration of mechanical ventilation was demonstrated depending on the virus detected. DISCUSSION: The use of the very sensitive multiplex PCR technique increased virus detection rates in both symptomatic and asymptomatic subjects. CONCLUSION: We have confirmed the frequency of RSV infections in a PICU and found that many patients without respiratory symptoms have respiratory infections caused by viruses. The impact of these infections on patient outcome should now be analyzed in order to demonstrate the role played by respiratory viruses.

[Recommendations for the use of diagnostic testing in low respiratory infections in children older than three months]. / Recommandations sur l'utilisation des nouveaux outils diagnostiques étiologiques des infections respiratoires basses de l'enfant de plus de trois mois.

Recommendations for the use of diagnostic testing in low respiratory infection in children older than 3 months were produced by the Groupe de Recherche sur les Avancées en Pneumo-Pédiatrie (GRAPP) under the auspices of the French Paediatric Pulmonology and Allergology Society (SP(2)A). The Haute Autorité de santé (HAS) methodology, based on formalized consensus, was used. A first panel of experts analyzed the English and French literature to provide a second panel of experts with recommendations to validate. Only the recommendations are presented here, but the full text is available on the SP(2)A website.