Potential for bacteriophage therapy for Staphylococcus aureus pneumonia with influenza A coinfection

2021 ◽  
Vol 16 (3) ◽  
pp. 135-142
Author(s):  
Peter G Speck ◽  
Morgyn S Warner ◽  
Shailesh Bihari ◽  
Andrew D Bersten ◽  
James G Mitchell ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Bacteriophage Therapy ◽  
New Antibiotics ◽  
Delivery Routes ◽  
Bacterial Coinfection ◽  
1918 Influenza ◽  
Staphylococcus Aureus Pneumonia ◽  
Alternative Antimicrobials

The ability of influenza A virus to evolve, coupled with increasing antimicrobial resistance, could trigger an influenza pandemic with great morbidity and mortality. Much of the 1918 influenza pandemic mortality was likely due to bacterial coinfection, including Staphylococcus aureus pneumonia. S. aureus resists many antibiotics. The lack of new antibiotics suggests alternative antimicrobials, such as bacteriophages, are needed. Potential delivery routes for bacteriophage therapy (BT) include inhalation and intravenous injection. BT has recently been used successfully in compassionate access pulmonary infection cases. Phage lysins, enzymes that hydrolyze bacterial cell walls and which are bactericidal, are efficacious in animal pneumonia models. Clinical trials will be needed to determine whether BT can ameliorate disease in influenza and S. aureus coinfection.

The Osteopathic Approach During the 1918 Influenza Pandemic, Featuring Newly Analyzed Case Reports

2021 ◽  
Vol 31 (2) ◽  
pp. 9-16
Author(s):  
Leslie M. Ching ◽  
Ashley Watson ◽  
Tyler Watson ◽  
Philip Ridgway
Keyword(s):  
Mortality Rate ◽  
Influenza A ◽  
Case Reports ◽  
Influenza Pandemic ◽  
Geographic Location ◽  
H1n1 Influenza ◽  
Patient Treatment ◽  
Osteopathic Medicine ◽  
1918 Influenza ◽  
Osteopathic Physicians

Abstract Osteopathic physicians played a pivotal role in treating patients suffering from the H1N1 influenza A virus of the 1918 Influenza Pandemic. This article focuses on case reports and questionnaire answers from the Journal of the American Osteopathic Association (JAOA), now the Journal of Osteopathic Medicine (JOM), and Osteopathic Physician concerning the modalities, techniques, and efficacy of osteopathic treatments of the 1918 pandemic. There are 19,565 patients who are represented in this analysis. The results are compared to the often-cited 110,120 patient cases reported by the JOM in 1920. Several different approaches, including lymphatic and visceral techniques, were widely used at the time, and their historic incorporation into patient treatment is explored. There is a discussion of the geographic location and characteristics of the practices. Statistical breakdown of mortality rate, the most commonly used approaches, somatic dysfunctions commonly treated, physician anecdotes, and other common remedies used by osteopathic physicians, are noted additionally. A comparison is done of the literature regarding the osteopathic approach for COVID-19. The newly analyzed case reports in this article demonstrate a similar mortality rate as in the 1920 JAOA article and illustrate the geographical distribution, treatment approaches, and personal stories of osteopaths during the pandemic.

scholarly journals Role of Sialic Acid Binding Specificity of the 1918 Influenza Virus Hemagglutinin Protein in Virulence and Pathogenesis for Mice

2009 ◽  
Vol 83 (8) ◽  
pp. 3754-3761 ◽  
Author(s):  
Li Qi ◽  
John C. Kash ◽  
Vivien G. Dugan ◽  
Ruixue Wang ◽  
Guozhong Jin ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Sialic Acid ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Binding Specificity ◽  
Influenza Viruses ◽  
Virulence Determinants ◽  
Sialic Acid Binding ◽  
1918 Influenza

ABSTRACT The 1918 influenza pandemic caused more than 40 million deaths and likely resulted from the introduction and adaptation of a novel avian-like virus. Influenza A virus hemagglutinins are important in host switching and virulence. Avian-adapted influenza virus hemagglutinins bind sialic acid receptors linked via α2-3 glycosidic bonds, while human-adapted hemagglutinins bind α2-6 receptors. Sequence analysis of 1918 isolates showed hemagglutinin genes with α2-6 or mixed α2-6/α2-3 binding. To characterize the role of the sialic acid binding specificity of the 1918 hemagglutinin, we evaluated in mice chimeric influenza viruses expressing wild-type and mutant hemagglutinin genes from avian and 1918 strains with differing receptor specificities. Viruses expressing 1918 hemagglutinin possessing either α2-6, α2-3, or α2-3/α2-6 sialic acid specificity were fatal to mice, with similar pathology and cellular tropism. Changing α2-3 to α2-6 binding specificity did not increase the lethality of an avian-adapted hemagglutinin. Thus, the 1918 hemagglutinin contains murine virulence determinants independent of receptor binding specificity.

scholarly journals A universal dual mechanism immunotherapy for the treatment of influenza virus infections

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xin Liu ◽  
Boning Zhang ◽  
Yingcai Wang ◽  
Hanan S. Haymour ◽  
Fenghua Zhang ◽  
...  
Keyword(s):  
Influenza A ◽  
Influenza Pandemic ◽  
Intraperitoneal Administration ◽  
Neuraminidase Inhibitor ◽  
Virus Infections ◽  
Free Virus ◽  
Current Therapies ◽  
Severe Infections ◽  
Infected Cells ◽  
1918 Influenza

Abstract Seasonal influenza epidemics lead to 3–5 million severe infections and 290,000–650,000 annual global deaths. With deaths from the 1918 influenza pandemic estimated at >50,000,000 and future pandemics anticipated, the need for a potent influenza treatment is critical. In this study, we design and synthesize a bifunctional small molecule by conjugating the neuraminidase inhibitor, zanamivir, with the highly immunogenic hapten, dinitrophenyl (DNP), which specifically targets the surface of free virus and viral-infected cells. We show that this leads to simultaneous inhibition of virus release, and immune-mediated elimination of both free virus and virus-infected cells. Intranasal or intraperitoneal administration of a single dose of drug to mice infected with 100x MLD50 virus is shown to eradicate advanced infections from representative strains of both influenza A and B viruses. Since treatments of severe infections remain effective up to three days post lethal inoculation, our approach may successfully treat infections refractory to current therapies.

scholarly journals Lingering prenatal effects of the 1918 influenza pandemic on cardiovascular disease

2009 ◽  
Vol 1 (1) ◽  
pp. 26-34 ◽  
Author(s):  
B. Mazumder ◽  
D. Almond ◽  
K. Park ◽  
E. M. Crimmins ◽  
C. E. Finch
Keyword(s):  
Cardiovascular Disease ◽  
World War Ii ◽  
Prenatal Exposure ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Maternal Malnutrition ◽  
Maternal Infections ◽  
Influenza A H1n1 ◽  
The Usa ◽  
1918 Influenza

Prenatal exposure to the 1918 influenza pandemic (Influenza A, H1N1 subtype) is associated with ⩾20% excess cardiovascular disease at 60 to 82 years of age, relative to cohorts born without exposure to the influenza epidemic, either prenatally or postnatally (defined by the quarter of birth), in the 1982–1996 National Health Interview Surveys of the USA. Males showed stronger effects of influenza on increased later heart disease than females. Adult height at World War II enlistment was lower for the 1919 birth cohort than for those born in adjacent years, suggesting growth retardation. Calculations on the prevalence of maternal infections indicate that prenatal exposure to even uncomplicated maternal influenza may have lasting consequences later in life. These findings suggest novel roles for maternal infections in the fetal programming of cardiovascular risk factors that are independent of maternal malnutrition.

scholarly journals Influenza A Virus Exacerbates Staphylococcus aureus Pneumonia in Mice by Attenuating Antimicrobial Peptide Production

2013 ◽  
Vol 209 (6) ◽  
pp. 865-875 ◽  
Author(s):  
Keven M. Robinson ◽  
Kevin J. McHugh ◽  
Sivanarayana Mandalapu ◽  
Michelle E. Clay ◽  
Benjamin Lee ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Peptide ◽  
Influenza A Virus ◽  
Influenza A ◽  
Staphylococcus Aureus Pneumonia

scholarly journals Childhood tolerance of severe influenza: a mortality analysis in mice

2017 ◽  
Vol 313 (6) ◽  
pp. L1087-L1095 ◽  
Author(s):  
Freeman Suber ◽  
Lester Kobzik
Keyword(s):  
Influenza A ◽  
Influenza Pandemic ◽  
Transcriptome Profiling ◽  
H1n1 Influenza ◽  
H1n1 Influenza Virus ◽  
Enhanced Resistance ◽  
Severe Influenza ◽  
1918 Influenza ◽  
Late Expression ◽  
Mortality Analysis

During the 1918 influenza pandemic, children experienced substantially lower mortality than adults, a striking but unexplained finding. Whether this was due to enhanced resistance (reduced virus load) or better tolerance (reduced impact of infection) has not been defined. We found that prepubertal mice infected with H1N1 influenza virus also showed greater survival than infected pubertal mice, despite similar virus loads. Transcriptome profiling of infected lungs identified estrogen as a regulator of susceptibility in both sexes and also linked better survival to late expression of IL-1β. Blocking puberty with gonadectomy or a gonadotropin-releasing hormone antagonist improved survival. Estrogen or testosterone (which can be converted to estrogen) restored susceptibility of gonadectomized pubertal mice to influenza mortality, but dihydrotestosterone (which cannot be converted to estrogen) did not. Estrogen receptor blockade with fulvestrant in both male and female pubertal mice resulted in improved survival, even when given 3 days after infection. Moreover, late, but not early, IL-1β neutralization after infection was also protective. These findings indicate that pubertal increases in estrogen in both sexes are associated with increased mortality during influenza. This helps explain the reduced mortality of children seen with influenza in 1918 and might also be relevant to childhood tolerance to many other infectious diseases.

scholarly journals Archival influenza virus genomes from Europe reveal genomic and phenotypic variability during the 1918 pandemic

2021 ◽  
Author(s):  
Livia V Patrono ◽  
Bram Vrancken ◽  
Matthias Budt ◽  
Ariane Duex ◽  
Sebastian Lequime ◽  
...  
Keyword(s):  
Influenza A ◽  
Influenza Pandemic ◽  
Phenotypic Variability ◽  
Genomic Diversity ◽  
Influenza A Viruses ◽  
Long Distance ◽  
Nucleoprotein Gene ◽  
1918 Influenza ◽  
Virus Genomes

The 1918 influenza pandemic was the deadliest respiratory pandemic of the 20th century and determined the genomic make-up of subsequent human influenza A viruses (IAV). Here, we analyze the first 1918 IAV genomes from Europe and from the first, milder wave of the pandemic. 1918 IAV genomic diversity is consistent with local transmission and frequent long-distance dispersal events and in vitro polymerase characterization suggests potential phenotypic variability. Comparison of first and second wave genomes shows variation at two sites in the nucleoprotein gene associated with resistance to host antiviral response, pointing at a possible adaptation of 1918 IAV to humans. Finally, phylogenetic estimates based on extended molecular clock modelling suggests a pure pandemic descent of seasonal H1N1 IAV as an alternative to the hypothesis of an intrasubtype reassortment origin.

scholarly journals Phenol-Soluble Modulin Peptides Contribute to Influenza A Virus-Associated Staphylococcus aureus Pneumonia

2017 ◽  
Vol 85 (12) ◽  
Author(s):  
Dominik Alexander Bloes ◽  
Emanuel Haasbach ◽  
Carmen Hartmayer ◽  
Tobias Hertlein ◽  
Karin Klingel ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Lung Epithelial Cells ◽  
Swine Flu ◽  
Content Type ◽  
Usa300 Strain ◽  
Mrsa Strains ◽  
Staphylococcus Aureus Pneumonia ◽  
The Impact

ABSTRACT Influenza A virus (IAV) infection is often followed by secondary bacterial lung infection, which is a major reason for severe, often fatal pneumonia. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains such as USA300 cause particularly severe and difficult-to-treat cases of IAV-associated pneumonia. CA-MRSA strains are known to produce extraordinarily large amounts of phenol-soluble modulin (PSM) peptides, which are important cytotoxins and proinflammatory molecules that contribute to several types of S. aureus infection. However, their potential role in pneumonia has remained elusive. We determined the impact of PSMs on human lung epithelial cells and found that PSMs are cytotoxic and induce the secretion of the proinflammatory cytokine interleukin-8 (IL-8) in these cells. Both effects were boosted by previous infection with the 2009 swine flu pandemic IAV H1N1 strain, suggesting that PSMs may contribute to lung inflammation and damage in IAV-associated S. aureus pneumonia. Notably, the PSM-producing USA300 strain caused a higher mortality rate than did an isogenic PSM-deficient mutant in a mouse IAV-S. aureus pneumonia coinfection model, indicating that PSMs are major virulence factors in IAV-associated S. aureus pneumonia and may represent important targets for future anti-infective therapies.

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