Influenza-induced acute respiratory distress syndrome during the 2010-2016 seasons: bacterial co-infections and outcomes by virus type and subtype.

OBJECTIVES: We aimed to describe bacterial co-infections and acute respiratory distress (ARDS) outcomes according to influenza type and subtype. METHODS: A retrospective observational study was conducted from 2012 to 2016 in patients admitted to the respiratory intensive care unit (ICU) of Marseille university hospital for influenza-induced ARDS. Microbiological investigations, including multiplex molecular respiratory panel testing and conventional bacteriological cultures, were performed as part of the routine ICU care on the bronchoalveloar lavage collected at admission. Bacterial co-infections, ICU mortality and respiratory function were investigated according to virus type and subtype. RESULTS: Among the 45 ARDS patients included, A(H1N1)pdm09 was the most frequent influenza virus identified (28/45 A(H1N1)pdm09, eight out of 45 A(H3N2) and nine out of 45 influenza B). Bacterial co-infections involving a total of 23 bacteria were diagnosed in 16/45 patients (36%). A(H1N1)pdm09 patients presented fewer bacterial co-infections (17.9% vs. 50.0% for A(H3N2) patients and 77.8% for B patients; p < 0.01). Overall, mortality at 90 days post admission was 33.3% (15/45), and there was no significant difference between influenza type and subtype. The need for extracorporeal membrane oxygenation was more frequent for A(H1N1)pdm2009 (20/28, 71.4%) and B patients (7/9, 77.8%) than the A(H3N2) subtype (1/8, 12.5%; p < 0.01). A(H1N1)pdm09-ARDS patients were associated with fewer ventilation-free days at day 28 (median (IQR): 0 (0-8) days) compared with other influenza-ARDS patients (15 (0-25) days, p < 0.05). DISCUSSION: In a population of influenza-induced ARDS, A(H1N1)pdm09 was associated with fewer bacterial co-infections but poorer respiratory outcomes. These data underline the major role of A(H1N1)pdm09 subtype on influenza disease severity.

Afebrile meningoencephalitis with transient central facial paralysis due to Toscana virus infection, southeastern France, 2014 [corrected].

We report a case of meningoencephalitis caused by Toscana virus (TOSV) with central facial paralysis lasting over two days acquired in south-eastern France. The patient was not febrile either before or during the course of the disease. The diagnosis was established by both real-time RT-PCR and virus isolation with complete genome sequencing. This case emphasises the need to consider TOSV in non-febrile neurological syndromes in people living in or having travelled to the Mediterranean area.

Toscana virus infections: a case series from France.

Toscana virus (TOSV) is a neglected sandfly-borne pathogen in Mediterranean countries. Although discovered four decades ago, articles that describe the clinical aspects are scarce and consist mostly of case reports, with few series of cases. We studied retrospectively symptomatic TOSV infections in patients hospitalized in Marseille (France) from 2004 to 2011. Seventeen patients were classified as probable or confirmed cases. Fourteen cases (82%) occurred between June and September, and 3 cases in March, April and November. Two cases were potentially imported from Croatia and Tuscany. All patients presented with fever and neurological signs were observed such as aseptic meningitis (n = 6), muscular symptoms (n = 3), or encephalitis (n = 4). The outcome was always favorable. At the acute stage, anti TOSV IgM were observed in 14/17 patients, neutralization tests were positive for 3/8 patients, and RT-PCR confirmed TOSV infections in 5/8 CSF specimens.

Increased incidence of acute parvovirus B19 infections in Marseille, France, in 2012 compared with the 2002-2011 period.

Human parvovirus B19 occurs worldwide and causes mild or asymptomatic disease in the form of cyclic local epidemics usually occurring in late winter and early summer. In 2012, a dramatic increase in cases was observed in the Public hospitals system of Marseille, with a total of 53 cases reported. Here, we describe the characteristics of this outbreak and compare it with the local epidemiology of B19V infections observed during the 2002-2011 period.

Fulminant Hepatitis Due to Father-to-Newborn Transmission of Herpes Simplex Virus type 1.

We describe a case of a severe neonatal infection by herpes simplex virus (HSV) type 1 acquired postnatally from his father. The delivery and the first days of life were normal. He developed liver failure and disseminated intravascular coagulation when he was 19 days old. He was treated with intravenous acyclovir and the outcome was favorable. This case underlines that prevention of post-natal transmission of HSV merits to be considered in educational pregnancy programs directed at mothers and fathers.

The viral etiology of an influenza-like illness during the 2009 pandemic.

Many viruses are known to cause influenza-like illness (ILI); however, in nearly 50% of patients, the etiologic agent remains unknown. The distribution of viruses in patients with ILI was investigated during the 2009 A/H1N1 influenza pandemic (A/H1N1p). From June 2009 to January 2010, 660 patients with suspected influenza were questioned and examined, and nasal swabs were collected. All patient samples were tested for influenza virus, and 286 negative nasal swabs were tested further for 18 other respiratory viruses using real-time RT-PCR. Two waves of ILI were observed in the epidemic curve (weeks 35-42 and 42-49). At least eight viruses co-circulated during this period: human rhinovirus (HRV) (58), parainfluenza 1-4 viruses (PIV) (9), human Coronavirus (hCoV) OC43 (9), enterovirus (5), adenovirus (AdV) (4), and human metapneumovirus (hMPV) (2); however, 204 samples remained negative for all viruses tested. ILI symptoms, according to the Centers for Disease Control and Prevention criteria for ILI definition, were reported in 75% of cases. These patients had positive swabs for A/H1N1p, HRV, hCoV-OC43, PIV, AdV, and hMPV without significant difference with non-ILI patients. This study found that many respiratory viruses circulated during this period and that the A/H1N1p did not impact on the kinetics of other respiratory viruses. The proportion of non-documented cases remains high. ILI could not distinguish A/H1N1p infection from that due to other respiratory viruses. However, in multivariate anlaysis, cough, chills, hyperemia, and dyspnea were associated significantly with influenza virus versus other respiratory viruses.

Evaluation of the Xpert Flu test and comparison with in-house real-time RT-PCR assays for detection of influenza virus from 2008 to 2011 in Marseille, France.

Rapid documentation of respiratory specimens can have an impact on the management of patients and their relatives in terms of preventive and curative measures. We compared the results of the Xpert(®) Flu assay (Cepheid) with three real-time RT-PCR assays using 127 nasopharyngeal samples, of which 75 were positive for influenza A (with 52 identified as A/H1N1-2009) and 52 were positive for influenza B. The Xpert(®) Flu assay presented a quasi-absence of non-interpretable tests, and showed sensitivity and specificity of 100% and 100% for Flu A, 98.4% and 100% for A/H1N1-2009, and 80.7% and 100% for Flu B.

Screening and detection of human enterovirus 71 infection by a real-time RT-PCR assay in Marseille, France, 2009-2011.

Enterovirus-positive samples diagnosed in Marseille (January 2009 to September 2011) were screened for EV71 by real-time RT-PCR. EV71 was detected in three children below the age of 2 years with no history of overseas travel; two of these cases were associated with severe clinical presentation. Viruses demonstrated genetic similarity to other European genogroup C2 strains. Strain MRS/09/3663 complete sequencing revealed 97.6% identity across the entire genome with a 2008 Singapore isolate, without signs of possible recombination events. To our knowledge, this is the first detection of EV71 infection in Marseille, France, that confirms the current circulation of EV71 in France.

A seroepidemiological study of pandemic A/H1N1(2009) influenza in a rural population of Mali.

The swine-origin H1N1 influenza A virus (pH1N1(2009)) started to circulate worldwide in 2009, and cases were notified in a number of sub-Saharan African countries. However, no epidemiological data allowing estimation of the epidemic burden were available in this region, preventing comprehensive comparisons with other parts of the world. The CoPanFlu-Mali programme studied a cohort of 202 individuals living in the rural commune of Dioro (southern central Mali). Pre-pandemic and post-pandemic paired sera (sampled in 2006 and April 2010, respectively) were tested by the haemagglutination inhibition (HI) method. Different estimates of pH1N1(2009) infection during the 2009 first epidemic wave were used (increased prevalence of HI titre of ≥1/40 or ≥1/80, seroconversions) and provided convergent attack rate values (12.4-14.9%), the highest values being observed in the 0-19-year age group (16.0-18.4%). In all age groups, pre-pandemic HI titres of ≥1/40 were associated with complete absence of seroconversion; and geometric mean titres were <15 in individuals who seroconverted and >20 in others. Important variations in seroconversion rate existed among the different villages investigated. Despite limitations resulting from the size and composition of the sample analysed, this study provides strong evidence that the impact of the pH1N1(2009) first wave was more important than previously believed, and that the determinants of the epidemic spread in sub-Saharan populations were quite different from those observed in developed countries.

Serological study of the 2009 pandemic due to influenza A H1N1 in the metropolitan French population.

We looked for evidence of antibodies to the 2009 influenza A/H1N1 pandemic virus in panels of sera from individuals living in metropolitan France, obtained either before, during or after the epidemic, using standard haemagglutination inhibition and microneutralization tests. The difference between seroprevalence values measured in post- and pre-epidemic panels was used as an estimate of seroconversion rate in different age groups (23.4% (0-24 years, age-group 0); 16.5% (25-34); 7.9% (35-44); 7.2% (45-54); 1.6% (55-64); and 3.1% (>65)), confirming that the distribution of cases in different age groups was similar to that of the seasonal H1N1 virus. During the pre-pandemic period low-titre cross-reactive antibodies were present in a large proportion of the population (presumably acquired against seasonal H1N1) whereas cross-reactive antibodies were detected in individuals over the age of 65 years with significantly higher prevalence and serological titres (presumably acquired previously against Spanish flu-related H1N1 strains). Clinical data and analysis of post-pandemic seroprevalence showed that few of these latter patients were infected by the influenza virus during the epidemic. In contrast, the majority of both clinical cases and seroconversions were recorded in the 0-24 age group and a global inverse relationship between prevalence of antibodies to pH1N1 in the pre-pandemic period and rate of seroconversion was observed amongst age groups. Our results emphasize the complex relationships involved in antigenic reactivity to pandemic and seasonal H1N1 viral antigens; hence the difficulty in distinguishing between low-titre specific and cross-reactive antibodies, establishing precise seroprevalence numbers and fully understanding the relationship between previous immunity to seasonal viruses and protection against the novel variant.

Comparative detection of enterovirus RNA in cerebrospinal fluid: GeneXpert system vs. real-time RT-PCR assay.

Enteroviruses (EVs) constitute the most common cause of aseptic meningitis in both children and adults. Molecular techniques have now been recognized as the reference standard for the diagnosis of EV infections, and the rapidity of the molecular diagnosis of EV meningitis has been shown to be a determining factor in the management of patients. The rapid documentation of EV RNA in cerebrospinal fluid (CSF) is key to adapting patient management and the therapeutic regimen. To shorten the time needed for virological documentation, we implemented EV RNA detection in two point-of-care (POC) laboratories. Here, we present the results of the POC detection of EV RNA with the Xpert EV kit on the GeneXpert integrated system, and a comparison with the real-time RT-PCR (rtRT-PCR) assay routinely used in the core virology laboratory. From January to September 2009, a total of 310 CSF samples were tested. The rtRT-PCR gave 81 positive, 225 negative and four 'indeterminate' results. POC results were concordant in 81.6% (253/310). Most of the discrepancies consisted of 'indeterminate' results at the POC level (16%). Calculated performances (excluding the indeterminate results) of the Xpert EV kit on the GeneXpert system in POC settings were 100%, 98.9%, 97.6% and 100% for Sensibility, Specificity, positive predictive value and negative predictive value, respectively. Taken together, these results indicate that the implementation of POC detection of EV RNA can provide robust results in <4 h, and may have a significant impact on patient management, therapeutic attitude, and hospitalization costs.

Low seroprevalence of sandfly fever Sicilian virus antibodies in humans, Marseille, France.

A seroprevalence study was carried out in the region of Marseille (south-eastern France) to address the public health importance of sandfly fever Sicilian virus (SFSV) and SFSV-like viruses, as recently recognized vectors of those viruses are present in this area. The low seroprevalence rate observed in this study suggests that SFSV is not likely to be of major medical importance in the Marseille area.

Measles among healthcare workers: a potential for nosocomial outbreaks.

We report here 14 cases of measles among healthcare workers (HCWs) in Public Hospitals of Marseilles, France that occurred between April and November 2010. All cases but one were under 30 years of age. Following the identification of these cases, we checked the immune status among 154 HCWs who volunteered to take part in the study and showed that 93% and 88% were immune against measles and mumps respectively. HCWs non-immunised against measles were all under 30 years of age.

Fatal case of Reye's syndrome associated with H3N2 influenza virus infection and salicylate intake in a 12-year-old patient.

We describe a fatal case of Reye's syndrome in a 12-year-old male patient during an influenza A (H3N2) infection for which he received salicylates. In the current situation of the novel A/H1N1 virus pandemic, we believe that it is of high importance to emphasize the risks associated with salicylate intake to avoid the reappearance of Reye's syndrome.

Dengue type 3 virus infections in European travellers returning from the Comoros and Zanzibar, February-April 2010.

In late February-early April 2010, five cases of dengue fever were diagnosed in returning travellers in Europe in EurotravNet sites in Sweden and France in patients with travel history to the Comoros and/or Zanzibar, Tanzania. Four cases were non-complicated dengue fever and one case dengue hemorrhagic fever. Three patients were viraemic at the time of diagnosis and infected with Dengue type 3 virus.

Interim report on the A/H1N1 influenza virus pandemic in Marseille, France, April-November 2009.

We report here the results of a 7-month survey of the influenza A/H1N1 pandemic in the Virology laboratory of the public hospitals of Marseille (April-November 2009). In total, 8 587 samples were analysed during this period, of which 1 974 (23%) were positive for the novel influenza variant. The analysis of results obtained using rapid influenza diagnostic tests (RIDTs) revealed a global sensitivity of 49.4% (vs. molecular qRT-PCR detection), strongly correlated with age groups (varying from 30% to 58% for patients >40 age and <10, respectively), indicating that RIDTs can be helpful in accelerating the management of suspected cases. Epidemiological analysis showed that the winter influenza wave began in October in Marseille (i.e. 2 to 3 months earlier than usual seasonal influenza outbreaks) and that the majority of autochthonous cases were observed in patients younger than 20 years old, with a low number of cases in patients over 60 years old. In November 2009, 22.2% (167/754) of patients with a laboratory diagnosis of influenza A/H1N1 infection were hospitalized, of which 9% (15/167) were admitted to an intensive care unit (ICU). Patients in the extreme age groups (>40 years old and <1) were significantly more often hospitalized than others, and 2.4% of hospitalized patients died. During the last 3 weeks of the period, the average number of bed-days attributable to H1N1sw-positive patients was 31.4, of which 5.9 were in ICUs.

Impact of diagnostic procedures on patient management and hospitalization cost during the 2000 and 2005 enterovirus epidemics in Marseilles, France.

Enteroviruses are frequent aetiological agents of central nervous system infections in humans. In 2000 and 2005, two large outbreaks of Echovirus 30 (a member of species human enterovirus B) were observed in the University Hospitals of Marseilles (France). Between the two epidemics, the diagnostic protocols for enterovirus infection were modified, moving from viral cultures and classic RT-PCR in 2000 to real-time RT-PCR in 2005. We compared some viral and epidemiological characteristics of the 2000 and 2005 outbreaks with special attention to diagnostic procedures and to the subsequent clinical management of patients. Despite similar virological and epidemiological characteristics during both outbreaks, our results show that real-time RT-PCR techniques used in 2005 noticeably shortened the period of time necessary to deliver diagnostic results and suggest that this was associated with a decrease in the duration of hospitalization for positive cases. In conclusion, this study suggests that the improvement of enterovirus diagnosis had a major financial impact on the management of the 2005 epidemic in Marseilles and may constitute an interesting example of how new diagnostic methods in microbiology can be self-financed through improvement in patient management.