Characteristics of human metapneumovirus infection in adults hospitalized for community-acquired influenza-like illness in France, 2012-2018: a retrospective observational study.

OBJECTIVES: To describe the prevalence, clinical features and complications of human metapneumovirus (hMPV) infections in a population of adults hospitalized with influenza-like illness (ILI). METHODS: This was a retrospective, observational, multicenter cohort study using prospectively collected data from adult patients hospitalized during influenza virus circulation, for at least 24 h, for community-acquired ILI (with symptom onset <7 days). Data were collected from five French teaching hospitals over six consecutive winters (2012-2018). Respiratory viruses were identified by multiplex reverse transcription polymerase chain reaction (RT-PCR) on nasopharyngeal specimens. hMPV + patients were compared with hMPV- patients, influenza+ and respiratory syncytial virus (RSV)+ patients using multivariate logistic regressions. Primary outcome was the prevalence of hMPV in patients hospitalized for ILI. RESULTS: Among the 3148 patients included (1449 (46%) women, 1988 (63%) aged 65 and over; 2508 (80%) with chronic disease), at least one respiratory virus was detected in 1604 (51%, 95% confidence interval (CI) 49-53), including 100 cases of hMPV (100/3148, 3% 95% CI 3-4), of which 10 (10%) were viral co-infection. In the hMPV + patients, mean length of stay was 7 days, 62% (56/90) developed a complication, 21% (14/68) were admitted to intensive care unit and 4% (4/90) died during hospitalization. In comparison with influenza + patients, hMPV + patients were more frequently >65 years old (adjusted odds ratio (aOR) = 3.3, 95% CI 1.9-6.3) and presented more acute heart failure during hospitalization (aOR = 1.8, 95% CI 1.0-2.9). Compared with RSV + patients, hMPV + patients had less cancer (aOR = 0.4, 95% CI 0.2-0.9) and were less likely to smoke (aOR = 0.5, 95% CI 0.2-0.9) but had similar outcomes, especially high rates of respiratory and cardiovascular complications. CONCLUSIONS: Adult hMPV infections mainly affect the elderly and patients with chronic conditions and are responsible for frequent cardiac and pulmonary complications similar to those of RSV infections. At-risk populations would benefit from the development of antivirals and vaccines targeting hMPV.

Detection of SARS-CoV-2 antibodies using commercial assays and seroconversion patterns in hospitalized patients.

OBJECTIVES: SARS-CoV-2 antibody assays are needed for serological surveys and as a complement to molecular tests to confirm COVID-19. However, the kinetics of the humoral response against SARS-CoV-2 remains poorly described and relies on the performance of the different serological tests. METHODS: In this study, we evaluated the performance of six CE-marked point-of-care tests (POC) and three ELISA assays for the diagnosis of COVID-19 by exploring seroconversions in hospitalized patients who tested positive for SARS-CoV-2 RNA. RESULTS: Both the ELISA and POC tests were able to detect SARS-CoV-2 antibodies in at least half of the samples collected seven days or more after the onset of symptoms. After 15 days, the rate of detection rose to over 80% but without reaching 100%, irrespective of the test used. More than 90% of the samples collected after 15 days tested positive using the iSIA and Accu-Tell® POC tests and the ID.Vet IgG ELISA assay. Seroconversion was observed 5 to 12 days after the onset of symptoms. Three assays suffer from a specificity below 90% (EUROIMMUN IgG and IgA, UNscience, Zhuhai Livzon). CONCLUSIONS: The second week of COVID-19 seems to be the best period for assessing the sensitivity of commercial serological assays. To achieve an early diagnosis of COVID-19 based on antibody detection, a dual challenge must be met: the immunodiagnostic window period must be shortened and an optimal specificity must be conserved.

Epidemiological survey in a day care center following toddler sudden death due to human metapneumovirus infection.

We report the sudden death of a 33-month-old child owing to acute respiratory distress syndrome due to human metapneumovirus (hMPV) infection. Of 30 children attending the same day care centre, 26% and 59% had hMPV and multiple infections, respectively; three of six children with pneumonia had a diagnosis of hMPV. hMPV infection is common in childhood viral co-infections but it can cause sudden death.

Usutu virus: A new threat?

Usutu virus (USUV) is an emerging arbovirus that was first isolated in South Africa in 1959. This Flavivirus is maintained in the environment through a typical enzootic cycle involving mosquitoes and birds. USUV has spread to a large part of the European continent over the two decades mainly leading to substantial avian mortalities with a significant recrudescence of bird infections recorded throughout Europe within the few last years. USUV infection in humans is considered to be most often asymptomatic or to cause mild clinical signs. Nonetheless, a few cases of neurological complications such as encephalitis or meningoencephalitis have been reported. USUV and West Nile virus (WNV) share many features, like a close phylogenetic relatedness and a similar ecology, with co-circulation frequently observed in nature. However, USUV has been much less studied and in-depth comparisons of the biology of these viruses are yet rare. In this review, we discuss the main body of knowledge regarding USUV and compare it with the literature on WNV, addressing in particular virological and clinical aspects, and pointing data gaps.

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.

Laboratory surveillance of arboviral infections in a southern France region colonized by Aedes albopictus.

The establishment of Aedes albopictus in southern France, a recognized competent vector for several arboviruses, represents a new threat for the local transmission and spread of what were until recently considered as tropical diseases. A preparedness and response plan, based on vigilance of both clinicians and laboratories, has introduced significant changes in guidelines and behaviour regarding patients' care specifically during the activity period of mosquitoes. In the present study, we report the results of a 1-year activity in arboviral infection diagnosis. A total of 141 patients were included in this retrospective study. The number of suspected imported and autochthonous cases was 69 and 72, respectively. A diagnosis of arboviral infection was confirmed for 15 (21·7%) suspected imported cases, with identification of 13 dengue viruses, one chikungunya virus and one Zika virus. No autochthonous cases were detected. This report illustrates the increase in requests for arboviral infection diagnosis and confirms the challenge with identifying autochthonous arboviral infection cases in many unspecific febrile syndromes.

Clinical characteristics and outcome of respiratory syncytial virus infection among adults hospitalized with influenza-like illness in France.

OBJECTIVES: The aim of this study was to analyse characteristics and outcome of respiratory syncytial virus (RSV) infection in adults hospitalized with influenza-like illness (ILI). METHODS: Patients hospitalized with ILI were included in this prospective, multicentre study carried out in six French hospitals during three consecutive influenza seasons (2012-2015). RSV and other respiratory viruses were detected by multiplex PCR in nasopharyngeal swabs. Risk factors for RSV infection were identified by backward stepwise logistic regression analysis. RESULTS: A total of 1452 patients hospitalized with ILI were included, of whom 59% (861/1452) were >65 years and 83% (1211/1452) had underlying chronic illnesses. RSV was detected in 4% (59/1452), and influenza virus in 39% (566/1452). Risk factors for RSV infection were cancer (adjusted OR 2.1, 95% CI 1.1-4.1, p 0.04), and immunosuppressive treatment (adjusted OR 2.0, 95% CI 1.1-3.8, p 0.03). Patients with RSV had a median length of stay of 9 days (6-25), and 57% of them (30/53) had complications, including pneumonia (23/53, 44%) and respiratory failure (15/53, 28%). Fifteen per cent (8/53) were admitted to an intensive care unit, and the in-hospital mortality rate was 8% (4/53). Pneumonia was more likely to occur in patients with RSV than in patients with RSV-negative ILI (44% (23/53) versus 26% (362/1393), p 0.006) or with influenza virus infection (44% versus 28% (157/560), p 0.02). CONCLUSION: RSV is an infrequent cause of ILI during periods of influenza virus circulation but can cause severe complications in hospitalized adults. Risk factors for RSV detection in adults hospitalized with ILI include cancer and immunosuppressive treatment. Specific immunization and antiviral therapy might benefit patients at risk.

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.

Chikungunya outbreak in Montpellier, France, September to October 2014.

In October 2014, an outbreak of 12 autochthonous chikungunya cases, 11 confirmed and 1 probable, was detected in a district of Montpellier, a town in the south of France colonised by the vector Aedes albopictus since 2010. A case returning from Cameroon living in the affected district was identified as the primary case. The epidemiological investigations and the repeated vector control treatments performed in the area and around places frequented by cases helped to contain the outbreak. In 2014, the chikungunya and dengue surveillance system in mainland France was challenged by numerous imported cases due to the chikungunya epidemic ongoing in the Caribbean Islands. This first significant outbreak of chikungunya in Europe since the 2007 Italian epidemic, however, was due to an East Central South African (ECSA) strain, imported by a traveller returning from West Africa. Important lessons were learned from this episode, which reminds us that the threat of a chikungunya epidemic in southern Europe is real.

[Childhood parvovirus B19 encephalitis]. / Encéphalite à parvovirus B19 de l'enfant.

INTRODUCTION: Human parvovirus B19 (PVB19) causes erythema infectiosum or 5(th) disease in childhood, which mainly affects children between 3 and 15 years of age. PVB19 infections have also been described in association with a variety of neurologic manifestations including encephalitis. CASE REPORT: This 3-year 8-month-old boy developed febrile encephalitis (mental status change with seizures and left limb hypertonia) associated with a rash. The electroencephalographs revealed focal slowing with some spikes in front of the left centro-temporo-occipital areas ; bacteriological and biochemical cerebrospinal fluid (CSF) analysis were normal, brain radiologic studies (tomography and magnetic resonance imaging) were normal. The diagnosis of encephalitis associated with PVB19 primo infection was based on viral DNA detection in the serum and CSF using PCR and on the specific immunoglobulin M (without immunoglobulin G) detection in the serum. DISCUSSION: In France, encephalitis etiology is unknown in 48% of the cases. PVB19 accounts for 4.3% of undiagnosed meningoencephalitis in children. Although there is no specific sign, seizures and rash are reported in about one-half and one-quarter of cases, respectively. CONCLUSION: Even if PVB19 research is not cited in the French or American infectious disease society recommendations on the diagnosis and management of infectious encephalitis, this virus may be responsible, especially in cases of child febrile rash. Therefore, PVB19 research seems reasonable if the clinical presentation is concordant in children due to its diagnostic simplicity and efficacy.

Monthly screening for BK viremia is an effective strategy to prevent BK virus nephropathy in renal transplant recipients.

BACKGROUND: BK polyomavirus virus (BKV) nephropathy (BKVN) is the most common viral infection that affects renal allografts. Because a specific antiviral therapy is lacking, BKVN may result in graft dysfunction and/or loss. We prospectively analyzed whether monthly nucleic acid testing (NAT) for BKV replication in blood and immediate reduction of immunosuppression (IS) could prevent BKVN. METHODS: NAT was performed at monthly intervals for 6 months and then at 12 months in 119 de novo renal transplant recipients. In viremic patients (presumptive BKVN), a graft biopsy was systematically performed and IS was immediately reduced. RESULTS: BKV viremia occurred in 13 (10.9%) patients after a median time of 90 days (23-241); 77% of patients were viremic before month 4. After reduction of IS, viral load was undetectable in 11 patients, remained low in 1, and continued to increase in 1 patient who developed definitive BKVN despite reduction of IS, and finally returned to dialysis 6 months after transplantation. CONCLUSION: BKV infection is an early complication. Monthly NAT in blood during the first 6 months and immediate reduction of IS in viremic patients almost completely prevent definitive BKVN.

Merkel cell polyomavirus DNA detection in lesional and nonlesional skin from patients with Merkel cell carcinoma or other skin diseases.

Background A novel polyomavirus, the Merkel cell polyomavirus (MCPyV), has recently been identified in Merkel cell carcinoma (MCC). Objectives To investigate the specificity of this association through the detection, quantification and analysis of MCPyV DNA in lesional and nonlesional skin biopsies from patients with MCC or with other cutaneous diseases, as well as in normal skin from clinically healthy individuals. Methods DNA was extracted from lesional and nonlesional skin samples of patients with MCC or with other cutaneous diseases and from normal-appearing skin of clinically healthy subjects. MCPyV DNA was detected by polymerase chain reaction (PCR) and quantified by real-time PCR. Additionally, the T antigen coding region was sequenced in eight samples from seven patients. Results MCPyV DNA was detected in 14 of 18 (78%) patients with MCC, five of 18 (28%) patients with other skin diseases (P = 0.007) and one of six (17%) clinically healthy subjects. In patients with MCC, viral DNA was detected in nine of 11 (82%) tumours and in 10 of 14 (71%) nontumoral skin samples (P = 0.66). MCPyV DNA levels were higher in MCC tumours than in nontumoral skin from patients with MCC, and than in lesional or nonlesional skin from patients with other cutaneous disorders. Signature mutations in the T antigen gene were not identified in the two MCC tumour specimens analysed. Conclusions High prevalence and higher levels of MCPyV DNA in MCC supports a role for MCPyV in tumorigenesis. However, the high prevalence of MCPyV in the nontumoral skin and in subjects without MCC suggests that MCPyV is a ubiquitous virus.

[West Nile virus infections in children]. / Infections à virus West Nile en pédiatrie.

West Nile Virus infection is an arbovirosis accidentally transmitted to humans from an aviary reservoir via an infected mosquito. Though a French surveillance network set up in 2001 reports low circulation in France, the virus is endemic in other territories. Approximately 80% of infected children remain asymptomatic, fever is seen in 20%, and very few develop a severe neurological disease in the patient's blood or spinal fluid. Treatment remains essentially symptomatic though new specific antiviral treatments and human immunization are currently being developed.

[Human bocavirus (HBoV)]. / Le bocavirus humain (HBoV).

The human bocavirus (HBoV) has been recently identified by means of molecular screening techniques in respiratory tract secretions from children with acute respiratory tract disease. This virus, which belongs to the Parvoviridae family, has been detected worldwide with a 5 to 10% prevalence among children with upper or lower respiratory tract infections, essentially during the winter period. A seroepidemiological study has shown that almost all the children have antibodies to HBoV by the age of five years, and HBoV infection seems to be rare in adults. HBoV is often detected in association with other respiratory viruses. This virus has also been detected in stools, but its role in gastroenteritis has not been yet established. Virological diagnostic of HBoV infection is based on the detection of viral DNA by PCR. Viral load determination by viral DNA quantitation in respiratory tract secretions could be a tool to differentiate between symptomatic HBoV infection and virus carriage.

Effect of HIV-1 and antiretroviral therapy on herpes simplex virus type 2: a prospective study in African women.

OBJECTIVES: To document the natural history of herpes simplex virus type 2 (HSV-2) in relation to HIV and highly active antiretroviral therapy (HAART) in Africa, a longitudinal study was conducted of women in the placebo arms of two randomised controlled trials of HSV-suppressive therapy in Burkina Faso. METHODS: 22 HIV-uninfected women (group 1), 30 HIV-1-infected women taking HAART (group 2), and 68 HIV-1-infected women not eligible for HAART (group 3) were followed over 24 weeks. HSV-2 DNA was detected on alternate weeks using real-time PCR from cervicovaginal lavages. Plasma HIV-1 RNA was measured every month. CD4 cell counts were measured at enrollment. RESULTS: Ulcers occurred on 1.9%, 3.1% and 7.2% of visits in groups 1, 2 and 3 (p = 0.02). Cervicovaginal HSV-2 DNA was detected in 45.5%, 63.3% and 67.6% of women (p = 0.11), and on 4.3%, 9.7% and 15.5% of visits in the three groups (p<0.001). Among HIV-infected women, cervicovaginal HSV-2 DNA was detected more frequently during ulcer episodes (adjusted risk ratio (aRR) 2.79, 95% CI 2.01 to 3.86) and less frequently among women practising vaginal douching (aRR 0.60, 95% CI 0.40 to 0.91). Compared with women not taking HAART and with CD4 cell counts of 500 cells/microl or greater, women on HAART had a similar risk of HSV-2 shedding (aRR 0.95, 95% CI 0.52 to 1.73), whereas women with CD4 cell counts of 200-500 cells/microl were more likely to shed HSV-2 (aRR 1.71, 95% CI 1.02 to 2.86). CONCLUSIONS: HSV-2 reactivations occur more frequently among HIV-infected women, particularly those with low CD4 cell counts, and are only partly reduced by HAART. HSV therapy may benefit HIV-infected individuals during HAART.