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Cited by 1,629Influenza Virus Research StudiesPneumonia and Respiratory InfectionsRespiratory viral infections research

Predominant Role of Bacterial Pneumonia as a Cause of Death in Pandemic Influenza: Implications for Pandemic Influenza Preparedness

Open access
Morens, David M., Taubenberger, Jeffery K., Fauci, Anthony S.·2008·The Journal of Infectious Diseases
DOI 10.1086/591708PMC PMC2599911
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Abstract

BACKGROUND: Despite the availability of published data on 4 pandemics that have occurred over the past 120 years, there is little modern information on the causes of death associated with influenza pandemics. METHODS: We examined relevant information from the most recent influenza pandemic that occurred during the era prior to the use of antibiotics, the 1918-1919 "Spanish flu" pandemic. We examined lung tissue sections obtained during 58 autopsies and reviewed pathologic and bacteriologic data from 109 published autopsy series that described 8398 individual autopsy investigations. RESULTS: The postmortem samples we examined from people who died of influenza during 1918-1919 uniformly exhibited severe changes indicative of bacterial pneumonia. Bacteriologic and histopathologic results from published autopsy series clearly and consistently implicated secondary bacterial pneumonia caused by common upper respiratory-tract bacteria in most influenza fatalities. CONCLUSIONS: The majority of deaths in the 1918-1919 influenza pandemic likely resulted directly from secondary bacterial pneumonia caused by common upper respiratory-tract bacteria. Less substantial data from the subsequent 1957 and 1968 pandemics are consistent with these findings. If severe pandemic influenza is largely a problem of viral-bacterial copathogenesis, pandemic planning needs to go beyond addressing the viral cause alone (e.g., influenza vaccines and antiviral drugs). Prevention, diagnosis, prophylaxis, and treatment of secondary bacterial pneumonia, as well as stockpiling of antibiotics and bacterial vaccines, should also be high priorities for pandemic planning.

Integrity signals

Registry

Crossref · 10.1086/591708

Cites

78 of 78 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

22 of 134 cited sources checked · 6 supported · 0 flagged · accuracy not yet measured

  • Findingcitation

    In the 14 of 96 1918-1919 autopsy series that did not report predominance of lung pneumopathogens, pneumopathogens accounted collectively for 37.4% of pneumonia deaths.

    “In the 14 of 96 autopsy series that did not report the predominance of lung pneumopathogens [29, 36, 41-53], pneumopathogens accounted collectively for 37.4% of pneumonia deaths.”
    Quote in the paperNot a substantial claim1 of 10 sources checked
    • cites [29] Lucke B Wight T Kime E Pathologic anatomy and bacteriology of influenza: epidemic of autumn, 1918 Arch Intern Med 1919 24 154 237 source
    • cites [36] Roos C Notes on the bacteriology, and on the selective action of B. influenzae Pfeiffer J Immunol 1919 4 189 201 source
    • cites [41] Little TR Discussion on influenza Proc R Soc Med (Great Britain) 1918 12 36 41 PMC2067067 19980424 source
    • cites [42] Rucker JB Wenner JJ Friedländer bacillus, the causative factor in bronchopneumonia following influenza Proc Pathol Soc Philadelphia 1918 21 41 2

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [43] Rucker JB Wenner JJ Friedlander bacillus the causative factor in bronchopneumonia following influenza N Y Med J 1918 108 1066 9

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [44] Abrahams A Hallows N French H A further investigation into influenzo-pneumococcal and influenzo-streptococcal septicæmia: epidemic influenzal “pneumonia” of highly fatal type and its relation to “purulent bronchitis” Lancet 1919 1 1 11 source
    • cites [45] Findlay GM Notes on the bacteriology of influenza epidemic in Lower Egypt Lancet 1919 1 1113 14 source
    • cites [46] Fiore G Contributo allo studio batteriologico dell’epidemia di influenza 1918 Riv Clin Pediatr (Firenze) 1919 17 281 303

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [47] Gibson HG Bowman FB MRC (Medical Research Council) The bacteriological flora of the respiratory tract in cases of influenza Special Report Series, No. 36. Studies of influenza in hospitals of the British Armies in France, 1918: part I. Abbeville Research Team 2 London His Majesty’s Stationery Office 1919 37 46

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [48] Medalia LS Influenza epidemic at Camp MacArthur: etiology, bacteriology, pathology, and specific therapy Boston Med Surg J 1919 180 323 30 source
    • Rests on an assumption: The 109 published autopsy series and 8398 autopsies are representative of influenza deaths during the 1918-1919 pandemic.
    • Rests on an assumption: Postmortem lung culture results reflect bacteria that contributed to death rather than postmortem contamination or incidental colonization.
  • Premisecitation

    Between 1890 and 1950, most observers believed fatal influenza was a polymicrobial infection in which an inciting agent of low pathogenicity acted synergistically with known pneumopathogenic bacteria.

    “Between 1890 and 1950, most observers believed fatal influenza to be a polymicrobial infection in which an inciting agent of low pathogenicity (either a bacterium such as Bacillus influenzae or a “filter passing agent”—most of which have now been identified as viruses) acted synergistically with known pneumopathogenic bacteria [13, 14, 20, 33, 64-66].”
    Quote in the paperNot a substantial claim1 of 7 sources checked
    • cites [13] Vaughan WT Influenza: an epidemiological study. Monograph series no. 1 Baltimore, Maryland American Journal of Hygiene 1921

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [14] Jordan EO Epidemic influenza: a survey Chicago, Illinois American Medical Association 1927

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [20] Opie EL Blake FG Rivers TM The pathology and bacteriology of pneumonia following influenza Chapter IV Opie EL Blake FG Small JC Rivers TM Epidemic respiratory disease. The pneumonias and other infections of the respiratory tract accompanying influenza and measles St Louis CV Mosby 1921 107 281

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [33] MacCallum WG Pathological anatomy of pneumonia associated with influenza; 23 plates Johns Hopkins Hosp Rep 1921 20 149 249

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [64] Leichtenstern O Mittheilungen über die Influenzaepidemie in Köln Dtsch Med Wochenschr 1890 16 212 5 320 1 388 9 485 6 509 11 642 3 665 6 936 40 957 8 source
    • cites [65] Maxwell ES Ward TG Van Metre TE The relation of influenza virus and bacteria in the etiology of pneumonia J Clin Invest 1949 28 307 18 16695680 PMC439604 source

      The opening section says that certain investigators viewed 1918 influenza as a primary viral illness followed by secondary bacterial pneumonia; the Discussion also describes mixed viral–bacterial infections. But the paper does not say that most observers held this view throughout 1890–1950, or establish a low-pathogenicity inciting agent as the historical consensus. Page numbers are unavailable in our copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [66] Taubenberger JK Hultin JV Morens DM Discovery and characterization of the 1918 pandemic influenza virus in historical context Antivir Ther 2007 12 581 91 17944266 PMC2391305 source
  • Interpretationreasoning

    Early and aggressive treatment, including antibiotics and intensive care, could save most patients with severe influenza-associated pneumonia.

    “suggests that early and aggressive treatment, including antibiotics and intensive care, could save most patients [84, 85]”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [84] Memoli MJ Morens DM Taubenberger JK Pandemic and seasonal influenza: therapeutic challenges Drug Discov Today 2008 13 590 5 18598914 PMC2556034 source

      The Introduction says treatment must account for influenza’s rapid progression and that therapies for secondary pneumonia are important. It also describes intensive-care needs, but does not say that early, aggressive treatment with antibiotics and intensive care could save most patients with severe influenza-associated pneumonia. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [85] Brundage JF Interactions between influenza and bacterial respiratory pathogens: implications for pandemic preparedness Lancet Infect Dis 2006 6 303 12 16631551 PMC7106411 source

      The ‘Interactions model: public health and clinical implications’ section says antibiotics may help prevent secondary bacterial infections and may be useful adjuncts to influenza countermeasures. It does not say that early treatment with antibiotics and intensive care could save most patients who already have severe influenza-associated pneumonia; its mention of intensive care concerns preparedness plans, not a demonstrated benefit. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Premisecitation

    In early 1930s, Shope's experimental studies with swine influenza A virus showed severe disease in an animal model only when virus and Hemophilus influenzae suis were administered together.

    “The issue was addressed anew in the early 1930s when Shope published a series of experimental studies that involved the just-discovered swine influenza A virus: severe disease in an animal model resulted only when the virus and Hemophilus influenzae suis were administered together [67].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [67] Shope RE Swine influenza. III. Filtration experiments and etiology J Exp Med 1931 54 373 85 19869924 PMC2132000 source
  • Interpretationcitation

    The pathogenic mechanisms of H5N1 may be atypical because the virus is poorly adapted to humans.

    “its pathogenic mechanisms may be atypical because the virus is poorly adapted to humans [88]”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [88] Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus: update on avian influenza A (H5N1) virus infection in humans N Engl J Med 2008 358 261 73 18199865 source

      The Viral Factors section (p. 4) says H5N1 does not readily infect humans and that mutations found in some human isolates appear insufficient for efficient human-to-human transmission. The Viral Replication section (p. 4) describes where the virus replicates, but the paper does not say its pathogenic mechanisms are atypical because it is poorly adapted to humans. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
  • Classified as probably not a substantial claim. 16
  • May combine two claims. 30
  • The quote only partly states this claim. 4

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The 1918-1919 pandemic produced a W-shaped age-specific mortality curve with peaks in infancy, around 20-40 years, and in the elderly.

    “The pandemic caused a “W-shaped” age-specific mortality curve, which exhibited peaks in infancy, between about 20–40 years of age, and in elderly individuals [3, 21].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [3] Morens DM Fauci AS The 1918 influenza pandemic: insights for the 21st century J Infect Dis 2007 195 1018 28 17330793 source
    • cites [21] Taubenberger JK Morens DM 1918 influenza: the mother of all pandemics Emerg Infect Dis 2006 12 15 22 16494711 PMC3291398 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The 1957 and 1968 pandemic viruses were descendants of the 1918 virus that acquired three (1957) or two (1968) new avian gene segments by reassortment.

    “The viruses that caused the 1957 and 1968 pandemics were descendants of the 1918 virus in which 3 (the 1957 virus) or 2 (the 1968 virus) new avian gene segments had been acquired by reassortment [21].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [21] Taubenberger JK Morens DM 1918 influenza: the mother of all pandemics Emerg Infect Dis 2006 12 15 22 16494711 PMC3291398 source

      The passage headed “What Was the Animal Host Origin of the Pandemic Virus?” says the 1957 and 1968 viruses arose by reassortment between an avian virus and the previously circulating human H1N1 strain; another passage describes the reassorted pandemic viruses as descendants of the 1918 virus. Our copy does not give the claimed counts of three new avian gene segments in 1957 and two in 1968. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    Staphylococcus aureus, a relatively minor cause of 1918 fatalities, was predominant in culture results from 1957-1958, and negative lung tissue cultures were more common, possibly due to widespread antibiotic administration.

    “Staphylococcus aureus, a relatively minor cause of the 1918 fatalities, was predominant in the culture results from 1957–1958 [21, 57-61], and negative lung tissue cultures were more common, possibly as a result of the widespread administration of antibiotics [57, 58, 61].”
    Quote in the paperNot a substantial claim3 of 6 sources checked
    • cites [21] Taubenberger JK Morens DM 1918 influenza: the mother of all pandemics Emerg Infect Dis 2006 12 15 22 16494711 PMC3291398 source

      The paper discusses 1918 influenza mortality and complicated respiratory infections (Abstract; no page given), but the passages found do not identify Staphylococcus aureus as a relatively minor cause of 1918 deaths. Searches for Staphylococcus aureus, 1957–1958 culture results, negative lung cultures, and antibiotics found no passage addressing those claims. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [57] Mark DD The pathology of 1957 (Asian) influenza Am Rev Tuberc Pulmon Dis 1959 79 440 9 13650115 source
    • cites [58] Robertson L Caley JP Moore J Importance of Staphylococcus aureus in pneumonia in the 1957 epidemic of influenza A Lancet 1958 2 233 6 13564806 source
    • cites [59] Louria DB Blumenfeld HL Ellis JT Kilbourne ED Rogers DE Studies on influenza in the pandemic of 1957–1958. II. Pulmonary complications of influenza J Clin Invest 1959 38 213 65 13620784 PMC444127 source

      The Discussion (page unavailable) says bacteria were almost invariably isolated from fatal 1918–19 cases and that S. aureus was the associated pathogen in a majority of the fatal influenza pneumonias it discusses from later years. It does not establish that staphylococci were a relatively minor cause of 1918 fatalities. More importantly, its section on primary influenza virus pneumonia argues that antibiotics were unlikely to have made the culture-negative lungs in its cases sterile, contrary to the proposed explanation. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [60] Oswald NC Shooter RA Curwen MP Pneumonia complicating Asian influenza Br Med J 1958 2 1305 11 13596593 PMC2027396 source

      The Pleural Effusion discussion reports that Staphylococcus aureus was common in pathological series of 1957 influenza deaths, supporting its prominence in those results. The paper does not establish that it was a minor cause of 1918 fatalities or that negative lung-tissue cultures were more common in 1957–1958 because of antibiotics; its discussion of antibiotic use does not link it to negative cultures. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [61] Oseasohn R Adelson L Kaji M Clinicopathologic study of thirty-three fatal cases of Asian influenza N Engl J Med 1959 260 509 18 13632920 source

  • May combine two claims.

    Premisecitation

    Bacillus influenzae tended to appear early in symptomatic influenza with diffuse bronchitis and/or bronchiolitis, sometimes infiltrating the bronchiolar submucosa, caused seroconversion, and was then typically replaced by other secondary organisms.

    “Bacillus influenzae tended to appear early in symptomatic influenza in association with diffuse bronchitis and/or bronchiolitis, sometimes infiltrating the bronchiolar submucosa [35]; it caused seroconversion [56] and was then typically replaced by other secondary organisms.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [35] Reckford FFD Acute alveolar and interstitial emphysema in influenza bronchopneumonia Pennsylvania Med J 1920 23 379 87

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [56] Wollstein M Pfeiffer’s bacillus and influenza: a serological study J Exp Med 1919 30 555 68 19868377 PMC2126671 source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • Rests on an assumption: Bacillus influenzae largely corresponds to modern Hemophilus influenzae.

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    In one study of approximately 9000 subjects followed from clinical influenza to resolution or autopsy, cultures of either pneumococci or streptococci were obtained from 164 of 167 lung tissue samples, with no negative lung culture results.

    “in one study of approximately 9000 subjects who were followed from clinical presentation with influenza to resolution or autopsy [40], researchers obtained, with sterile technique, cultures of either pneumococci or streptococci from 164 of 167 lung tissue samples.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [40] Hirsch EF McKinney M An epidemic of pneumococcus bronchopneumonia J Infect Dis 1919 24 594 617 source

      The Introduction (p. 594) reports 9,037 hospital admissions during the epidemic, and the postmortem investigation plan (approximately p. 596) calls for culturing exudates from consolidated lung tissue. The passages in our copy do not establish that all patients were followed to resolution or autopsy, or report 164 positive cultures among 167 lung samples with no negative results. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In rhesus monkeys, human influenza viruses given intranasally were not pathogenic but could be made pathogenic by nasopharyngeal instillation of otherwise nonpathogenic bacteria.

    “In rhesus monkeys, human influenza viruses given intranasally were not pathogenic, but could be made so by nasopharyngeal instillation of otherwise nonpathogenic bacteria [69].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [69] Wilson HE Saslaw S Doan CA Woolpert OC Schwab JL Reactions of monkeys to experimental mixed influenza and Streptococcus infections. An analysis of the relative roles of humoral and cellular immunity, with the description of an intercurrent nephritic syndrome J Exp Med 1947 85 199 215 19871608 PMC2135694 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    A body of experimental research over the last three decades has identified possible mechanisms by which influenza virus and bacterial coinfection might affect pathogenicity, including viral neuraminidase-induced exposure of bacterial adherence receptors, bacterial neuraminidase-induced upregulation of influenza infection, interleukin 10-induced susceptibility to pneumococci and possibly staphyloc

    “As reviewed recently by McCullers [75], a body of experimental research during the last 3 decades has identified possible mechanisms by which coinfection with the influenza virus and bacteria might affect pathogenicity. These include viral neuraminidase (NA)–induced exposure of bacterial adherence receptors; bacterial NA-induced upregulation of influenza infection; interleukin 10–induced suscept”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [75] McCullers JA Insights into the interaction between influenza virus and pneumococcus Clin Microbiol Rev 2006 19 571 82 16847087 PMC1539103 source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [76] van der Sluijs KF Nijhuis M Levels JHM Influenza-induced expression of indoleamine 2,3-dioxygenase enhances interleukin-10 production and bacterial outgrowth during secondary pneumococcal pneumonia J Infect Dis 2006 193 214 22 16362885 source

      The introduction (p. 1) says excessive IL-10 was critically involved in bacterial outgrowth during postinfluenza pneumococcal pneumonia in mice; the Discussion (p. 6) also reports that neutralizing IL-10 reduced bacterial loads. The paper does not establish the claimed neuraminidase mechanisms or IL-10-induced susceptibility to staphylococci, although it mentions staphylococci as a cause of postinfluenza pneumonia. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [77] Navarini AA Recher M Lang KS Increased susceptibility to bacterial superinfection as a consequence of innate antiviral responses Proc Natl Acad Sci U S A 2006 103 15535 9 17030789 PMC1622858 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Autopsy studies were uncommon during the 1968 influenza pandemic.

    “The 1968 influenza pandemic was mild, and autopsy studies were uncommon [21].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [21] Taubenberger JK Morens DM 1918 influenza: the mother of all pandemics Emerg Infect Dis 2006 12 15 22 16494711 PMC3291398 source

      Our copy discusses archival autopsy materials from 1918 (Abstract, page unavailable), but does not address how common autopsy studies were during the 1968 pandemic. Searches for 1968, autopsy studies, and related terms found no passage supporting that point. (LLM, conf=0.75)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The 1968 influenza pandemic was mild.

    “The 1968 influenza pandemic was mild, and autopsy studies were uncommon [21].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [21] Taubenberger JK Morens DM 1918 influenza: the mother of all pandemics Emerg Infect Dis 2006 12 15 22 16494711 PMC3291398 source

  • May combine two claims.

    Premisecitation

    During the 1940s, studies in ferrets, mice, and rats established that influenza virus combined with any of several pneumopathic bacteria acted synergistically to produce higher disease incidence, higher death rate, or shortened time to death; antibiotics given shortly after combined infection mitigated or eliminated these effects.

    “During the 1940s, additional studies in ferrets, mice, and rats established that the influenza virus in combination with any of several pneumopathic bacteria acted synergistically to produce either a higher incidence of disease, a higher death rate, or a shortened time to death [70-73]; these effects could be mitigated or eliminated if antibiotics were given shortly after establishment of combined”
    Quote in the paperSubstantial claim1 of 4 sources checked
    • cites [70] Glover RE Spread of infection from the respiratory tract of the ferret. II. Association of influenza A virus and Streptococcus group C Br J Exp Pathol 1941 22 98 107

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [71] Schwab JL Blubaugh FC Woolpert OC The response of mice to the intranasal inoculation of mixtures of Streptococcus hemolyticus and influenza virus J Bacteriol 1941 41 59 60

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [72] Francis T Vicente de Torregrosa M Combined infection of mice with H. influenzae and influenza virus by the intranasal route J Infect Dis 1945 76 70 7 source
    • cites [73] Harford CG Smith MR Wood WB Sulfonamide chemotherapy of combined infection with influenza virus and bacteria J Exp Med 1946 83 505 18 20983719 source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In some experimental animal models, certain H5N1 strains have caused severe pathology different from that of circulating human influenza viruses, which in those models produce disease resembling self-limited seasonal influenza in humans.

    “in certain experimental animal models [e.g., 89], some strains have induced severe pathology that differs from the findings associated with circulating human influenza viruses (which, in these models, cause disease resembling self-limited seasonal influenza in humans [90])”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [89] Salomon R Franks J Govorkova EA The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04 J Exp Med 2006 203 689 97 16533883 PMC2118237 source
    • cites [90] Reuman PD Keely S Schiff GM James N Assessment of signs of influenza illness in the ferret model J Virol Methods 1989 24 27 34 2760163 source

  • The quote only partly states this claim.

    Findingown data

    The 58 recut lung tissue specimens from 1918-1919 influenza autopsies uniformly showed severe changes consistent with bacterial pneumonia.

    “The postmortem samples we examined from people who died of influenza during 1918–1919 uniformly exhibited severe changes indicative of bacterial pneumonia.”
    • Also stated in: § Histologic examination of lung tissue from 1918 victims · hedged
      “The examination of recut lung tissue sections from 1918–1919 influenza case material revealed, in virtually all cases, compelling histologic evidence of severe acute bacterial pneumonia, either as the predominant pathology or in conjunction with underlying pathologic features now believed to be associated with influenza virus infection [10, 24] (figure 1).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The 58 autopsy specimens available from the National Tissue Repository are representative of 1918-1919 influenza fatalities.

  • The quote only partly states this claim.

    Findingown data

    The majority of the 58 examined cases showed asynchronous histopathological changes, with different stages of infection from early bronchiolar changes to severe bacterial parenchymal destruction in focal areas.

    “The majority of the cases examined demonstrated asynchronous histopathological changes, in which the various stages of development of the infectious process, from early bronchiolar changes to severe bacterial parenchymal destruction, were noted in focal areas.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The 58 autopsy specimens available from the National Tissue Repository are representative of 1918-1919 influenza fatalities.

  • May combine two claims.

    Findingown data

    Of 2007 pneumococcal isolates from 1918-1919, 874 (43.5%) were serotyped; type I accounted for 14.2%, type II 18.6%, type IIa 3.0%, type III 21.1%, and type IV 43.1%.

    “Of 2007 pneumococcal isolates, 874 (43.5%) were serotyped by agglutination. Type I was isolated from 124 (14.2%) of 874 subjects; type II from 163 (18.6%); type IIa from 26 (3.0%); type III from 184 (21.1%); and type IV, a category containing diverse and, at the time, untypeable organisms, from 377 (43.1%).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The 109 published autopsy series and 8398 autopsies are representative of influenza deaths during the 1918-1919 pandemic.

  • May combine two claims.

    Findingown data

    Cultures of blood samples in 30 military and 12 civilian 1918-1919 series, examining 1887 subjects, were positive in 70.3% of cases and typically contained either pneumococci or streptococci in pure culture.

    “Cultures of blood samples in 30 military and 12 civilian series, which examined a total of 1887 subjects (table 2), had positive results in 70.3% of cases and typically contained either pneumococci or streptococci in pure culture.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The 109 published autopsy series and 8398 autopsies are representative of influenza deaths during the 1918-1919 pandemic.
    • Rests on an assumption: Postmortem lung culture results reflect bacteria that contributed to death rather than postmortem contamination or incidental colonization.

  • May combine two claims.

    Findingcitation

    Published autopsies for 1918-1919 pandemic victims generally showed histopathological asynchrony, as did the 58 autopsy cases reviewed.

    “As was true for the 58 autopsy cases we reviewed (see above), published autopsies for victims of the 1918–1919 pandemic generally showed histopathological asynchrony [20].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Opie EL Blake FG Rivers TM The pathology and bacteriology of pneumonia following influenza Chapter IV Opie EL Blake FG Small JC Rivers TM Epidemic respiratory disease. The pneumonias and other infections of the respiratory tract accompanying influenza and measles St Louis CV Mosby 1921 107 281

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Findingcitation

    Surprising aspects included predominance of bronchopneumonia and lobular pneumonia rather than lobar pneumonia, consistent with diffuse predisposing bronchiolar damage.

    “(4) the predominance of bronchopneumonia and lobular pneumonia, as opposed to lobar pneumonia, consistent with diffuse predisposing bronchiolar damage [27-33].”
    Quote in the paperNot a substantial claim0 of 7 sources checked
    • cites [27] Goodpasture EW The significance of certain pulmonary lesions in relation to the etiology of influenza Am J Med Sci 1919 158 863 70 19680020 source
    • cites [28] Klotz O Members of the Faculty of the School of Medicine, University of Pittsburgh The pathology of epidemic influenza Studies on epidemic influenza comprising clinical and laboratory investigations by Members of the Faculty of the School of Medicine, University of Pittsburgh Pittsburgh University of Pittsburgh 1919 207 294

      Not checked in the free run.

    • cites [29] Lucke B Wight T Kime E Pathologic anatomy and bacteriology of influenza: epidemic of autumn, 1918 Arch Intern Med 1919 24 154 237 source
    • cites [30] MacCallum WG Pathology of epidemic pneumonia in camps and cantonments in 1918 Med Rec 1919 95 776 84

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [31] Tobias JW Anatomía Patológica de la grippe pandémica Rev Med Univ Buenos Aires 1920 17 109 99

      Not checked in the free run.

    • cites [32] Winternitz MC Wason IM McNamara FP The pathology of influenza New Haven Yale University Press 1920

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [33] MacCallum WG Pathological anatomy of pneumonia associated with influenza; 23 plates Johns Hopkins Hosp Rep 1921 20 149 249

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Findingcitation

    In those 14 series, the remaining deaths were associated with nonpneumopathogenic other bacteria (36.1% of cultures), Bacillus influenzae (18.8%), and no bacterial growth (7.7%).

    “The rest of the deaths were associated collectively with either culture of nonpneumopathogenic “other bacteria,” such as nonhemolytic and viridans streptococci, “green-producing streptococci” [54], probably largely corresponding to α-hemolytic streptococci, uncharacterized diplostreptococci, Micrococcus (Moraxella) catarrhalis, Bacillus (Escherichia) coli, Klebsiella species, and complex mixed b”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] Tunnicliff R Observations on green producing cocci of influenza J Infect Dis 1920 26 405 17 source
    • Rests on an assumption: The 109 published autopsy series and 8398 autopsies are representative of influenza deaths during the 1918-1919 pandemic.
    • Rests on an assumption: Postmortem lung culture results reflect bacteria that contributed to death rather than postmortem contamination or incidental colonization.

  • May combine two claims.

    Findingnone given

    Surprising aspects included frequent pneumonia caused by mixed pneumopathogens, especially pneumococci and streptococci, and by other mixed upper respiratory-tract bacteria.

    “(2) the frequency of pneumonia caused by both mixed pneumopathogens (particularly pneumococci and streptococci) and by other mixed upper respiratory–tract bacteria;”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Surprising aspects included aggressive bacterial invasion of the lung, often with phenomenal numbers of bacteria and neutrophils, extensive necrosis, vasculitis, and hemorrhage.

    “(3) the aggressiveness of bacterial invasion of the lung, often resulting in “phenomenal” [30] numbers of bacteria and polymorphonuclear neutrophils, as well as extensive necrosis, vasculitis, and hemorrhage [20, 32, 33];”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [30] MacCallum WG Pathology of epidemic pneumonia in camps and cantonments in 1918 Med Rec 1919 95 776 84

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [20] Opie EL Blake FG Rivers TM The pathology and bacteriology of pneumonia following influenza Chapter IV Opie EL Blake FG Small JC Rivers TM Epidemic respiratory disease. The pneumonias and other infections of the respiratory tract accompanying influenza and measles St Louis CV Mosby 1921 107 281

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [32] Winternitz MC Wason IM McNamara FP The pathology of influenza New Haven Yale University Press 1920

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [33] MacCallum WG Pathological anatomy of pneumonia associated with influenza; 23 plates Johns Hopkins Hosp Rep 1921 20 149 249

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The isolation rates in the 14 series were similar to those in series reporting predominance of pneumopathogens, but with higher isolation rates for other bacteria offsetting lower rates for pneumococci, streptococci, and staphylococci.

    “These findings reflect rates of bacterial isolation similar to those of the series that reported the predominance of pneumopathogens (above and table 1), but with higher isolation rates for “other bacteria” offsetting the lower isolation rates for pneumococci, streptococci and staphylococci.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The 109 published autopsy series and 8398 autopsies are representative of influenza deaths during the 1918-1919 pandemic.
    • Rests on an assumption: Postmortem lung culture results reflect bacteria that contributed to death rather than postmortem contamination or incidental colonization.

  • May combine two claims.

    Findingown data

    Cultures of pleural or empyema fluid in 23 military and 12 civilian 1918-1919 series, examining 1245 subjects, most commonly recovered streptococci or pneumococci in all but 7 series; in 4 series mixed pneumopathogens predominated, and in 3 series Staphylococcus aureus predominated.

    “Cultures of pleural or empyema fluid, reported in 23 military and 12 civilian series examining a total of 1245 subjects (table 2), revealed either streptococci or pneumococci as the most commonly recovered organism in all but 7 series: in 4 series mixed pneumopathogens predominated, and in 3 series Staphylococcus aureus predominated.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The 109 published autopsy series and 8398 autopsies are representative of influenza deaths during the 1918-1919 pandemic.
    • Rests on an assumption: Postmortem lung culture results reflect bacteria that contributed to death rather than postmortem contamination or incidental colonization.

  • Classified as probably not a substantial claim.

    Findingown data

    From more than 2000 publications, the authors carefully examined 1539 reports containing human pathologic and/or bacteriologic findings.

    “From more than 2000 such publications, we carefully examined the 1539 reports that contained human pathologic and/or bacteriologic findings”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Findingown data

    The review examined 109 published autopsy series that provided useful bacteriologic information from 173 autopsy series and reported 8398 individual autopsy investigations in 15 countries.

    “109 of which provided useful bacteriologic information derived from 173 autopsy series. These series reported 8398 individual autopsy investigations undertaken in 15 countries”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The 109 published autopsy series and 8398 autopsies are representative of influenza deaths during the 1918-1919 pandemic.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    The 109 series comprised 96 postmortem lung tissue culture series, 42 blood culture series, and 35 pleural fluid culture series.

    “96 postmortem lung tissue culture series, 42 blood culture series, and 35 pleural fluid culture series.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The 109 published autopsy series and 8398 autopsies are representative of influenza deaths during the 1918-1919 pandemic.

  • May combine two claims.

    Findingnone given

    Influenza-associated pneumonia cases have tended to occur in elderly people, who seldom undergo autopsy.

    “cases have tended to occur in elderly individuals, who rarely undergo autopsy.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    The 1918 pandemic and later pandemics differed in the spectrum and extent of secondary bacterial pneumonia, including a shift in the antibiotic era to predominantly staphylococcal secondary pneumonia and a marked decrease in Haemophilus influenzae involvement.

    “The 1918 pandemic and subsequent pandemics differed with respect to the spectrum and extent of secondary bacterial pneumonia (e.g., the switch in prevalence during the antibiotic era to predominantly staphylococcal secondary pneumonia, as opposed to streptococcal, pneumococcal, and mixed secondary pneumonia; and the greatly decreased involvement of Bacillus [Hemophilus] influenzae)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    US influenza pandemic preparedness strategies assume three severity levels corresponding to the 1918-1919 H1N1, 1957-1958 H2N2, and 1968-1969 H3N2 pandemics.

    “Influenza pandemic preparedness strategies in the United States [2] assume 3 levels of potential severity corresponding to the 20th century pandemics of H1N1 “Spanish flu” (1918–1919), H2N2 “Asian flu” (1957–1958), and H3N2 “Hong Kong flu” (1968–1969)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] United States Department of Health and Human Services (HHS) HHS pandemic influenza plan Washington, DC US Government Printing Office 2005 Available at: http://www.hhs.gov/pandemicflu/plan/pdf/HHSPandemicInfluenzaPlan.pdf 16 June 2008

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Extrapolation from 1918-1919 pandemic data to the current US population and age profile has led US government officials to plan for more than 1.9 million excess deaths during a severe pandemic.

    “Extrapolation from 1918–1919 pandemic data to the current population and age profile has led United States government officials to plan for more than 1.9 million excess deaths during a severe pandemic [2].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] United States Department of Health and Human Services (HHS) HHS pandemic influenza plan Washington, DC US Government Printing Office 2005 Available at: http://www.hhs.gov/pandemicflu/plan/pdf/HHSPandemicInfluenzaPlan.pdf 16 June 2008

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The increased fatality rate in the three high-risk age groups during 1918-1919 was mainly due to more frequent bronchopneumonia, not to increased influenza incidence or increased bronchopneumonia case-fatality.

    “The increased fatality rate in the 3 high-risk age groups was predominantly due to the increased frequency of bronchopneumonia, not to increased incidence of influenza or an increased bronchopneumonia case-fatality rate [19].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Collins SD Age and sex incidence of influenza and pneumonia morbidity and mortality in the epidemic of 1928–29 with comparative data for the epidemic of 1918–19 Public Health Rep 1931 46 1909 37 source

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing). May combine two claims.

    Premisecitation

    Primary panbronchitis was thought to reflect rapidly spreading epithelial cytolytic infection of the entire bronchial tree, leading to secondary bacterial spread along denuded epithelium and focal bronchiolar infections breaking into lung parenchyma.

    “Primary “panbronchitis” [35] was thought to reflect rapidly spreading epithelial cytolytic infection of the entire bronchial tree [32, 35, 36]; this was thought to have led to the secondary spread of enormous numbers of bacteria along the denuded bronchial epithelium to every part of the bronchial tree, following which focal bronchiolar infections broke through into the lung parenchyma.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [35] Reckford FFD Acute alveolar and interstitial emphysema in influenza bronchopneumonia Pennsylvania Med J 1920 23 379 87

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [32] Winternitz MC Wason IM McNamara FP The pathology of influenza New Haven Yale University Press 1920

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [36] Roos C Notes on the bacteriology, and on the selective action of B. influenzae Pfeiffer J Immunol 1919 4 189 201 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Among the ≥60% of individuals who survived severe 1918-1919 pneumonia, severe chronic pulmonary damage was apparently uncommon.

    “Among the ≥60% of individuals who survived such severe pneumonia, severe chronic pulmonary damage was apparently uncommon [37, 38].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [37] Wynn WH Chronic influenzal fibrosis of the lungs Lancet 1927 2 964 7 source
    • cites [38] Nuzum JW Pilot I Stangl FH Bonar BE Pandemic influenza and pneumonia in a large civil hospital J Am Med 1918 71 1562 5 12100

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationown data

    In 11 of the 14 studies, pneumococcal typing antisera were unavailable, and many cultured other bacteria were reported as gram-positive diplococci, streptococci, or diplostreptococci, consistent with the possibility that some unidentified organisms may have been pneumopathogens.

    “It is noteworthy that pneumococcal typing antisera were unavailable in 11 of these 14 studies, and that many of the cultured “other” bacteria were reported as “gram-positive diplococci,” “streptococci,” or “diplostreptococci” (data not shown), consistent with the possibility that in this early era of bacterial typing, some of the unidentified organisms in the culture may have been pneumopathogens.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    The evidence supports a mechanism in which the virus is highly damaging to bronchial and bronchiolar epithelial cells, spreads quickly and widely down the respiratory tree, injures the epithelium enough to breach the mucociliary barrier against bacterial spread, and, if it reaches the distal respiratory tree, opens a direct route for secondary bacterial spread and creates conditions favorable to细菌

    “The data are consistent with a natural history in which the virus, highly cytopathic to bronchial and bronchiolar epithelial cells, extends rapidly and diffusely down the respiratory tree, damages the epithelium sufficiently to break down the mucociliary barrier to bacterial spread”
    • Also stated in: § DISCUSSION · hedged
      “and if able to gain access to the distal respiratory tree—perhaps on the basis of receptor affinity [80]—creates both a direct pathway for secondary bacterial spread and an environment (cell necrosis and proteinaceous edema fluid) favorable to bacterial growth.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [80] Stevens J Blixt O Glaser L Glycan microarray analysis of the hemagglutinins from modern and pandemic influenza viruses reveals different receptor specificities J Mol Biol 2006 355 1143 55 16343533 source

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    The authors searched major bibliographic sources for papers in all languages and tables of contents of major journals in English, German, and French, and searched identified papers for additional citations.

    “we searched major bibliographic sources [e.g., 11–17] for papers in all languages and tables of contents of major journals in English, German, and French; in addition, we searched all of the papers we identified for additional citations.”
    Quote in the paperSubstantial claim0 of 7 sources checked
    • cites [11] Billings JS Fletcher R Garrison FH Index Medicus 18 Series II Washington, DC Government Printing Office 1903–1920

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [12] Library of the Surgeon General’s Office, United States Army Index-catalogue of the Library of the Surgeon-General’s Office, United States Army. Authors and Subjects 10 Series III Washington, DC US Government Printing Office 1918–1932

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [13] Vaughan WT Influenza: an epidemiological study. Monograph series no. 1 Baltimore, Maryland American Journal of Hygiene 1921

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [14] Jordan EO Epidemic influenza: a survey Chicago, Illinois American Medical Association 1927

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [15] Thomson D Thomson R Annals of the Pickett-Thomson Research Laboratory Volume X. Influenza (Part II) With special reference to the complications and sequellæ, bacteriology of influenzal pneumonia, pathology, epidemiological data, prevention and treatment London Baillière, Tindall & Cox 1934 source
    • cites [16] Phillips H Killingray D The Spanish Influenza Pandemic of 1918–19. New Perspectives London Routledge 2003 source
    • cites [17] Byerly CR Fever of War: the influenza epidemic in the U. S. Army during World War I New York New York University Press 2005

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    The study stratified data a priori by military versus civilian populations and by quality of lung tissue culture results, defining higher quality as series reporting both presence and absence of negative cultures and bacterial components of mixed cultures.

    “A priori, we stratified data by military and civilian populations (see Discussion), and by the quality of lung tissue culture results, considering to be of “higher quality” the 68 autopsy series with lung tissue culture results that reported, for all autopsies, both the presence and absence of negative culture results and the bacterial components of mixed culture results.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    If a future pandemic is caused by a derivative of the current highly pathogenic avian H5N1 virus, lessons from earlier pandemics may not apply strictly.

    “If, as some fear, a future pandemic is caused by a derivative of the current highly pathogenic avian H5N1 virus, lessons from previous pandemics may not be strictly applicable.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    Because few autopsy reports and no autopsy series addressed nonpulmonary conditions, nonpulmonary causes of death were not considered.

    “Because few autopsy reports and, to our knowledge, no autopsy series addressed conditions other than predominantly pulmonary complications, nonpulmonary causes of death are not considered here.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    Possible additional factors include antibiotic and antiviral use, influenza and bacterial vaccination rates, and demographic and social factors.

    “These might include the use of antibiotics and antiviral agents, the rate of influenza vaccination and bacterial vaccination, and demographic and social factors.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The viral cause and timing of the next influenza pandemic cannot be predicted.

    “The viral etiology of and timing of the next influenza pandemic cannot be predicted [87].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [87] Taubenberger JK Morens DM Fauci AS The next influenza pandemic: can it be predicted? JAMA 2007 297 2025 27 17488968 PMC2504708 source
40 of 40

  • The paper relies on this without support.

    The 58 autopsy specimens available from the National Tissue Repository are representative of 1918-1919 influenza fatalities.

    “These materials, sent during the pandemic from various United States military bases to the National Tissue Repository of the Armed Forces Institute of Pathology [8-10], represent all known influenza cases from this collection for which lung tissue is available.”

  • The paper relies on this without support.

    The 109 published autopsy series and 8398 autopsies are representative of influenza deaths during the 1918-1919 pandemic.

    “These series reported 8398 individual autopsy investigations undertaken in 15 countries”

  • The paper relies on this without support.

    Postmortem lung culture results reflect bacteria that contributed to death rather than postmortem contamination or incidental colonization.

    “Negative lung culture results were uncommon in the 96 identified military and civilian autopsy series, which examined 5266 subjects (4.2% of results overall) (table 1; full bibliographic list available at http://www3.niaid.nih.gov/topics/Flu/1918/bibliography.htm).”

  • The paper relies on this without support.

    Bacillus influenzae largely corresponds to modern Hemophilus influenzae.

    “Bacillus influenzae (largely corresponding to the modern Hemophilus influenzae)”

  • The paper relies on this without support.

    The prevalent upper respiratory tract bacteria in a future pandemic will be capable of causing severe secondary bacterial pneumonia when influenza virus damages the respiratory epithelium.

    “precipitating severe disease associated with prevalent colonizing bacteria.”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Abstract misstates the number of autopsy series

    Minor

    The abstract calls the 109 sources autopsy series, but the Methods identify them as 109 reports containing 173 autopsy series.

1 of 1

Cites

Flagged first, then by citations

2 of the 80 references couldn’t be matched to a known paper.

Research works printed but not linked: 26

  1. Cruveilhier L. Action du serum antipneumococcique au cours de la pneumonie et dans les complications de la grippe. Annales de l'Institut Pasteur 1919; 33:448-61.
  2. Dauer CC, 1961, Am Rev Respir Dis, 83, 15
  3. Vaughan WT. Influenza: an epidemiological study. Monograph series no. 1. Baltimore, Maryland: American Journal of Hygiene, 1921.
  4. Byerly CR. Fever of War: the influenza epidemic in the U. S. Army during World War I. New York: New York University Press, 2005.
  5. Reid AH, 1999, Lab Invest, 79, 95
  6. Mulder J, Hers JFP. Influenza. Groningen: Wolters-Noordhoff, 1972.
  7. Klotz O, 1919, University of Pittsburgh. Pittsburgh: University of Pittsburgh, 207
  8. MacCallum WG, 1919, Med Rec, 95, 776
  9. Tobias JW, 1920, Rev Med Univ Buenos Aires, 17, 109
  10. MacCallum WG, 1921, Johns Hopkins Hosp Rep, 20, 149
  11. Reckford FFD, 1920, Pennsylvania Med J, 23, 379
  12. Nuzum JW, 1918, J Am Med, 71, 1562
  13. Holm ML, 1919, France. Bull Johns Hopkins Hosp, 30, 324
  14. Little TR, 1918, Proc R Soc Med (Great Britain), 12, 36
  15. Rucker JB, 1918, Proc Pathol Soc Philadelphia, 21, 41
  16. Rucker JB, Wenner JJ. Friedlander bacillus the causative factor in bronchopneumonia following influenza. N Y Med J 1918; 108:1066-9.
  17. Fiore G, 1919, Riv Clin Pediatr (Firenze), 17, 281
  18. Moses A, 1919, Bras Med, 33, 37
  19. Baker SL, 1920, Haslar. J R Nav Med Serv, 6, 446
  20. Harkavy J, 1920, Am J Roentgenol, 7, 109
  21. Mark DD, 1959, Am Rev Tuberc Pulmon Dis, 79, 440
  22. MacCallum WG, 1918, Trans South Surg Assoc, 19, 180
  23. Brightman IJ, 1935, Yale J Biol Med, 8, 127
  24. Glover RE, 1941, Br J Exp Pathol, 22, 98
  25. Schwab JL, 1941, J Bacteriol, 41, 59
  26. Logan WR, 1921, Edinburgh Med J, 26, 294

Cited by

Sorted by citations

Related

Authors
Morens, D. M., Taubenberger, J. K., & Fauci, A. S.
Affiliations
National Institutes of Health (US)
Corresponding author
Morens, David M.
ORCID
Venue
The Journal of Infectious Diseases
Publisher
Oxford University Press (OUP)
Published
2008-10
Volume
198
Issue
7
Pages
962-970
ISSN
  • 0022-1899 (ISSN-L)
  • 1537-6613
DOI
10.1086/591708
PMC
PMC2599911
OpenAlex
W2167944937
Cited by
1,625
References
80
Citations by year
2026: 42 · 2025: 65 · 2024: 69 · 2023: 101 · 2022: 132 · 2021: 165 · 2020: 139 · 2019: 64 · 2018: 74 · 2017: 70 · 2016: 70 · 2015: 83 · 2014: 66 · 2013: 89 · 2012: 87
FWCI
76.20
Type
journal article
Language
en
Open access
Locations
  • The Journal of Infectious Diseases (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (Z99 AI999999)
  • National Institute of Allergy and Infectious Diseases
  • U.S. National Library of Medicine
Topics
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
  • Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
  • Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
Keywords
pandemic influenza, bacterial pneumonia, secondary bacterial pneumonia, causes of death, upper respiratory tract bacteria, pandemic preparedness, bacterial vaccines, autopsy findings
MeSH terms
Autopsy, Disease Outbreaks, Humans, Influenza, Human, Lung, Time Factors, Pneumonia, Bacterial, Influenza A Virus, H5N1 Subtype

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-01.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-01.

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