The relationship between influenza and pneumonia

1.The results are reported of a study cases of pneumonia, of upper respiratory indection and of family contacts of cases of pneumoia for evidence of influenza-virus infection between October 1947 and April 1949.2. During an inter-epidemic period in relation to influenza, two sporadic cases of influenza-virus A infection were detected, one in a case of pneumo-coccal pneumonia and the other in a family contact of a case of pneumonia. These were the only instances of virus infection detected amoung 158 individuals including seventy-eight cases of pneumonia.3. The epidemic of influenza from February to April 1949 was associated with an increase in number of notified cases of pneumonia, particularly in those over 45 years of age compared with the notifications in 1948. Deaths from pneumonia also increased, particularly in those of 65years or over.4. During the period of influenza prevalence, direct tests of specimens in eggs and serological tests gave positive evidence of influenza prevalence, direct tests of specimens in eggs and serological tests gave positve evidence of influenza virus A infection in many instances. Twenty-six of forty-one cases of upper respiratory infection between February and April 1949 were positive for influenza A and one was a case of influenza B.5. Eifgteen of fifty-five cases of pneumococcal and staphyococcal pneumoniaccal and staphylococcal pneumonia, eight of fifteen cases of bronchitis, one of two cases of bronchiectasis and four of six cases of congestive heart failure gave serological or cultural evidence of influenza virus A infection during the period of February to April 1949.6. The mechanism of influenza-virus infection in relation to bacterial infection of the lower respiratory tract is discussed.

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Severe Influenza Virus Infection in Children Admitted to the PICU: Comparison of Influenza A and Influenza B Virus Infection

Journal of Medical Virology ◽

10.1002/jmv.27400 ◽

2021 ◽

Author(s):

Pınar YAZICI ÖZKAYA ◽

Eşe Eda TURANLI ◽

Hamdi METİN ◽

Ayça Aydın UYSAL ◽

Candan ÇİÇEK ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza A ◽

Influenza Virus Infection ◽

Influenza B Virus ◽

Influenza B ◽

Severe Influenza ◽

B Virus

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Serum High-Mobility-Group Box 1 as a Biomarker and a Therapeutic Target during Respiratory Virus Infections

mBio ◽

10.1128/mbio.00246-18 ◽

2018 ◽

Vol 9 (2) ◽

Cited By ~ 16

Author(s):

Mira C. Patel ◽

Kari Ann Shirey ◽

Marina S. Boukhvalova ◽

Stefanie N. Vogel ◽

Jorge C. G. Blanco

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza A ◽

Influenza Virus Infection ◽

High Mobility ◽

Influenza B Virus ◽

Influenza B ◽

Lung Pathology ◽

B Virus ◽

Cotton Rats

ABSTRACT Host-derived “danger-associated molecular patterns” (DAMPs) contribute to innate immune responses and serve as markers of disease progression and severity for inflammatory and infectious diseases. There is accumulating evidence that generation of DAMPs such as oxidized phospholipids and high-mobility-group box 1 (HMGB1) during influenza virus infection leads to acute lung injury (ALI). Treatment of influenza virus-infected mice and cotton rats with the Toll-like receptor 4 (TLR4) antagonist Eritoran blocked DAMP accumulation and ameliorated influenza virus-induced ALI. However, changes in systemic HMGB1 kinetics during the course of influenza virus infection in animal models and humans have yet to establish an association of HMGB1 release with influenza virus infection. To this end, we used the cotton rat model that is permissive to nonadapted strains of influenza A and B viruses, respiratory syncytial virus (RSV), and human rhinoviruses (HRVs). Serum HMGB1 levels were measured by an enzyme-linked immunosorbent assay (ELISA) prior to infection until day 14 or 18 post-infection. Infection with either influenza A or B virus resulted in a robust increase in serum HMGB1 levels that decreased by days 14 to 18. Inoculation with the live attenuated vaccine FluMist resulted in HMGB1 levels that were significantly lower than those with infection with live influenza viruses. RSV and HRVs showed profiles of serum HMGB1 induction that were consistent with their replication and degree of lung pathology in cotton rats. We further showed that therapeutic treatment with Eritoran of cotton rats infected with influenza B virus significantly blunted serum HMGB1 levels and improved lung pathology, without inhibiting virus replication. These findings support the use of drugs that block HMGB1 to combat influenza virus-induced ALI. IMPORTANCE Influenza virus is a common infectious agent causing serious seasonal epidemics, and there is urgent need to develop an alternative treatment modality for influenza virus infection. Recently, host-derived DAMPs, such as oxidized phospholipids and HMGB1, were shown to be generated during influenza virus infection and cause ALI. To establish a clear link between influenza virus infection and HMGB1 as a biomarker, we have systematically analyzed temporal patterns of serum HMGB1 release in cotton rats infected with nonadapted strains of influenza A and B viruses and compared these patterns with a live attenuated influenza vaccine and infection by other respiratory viruses. Towards development of a new therapeutic modality, we show herein that blocking serum HMGB1 levels by Eritoran improves lung pathology in influenza B virus-infected cotton rats. Our study is the first report of systemic HMGB1 as a potential biomarker of severity in respiratory virus infections and confirms that drugs that block virus-induced HMGB1 ameliorate ALI.

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Routine blood parameters can detect early influenza virus infection in children

10.21203/rs.3.rs-54705/v1 ◽

2020 ◽

Author(s):

Ronghe Zhu ◽

Qiu Wang ◽

Cuie Chen ◽

Xixi Zhang ◽

Chaosheng Lu ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza A Virus ◽

Influenza A ◽

Influenza Virus Infection ◽

Blood Parameters ◽

Influenza B ◽

Cutoff Value ◽

Routine Blood ◽

Influenza A Virus Infection

Abstract Purpose We aimed to explore the value of Routine blood parameters, such as the lymphocyte (LYM) count, platelet (PLT) count, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), LYM*PLT and mean platelet volume-to-platelet ratio (MPV/PLT), are widely used to predict the prognosis of infectious diseases, for predicting influenza virus infection in children. Methods We conducted a single-center, retrospective, observational study on fever with influenza-like symptom in pediatric outpatients in different age groups and evaluated the predictive value of various routine blood parameters within 48 hours of the onset of fever after influenza virus infection. Results The LYM count, PLT count, LMR and LYM*PLT were lower, and the NLR and MPV/PLT were higher in the infected children. The LYM count, LMR and LYM*PLT in the infected group were lower in the 1- to 6-year-old group, and the LMR and LYM*PLT in the infected group were lower in the > 6-year-old group. In the 1- to 6-year-old group, the cutoff value of the LMR for predicting influenza A virus infection was 3.75, the sensitivity was 81.87%, the specificity was 84.31%, and the AUC was 0.886; the cutoff value of the LMR for predicting influenza B virus infection was 3.71, the sensitivity was 73.58%, the specificity was 84.31%, and the AUC was 0.843. In the > 6-year-old group, the cutoff value of the LMR for predicting influenza A virus infection was 3.05, the sensitivity was 89.27%, the specificity was 89.61%, and the AUC was 0.949; the cutoff value of the LMR for predicting influenza B virus infection was 2.88, the sensitivity was 83.19%, the specificity was 92.21%, and the AUC was 0.924. Conclusions Routine blood tests are simple, inexpensive and easy to perform, and they are useful for predicting influenza virus infection in children. The LMR had the strongest predictive value for influenza virus infection in children older than 1 year, especially influenza A virus infection.

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Association Between the Respiratory Microbiome and Susceptibility to Influenza Virus Infection

Clinical Infectious Diseases ◽

10.1093/cid/ciz968 ◽

2019 ◽

Vol 71 (5) ◽

pp. 1195-1203 ◽

Cited By ~ 8

Author(s):

Tim K Tsang ◽

Kyu Han Lee ◽

Betsy Foxman ◽

Angel Balmaseda ◽

Lionel Gresh ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza A ◽

Influenza Infection ◽

Influenza Virus Infection ◽

Fold Increase ◽

Transmission Model ◽

Influenza B ◽

Household Contacts ◽

Index Cases

Abstract Background Previous studies suggest that the nose/throat microbiome may play an important role in shaping host immunity and modifying the risk of respiratory infection. Our aim is to quantify the association between the nose/throat microbiome and susceptibility to influenza virus infection. Methods In this household transmission study, index cases with confirmed influenza virus infection and their household contacts were followed for 9–12 days to identify secondary influenza infections. Respiratory swabs were collected at enrollment to identify and quantify bacterial species via high-performance sequencing. Data were analyzed by an individual hazard-based transmission model that was adjusted for age, vaccination, and household size. Results We recruited 115 index cases with influenza A(H3N2) or B infection and 436 household contacts. We estimated that a 10-fold increase in the abundance in Streptococcus spp. and Prevotella salivae was associated with 48% (95% credible interval [CrI], 9–69%) and 25% (95% CrI, 0.5–42%) lower susceptibility to influenza A(H3N2) infection, respectively. In contrast, for influenza B infection, a 10-fold increase in the abundance in Streptococcus vestibularis and Prevotella spp. was associated with 63% (95% CrI, 17–83%) lower and 83% (95% CrI, 15–210%) higher susceptibility, respectively. Conclusions Susceptibility to influenza infection is associated with the nose/throat microbiome at the time of exposure. The effects of oligotypes on susceptibility differ between influenza A(H3N2) and B viruses. Our results suggest that microbiome may be a useful predictor of susceptibility, with the implication that microbiome could be modulated to reduce influenza infection risk, should these associations be causal.

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INFLUENZA VIRUS INFECTION IN THE HAMSTER

Journal of Experimental Medicine ◽

10.1084/jem.88.3.343 ◽

1948 ◽

Vol 88 (3) ◽

pp. 343-353 ◽

Cited By ~ 15

Author(s):

William F. Friedewald ◽

Edward W. Hook

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza A ◽

High Titer ◽

Influenza Virus Infection ◽

The Body ◽

Red Cells ◽

Influenza B Virus ◽

Influenza B ◽

Lung Lesions

A study of influenza virus infection in the hamster has yielded the following results: 1. Two influenza A strains (Ga. 47 and PR8) multiplied readily in the hamster lung, although no lung lesions were produced during six serial passages. On further passage both viruses abruptly acquired the capacity to produce pulmonary consolidation and death of the animals. 2. Extracts of the lungs during the early passages contained complement-fixing antigen and infectious virus, as revealed by titration in mice and embryonated eggs. Agglutinins for chicken, human, and guinea pig red cells, however, were not demonstrable at this time. With further passage a close correlation was observed between the capacity of the virus to produce lung lesions in the hamster and to agglutinate mammalian types of red cells. In addition, quantitative changes in the virus population were demonstrated in the lung extracts by complement fixation tests and titrations in mice and eggs. 3. Incubation at 37°C. was effective in bringing out agglutinins in high titer for chicken red cells in lung extracts, which originally failed to agglutinate chicken cells but agglutinated mammalian red cells. This method did not increase the titers of mammalian cell agglutinins. 4. The body temperature of the hamster was found to decrease within 1 to 4 days after inoculation of influenza virus. In the early passages the temperature returned to normal within 24 hours, but with the development of the pathogenic strain of virus the temperature remained at subnormal levels until death. 5. The Lee strain of influenza B virus produced pulmonary lesions in the hamster on the first passage and no increase in pathogenicity of the virus occurred during eleven serial passages. Virus was demonstrable in extracts of the lungs by all the methods used and no difference was observed in its capacity to agglutinate fowl and mammalian types of red cells. The implications of these findings are considered briefly in the discussion.

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Hemagglutinin and Neuraminidase Antibodies Are Induced in an Age- and Subtype-Dependent Manner after Influenza Virus Infection

Journal of Virology ◽

10.1128/jvi.01385-19 ◽

2020 ◽

Vol 94 (7) ◽

Author(s):

Sook-San Wong ◽

Ben Waite ◽

Jacqui Ralston ◽

Tim Wood ◽

G. Edwin Reynolds ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza A ◽

Natural Infection ◽

Influenza Virus Infection ◽

Immunological Memory ◽

Influenza B Virus ◽

Influenza B ◽

Dependent Manner ◽

Response Dynamics

ABSTRACT Despite evidence that antibodies targeting the influenza virus neuraminidase (NA) protein can be protective and are broadly cross-reactive, the immune response to NA during infection is poorly understood compared to the response to hemagglutinin (HA) protein. As such, we compared the antibody profile to HA and NA in two naturally infected human cohorts in Auckland, New Zealand: (i) a serosurvey cohort, consisting of pre- and post-influenza season sera from PCR-confirmed influenza cases (n = 50), and (ii) an immunology cohort, consisting of paired sera collected after PCR-confirmation of infection (n = 94). The induction of both HA and NA antibodies in these cohorts was influenced by age and subtype. Seroconversion to HA was more frequent in those <20 years old (yo) for influenza A (serosurvey, P = 0.01; immunology, P = 0.02) but not influenza B virus infection. Seroconversion to NA was not influenced by age or virus type. Adults ≥20 yo infected with influenza A viruses were more likely to show NA-only seroconversion compared to children (56% versus 14% [5 to 19 yo] and 0% [0 to 4 yo], respectively). Conversely, children infected with influenza B viruses were more likely than adults to show NA-only seroconversion (88% [0 to 4 yo] and 75% [5 to 19 yo] versus 40% [≥20 yo]). These data indicate a potential role for immunological memory in the dynamics of HA and NA antibody responses. A better mechanistic understanding of this phenomenon will be critical for any future vaccines aimed at eliciting NA immunity. IMPORTANCE Data on the immunologic responses to neuraminidase (NA) is lacking compared to what is available on hemagglutinin (HA) responses, despite growing evidence that NA immunity can be protective and broadly cross-reactive. Understanding these NA responses during natural infection is key to exploiting these properties for improving influenza vaccines. Using two community-acquired influenza cohorts, we showed that the induction of both HA and NA antibodies after infection is influenced by age and subtypes. Such response dynamics suggest the influence of immunological memory, and understanding how this process is regulated will be critical to any vaccine effort targeting NA immunity.

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Prevalence of Influenza Virus Type and Subtype at Siriraj Hospital, Bangkok, Thailand During 2013 - 2017

Ramathibodi Medical Journal ◽

10.33165/rmj.2020.43.3.241918 ◽

2020 ◽

Vol 43 (3) ◽

pp. 1-7

Author(s):

Nattapol Narong ◽

Siriwat Manajit ◽

Sirikarn Athipanyasil ◽

Niracha Athipanyasilp ◽

Ruengpung Sutthent ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza A ◽

Influenza Virus Infection ◽

Respiratory Illness ◽

Influenza B Virus ◽

Influenza B ◽

Influenza A H1n1 ◽

B Virus ◽

Siriraj Hospital

Background: Influenza A (pandemic and seasonal H1/H3) and influenza B viruses were the predominant circulating seasonal influenza strains. Following its massive outbreak in 2009 globally, including Thailand, influenza A (H1N1) pdm09 viruses have replaced the previous seasonal H1 strain and become one of the circulating strains ever since. Both influenza A and B viruses are highly contagious and potentially cause respiratory illness ranging from mild to severe. Objective: To determine the prevalence of types and subtypes of circulating influenza virus strains in Bangkok, Thailand during 2013 - 2017. Methods: The 4385 nasopharyngeal wash specimens were collected from patients presented with influenza-like illness from January 2013 to December 2017 at Siriraj Hospital, Bangkok, Thailand. Influenza virus types and subtypes were determined using real-time RT-PCR technique. Clinical characteristics of patients infected with influenza A viruses and influenza B virus were compared and analyzed. Results: Of 4385 nasopharyngeal wash specimens, the prevalence of influenza virus infection during 2013 - 2017 was 18.22% (n = 799). Of 799 influenza-positive samples, 608 (76.09%) and 191 (23.90%) samples were positive for influenza A and influenza B viruses, respectively. Most patients were presented with fever, cough, and runny nose; however, patients infected with influenza A virus generally had higher severity than those with influenza B virus infection (P < .05). Conclusions: The findings provided the characteristics of influenza virus types and subtypes at Siriraj Hospital, Bangkok, Thailand during 2013 - 2017. Sporadic cases of influenza occurred all year round, but the incidence peaked in March 2014 and August 2017. The outcomes of this study are potentially useful for prevention, treatment, and disease monitoring.

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Salivary Blockade Protects the Lower Respiratory Tract of Mice from Lethal Influenza Virus Infection

Journal of Virology ◽

10.1128/jvi.00624-17 ◽

2017 ◽

Vol 91 (14) ◽

Cited By ~ 11

Author(s):

Karen Ivinson ◽

Georgia Deliyannis ◽

Leanne McNabb ◽

Lara Grollo ◽

Brad Gilbertson ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Respiratory Tract ◽

Lower Respiratory Tract ◽

Influenza A ◽

Lethal Dose ◽

Laboratory Mouse ◽

Influenza Virus Infection ◽

Upper Respiratory Tract ◽

Upper Respiratory

ABSTRACT It is possible to model the progression of influenza virus from the upper respiratory tract to the lower respiratory tract in the mouse using viral inoculum delivered in a restricted manner to the nose. In this model, infection with the A/Udorn/307/72 (Udorn) strain of virus results ultimately in high viral titers in both the trachea and lungs. In contrast, the A/Puerto Rico/8/34 (PR8) strain causes an infection that is almost entirely limited to the nasal passages. The factors that govern the progression of virus down the respiratory tract are not well understood. Here, we show that, while PR8 virus grows to high titers in the nose, an inhibitor present in the saliva blocks further progression of infection to the trachea and lungs and renders an otherwise lethal dose of virus completely asymptomatic. In vitro, the salivary inhibitor was capable of potent neutralization of PR8 virus and an additional 20 strains of type A virus and two type B strains that were tested. The exceptions were Udorn virus and the closely related H3N2 strains A/Port Chalmers/1/73 and A/Victoria/3/75. Characterization of the salivary inhibitor showed it to be independent of sialic acid and other carbohydrates for its function. This and other biochemical properties, together with its virus strain specificity and in vivo function, indicate that the mouse salivary inhibitor is a previously undescribed innate inhibitory molecule that may have evolved to provide pulmonary protection of the species from fatal influenza virus infection. IMPORTANCE Influenza A virus occasionally jumps from aquatic birds, its natural host, into mammals to cause outbreaks of varying severity, including pandemics in humans. Despite the laboratory mouse being used as a model to study influenza virus pathogenesis, natural outbreaks of influenza have not been reported in the species. Here, we shed light on one mechanism that might allow mice to be protected from influenza in the wild. We show that virus deposited in the mouse upper respiratory tract will not progress to the lower respiratory tract due to the presence of a potent inhibitor of the virus in saliva. Containing inhibitor-sensitive virus to the upper respiratory tract renders an otherwise lethal infection subclinical. This knowledge sheds light on how natural inhibitors may have evolved to improve survival in this species.

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Impact of influenza virus during pregnancy: from disease severity to vaccine efficacy

Future Virology ◽

10.2217/fvl-2020-0024 ◽

2020 ◽

Vol 15 (7) ◽

pp. 441-453

Author(s):

Ana Vazquez-Pagan ◽

Rebekah Honce ◽

Stacey Schultz-Cherry

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Immune Responses ◽

Pregnant Women ◽

Disease Severity ◽

Influenza A ◽

Antiviral Treatment ◽

Influenza Virus Infection ◽

Severe Influenza ◽

The Impact

Pregnant women are among the individuals at the highest risk for severe influenza virus infection. Infection of the mother during pregnancy increases the probability of adverse fetal outcomes such as small for gestational age, preterm birth and fetal death. Animal models of syngeneic and allogeneic mating can recapitulate the increased disease severity observed in pregnant women and are used to define the mechanism(s) of that increased severity. This review focuses on influenza A virus pathogenesis, the unique immunological landscape during pregnancy, the impact of maternal influenza virus infection on the fetus and the immune responses at the maternal–fetal interface. Finally, we summarize the importance of immunization and antiviral treatment in this population and highlight issues that warrant further investigation.

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A Fungal Cu/Zn-Containing Superoxide Dismutase Enhances the Therapeutic Efficacy of a Plant Polyphenol Extract in Experimental Influenza Virus Infection

Zeitschrift für Naturforschung C ◽

10.1515/znc-2010-5-616 ◽

2010 ◽

Vol 65 (5-6) ◽

pp. 419-428 ◽

Cited By ~ 1

Author(s):

Julia Serkedjieva ◽

Tsvetanka Stefanova ◽

Ekaterina Krumova

Keyword(s):

Superoxide Dismutase ◽

Influenza Virus ◽

Virus Infection ◽

Protective Effect ◽

Influenza A ◽

Influenza Virus Infection ◽

Protective Role ◽

Combined Application ◽

Combined Use ◽

Experimental Influenza

The combined protective effect of a polyphenol-rich extract, isolated from Geranium sanguineum L. (PC), and a novel naturally glycosylated Cu/Zn-containing superoxide dismutase, produced from the fungal strain Humicula lutea 103 (HL-SOD), in the experimental influenza A virus infection (EIVI) in mice, induced with the virus A/Aichi/2/68 (H3N2), was investigated. The combined application of HL-SOD and PC in doses, which by themselves do not defend significantly mice in EIVI, resulted in a synergistically increased protection, determined on the basis of protective indices and amelioration of lung injury. Lung weights and consolidation as well as infectious lung virus titers were all decreased significantly parallel to the reduction of the mortality rates; lung indices were raised. The excessive production of reactive oxygen species (ROS) by alveolar macrophages (aMØ) as well as the elevated levels of the lung antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), induced by EIVI, were brought to normal. For comparative reasons the combined protective effect of PC and vitamin C was investigated. The obtained results support the combined use of antioxidants for the treatment of influenza virus infection and in general indicate the beneficial protective role of combinations of viral inhibitors of natural origin with diverse modes of action.

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