Long-term transmission of measles virus in Central and continental Western Europe.

The World Health Organization (WHO) has adopted an elimination goal for measles and rubella, which is supposed to be met in the WHO European Region (EUR) by 2015. For verification of elimination, it is required that the genotyping data of detected measles viruses provide evidence for the interruption of endemic transmission. In order to record and assess the extent of endemic measles virus (MV) circulation in a part of the EUR, we analyzed transmission chains of the epidemiologically most relevant MV variants identified in Central and continental Western Europe (CCWE) from 2006 to 2013. Based on MV sequence data deposited in the WHO global database for molecular surveillance of measles (MeaNS), the circulation period was calculated for each MV variant at the country-level and for the entire region of CCWE. The MV variants "D5-Okinawa," "D4-Hamburg," "D4-Manchester," and "D8-Frankfurt-Main" spread widely in CCWE; they caused large and long-lasting outbreaks with secondary spread that resulted in additional outbreaks. Nation-wide outbreaks (epidemics) with thousands of measles cases occurred in four countries (Switzerland, France, Bulgaria, and Romania) and were characterized by continuous detection of the same MV variant for more than 12 months suggesting endemic transmission. In the entire region of CCWE, the circulation period of the four predominant MV variants ranged from 18 to 44 months. The long-lasting MV transmission which affected predominantly unvaccinated individuals in different hard-to-reach groups and in the general population is not consistent with the measles elimination goal. Additional efforts are necessary to meet the elimination target in the EUR.

Adult patients hospitalized for measles in France, in the 21st century.

BACKGROUND: An epidemic of measles broke out in France in 2008. We designed a retrospective study focusing on adults hospitalized for measles in 2010/2011. METHODS: A case was any patient aged more than 15 years, hospitalized (September 2010 to September 2011) with a typical rash or a biological diagnosis. Data was collected with standardized questionnaires in participating hospitals. RESULTS: Four hundred and sixty cases were reported: sex-ratio (M/F) = 0.93, median age 26 years (σ = 8.8). Twenty-nine cases were severe (6.5%), 27 of which hospitalized in an ICU. Three hundred and twelve (68%) cases had elevated serum transaminases (EST), 155 (34%) cases had pneumonia, 34 (7%) cases had elevated serum creatinine (ESC), four (0.9%) cases had elevated serum amylase and lipase (ESAL), and three (0.7%) cases had neurological symptoms. One hundred and four (23%) patients presented simultaneously with EST and pneumonia. One patient presenting with severe pneumonia died (0.2%). One hundred and ten (24%) patients received antibiotics during a median seven days. CONCLUSION: Measles can present as various syndromes in adults and be responsible for a high burden during outbreaks. The immediate outcome is favorable in most patients. Long-term outcome needs further investigations to identify possible late complications.

Surveillance of equine influenza viruses through the RESPE network in France from November 2005 to October 2010.

REASONS FOR PERFORMING THE STUDY: The Réseau d'Epidémio-Surveillance en Pathologie Equine (RESPE, the French epidemiological network for equine diseases) is a network for epidemio-surveillance of major equine diseases based around sentry veterinarians in France. OBJECTIVE: The aim of this study was to evaluate the contribution of RESPE to efficient surveillance of equine influenza virus (EIV) in France. STUDY DESIGN: Retrospective cross-sectional study. METHODS: From November 2005 to October 2010, epidemiological and phylogenetic studies were performed on 1426 nasopharyngeal swabs received at the Frank Duncombe Laboratory. Detection was performed by real-time reverse transcription polymerase chain reaction using original primers and probes designed in the matrix protein gene. Phylogenetic analysis was carried out on the HA1 part of haemagglutinin gene amplified from 47 positive-testing samples. Epidemiological information was provided with the majority of samples submitted through RESPE. RESULTS: Of the 920 samples submitted by RESPE-associated veterinarians, 121 (13.1%) from 42 premises were positive for EIV, compared to 26 (5.1%) of the 607 samples received from non-RESPE associated veterinarians. The most extensive outbreak was observed between February and May 2009, affecting 70 horses on 23 premises, 15 of which were managed by RESPE-associated veterinarians. All strains belonged to the American lineage, Florida sublineage, Clade 1 and Clade 2. Clade 1 was identified only during the Grosbois episode. CONCLUSION: RESPE improved detection of EIV in France, enabled characterisation of the virus strains, yielded valuable information relating to the epidemiology of the disease and identified vaccine breakdown. POTENTIAL RELEVANCE: Implementation of a similar surveillance network in other countries may reduce the economic losses associated with outbreaks of EIV.

[Measles in France]. / Rougeole : que retenir de l'année 2011 ?

Measles is one of the most contagious diseases implicated in an outbreak in Western Europe for a few years. In France, the outbreak began in 2008, especially in the southern regions. Most of the cases are mild but deleterious effects can occur in infants, during the pregnancy, or in immunosuppressive patients. Pneumonia and encephalitis are the major complications in these patients. Measles illness during pregnancy results in a higher risk of premature labor, spontaneous abortion, and low-birthweight infants. Death from measles was reported in approximately 0.3% of cases. The National Reference Center for measles and paramyxoviridae is implicated in biological confirmation of cases and epidemiologic surveillance. Virologic diagnosis consists in a direct detection of viral RNA (real time PCR), or indirect detection of the immune response (IgM and IgG) in saliva samples. The measles genotype is determined by sequencing a 450 nucleotids fragment of the N gene, as the World Health Organization (WHO) recommendation. This molecular analysis helps determine the geographic origin of the virus and the viral strains circulating in the country. In 2011, 3105 specimens were received. PCR was positive for 1990 patients (64%), with a large majority of children younger than 2 years of age and young adults. The most important cause of measles resurgence is low vaccination coverage. The role of pediatricians is important in order to achieve the goal of 95% of vaccination coverage established by the WHO.

[Measles in pregnancy: a review]. / Rougeole chez la femme enceinte : mise au point.

Although measles is usually considered a benign viral disease of childhood, people may be affected whatever their age with severe pneumologic or neurologic consequences are more frequent before 5 years old and after 20 years old. The consequences of a congenital measles, defined as a newborn eruption within 10 days after birth, can be dramatic. The incidence of measles has significantly decreased since first vaccines were introduced in the late 1960s. In France, active immunization for measles is proposed since 1983. Since the beginning of 2008, France has been experiencing a measles outbreak with more than 17,000 notified cases. The current measles outbreak affects more particularly very young children and young adults and, among these, pregnant women. Measles during pregnancy may be severe mainly due to pneumonia. Measles is associated with a risk of miscarriage and prematurity, but congenital anomalies have not been described. If rash occurs near term, the consequences of congenital measles could be severe. Prevention of measles in pregnant women is based on improving immunization coverage, currently insufficient to eradicate virus circulation. The aim of this review is to state on the latest data concerning measles virus, give latest vaccine recommendations, and also to suggest management of measles contact or measles infection during pregnancy.

Outbreak of equine herpesvirus myeloencephalopathy in France: a clinical and molecular investigation.

Equid herpesvirus 1 (EHV-1)-associated myeloencephalopathy (EHM) is a disease affecting the central nervous system of horses. Despite the constantly increasing interest about this syndrome, epidemiological data are limited especially when related to the description of large outbreaks. The aim of this article is to describe clinical, virological and molecular data obtained throughout a severe outbreak of EHM, with emphasis on laboratory diagnostic methods. The epidemic disease concerned a riding school in France where 7/66 horses aged 12-22 years developed signs of neurological disease in July 2009. Diagnosis of EHM was supported by EHV-1 detection using both real-time PCR and virus culture, and SNP-PCR test for viral strain characterization. EHM morbidity was 10.6% (7/66), mortality was 7.5% (5/66) and case fatality rate was 71.4% (5/7). Clinical presentation of the disease was characterized by the fact that fever was systematically present within 2 days before the severe neurological signs were noted. EHV-1 was detected by PCR in each available blood and nasal swab samples. Neuropathogenic strain only (G(2254) ) was isolated during the current outbreak; C(t) values, used as an indicative level of the viral load, ranged 26.0-37.0 among the six sampled horses. The amount of virus in biological samples was not systematically related to the intensity of the clinical signs being observed. In conclusion, this article described a severe outbreak of EHM while limited in time and restricted to one premise. Molecular data strongly suggested taking into account any low viral load as being a potential risk factor for neurological manifestations.

Appearance of a novel measles G3 strain in multiple European countries within a two month period, 2010.

During late 2010, a previously unrecognised strain of measles genotype G3 virus was identified in five different European countries by the World Health Organization Measles and Rubella Laboratory Network.Apart from one, none had a travel history to south-east Asia, the usual source of G3 viruses, although epidemiological links could be established between some of the cases. This case series illustrates the value of genotyping and sequencing in tracking measles infections, and identifying otherwise unrecognised chains of transmission.

[Lymphocytic choriomeningitis virus and fetal anomalies]. / Infection par le virus de la chorioméningite lymphocytaire et fœtopathies.

OBJECTIVE: Lymphocytic choriomeningitis virus (LCMV), a rodent-borne arenavirus, is an uncommonly recognized cause of severe congenital viral infection. The incidence of this infection during pregnancy is still unknown. Our study aimed to evaluate LCMV infection frequency in pregnancy with fetal neurological abnormalities of unknown etiology. MATERIAL AND METHODS: Samples obtained during three years from 160 pregnant women were retrospectively analysed: 155 maternal sera, 150 amniotic fluids (AF) and 12 fetal sera (FS). Congenital neurological anomalies were diagnosed but TORCH and culture investigations were negatives. Serological analysis was performed with L929 cells infected with the Armstrong strain of LCMV. IgG and IgM antibodies against CMLV were researched by immunofluorescence assay using these infected cells. Interferon alpha was also assayed for AF and FS. RESULTS: No positive serology was found in any of the 317 samples investigated even when interferon alpha was detected. CONCLUSION: This result confirms the rarity of LCMV infection in France. Nevertheless, at the light of the recent literature, this teratogenic pathogen should be considered in pregnancy with unexplained congenital malformation, especially after rodent exposure.

Description of the first recorded major occurrence of equine viral arteritis in France.

REASONS FOR PERFORMING STUDY: The vast majority of equine arteritis virus (EAV) infections are inapparent or relatively mild, but may occasionally cause outbreaks of equine viral arteritis. The event observed in France during the summer of 2007 was the most important seen in the country, with mortality and disruption of economic activity. OBJECTIVES: To describe the different stages seen during the outbreak and to show how molecular tools were used for both the detection and management of the crisis. METHODS: EAV detection was performed by real-time reverse transcription-polymerase chain reaction (RT-PCR) in blood, nasal swabs, semen or organ samples. Characterisation of EAV strains was performed by sequencing the ORF5 fragment. RESULTS: The outbreak affected 18 premises in 5 counties in western France, which represented the index, 8 primary and 9 secondary premises. Artificial insemination in draught horses was responsible for the virus spread. Eight mortality cases were observed, including one fetus, 5 young foals and 2 mature horses. Forty-three individuals had positive results by real-time RT-PCR. The range of measured cycle threshold (Ct) values varied from 19.8 to 40.4 depending on the biological samples. Phylogenetic analysis revealed that the 33 isolated strains all clustered within the EU-2 subgroup. CONCLUSIONS: The mortality rate attests to the virulence of the strain involved in this outbreak. Real-time RT-PCR was used for the first time in order to follow-up an epidemic disease in horses. POTENTIAL RELEVANCE: The early detection of 3 signals with high Ct values attest the importance of taking low signals into account in field conditions.

Spotlight on measles 2010: update on the ongoing measles outbreak in France, 2008-2010.

Since early 2008, France has been experiencing a measles outbreak with almost 5,000 notified cases as of 30 June 2010, including three measles-related deaths. The proportion of cases 20 years or older reached 38% during the first half of 2010. This situation is the consequence of insufficient vaccine coverage (90% at age 24 months in 2007) that led to the accumulation of susceptibles over the last years. It underlines the need for additional measures targeting susceptible children and young adults.

[Bronchiolitis viruses]. / Les virus des bronchiolites aiguës.

In Normandy (France), human respiratory syncytial virus (hRSV) was detected in 64.1% of acute bronchiolitis in hospitalized children, rhinovirus in 26.8%, human metapneumovirus (hMPV) in 7.6%, and parainfluenza virus (PIV) in 3.4%. The viruses causing acute bronchiolitis in the community were hRSV (42%), rhinovirus (19.5%), coronavirus (8%), PIV (3.5%), and hMPV (2.5%). In 53.7% of the cases, hRSV infected infants (86.9%), 53.7% being less than 6 months of age. Of the hRSV cases, 48.2% were detected in November and December and 44.5% in January and February. The hRSV epidemic started the 1st or 2nd week of October but it varied from one year to another and from one region to another. hRSV acute bronchiolitis increased from 261 cases in epidemics from 1999-2003 to 341 cases from 2004-2009. Rhinoviruses gave acute bronchiolitis in 38.4% of cases. A rate of 54.6% of viruses was detected in September and October and 38.5% in March and April. A total of 34.2% of infected infants were under 6 months of age, 37.8% between 6 months and 2 years, and 19.5% were between 2 and 5 years old. hMPV epidemics coincided with hRSV epidemics, but they accounted for one-sixth the number of cases. HMPV infected infants (74%) who were older than those infected with hRSV, and the diagnosis was bronchiolitis (59%) and pneumonia (17%). PIV infections (about 100 cases per year) included PIV3 (62.7%), PIV1 (25.3%), and PIV2 (7.3%). PIV1 infections occurred every 2 years in the fall. PIV3 infections were observed every year during the fall and winter, with peaks of infections in the spring in the years without PIV1. There were acute cases of bronchiolitis in 29.8% of PIV3 infections and 18.3% in PIV1 infections.

[Seasonal flu]. / La grippe saisonnière.

Seasonal flu is caused by influenza viruses A and B. These enveloped viruses have a genome made up of seven or eight RNA fragments. The different subtypes are determined by the nature of the two surface glycoproteins HA and NA. Seasonal flu is an epidemic wintertime illness occurring in temperate climate zones. Its epidemiology is linked to the great variability of the virus in time, necessitating an alert system that detects dominating circulating variants each year and that determines the vaccination composition. Clinical flu symptoms are not sufficiently specific to allow for diagnosis with virological tests. This is especially true during non-epidemic periods as well as in subjects older than 65 and younger than five. Children are especially vulnerable to influenza virus infections. Hospitalization occurs more frequently, the younger the child. In children younger than two years, the infection can be pauci-symptomatic and is sometimes detected from non-respiratory symptoms such as lethargy, convulsions, and dizziness. In all cases of respiratory syndrome compatible with influenza virus infection in hospitalized subjects, virological flu diagnosis is of utmost interest. Several tools are available to allow for direct viral detection in respiratory specimens: cell culture isolation, antigenic detection, RNA molecular detection. Choice of method is based on the characteristics of the test: sensibility, specificity, speed and ease of realization, and cost.

[Human metapneumovirus]. / Métapneumovirus humain.

The human metapneumovirus (hMPV) is a new Pneumovirinae related to the avian metapneumovirus type C. hMPV genome differs from human respiratory syncytial virus (RSV) genome by the gene order and the lack of nonstructural genes. Two genetic sub-groups and four sub-types of hMPV are identified. hMPV infections evolve as regular winter outbreaks which have roughly the same size and overlaping RSV epidemics. Among hospitalized children in Caen, hMPV is detected in 9.7% of the cases after RSV (37%), rhinovirus (18%), influenza virus (14.5%), adenovirus (9%), and parainfluenza virus (5%). Most of hMPV infections are observed in children suffering from bronchiolitis, but the localization to lower respiratory tract and the severity of the disease are less frequent in comparison with RSV infections. hMPV is very difficult to isolate using cell culture. Up to now, the only way for hMPV diagnosis was the TS-CRP assays. But the recent apparition of direct antigenic tests allows us to get a fair, rapid, and economic diagnostic tool.

[Human coronaviruses]. / Coronavirus humains (HCoV).

Coronaviruses are a large group of viruses and infect a lot of species of mammals and birds. Five coronaviruses currently infect humans: HCoVs 229E and OC43, identified in the 1960s, SARS-CoV identified in March 2003 during the SARS epidemic, and the HCoVs NL63 and HKU1, identified in 2004 and 2005 respectively. The genome of the coronaviruses is a linear, non-segmented, positive-sense single-stranded RNA molecule of approximately 30kb. The evolution of these viruses occurs through some features: the generation of multiple mutants during the replication resulting on a quasispecies structure of the viral population, the demonstrated ability of coronaviruses to establish persistent infections, the flexibility of the genome due to a high frequency of homologue or heterologue recombinations, the ability to jump barrier species and to adapt to the new environment. Two epidemiologic pictures of HCoV infections have to be distinguished: as suggested by recent studies, HCoVs except SARS-CoV, are distributed worldwide and cocirculate during seasonal outbreaks. The distribution of the different HCoV species varies according to the geographic area and season. In contrast, the SARS-CoV is responsible of the first emerging infectious disease of this millennium, infecting more than 8000 people between November 2002 and July 2003. Its circulation has been stopped by drastic public health policy. Human coronaviruses may be also involved in enteric and neurologic diseases. The detection of these viruses is difficult and mainly based on molecular assays (RT-PCR). There is no established specific therapy to date.

Study of influenza C virus infection in France.

From November 2004 to April 2007, specimens were obtained from 2,281 patients with acute respiratory tract illness in Normandy, France. Eighteen strains of influenza C virus were detected in these samples using a combined tissue culture/RT-PCR diagnostic method. Most patients with influenza C virus infection (13/18) were infants or young children (<2 years of age). The most frequent symptoms were fever and cough, and the clinical presentation of influenza C virus infection was similar to that of other respiratory viruses. Thirteen of the 18 infected patients were hospitalized; 3 presented with a severe lower respiratory infection. The hemagglutinin-esterase (HE) gene of 10 isolates was sequenced to determine the lineages of the circulating influenza C viruses. Phylogenetic analysis revealed that most of the isolated strains had an HE gene belonging to the C/Yamagata/26/81-related lineage. These results show that influenza C virus regularly circulates in Normandy and generally causes a mild upper respiratory infection. Because the differential clinical diagnosis of influenza C virus infection is not always easy, it is important to identify viral strains for both patient management and epidemiological purposes.