Influenzae Serotype Research Articles

Adjuvanted nanoliposomes displaying six hemagglutinins and neuraminidases as an influenza virus vaccine

Inclusion of defined quantities of the two major surface proteins of influenza virus, hemagglutinin (HA) and neuraminidase (NA), could benefit seasonal influenza vaccines. Recombinant HA and NA multimeric proteins derived from three influenza serotypes, H1N1, H3N2, and type B, are surface displayed on nanoliposomes co-loaded with immunostimulatory adjuvants, generating "hexaplex" particles that are used to immunize mice. Protective immune responses to hexaplex liposomes involve functional antibody elicitation against each included antigen, comparable to vaccination with monovalent antigen particles. When compared to contemporary recombinant or adjuvanted influenza virus vaccines, hexaplex liposomes perform favorably in many areas, including antibody production, Tcell activation, protection from lethal virus challenge, and protection following passive sera transfer. Based on these results, hexaplex liposomes warrant further investigation as an adjuvanted recombinant influenza vaccine formulation.

A-292 The Use of Third-Party Controls During Covid-19 Pandemic: An Alternative to the Lack of Other Respiratory Infections

Abstract Background Since SARS-CoV-2 spread widely around the world, previously well-established infectious patterns have changed. The introduction of a new respiratory pathogen, together with changes in human behaviour, such as restrictions on social interactions and the use of facemasks, led to a decrease in the circulation of influenza and respiratory syncytial viruses. This phenomenon, together with the collapse of the healthcare system, significantly decreased the availability of certain types of samples for use in clinical studies to evaluate the performance of in vitro diagnostic products. To overcome this issue, EQA programmes are an excellent alternative. This material has been designed to be used in any equipment, kit or following any specific protocol, as the aim is to mimic human specimens. Thus, the CE-IVD Vitassay qPCR FluA + FluB + RSV, an assay for the detection and differentiation of Flu A, Flu B and RSV, has been routinely tested with material from QCMD programmes containing different strains and serotypes of Influenza and RSV. Methods Vitassay qPCR FluA + FluB + RSV (Vitassay Healthcare SLU, Huesca, Spain) is a commercial kit consisting in a ready-to-use lyophilized master mix. This kit has been blindly tested with controls from 4 QCMD panels including RSV, influenza A and B (2020–2022). Each panel consist of 10 specimens in transport media, which were handled following the programme indications. RNA was extracted using automatic extraction (MagDEA Dx SV kit on the 12gC or Vitassay Microorganism-NA Isolation kit on the KingFisher Flex Automatic platform). Amplification was performed on BioRad systems (CFX96 and CFX96 OPUS). Interpretation of the results was done following manufacturer’s instructions. Sensitivity, specificity, and Likelihood Ratio have been calculated with a 95% confidence interval using the software MetaDiSC 1.4. Results In total, 40 human-like samples from QCMD EQA programmes were analysed with Vitassay qPCR Flu A + Flu B + RSV during Covid-19 Pandemic. Vitassay reported 14 Influenza A positive samples, 11 influenza B and 12 RSV positive samples; all of them were correctly detected when compared the initial characterisation. For Flu A sensitivity and specificity were of 1 (0,76–1) and 1 (0.86–1), LR+ 52.2 (3.34–814.62), LR− 0.034 (0.002–0.51). For Flu B sensitivity and specificity were of 1 (0.71–1) and 1 (0.88–1), LR+ 57.5 (3.67–900.49), LR− 0.042 (0.003–0.63). For RSV sensitivity and specificity were of 1 (0,73–1) and 1 (0.87–1), LR+ 55.76 (3.56–872.35), LR− 0.039 (0.003–0.59). Conclusions Third party controls are an excellent alternative to clinical samples, especially in extraordinary circumstances. In addition, they allow to introduce different strains and variants, such as the QCMD specimens tested. Among these, we could find a such as H1N1 and H3N2 Influenza A serotypes, Influenza B Yamagata and Victoria and RSV A and B, which were properly detected by Vitassay multiplex. In addition, Vitassay extraction kit showed satisfactory results as all samples were properly detected when used in combination with Vitassay qPCR Flu A + Flu B + RSV.

Epidemic Trends and Biofilm Formation Mechanisms of Haemophilus influenzae: Insights into Clinical Implications and Prevention Strategies.

Haemophilus influenzae (H. influenzae) is a significant pathogen responsible for causing respiratory tract infections and invasive diseases, leading to a considerable disease burden. The Haemophilus influenzae type b (Hib) conjugate vaccine has notably decreased the incidence of severe infections caused by Hib strains, and other non-typable H. influenzae (NTHi) serotypes have emerged as epidemic strains worldwide. As a result, the global epidemic trends and antibiotic resistance characteristics of H. influenzae have been altered. Researches on the virulence factors of H. influenzae, particularly the mechanisms underlying biofilm formation, and the development of anti-biofilm strategies hold significant clinical value. This article provides a summary of the epidemic trends, typing methods, virulence factors, biofilm formation mechanisms, and prevention strategies of H. influenzae. The increasing prevalence of NTHi strains and antibiotic resistance among H. influenzae, especially the high β-lactamase positivity and the emergence of BLNAR strains have increased clinical difficulties. Understanding its virulence factors, especially the formation mechanism of biofilm, and formulating effective anti-biofilm strategies may help to reduce the clinical impact. Therefore, future research efforts should focus on developing new approaches to prevent and control H. influenzae infections.

Trends in invasive Haemophilus influenzae serotype a disease in England from 2008–09 to 2021–22: a prospective national surveillance study

Invasive Haemophilus influenzae serotype a (Hia) disease is rare, with most cases reported among Indigenous populations in North America. In England, national surveillance was enhanced following an increase in laboratory-confirmed invasive Hia disease since the 2016-17 epidemiological year. This study aimed to describe the epidemiological trends, clinical characteristics of cases, and assess potential genomic drivers. Hospital laboratories in England routinely submit invasive H influenzae isolates to the UK Health Security Agency for confirmation and serotyping. In this prospective national surveillance study we contacted the general practitioners and clinicians of all patients with laboratory-confirmed invasive Hia from the 2008-09 to the 2021-22 epidemiological year to complete a clinical questionnaire on demographics, underlying conditions, clinical presentation, complications, outcomes, and travel history of the patient. All Hia invasive isolates from residents in England were included in the study; non-invasive isolates were excluded. Multilocus sequence typing (MLST), whole genome single-nucleotide polymorphism, and k-mer-based analysis of bacterial isolates were performed following Illumina whole-genome sequencing (WGS). Outcomes included epidemiological trends, clinical characteristics of confirmed Hia cases, and genomic analyses. From the 2008-09 to the 2021-22 epidemiological years, there were 52 cases of invasive infection with H influenzae serotype a in England (25 [48%] in female patients and 27 [52%] in male patients). There were zero to two annual Hia cases (accounting for <0·5% of serotyped H influenzae isolates) until 2015-16, after which cases increased across England to 19 cases in 2021-22 (incidence 0·03 cases per 100 000), when Hia accounted for 19 (4%) of 484 serotyped H influenzae isolates, 19 (19%) of 100 capsulated cases, and 37% (19 of 52) of all H influenzae cases between 2008-09 and 2021-22. Most of the recent increase in cases occurred among individuals aged 65 years and older (17 [33%] of 52), who typically presented with bacteraemic pneumonia (13 [76%] of 17), and infants younger than 1 year, who had the highest incidence and were more likely to present with meningitis (five [50%] of ten). Overall case fatality rate was 7·7% (95% CI 2·1-19·7; four of 52 patients). WGS found that closely related MLST sequence types ST1511 (20 [39%] of 51), ST23 (13 [25%] of 51), and ST56 (seven [14%] of 51) accounted for most cases, with no evidence of serotype b strains switching capsule to Hia. Duplication of the capsule operon, associated with more severe disease, was present in 32 (80%) of 40 of these sequence types. Analysis of the core and accessory genome content grouped most isolates into a single strain. The persistent increase in invasive Hia cases across England and across all age groups suggests widespread transmission, consistent with reports from other European countries, and will require close monitoring. UK Health Security Agency.

A highly efficient and accurate method of detecting and subtyping Influenza A pdm H1N1 and H3N2 viruses with newly emerging mutations in the matrix gene in Eastern Taiwan.

The rapid identification of Influenza A virus and its variants, which cause severe respiratory diseases, is imperative to providing timely treatment and improving patient outcomes. Conventionally, two separate assays (total test duration of up to 6 h) are required to initially differentiate Influenza A and B viruses and subsequently distinguish the pdm H1N1 and H3N2 serotypes of Influenza A virus. In this study, we developed a multiplex real-time RT-PCR method for simultaneously detecting Influenza A and B viruses and subtyping Influenza A virus, with a substantially reduced test duration. Clinical specimens from hospitalized patients and outpatients with influenza-like symptoms in Eastern Taiwan were collected between 2011 and 2015, transported to Hualien Tzu Chi Hospital, and analyzed. Conventional RT-PCR was used to subtype the isolated Influenza A viruses. Thereafter, for rapid identification, the multiplex real-time RT-PCR method was developed and applied to identify the conserved regions that aligned with the available primers and probes. Accordingly, a multiplex RT-PCR assay with three groups of primers and probes (MAF and MAR primers and MA probe; InfAF and InfAR primers and InfA probe; and MBF and MBR primers and MB probe) was established to distinguish these viruses in the same reaction. Thus, with this multiplex RT-PCR assay, Influenza B, Influenza A pdm H1N1, and Influenza A H3N2 viruses were accurately detected and differentiated within only 2.5 h. This multiplex RT-PCR assay showed similar analytical sensitivity to the conventional singleplex assay. Further, the phylogenetic analyses of our samples revealed that the characteristics of these viruses were different from those reported previously using samples collected during 2012-2013. In conclusion, we developed a multiplex real-time RT-PCR method for highly efficient and accurate detection and differentiation of Influenza A and B viruses and subtyping Influenza A virus with a substantially reduced test duration for diagnosis.

In-hospital incidence of and risk factors for influenza-associated respiratory failure.

Respiratory failure (RF) is the most important complication of influenza virus infection. Its definition and incidence are heterogeneous in the literature. This systematic review and meta-analysis aim to determine the incidence of and risk factors for RF in patients hospitalized with influenza. Electronic databases were searched for articles on RF in patients hospitalized for influenza infection up to December 2021 regardless of their geographical location. Observational and experimental studies were considered for inclusion, excluding case series. The Newcastle-Ottawa and Johanna Briggs scales were used for quality assessment. A random-effects meta-analysis was performed, followed by subgroup analyses according to, among others, presence/absence of pneumonia, RF definition, serotype and time period. PRISMA guidelines were followed for this review. Thirty-six studies were finally included in the meta-analysis. Overall, RF incidence was 24% (range 5%-85%, 95% confidence interval [95CI] 19%-31%). Significantly higher incidences of RF were found in patients with pneumonia (42%, 95CI 28%-57%, p= .006), when RF was defined as hypoxemia (58%, 95CI 31%-81%, p< .001), and during the 2009 pandemic (25%, 95CI 16%-36%) and postpandemic period (23%, 95CI 15%-34%, p= .01). No differences were found between human influenza serotypes. Assessment of risk factors associated with the development of RF was not possible due to their inconsistent and heterogeneous reporting. Respiratory failure is frequent in hospitalized influenza patients, especially in patients with pneumonia and since the 2009 pandemic, although its definition and reporting widely vary in the literature. This complicates its characterization and comparison between cohorts and with other respiratory viruses.

Footprints of swine influenza H1N1 and H3N2 in pigs from southern Kaduna, Nigeria

Influenza A virus presents a significant public health burden worldwide, with the 1918 Spanish flu pandemic being the most dramatic example. Swine influenza viruses can be transmitted to humans through occupational exposures and in live pig markets. Novel variants can emerge in pigs because they can be infected by human, avian and swine strains. This study was carried out to determine the seroprevalence and serotypes of swine influenza in pigs from a major slaughter slab in southern Kaduna. Using competitive ELISA and haemagglutination-inhibition (HI) assays, 305 swine sera were analysed. The result showed an overall seroprevalence of 28.20% (n=86), with H3N2 7.87% (n=24) emerging as the most dominant subtype in circulation. Concurrent antibody detection of H1N1 in 5.26% (n=16) was also detected in boar 2.62% (n=8) and sows 2.62% (n=8). This study revealed swine Influenza H1N1 and H3N2 serotypes are in circulation in pigs in Kaduna State, and that reassortment in the instance of co-infection of swine host is possible.

Discovery and optimization of new 6, 7-dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline derivatives as potent influenza virus PAN inhibitors

Annual unpredictable efficacy of vaccines, coupled with emerging drug resistance, underlines the development of new antiviral drugs to treat influenza infections. The N-terminal domain of the PA (PAN) endonuclease is both highly conserved across influenza strains and serotypes and is indispensable for the viral lifecycle, making it an attractive target for new antiviral therapies. Here, we describe the discovery of a new class of PAN inhibitors derived from recently identified, highly active hits for PAN endonuclease inhibition. By use of structure-guided design and systematic SAR exploration, the hits were elaborated through a fragment growing strategy, giving rise to a series of 1, 3-cis-2-substituted-1-(3, 4-dihydroxybenzyl)-6, 7-dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylic acid derivatives as potent PAN inhibitors. This approach ultimately resulted in the development of a new lead compound 13e, which exhibited an EC50 value of 4.50 μM against H1N1 influenza virus in MDCK cells.

Synergistic pathogenesis of chicken infectious anemia virus and J subgroup of avian leukosis virus

As important immunosuppressive viruses, chicken infectious anemia virus (CIAV) and subgroup J avian leukosis virus (ALV-J) have caused huge economic losses to the poultry industry globally. Recently, the co-infection of CIAV and ALV-J frequently occurred in the domestic chicken flocks in China. However, the synergistic pathogenesis of CIAV and ALV-J has not been fully investigated. Here, a co-infection study was performed to further understand the potential synergistic pathogenesis of CIAV and ALV-J. In vitro study showed that CIAV could promote the replication of ALV-J in HD11 cells, but ALV-J could not increase the replication of CIAV. Chicken infection study showed both CIAV and ALV-J with synergistic effects caused significant body weight loss to the infected chickens. Although ALV-J had no effect on CIAV viral shedding and tissue load, CIAV did significantly increase ALV-J viremia, viral shedding and tissue load in the co-infection group. Moreover, both CIAV and ALV-J could significantly inhibit the humoral immunity to H9N2 influenza virus and serotype 4 fowl adenovirus (FAdV-4). All these data demonstrate the synergistic pathogenesis for the co-infection of CIAV and ALV-J, and highlight the positive effect of CIAV on the pathogenesis of ALV-J.

Bacterial factors required for Streptococcus pneumoniae coinfection with influenza A virus

BackgroundStreptococcus pneumoniae is a common cause of post-influenza secondary bacterial infection, which results in excessive morbidity and mortality. Although 13-valent pneumococcal conjugate vaccine (PCV13) vaccination programs have decreased the incidence of pneumococcal pneumonia, PCV13 failed to prevent serotype 3 pneumococcal disease as effectively as other vaccine serotypes. We aimed to investigate the mechanisms underlying the co-pathogenesis of influenza virus and serotype 3 pneumococci.MethodsWe carried out a genome-wide screening of a serotype 3 S. pneumoniae transposon insertion mutant library in a mouse model of coinfection with influenza A virus (IAV) to identify the bacterial factors required for this synergism.ResultsDirect, high-throughput sequencing of transposon insertion sites identified 24 genes required for both coinfection and bacterial infection alone. Targeted deletion of the putative aminotransferase (PA) gene decreased bacterial growth, which was restored by supplementation with methionine. The bacterial burden in a coinfection with the PA gene deletion mutant and IAV in the lung was lower than that in a coinfection with wild-type pneumococcus and IAV, but was significantly higher than that in an infection with the PA gene deletion mutant alone. These data suggest that IAV infection alters host metabolism to benefit pneumococcal fitness and confer higher susceptibility to pneumococcal infection. We further demonstrated that bacterial growth was increased by supplementation with methionine or IAV-infected mouse lung homogenates.ConclusionsThe data indicates that modulation of host metabolism during IAV infection may serve as a potential therapeutic intervention against secondary bacterial infections caused by serotype 3 pneumococci during IAV outbreaks in the future.

641. Carriage and Genetics of Haemophilus influenzae Serotype A (Hia) in Alaska, 2018

Background Haemophilus influenzae serotype a (Hia) is an important cause of infection among Alaska Native children. In 2018, 4 invasive Hia cases (iHia) occurred in an Alaska community. Our response aimed to prevent more iHia and evaluate Hia carriage in the community. Whole genome sequencing (WGS) was performed to compare Hia from iHia patients across Alaska in 2018, and from healthy outbreak community members.MethodsWe collected oropharyngeal (OP) samples from outbreak community members. Children aged < 10 years and people in close contact with cases (contacts) were offered rifampin prophylaxis. A second set of OP samples was collected 8 weeks later. Isolates from iHia from across the state were collected as part of the state surveillance. Hia was detected by PCR and culture, then characterized by antimicrobial susceptibility and WGS.ResultsAt baseline, contacts had a higher prevalence of Hia carriage than non-contacts (4/27(14.8%) vs 7/364(1.9%), p=0.0043). Eight weeks after rifampin prophylaxis, carriage prevalence did not significantly change among contacts (5/42(11.9%) to 6/25(24%), p=0.18) or non-contacts (7/368(1.9%) to 2/114(1.8%), p=0.47). Phylogenetic analysis of 19 iHia isolates and 15 isolates from healthy outbreak community members, revealed two major clades that differed by an average of 300 core single nucleotide polymorphisms (SNPs). Invasive and carriage isolates from the outbreak community were clustered in one clade, along with 3 non-outbreak iHia isolates. Isolates from this community differed from each other by an average of 1.2 core SNPs. Comparative genomics did not reveal any genetic mutations that distinguished carriage from invasive isolates. Three (20%) community isolates were rifampin-resistant and had a previously unreported mutation in the rpoB gene.ConclusionWe found Hia carriage prevalence was highest among persons in contact with iHia cases. Long-term community carriage was not affected by rifampin prophylaxis, possibly due to staggered prophylaxis. In the outbreak community, Hia isolates from carriers were nearly genetically identical to iHia isolates. Overall, iHia isolates from Alaska in 2018 were genetically similar. The mutation conferring rifampin resistance is concerning, as rifampin is used to prophylax contacts of iHia cases.Disclosures All Authors: No reported disclosures

Invasive Haemophilus influenzae Infections in Germany After the Introduction of Routine Childhood Immunization, 2001-2016.

Background Haemophilus influenzae (Hi) serotype b (Hib) vaccination was introduced in Germany in 1990. This study presents a comprehensive overview on the burden of invasive Hi infections for 2001–2016, including serotype distribution and ampicillin resistance.MethodsNationwide data from statutory disease surveillance (2001–2016) were linked with laboratory surveillance data (2009–2016). Besides descriptive epidemiology, statistical analyses included multiple imputation to estimate secular trends.ResultsIn 2001–2016, 4044 invasive Hi infections were reported. The mean incidence was 3.0 per million inhabitants, higher in males (3.2 vs 2.9 in females) and in the age groups <1 year (15.2) and ≥80 years (15.5). Nontypeable Hi (NTHi) caused 81% (n = 1545) of cases in 2009–2016. Of capsulated cases, 69% were serotype f and 17% serotype b. Of Hib cases eligible for vaccination, 10% (3/29) were fully vaccinated. For 2009–2016, significant increasing trends were observed for NTHi and Hif infections in the age groups <5 years and ≥60 years and for ampicillin resistance in NTHi.ConclusionsThis is one of the most comprehensive Hi data analyses since the introduction of Hib vaccines. NTHi and Hif cause an increasing disease burden among elderly patients and infants. Ampicillin resistance in NTHi must be considered in the treatment of invasive Hi infections.

Predicting the dominant influenza A serotype by quantifying mutation activities

ObjectivesCharacterizing and predicting the evolutionary process of influenza, which remains challenging, are of importance in capturing the patterns of influenza activities and the development of prevention and control strategies. In this study, we quantified genetic mutation activity and developed a statistical model to predict dominant influenza A serotype with limited sequencing data. Data and methodsA total number of 8097 and 7090 HA sequences for A/H1N1 and A/H3N2 were collected from 2008/09 to 2018/19 flu season in seven countries or regions. And g-measure, which reflected the overall level of genetic activity through time, was considered to predict dominant flu serotype in population. ResultsThe model discriminated the influenza serotypes well with the sensitivity = 0.84, precision = 0.79 and AUC = 0.78 (95% CI: 0.54 - 0.97), and explained 42% of the serotypes variability with the R2. ConclusionsOur study suggests that the dominance of flu serotype in population can be well discriminated by genetic mutation activities from sample strains. By the data-driven computational framework, the genetic mutation can be quantified to trace the genetic activities on a real-time basis, and provide early warning for the coming flu season.

Epidemiology of Invasive Haemophilus influenzae Serotype a Disease-United States, 2008-2017.

Haemophilus influenzae serotype a (Hia) can cause invasive disease similar to serotype b; no Hia vaccine is available. We describe the epidemiology of invasive Hia disease in the United States overall and specifically in Alaska during 2008-2017. Active population- and laboratory-based surveillance for invasive Hia disease was conducted through Active Bacterial Core surveillance sites and from Alaska statewide invasive bacterial disease surveillance. Sterile-site isolates were serotyped via slide agglutination or real-time polymerase chain reaction. Incidences in cases per 100 000 were calculated. From 2008 to 2017, an estimated average of 306 invasive Hia disease cases occurred annually in the United States (estimated annual incidence: 0.10); incidence increased by an average of 11.1% annually. Overall, 42.7% of cases were in children aged <5 years (incidence: 0.64), with highest incidence among children aged <1 year (1.60). Case fatality was 7.8% overall and was highest among adults aged ≥65 years (15.1%). Among children aged <5 years, the incidence was 17 times higher among American Indian and Alaska Native (AI/AN) children (8.29) than among children of all other races combined (0.49). In Alaska, incidences among all ages (0.68) and among children aged <1 year (24.73) were nearly 6 and 14 times higher, respectively, than corresponding US incidences. Case fatality in Alaska was 10.2%, and the vast majority (93.9%) of cases occurred among AI/AN. Incidence of invasive Hia disease has increased since 2008, with the highest burden among AI/AN children. These data can inform prevention strategies, including Hia vaccine development.

The cellular and humoral immune response to influenza vaccination is comparable in asthmatic and healthy subjects

ABSTRACT Annual influenza vaccination is recommended as a preventive measure for all patients with asthma since asthma exacerbations in children and adults are associated to viral infections including influenza. There is concern about the adequate immune response in asthmatics with ICS treatment. The production of antibodies to influenza in asthmatics has been demonstrated. However, cellular immunity is poorly understood. The aim of the study was to compare the humoral and cellular immune responses to influenza vaccine in asthmatic and healthy subjects. Twenty-five asthmatic patients attending the Allergy and Clinical Immunology Service at the Hospital General de Mexico and 25 healthy adults were included. Blood samples were obtained before, 4 and 12 months after immunization with influenza vaccine, influenza-specific antibodies were determined by the hemagglutination inhibition test and influenza-specific memory B, TCD4+, and TCD8 + lymphocytes were determined by flow cytometry. All the asthmatic patients received ICS treatment. The Geometric Mean titers for all influenza serotypes were similar in both groups; seropositivity and the cellular immune response increased in both groups over time and was comparable. Influenza vaccination in asthmatic patients with immunotherapy and ICS achieved protective antibody levels and cellular immunity over time comparable to healthy subjects.

Influenza in patients with cancer after 2009 pandemic AH1N1: An 8-year follow-up study in Mexico.

BackgroundImmunosupressed patients are at high risk of influenza‐related complications. Influenza AH1N1 has been hypothesized to induce worse outcomes in patients with malignancies, but after the A(H1N1)pdm09 few publications have analyzed the presentation and complications related to influenza afterward.ObjectivesWe aimed to describe the characteristics, risk factors, and outcomes of influenza in an oncologic center after the 2009 pandemic and to compare our case distribution to the National community acquired influenza databases in Mexico and the United States.MethodsWe reviewed the cases of confirmed influenza in patients with cancer from an oncological center in Mexico from April 2009 to April 2017. Data on severity and influenza type, malignancy, comorbidities, and outcomes were recorded. We correlated data between the Centers for Disease Control and Prevention (CDC) in the United States and SISVEFLU (Influenza Surveillance Program) in Mexico.ResultsOne hundred eighty‐eight patients were included; 75 (39.9%) had a solid neoplasm and 113 (60.1%) had hematologic malignancies. AH1N1 was the most frequent influenza type (54.2%). Patients with hematologic malignancies had more pneumonia (55% vs 25%, P < .001), needed more hospitalizations (75% vs 39% P < .001), had higher all‐cause mortality at 30 days (20% vs 9% P = .048) and influenza‐associated mortality (17% vs 7% P = .041). Thirty (16%) patients died within 30 days, and 24 (12.7%) were related to influenza. Influenza type was not associated with worse outcomes. Yearly occurrence of influenza reported by the CDC and SISVEFLU showed a significant correlation (ρ = 0.823, P = .006).ConclusionsAH1N1 was the dominant serotype. Patients with hematologic malignancies had more severe influenza and presented worse outcomes. Annual SISVEFLU and CDC surveillance information showed a similar distribution of cases along time but influenza serotypes did not match for all seasons.

1604. Response to a Cluster of Haemophilus influenzae Serotype A Cases in a Small Alaska Community, 2018

BackgroundBetween May and July 2018, four invasive cases of Haemophilus influenzae type a (Hia) occurred in a remote Alaska community. A public health response was performed to prevent further illness and to understand local Hia transmission.MethodsThe team identified close contacts of the Hia patients, collected oropharyngeal (OP) swabs and provided prophylactic rifampin. Close contacts were persons who spent ≥4 hours with a Hia patient for ≥ 5 of the 7 days preceding hospitalization. Five days later, OP swabs were collected community-wide and prophylactic rifampin was offered to community members aged <10 years. Eight weeks later, OP swabs were collected from all willing community members. Samples were tested using PCR and culture to identify Hi carriage.ResultsNo Hia cases occurred in this community after the response. The pretreatment carriage prevalence is shown in Figure 1. There was a significant difference in prevalence of Hia carriage between contacts (4/27, 14.8%) and non-contacts (7/364, 1.9%) (P = 0.0043). Contacts aged <10 years were significantly more likely to carry Hia compared with contacts aged ≥10 years (11/18 [61.1%] vs. 3/34 [8.8%], P = 0.0001). The case households had the highest proportion of individuals who carried Hia at any time, with 54%–60% of individuals in three case households carrying Hia at least once. Hia carriage was eliminated in two carriers who completed treatment and were tested immediately after rifampin prophylaxis. Testing 8 weeks later found that the prevalence of carriage did not significantly change in the contacts (5/42 [11.9%] to 6/25 [24%], P = 0.18) or the non-contacts (7/368 [1.9%] to 2/114 [1.8%], P = 0.47).ConclusionChildren aged <10 years who had close contact with the Hia patients were the most likely to carry Hia. These findings suggest that people who do not have close contact do not benefit from prophylaxis as they have very low Hia carriage. While rifampin prophylaxis eliminated carriage of Hia in the short term, carriage prevalence did not change in the long term. Further research is needed to understand why contacts have such a high prevalence of carriage even after receiving appropriate prophylactic medication. Disclosures All authors: No reported disclosures.

Continuing surveillance of invasive Haemophilus influenzae disease in northwestern Ontario emphasizes the importance of serotype a and non-typeable strains as causes of serious disease: a Canadian Immunization Research Network (CIRN) Study.

In the post-Haemophilus influenzae serotype b (Hib) vaccine era, invasive H. influenzae serotype a (Hia) disease emerged in Canadian First Nation, Inuit, and Alaskan Indigenous populations. Previous studies by our group found a high incidence of invasive Hia disease in northwestern Ontario. We retrospectively reviewed 24 cases (4 pediatric and 20 adult) of invasive H. influenzae disease hospitalized at the northwestern Ontario regional hospital between August 2011 and June 2018. The objectives were to further document the changing epidemiology of invasive H. influenzae disease in the region and to discuss potential control measures. Twenty-two H. influenzae isolates were serotyped and characterized using molecular-biological methods. Of the serotyped cases, there were 2 Hib, 9 Hia, and 11 non-typeable (NTHi). All Hia isolates belonged to the most common sequence types (ST) found in Canada (ST-23 and ST-929); 8 out of 9 were pan susceptible to antibiotics. One (11%) of 9 Hia and 5 (45%) of 11 NTHi cases were fatal. Our data on the consistent presence of serious invasive H. influenzae disease, with 41% prevalence of Hia (9 out of 22 serotyped isolates) and 50% prevalence of NTHi strains (11 out of 22), emphasize the importance of continued surveillance of H. influenzae in the post-Hib vaccine era and are critical information to inform potential vaccine development.

An Experimental Study on Apoptosis in Lymphoid Tissues of SPF Chicken after Avian Influenza Serotypes H9N2 Infection

Background and purpose: Influenza virus induces cell death in animals and human through necrosis and apoptosis. The present study is an attempt to experimentally examine the type of cell death in lymphoid tissue of chicken infected by avian influenza serotype H9N2 (A/chicken/Iran/772/2000). Methodology: Twenty SPF three weeks old chickens were grouped in two identical groups. The treatment group was infected by influenza virus (0.2ml, dilution 1:10, titration EID 50 107.5) and the control group received saline serum of the same volume through intranasal inoculation. Spleen, thymus, bursa of fabricius tissue specimens were collected after 72hrs. Afterward, microscopic intersections (5-6µm) stabilized in buffer formalin (10%) and marked by hematoxylin-eosin were prepared from the specimens.Findings: Histopathological examination of lymphoid tissues of the treatment and control chickens showed necrosis, apoptosis, and lymphoid depletion in lymphoid tissues of the treatment group. The difference between treatment and control groups in terms of apoptosis in spleen tissue was significant (p&lt;0.001); however, the difference in thymus and bursa of fabricius tissues was not significant. As to necrosis and lymphoid depletion, there was a significant difference between the two groups with regard to spleen, thymus, and bursa fabricius tissues. (p&lt;0.001)Conclusion: The survey showed that avian influenza serotype H9N2 can cause damages to lymphoid tissues through inducing apoptosis and necrosis

Atypical causes of bacterial osteoarticular infections in immunocompetent children.

Caring for a child with an osteoarticular infection or considering the possibility of an osteoarticular infection in a child is one of the most common clinical dilemmas encountered by clinicians caring for children. In such a scenario, one most often considers infection with frequently encountered pathogens such as Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae or Kingella kingae. A large variety of opportunistic osteoarticular pathogens may be found in the immunosuppressed patient or the postoperative or post-trauma patient, due to breaches in the immune system and nosocomial or post-traumatic exposure to multiple organisms. However, an enlarging spectrum of less commonly encountered bacterial pathogens is also increasingly appreciated in community-acquired osteoarticular infections in otherwise healthy children, particularly in this era of pneumococcal and Haemophilus influenzae serotype B immunization. Given the limitations of culture-based detection methods in osteoarticular infections and the potentially unique therapeutic and diagnostic approaches necessitated by some of these pathogens, an awareness of these infections is necessary for proper detection and management. This review will discuss less commonly encountered bacterial osteoarticular pathogens that may infect otherwise healthy children, with emphasis on the epidemiology, diagnosis and treatment of each.