Sex: F
Vaccine: FLUX
Symptoms: Chest X-ray normal, Death, Gene sequencing, H3N2 influenza, Influenza
Clinical narrative: Suspected vaccination failure; Influenza A/H3N2 virus infection; This case was reported in a literature article and described the occurrence of vaccination failure in a 86-year-old female subject who received Flu vaccine for prophylaxis.  Previously administered products included Influenza vaccine (at some point of time during the last 5 influenza seasons). Concurrent medical conditions included immunocompromised.   On an unknown date, less than a year after receiving Flu vaccine, the subject developed vaccination failure. Serious criteria included death, hospitalization and GSK medically significant. Additional event(s) included influenza a virus infection with serious criteria of death and hospitalization. The outcome of vaccination failure was fatal. The outcome(s) of the additional event(s) included influenza a virus infection (fatal). The reported cause of death was influenza.   The investigator considered that there was a reasonable possibility that the vaccination failure and influenza a virus infection may have been caused by Flu vaccine.   Relevant Tests: The nasopharyngeal (NP) swab sample was collected on 1 January 2015. The sample was sent to the laboratory for influenza testing. The patient was diagnosed influenza A/H3N2 virus infection (confirmed by Film Array). Total deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) were extracted from samples and subjected to 16S rRNA gene sequencing for microbiota profiling and influenza virus gene segment sequencing, respectively. Linear discriminant analysis and effective size comparisons (LEfSe) was used to identify signature taxonomic groups and features that were most likely to significantly characterize the influenza-related compositional differences of the microbiota and defined bacterial community types using Dirichlet multinomial mixture (DMM) models.  k-mer analysis was performed to identify underlying influenza virus sequence signatures for each sample and compared them to each other, visualized this measure of genetic distance by multidimensional scaling. Influenza virus sequencing and 16S rRNA gene sequencing for the sample was done. The cluster identified for influenza A/H3N2 was corresponding to the 3C.2a genetic clade. The patient was not diagnosed with pneumonia by chest X ray. Diagnostic results (unless otherwise stated, normal values were not provided):  In 2015, Gene sequencing result was see text unknown, Influenza virus test positive result was influenza A/H3N2 virus infection unknown and X-ray result was see text unknown.  Additional information was provided.  This case was reported in a literature article and described the suspected vaccination failure in a 86 years old female who was vaccinated with unspecified influenza vaccine (manufacturer unknown) for prophylaxis. This case corresponds to supplementary table S1 reported in this literature article.  The patient was part of cross-sectional study that aimed to characterize the microbiota of the nasopharynx by analyzing samples from individuals diagnosed with influenza A virus (IAV) H3N2 or influenza B virus (IBV) (Yamagata or Victoria) infections during the 2014-2015 influenza season and in healthy controls. The study investigated in more detail the relationship between host factors, such as age or vaccination status, and the respiratory microbiome in a specific influenza season that could help to better identify factors that contributed to influenza disease severity. The patient received influenza virus vaccine at some point of time during the last 5 influenza seasons. The patient was immunocompromised. No information on patient's medical or family history or concomitant medication or concurrent condition was provided.  On an unspecified date during the 2014-2015 influenza season, the patient received unspecified influenza vaccine (administration route and site unspecified; dosages unknown; batch number not provided). The age at vaccination was not provided but it could be 85 or 86 years old.  On an unspecified date at 86 years of age, during the 2014-2015 influenza season, an unknown period (in same season) after vaccination, the patient was hospitalized and the nasopharyngeal (NP) swab sample (sample ID A213) was collected on 1 January 2015. The sample was sent to the laboratory for influenza testing. The patient was diagnosed influenza A/H3N2 virus infection (confirmed by Film Array). Total deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) were extracted from samples and subjected to 16S rRNA gene sequencing for microbiota profiling and influenza virus gene segment sequencing, respectively. Linear discriminant analysis and effective size comparisons (LEfSe) was used to identify signature taxonomic groups and features that were most likely to significantly characterize the influenza-related compositional differences of the microbiota and defined bacterial community types using Dirichlet multinomial mixture (DMM) models.  k-mer analysis was performed to identify underlying influenza virus sequence signatures for each sample and compared them to each other, visualized this measure of genetic distance by multidimensional scaling. Influenza virus sequencing and 16S rRNA gene sequencing for the sample was done. The cluster identified for influenza A/H3N2 was corresponding to the 3C.2a genetic clade. The patient was not diagnosed with pneumonia by chest X ray. On an unspecified date, the patient died. It was unknown if an autopsy was performed. [In this study, the influenza virus-infected individuals had a slightly lower prevalence and abundance of Streptococcus, an enrichment of Dolosigranulum, and very low prevalence of Corynebacterium. 4 microbial community types (NP types) in the subjects tested. NP type A was significantly enriched in influenza infection, while NP type B dominated in the control group. While both community types C and D were slightly enriched in influenza patients, it was not at a significant level. In the influenza virus-infected subjects only, the less common influenza-associated NP type D was found predominantly in the young (less than 18 years old). NP type A was comprised primarily of Streptococcus and Dolosigranulum; NP type B, enriched was dominated by a combination of Streptococcus, Corynebacterium, and Comamonadaceae. NP type C was dominated by Moraxella, while NP type D had an overrepresentation of Staphylococcus. The different communities did not associate differently with either of the flu types (IAV versus IBV)]. This case has been considered as suspected vaccination failure being time to onset was unknown.  This case has been considered as serious due to death/suspected vaccination failure/hospitalisation.  Treatment was unknown.  The outcome of event was death.   The authors stated, "Influenza infection was shown to be significantly associated with microbial composition of the nasopharynx according to the virus type and the vaccination status of the patient. We identified four microbial community types across the combined cohort of influenza patients and healthy individuals with one community type most representative of the influenza virus-infected group. We also identified microbial taxa for which relative abundance was significantly higher in the unvaccinated elderly group; these taxa include species known to be associated with pneumonia. Our results suggest that there is a significant association between the composition of the microbiota in the nasopharynx and the influenza virus type causing the infection. We observe that vaccination status, especially in more senior individuals, also has an association with the microbial community profile. This indicates that vaccination against influenza, even when ineffective to prevent disease, could play a role in controlling secondary bacterial complications. The reasons for enhanced susceptibility to severe bacterial disease after influenza infection remain poorly defined. viral infection can disrupt this equilibrium and cause loss of some microbial populations and/or overgrowth of other pathogens, resulting in disease. Disruption of the URT microbiota has been found to be associated with community-acquired pneumonia. Even an unmatched influenza vaccine could prevent severe disease by modulating the respiratory bacterial communities. IAV and IBV virus infections were associated with a significantly different microbial community profile than that for uninfected individuals. Overall, these observations suggest that Corynebacterium could potentially protect the respiratory tract from pathogenic bacteria such as S. aureus and S. pneumoniae that are the most common cause of post-influenza pneumonia. We studied the composition of the nasopharynx microbiota at diagnosis, we cannot determine whether differences between healthy controls and influenza virus-infected individuals are due to the infection, the presence of a microbial community that predisposes to infection, or a combination of both. The effectiveness of the influenza vaccine varies in different seasons due to a number of factors, such as vaccine strain mismatch and host immune status, including history of previous influenza vaccination. We suggest that another potential factor is the host microbiome. It showed that in influenza virus-infected individuals the lack of vaccination in the current season is associated with the enrichment of different microbial taxa, such as Moraxella and Streptococcus, depending on the type of influenza virus (IAV versus IBV)".  The authors concluded, "Our aims in this study were to determine whether the microbiota of the nasopharynx was different in individuals with influenza infection and to identify factors associated with the variations observed between infected subjects in different age groups. We found that during influenza infection, the nasopharyngeal microbiota of vaccinated individuals was strongly associated with higher levels of specific microbial taxa, with different microbial profiles relative to virus types and clades. These observations provide new insight into influenza infection and highlight a need for more studies to explore the mechanism of how influenza vaccines-live attenuated or killed-interact with the respiratory microbiota".  This is 1 of the 127 valid cases reported in the same literature article.      Lab Comments: The nasopharyngeal (NP) swab sample  was collected on 1 January 2015. The sample was sent to the laboratory for influenza testing. The patient was diagnosed influenza A/H3N2 virus infection (confirmed by Film Array). Total deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) were extracted from samples and subjected to 16S rRNA gene sequencing for microbiota profiling and influenza virus gene segment sequencing, respectively. Linear discriminant analysis and effective size comparisons (LEfSe) was used to identify signature taxonomic groups and features that were most likely to significantly characterize the influenza-related compositional differences of the microbiota and defined bacterial community types using Dirichlet multinomial mixture (DMM) models.  k-mer analysis was performed to identify underlying influenza virus sequence signatures for each sample and compared them to each other, visualized this measure of genetic distance by multidimensional scaling. Influenza virus sequencing and 16S rRNA gene sequencing for the sample was done. The cluster identified for influenza A/H3N2 was corresponding to the 3C.2a genetic clade. The patient was not diagnosed with pneumonia by chest X ray.; Reported Cause(s) of Death: Influenza A/H3N2 virus infection