Pdm09 Infection Research Articles

Serum 25-Hydroxyvitamin D Was Not Associated with Influenza Virus Infection in Children and Adults in Hong Kong, 2009–201

Background: Some studies have hypothesized that vitamin D may have a role to play in protection against influenza virus infections and illnesses, and that seasonal fluctuation in serum 25-hydroxyvitamin D [25(OH)D] may affect seasonal patterns of influenza virus infections.Objective: We aimed to investigate whether serum 25(OH)D concentrations were associated with the incidence of influenza virus infections and illnesses in children and adults in Hong Kong.Methods: In 2009–2010, 3030 children and adults of all ages from 796 households in Hong Kong were followed up to identify acute respiratory illnesses. Sera from 2694 participants were collected at baseline and after ∼1 mo, 6 mo, and 12 mo. Influenza virus infections were confirmed by reverse transcriptase–polymerase chain reaction performed on nasal and throat swab samples collected during illness episodes. Serologic evidence of influenza virus infection was measured by hemagglutination inhibition assays in unvaccinated participants. The serum 25(OH)D concentrations were measured after collection of all specimens. Each individual’s baseline serum 25(OH)D concentration on 1 January 2010 was predicted by a random-effects linear regression model.Results: We found that, in children and adults who had not received a seasonal influenza vaccine, baseline serum 25(OH)D concentrations (<50 nmol/L compared with ≥50 nmol/L) were not statistically significantly associated with serologic evidence of influenza A(H1N1)pdm09 (RR, 1.18; 95% CI: 0.85, 1.65) or seasonal influenza virus infections [including A(H3N2) and B virus] (RR, 1.13; 95% CI: 0.86, 1.49). In all participants, baseline serum 25(OH)D concentrations were not statistically significantly associated with polymerase chain reaction–confirmed influenza virus infection (RR, 1.15; 95% CI: 0.73, 1.83) and influenza-like illness (RR, 1.18; 95% CI: 0.98, 1.43).Conclusions: These findings indicate that lower serum vitamin D concentrations may not contribute to the seasonality of influenza and are not associated with an increased risk of influenza virus infections in persons of all ages in Hong Kong.

Non-neutralizing antibodies induced by seasonal influenza vaccine prevent, not exacerbate A(H1N1)pdm09 disease.

The association of seasonal trivalent influenza vaccine (TIV) with increased infection by 2009 pandemic H1N1 (A(H1N1)pdm09) virus, initially observed in Canada, has elicited numerous investigations on the possibility of vaccine-associated enhanced disease, but the potential mechanisms remain largely unresolved. Here, we investigated if prior immunization with TIV enhanced disease upon A(H1N1)pdm09 infection in mice. We found that A(H1N1)pdm09 infection in TIV-immunized mice did not enhance the disease, as measured by morbidity and mortality. Instead, TIV-immunized mice cleared A(H1N1)pdm09 virus and recovered at an accelerated rate compared to control mice. Prior TIV immunization was associated with potent inflammatory mediators and virus-specific CD8 T cell activation, but efficient immune regulation, partially mediated by IL-10R-signaling, prevented enhanced disease. Furthermore, in contrast to suggested pathological roles, pre-existing non-neutralizing antibodies (NNAbs) were not associated with enhanced virus replication, but rather with promoted antigen presentation through FcR-bearing cells that led to potent activation of virus-specific CD8 T cells. These findings provide new insights into interactions between pre-existing immunity and pandemic viruses.

Antibodies Against the Current Influenza A(H1N1) Vaccine Strain Do Not Protect Some Individuals From Infection With Contemporary Circulating Influenza A(H1N1) Virus Strains.

During the 2013–2014 influenza season, nearly all circulating 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) strains possessed an antigenically important mutation in hemagglutinin (K166Q). Here, we performed hemagglutination-inhibition (HAI) assays, using sera collected from 382 individuals prior to the 2013–2014 season, and we determined whether HAI titers were associated with protection from A(H1N1)pdm09 infection. Protection was associated with HAI titers against an A(H1N1)pdm09 strain possessing the K166Q mutation but not with HAI titers against the current A(H1N1)pdm09 vaccine strain, which lacks this mutation. These data indicate that contemporary A(H1N1)pdm09 strains are antigenically distinct from the current A(H1N1)pdm09 vaccine strain.

Letter to the editor: Regarding the editorial by Penttinen and Friede

To the editor: In the editorial by Penttinen and Friede, the authors summarised data from 2015 to 2016 on live attenuated influenza vaccine (LAIV) effectiveness in a Table and used the data in the Table to make several conclusions [1]. Unfortunately, the Table has several errors and, therefore, misrepresents the available data and studies. On 26 June 2016, the United States (US) Advisory Committee for Immunization Practices (ACIP) recommended that LAIV not be used during the 2016/17 season in the US [2]. Among all studies using a test-negative case–control design (TNCCD), the study from the US Centers for Disease Control and Prevention (CDC) (US Influenza Vaccine Effectiveness (VE) network) and the US Department of Defence (DoD) study (US Air Force School of Aerospace Medicine (USAFSAM) Sentinel Provider network) had the largest number of influenza A(H1N1)pdm09-infected children aged 2–17 years and larger or comparable numbers of children who received LAIV; these numbers were not correctly shown in the Table in the editorial. The US CDC study included 133 children aged 2–17 years who received LAIV (23 LAIV-vaccinated children had influenza A(H1N1)pdm09 infection) and 1,078 children who were unvaccinated. The US DoD study included 93 children vaccinated with LAIV (23 LAIV-vaccinated children had influenza A(H1N1)pdm09 infection) and 338 unvaccinated children (personal communication September 2016, Susan Federinko, USAFSAM). The youngest age for which LAIV is licensed for use in the US is two years; the US CDC VE estimates refer to children aged 2–17 years. The sample sizes for the other studies in the Table should also be consistently reported so that the same numerical comparisons are available for each study.

Detection of parainfluenza virus in immunocompromised and immunocompetent patients in a tertiary hospital in Sao Paulo, Brazil

Parainfluenza virus infections (PIV) were evaluated in patients with mild and severe infections through real time PCR. One thousand and sixty-seven samples were collected from subjects as follows: 233 adult renal transplanted outpatients, 129 children with congenital heart disease, 381 with adult hematopoietic stem cell patients and 324 hospitalized patients suspected of influenza A (H1N1) pdm09 infection. PIV was detected in 74 (6.9%) samples. VPI-3 was the most frequent (60.8%) and a higher risk was observed for older adults (p = 0.018) and for those who were hematopoietic stem cell transplanted. Further studies are needed to understand the VPI role in patients' at risk for developing serious illness.

The priming effect of previous natural pandemic H1N1 infection on the immunogenicity to subsequent 2010-2011 influenza vaccination in children: a prospective cohort study

BackgroundThe effect of previous natural pandemic H1N1 (H1N1 pdm09) influenza infection on the immunogenicity to subsequent inactivated influenza vaccination in children has not been well studied. We aimed to evaluate the effect of H1N1 pdm09 natural infection and vaccination on the immunogenicity to subsequent 2010-2011 seasonal inactivated influenza vaccination in children.MethodsFrom October 2010 to May 2011, we conducted an open-label, multi-center study in children aged 6 months -18 years in Korea. We measured antibody titers with a hemagglutination-inhibition (HI) assay at baseline, 1 month, and 6 months after vaccination with trivalent split or subunit vaccines containing H1N1 pdm, A/H3N2, and B. The subjects were classified into 4 groups depending on the presence of laboratory-confirmed H1N1 pdm09 infection and/or vaccination in the 2009-2010 season; Group I: vaccination (-)/infection(-), Group II: vaccination (-)/infection(+), Group III: vaccination (+)/infection(-), Group IV: vaccination (+)/infection(+).ResultsAmong the subjects in group I, 47 subjects who had a baseline titer >1:10 were considered to have an asymptomatic infection. They were included into the final group II (n = 80). We defined the new group II as the infection-primed (IP) group and group III as the vaccine-primed (VP) group. Seroconversion rate (57.5 % vs 35.9 %, p = 0.001), seroprotection rate at 6 months after vaccination (70.8 % vs 61.8 %, p = 0.032), and GMT at 1 month after vaccination (129.9 vs 66.5, p = 0.002) were significantly higher in the IP group than in the VP group. In the 9–18 year-old group, seroconversion rate and immunogenicity at 1 and 6 months were significantly higher in the IP group than in the VP group. However in the 1–7 year-old age group, there was no significant difference between the two groups.ConclusionsPrevious H1N1 pdm09 infection appears to have positive effects on immunogenicity of subsequent inactivated influenza vaccines against H1N1 pdm09 in older children.

Effect of Occupational Exposure on A(H1N1)pdm09 Infection and Hospitalization.

To analyze relationships between occupational exposure and influenza infection and hospitalization during the 2009-2010 pandemic wave and the 2010-2011 influenza seasonal epidemic in Spain. Occupations were classified as high, medium, or low risk of influenza exposure. To assess the risk of infection, 588 outpatient cases of influenza confirmed by reverse-transcription polymerase-chain-reaction (RT-PCR) were compared with 588 outpatients without influenza symptoms. To assess the risk of hospitalization, 337 outpatient influenza cases were compared with 337 inpatient influenza cases. The high risk of occupational exposure group was composed only of health care workers. After adjustment for age, sex, vaccination status, and predictive variables of influenza infection, patients with a high risk of occupational exposure had an aOR of 2.14 (95%CI: 1.25-3.66) of being an outpatient influenza case and an aOR of 0.43 (95%CI: 0.20-0.95) of being an inpatient influenza case, compared with those with a low risk. A high risk of occupational exposure is a risk factor for influenza infection but not for hospitalization.

Weight and prognosis for influenza A(H1N1)pdm09 infection during the pandemic period between 2009 and 2011: a systematic review of observational studies with meta-analysis

Background: In 2009, a novel influenza A(H1N1)pdm09 virus was detected and caused influenza pandemic. It is important to identify the risk factors for severe outcomes. However, inconsistent results regarding the effect of obesity were reported in previous studies.Methods: We conducted a systematic review to assess the association between obesity and poor prognosis for laboratory-confirmed A(H1N1)pdm09 influenza. We searched three English databases and three Chinese databases for relevant studies from April 2009 to October 2015: PubMed, the Cochrane library, Embase, CNKI, CBM, and Wanfang. Two investigators independently identified eligible articles, assessed quality using NOS, and extracted data. We performed meta-analyses and meta-regressions to estimate the association between weight and poor prognosis for influenza A(H1N1)pdm09 infection, when data were available.Results: We identified 22 articles enrolling 25,189 laboratory confirmed patients. The pooled estimates indicated obesity significantly increased the risk of fatal and critical complications of influenza A(H1N1)pdm09 infection (for fatal, OR = 1.81, 95% CI: 1.23−2.65; for critical complications, OR = 1.67, 95% CI: 1.13−2.47). However, we found significant interaction between early antiviral treatment and obesity (β = −0.28). After adjustment for early antiviral treatment, relationship between obesity and poor outcomes disappeared (OR = 1.14, 95% CI: 0.94−1.39).Conclusions: The results of the meta-analyses showed obesity significantly increased the risk of death, critical complications, and severe complications for influenza A(H1N1)pdm09 infection, especially among high-quality studies and in Asia region. Importantly, the result from our meta-regression indicated that the conclusion should be interpreted with caution, because early antiviral treatment might be a key confounding factor.

Burden of acute respiratory disease of epidemic and pandemic potential in the WHO Eastern Mediterranean Region: A literature review

There are gaps in the knowledge about the burden of severe respiratory disease in the Eastern Mediterranean Region (EMR). This literature review was therefore conducted to describe the burden of epidemicand pandemic-prone acute respiratory infections (ARI) in the Region which may help in the development of evidence-based disease prevention and control policies. Relevant published and unpublished reports were identified from searches of various databases; 83 documents fulfilled the search criteria. The infections identified included: ARI, avian influenza A(H5N1), influenza A(H1N1)pdm09 and Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Pneumonia and ARIs were leading causes of disease and death in the Region. Influenza A(H1N1) was an important cause of morbidity during the 2009 pandemic. This review provides a descriptive summary of the burden of acute respiratory diseases in the Region, but there still remains a lack of necessary data.

Hospitalization Risk Due to Respiratory Illness Associated with Genetic Variation at IFITM3 in Patients with Influenza A(H1N1)pdm09 Infection: A Case-Control Study.

BackgroundRecent studies suggest an association between the Interferon Inducible Transmembrane 3 (IFITM3) rs12252 variant and the course of influenza infection. However, it is not clear whether the reported association relates to influenza infection severity. The aim of this study was to estimate the hospitalization risk associated with this variant in Influenza Like Illness (ILI) patients during the H1N1 pandemic influenza.MethodsA case-control genetic association study was performed, using nasopharyngeal/oropharyngeal swabs collected during the H1N1 pandemic influenza. Laboratory diagnosis of influenza infection was performed by RT-PCR, the IFITM3 rs12252 was genotyped by RFLP and tested for association with hospitalization. Conditional logistic regression was performed to calculate the confounder-adjusted odds ratio of hospitalization associated with IFITM3 rs12252.ResultsWe selected 312 ILI cases and 624 matched non-hospitalized controls. Within ILI Influenza A(H1N1)pdm09 positive patients, no statistical significant association was found between the variant and the hospitalization risk (Adjusted OR: 0.73 (95%CI: 0.33–1.50)). Regarding ILI Influenza A(H1N1)pdm09 negative patients, CT/CC genotype carriers had a higher risk of being hospitalized than patients with TT genotype (Adjusted OR: 2.54 (95%CI: 1.54–4.19)).ConclusionsThe IFITM3 rs12252 variant was associated with respiratory infection hospitalization but not specifically in patients infected with Influenza A(H1N1)pdm09.

The His131Arg substitution in the FCGR2A gene (rs1801274) is not associated with the severity of influenza A(H1N1)pdm09 infection.

BackgroundThe virulence and pathogenicity of different influenza strains are responsible for a more or less severe disease. Recent studies have attempted to understand how host genetic factors may influence the clinical presentation of the disease. In the present study, the His131Arg (rs1801274) polymorphism was investigated in individuals from a Brazilian admixed population with a diagnosis of influenza A(H1N1)pdm09 infection.MethodsIn the present study, the influence of the His131Arg (rs1801274) polymorphism, a variant of the FCGR2A gene, was investigated in 436 patients with a diagnosis of influenza A(H1N1)pdm09, evaluated at health services in the northern and northeastern regions of Brazil between June 2009 and August 2010. Patients were divided into a group of non-hospitalized patients (n = 192) and a group of hospitalized patients (n = 244; 100 of them died).ResultsNo significant difference in the allele or genotype frequencies of the rs1801274 polymorphism was observed between groups (p = 0.952 and p = 0.388). Multinomial logistic regression showed no effect of the rs1801274 polymorphism on severity or death of patients from the Brazilian admixed population (p = 0.368 and p = 0.469).ConclusionsThe rs1801274 polymorphism is not associated with severe disease in patients infected with influenza A(H1N1)pdm09.

In-Depth Analysis of HA and NS1 Genes in A(H1N1)pdm09 Infected Patients.

In March/April 2009, a new pandemic influenza A virus (A(H1N1)pdm09) emerged and spread rapidly via human-to-human transmission, giving rise to the first pandemic of the 21th century. Influenza virus may be present in the infected host as a mixture of variants, referred to as quasi-species, on which natural and immune-driven selection operates. Since hemagglutinin (HA) and non-structural 1 (NS1) proteins are relevant in respect of adaptive and innate immune responses, the present study was aimed at establishing the intra-host genetic heterogeneity of HA and NS1 genes, applying ultra-deep pyrosequencing (UDPS) to nasopharyngeal swabs (NPS) from patients with confirmed influenza A(H1N1)pdm09 infection. The intra-patient nucleotide diversity of HA was significantly higher than that of NS1 (median (IQR): 37.9 (32.8–42.3) X 10−4 vs 30.6 (27.4–33.6) X 10−4 substitutions/site, p = 0.024); no significant correlation for nucleotide diversity of NS1 and HA was observed (r = 0.319, p = 0.29). Furthermore, a strong inverse correlation between nucleotide diversity of NS1 and viral load was observed (r = - 0.74, p = 0.004). For both HA and NS1, the variants appeared scattered along the genes, thus indicating no privileged mutation site. Known polymorphisms, S203T (HA) and I123V (NS1), were observed as dominant variants (>98%) in almost all patients; three HA and two NS1 further variants were observed at frequency >40%; a number of additional variants were detected at frequency <6% (minority variants), of which three HA and four NS1 variants were novel. In few patients multiple variants were observed at HA residues 203 and 222. According to the FLUSURVER tool, some of these variants may affect immune recognition and host range; however, these inferences are based on H5N1, and their extension to A(H1N1)pdm09 requires caution. More studies are necessary to address the significance of the composite nature of influenza virus quasi-species within infected patients.

A Large Proportion of the Mexican Population Remained Susceptible to A(H1N1)pdm09 Infection One Year after the Emergence of 2009 Influenza Pandemic.

BackgroundThe 2009 H1N1 influenza pandemic initially affected Mexico from April 2009 to July 2010. By August 2010, a fourth of the population had received the monovalent vaccine against the pandemic virus (A(H1N1)pdm09). To assess the proportion of the Mexican population who remained potentially susceptible to infection throughout the summer of 2010, we estimated the population seroprevalence to A(H1N1)pdm09 in a serosurvey of blood donors.MethodsWe evaluated baseline cross-reactivity to the pandemic strain and set the threshold for seropositivity using pre-pandemic (2005–2008) stored serum samples and sera from confirmed A(H1N1)pdm09 infected individuals. Between June and September 2010, a convenience sample serosurvey of adult blood donors, children, and adolescents was conducted in six states of Mexico. Sera were tested by the microneutralization (MN) and hemagglutination inhibition (HI) assays, and regarded seropositive if antibody titers were equal or exceeded 1:40 for MN and 1:20 for HI. Age-standardized seroprevalence were calculated using the 2010 National Census population.ResultsSera from 1,484 individuals were analyzed; 1,363 (92%) were blood donors, and 121 (8%) children or adolescents aged ≤19 years. Mean age (standard deviation) was 31.4 (11.5) years, and 276 (19%) were women. A total of 516 (35%) participants declared history of influenza vaccination after April 2009. The age-standardized seroprevalence to A(H1N1)pdm09 was 48% by the MN and 41% by the HI assays, respectively. The youngest quintile, aged 1 to 22 years, had the highest the seroprevalence; 61% (95% confidence interval [CI]: 56, 66%) for MN, and 56% (95% CI: 51, 62%) for HI.ConclusionsDespite high transmission of A(H1N1)pdm09 observed immediately after its emergence and extensive vaccination, over a half of the Mexican population remained potentially susceptible to A(H1N1)pdm09 infection. Subsequent influenza seasons with high transmission of A(H1N1)pdm09, as 2011–2012 and 2013–2014, are compatible with these findings.

Autophagy is involved in regulating the immune response of dendritic cells to influenza A (H1N1) pdm09 infection.

Autophagy can mediate antiviral immunity. However, it remains unknown whether autophagy regulates the immune response of dendritic cells (DCs) to influenza A (H1N1) pdm09 infection. In this study, we found that infection with the H1N1 virus induced DC autophagy in an endocytosis-dependent manner. Compared with autophagy-deficient Beclin-1(+/-) mice, we found that bone-marrow-derived DCs from wild-type mice (WT BMDCs) presented a more mature phenotype on H1N1 infection. Wild-type BMDCs secreted higher levels of interleukin-6 (IL-6), tumour necrosis factor- α (TNF-α), interferon-β (IFN-β), IL-12p70 and IFN-γ than did Beclin-1(+/-) BMDCs. In contrast to Beclin-1(+/-) BMDCs, H1N1-infected WT BMDCs exhibited increased activation of extracellular signal-regulated kinase, Jun N-terminal kinase, p38, and nuclear factor-κB as well as IFN regulatory factor 7 nuclear translocation. Blockade of autophagosomal and lysosomal fusion by bafilomycin A1 decreased the co-localization of H1N1 viruses, autophagosomes and lysosomes as well as the secretion of IL-6, TNF-α and IFN-β in H1N1-infected BMDCs. In contrast to Beclin-1(+/-) BMDCs, H1N1-infected WT BMDCs were more efficient in inducing allogeneic CD4(+) T-cell proliferation and driving T helper type 1, 2 and 17 cell differentiation while inhibiting CD4(+) Foxp3(+) regulatory T-cell differentiation. Moreover, WT BMDCs were more efficient at cross-presenting the ovalbumin antigen to CD8(+) T cells. We consistently found that Beclin-1(+/-) BMDCs were inferior in their inhibition of H1N1 virus replication and their induction of H1N1-specific CD4(+) and CD8(+) T-cell responses, which produced lower levels of IL-6, TNF-α and IFN-β in vivo. Our data indicate that autophagy is important in the regulation of the DC immune response to H1N1 infection, thereby extending our understanding of host immune responses to the virus.

Neurological Complications of Novel Influenza A (H1N1) pdm09 Infection: Report of Two Cases and a Systematic Review of the Literature

Background: Neurological complications of Influenza A (H1N1) pdm09 in adults are rarely reported in the literature. The aim of this study is to report a case of Influenza A (H1N1) pdm09 acute necrotizing encephalitis (ANE) and another case of acute hemorrhagic leukoencephalopathy (AHLE) and to review the neurological complications of this disorder in adults. Methods: We conducted a search on Medline, Ovid, EMBASE, ProQuest and PubMed databases using the key words (neurological complications of H1N1 in adults). We also added to the search results those articles which were not found in the search but exist in the literature under different search words. Only papers written in English published from March 2009 to December 2015 were included. Demographic data and clinical diagnosis of neurological complications and outcomes in adults including death, neurological sequalea or recovery after influenza A (H1N1) pdm09 infection have been reviewed. Results: we included 37 articles presenting a total of 261 adult patients with neurologic complications following Influenza A (H1N1) pdm09 infection. In addition, a case of influenza A (H1N1) pdm09 acute necrotizing encephalitis (ANE) and another case of acute hemorrhagic leukoencephalopathy (AHLE) arising from our own neurological practice were also included. Conclusion: In conclusion, this study demonstrates that influenza A (H1N1) pdm09 is both a pandemic and a seasonal (sporadic) disease. We speculate that most of the neurological complications are immune mediated and calling for further studies to test for the potential benefits of early steroids use in the disease. We are calling for an international collaboration and registry for Influenza A (H1N1) pdm09 infection.

Seroprevalence of Influenza A (H1N1) pdm09 Infection and Risk Factors Associated in Pikine, Dakar Region, Senegal

There is lack of data describing the A (H1N1) pdm09 virus pandemic in Africa. In 2011, we carried out a crosssectional study that aimed to estimate the prevalence of A (H1N1) pdm09 serology in the general population of Pikine, in the region of Dakar, Senegal. 2669 persons from 347 households were tested for A (H1N1) pdm09 using a hemagglutination inhibition test (threshold of 1/80). The general seroprevalence was of 49,0%. Our result showed a pronounced heterogeneity according to neighborhood (16,7%-71%). Multilevel analysis showed that “covering one’s mouth while coughing” was the only variable related to a reduction of A (H1N1) pdm09 infection (OR=0.50 (0.25- 0.98)). Additionally, variance analysis showed significant effects of neighborhood and household. In conclusion, this study showed intense circulation of the A (H1N1) pdm09 virus among the general population in Pikine. The «Neighborhood» and «household» effects identified require elucidation in order to understand the epidemiology of this epidemic.

Comparison of Rapid Antigen Test with RT-PCR in the Diagnosis of Influenza A (H1N1) pdm09 Infection

Comparison of Rapid Antigen Test with RT-PCR in the Diagnosis of Influenza A (H1N1) pdm09 Infection

Influenza A(H1N1)pdm09 and postpandemic influenza in Lithuania.

The objective of this study is to describe the clinical and epidemiological characteristics of patients hospitalized in Lithuania who are infected with influenza A(H1N1)pdm09 and to compare pandemic A(H1N1) pdm09 infection with postpandemic.In total, 146 subjects hospitalized with influenza A(H1N1) pdm09 were identified from 2009–2011. There were 53 during the initial pandemic wave in the summer of 2009, 69 during the peak pandemic period, and 24 during the “postpandemic” period that we included in this study. There were 22 subjects who died after laboratory confirmation of influenza A(H1N1)pdm09.No deaths were documented during the first wave. Subjects presenting during the peak of pandemic influenza had a greater incidence of fever (100% vs 77.4%; p<0.001), dry cough (95.7% vs 82.7%; p=0.01), and vomiting (26.1% vs 1.9%, p<0.001) as compared with patients infected during the first wave. The rate of bacterial pneumonia was 18.8% (13/69) during the peak pandemic period and 12.5% (3/24, p=0.754) during the postpandemic period. None of the postpandemic influenza subjects’ intensive care unit stays were due to pneumonia.The hospitalized early 2009 H1N1 pandemic cases and postpandemic cases were milder compared with those at the peak of pandemic activity.

Procalcitonin (PCT) levels for ruling-out bacterial coinfection in ICU patients with influenza: A CHAID decision-tree analysis

To define which variables upon ICU admission could be related to the presence of coinfection using CHAID (Chi-squared Automatic Interaction Detection) analysis. A secondary analysis from a prospective, multicentre, observational study (2009-2014) in ICU patients with confirmed A(H1N1)pdm09 infection. We assessed the potential of biomarkers and clinical variables upon admission to the ICU for coinfection diagnosis using CHAID analysis. Performance of cut-off points obtained was determined on the basis of the binominal distributions of the true (+) and true (-) results. Of the 972 patients included, 196 (20.3%) had coinfection. Procalcitonin (PCT; ng/mL 2.4 vs. 0.5, p<0.001), but not C-reactive protein (CRP; mg/dL 25 vs. 38.5; p=0.62) was higher in patients with coinfection. In CHAID analyses, PCT was the most important variable for coinfection. PCT <0.29ng/mL showed high sensitivity (Se=88.2%), low Sp (33.2%) and high negative predictive value (NPV=91.9%). The absence of shock improved classification capacity. Thus, for PCT <0.29ng/mL, the Se was 84%, the Sp 43% and an NPV of 94% with a post-test probability of coinfection of only 6%. PCT has a high negative predictive value (94%) and lower PCT levels seems to be a good tool for excluding coinfection, particularly for patients without shock.

The environmental deposition of influenza virus from patients infected with influenza A(H1N1)pdm09: Implications for infection prevention and control.

In a multi-center, prospective, observational study over two influenza seasons, we sought to quantify and correlate the amount of virus recovered from the nares of infected subjects with that recovered from their immediate environment in community and hospital settings. We recorded the symptoms of adults and children with A(H1N1)pdm09 infection, took nasal swabs, and sampled touched surfaces and room air. Forty-two infected subjects were followed up. The mean duration of virus shedding was 6.2 days by PCR (Polymerase Chain Reaction) and 4.2 days by culture. Surface swabs were collected from 39 settings; 16 (41%) subject locations were contaminated with virus. Overall, 33 of the 671 (4.9%) surface swabs were PCR positive for influenza, of which two (0.3%) yielded viable virus. On illness Day 3, subjects yielding positive surface samples had significantly higher nasal viral loads (geometric mean ratio 25.7; 95% CI 1.75, 376.0, p=0.021) and a positive correlation (r=0.47, p=0.006) was observed between subject nasal viral loads and viral loads recovered from the surfaces around them. Room air was sampled in the vicinity of 12 subjects, and PCR positive samples were obtained for five (42%) samples. Influenza virus shed by infected subjects did not detectably contaminate the vast majority of surfaces sampled. We question the relative importance of the indirect contact transmission of influenza via surfaces, though our data support the existence of super-spreaders via this route. The air sampling results add to the accumulating evidence that supports the potential for droplet nuclei (aerosol) transmission of influenza.