Epidemiological evidence of an early wave of the 1918 influenza pandemic in New York

[Snowy Owl]

Epidemiological evidence of an early wave of the 1918 influenza pandemic in New York City
<nobr>Donald R. Olson^*,</nobr>, <nobr>Lone Simonsen</nobr>, <nobr>Paul J. Edelson^,^?</nobr>, and <nobr>Stephen S. Morse^*,^?</nobr>
<nobr>
</nobr>
<nobr>^{http://www.pnas.org/cgi/content/full/pnas;102/31/11059}</nobr>
<nobr>
</nobr>
<nobr></nobr>MEDICAL SCIENCES


<nobr></nobr><nobr></nobr>

Abstract
The 1918 "Spanish flu" was the fastest spreading and most deadlyinfluenza pandemic in recorded history.

Hypotheses of its originhave been based on a limited collection of case and outbreakreports from before its recognized European emergence in thesummer of 1918. These anecdotal accounts, however, remain insufficientfor determining the early diffusion and impact of the pandemicvirus.

Using routinely collected monthly age-stratified mortalitydata, we show that an unmistakable shift in the age distributionof epidemic deaths occurred during the 1917/1918 influenza seasonin New York City.

The timing, magnitude, and age distributionof this mortality shift provide strong evidence that an earlywave of the pandemic virus was present in New York City duringFebruary-April 1918.
The origin of the 1918 influenza pandemic remains elusive. Thecauses for its transmissibility, virulence, and unique age patternremain inadequately understood. In less than 2 years, the pandemickilled >675,000 people in the United States (1) and 40-100million worldwide (2, 3), with the majority of deaths occurringamong those <45 years old (4).

Analysis of viral RNA recoveredfrom preserved lung-tissue samples from geographically distantregions confirms that the pandemic wave in the northern hemispherein the autumn of 1918 and its recrudescence in winter 1919 werecaused by an A/H1N1 influenza virus with a highly conservedhemagglutinin gene identified in two antigenic configurations(5-7).

Whether the epidemic recognized as "Spanish flu" in Europein the summer of 1918 (4) was caused by a similarly conservedvirus is unknown, and whether anecdotal cases and outbreaksreported from Europe in 1916 and 1917 (8) and the United Statesin early 1918 (9-11) were caused by a virus related to the pandemicvirus remains speculative.

At the peak of the catastrophic wave in the autumn of 1918,an influenza-like epidemic the preceding spring was retrospectivelydescribed as an early wave of the pandemic (9).

At the end ofthe 1918/1919 season, an epidemiological study suggested thatthis early precursor wave had caused epidemic mortality in Atlanticseaboard cities before central and western U.S. cities (10).A limited collection of eyewitness case and outbreak reports,however, led to the consensus view that the pandemic emergedin a mild wave in the spring of 1918 from an isolated ruralregion in the central United States (11). This view became widelyaccepted (12-15), without rigorous reevaluation of the originalevidence

Reanalysis of contemporary studies and routinely collected datamay provide insight into the epidemiology of the 1918 pandemic(16-18). A characteristic feature of influenza epidemiologyhas historically been that the burden of excess mortality ininterpandemic seasons occurs primarily in older age groups,whereas the burden in pandemic seasons shifts disproportionatelyto younger ages (19).
During and following each of the threemajor 20th-century pandemics in which this pattern occurred,in subsequent epidemic seasons, the burden of mortality shiftedproportionally back to older age groups (19, 20).

In this study,we compare age-specific mortality patterns from influenza epidemicsin New York City from 1911 to 1921.

Although absolute confirmationof a precursor wave depends on recovery of viral RNA, we presenthere an epidemiological analysis showing that the pattern ofage-specific epidemic excess mortality shifted strongly towardyounger age groups in the winter preceding the pandemic wavein the autumn of 1918.

This result provides evidence that aprepandemic herald wave of mortality occurred during February-April1918 in New York City.

Materials and Methods
We obtained historical monthly mortality statistics from NewYork City Health Department records. All-cause and pneumoniaand influenza (P&I) deaths from 1907 to 1921 were used inour all-ages analyses. All-cause deaths during 1911-1921, stratifiedinto six age groups (<5, 5-14, 15-24, 25-44, 45-64, and 65),were used in our age-specific analyses. We standardized observeddeaths by length of month and calculated rates by using NewYork City population estimates linearly interpolated from 1910and 1920 U.S. census reports.

The model approach we used was originally developed for measuringthe impact of influenza epidemics by estimating an expectedbaseline level to which observed epidemic period deaths werecompared (21-23). Other studies have similarly estimated baselinemortality from weekly or monthly deaths, exclusive of epidemicperiods, by using least-squares regression with sinusoidal terms.Although alternatives have been developed (24-26) and variationson this model have continued to be widely used (27-30), excessmortality remains an insensitive measure of severity, particularlyin pediatric populations (1). We used the same monthly baselineequation with annual and 6-month-cycle terms for total P&Iand for total and age-specific all-cause mortality analyses:


Our estimate of expected deaths at time t (M_t) was determinedby the constant ₀, secular trend ₁, annual predictors ₁ and₁, semiannual predictors ₂ and ₂, and an error term e_t, derivedfrom linear regression of nonepidemic monthly mortality data.

We purged months that the New York City Health Department reportedincreased respiratory disease activity or a major mortalityevent such as summer diarrheal epidemics, the 1915/1916 influenzaepidemic, the 1916 polio epidemic, or the 1917 heat wave. Foreach available 5-year period of mortality data, we projectedout the expectation and an arbitrarily defined 95% confidencelimit and purged months exceeding this threshold. Each 5-yearseries and annual forecast was for August through July

To focus on the most severe seasons, we arbitrarily definedan influenza season epidemic as two or more consecutive monthswhen observed P&I mortality exceeded the upper 95% confidencelimit of the baseline. Excess deaths were calculated for eachepidemic season as the difference between expected and observedmortality for the consecutive epidemic months. Total and age-specificestimates of excess deaths were determined for the same months.Seasonal excess deaths from all-cause and P&I data for theentire population were compared, along with all-cause <45and 45 excess death estimates. Due to the characteristic 1918pattern of mortality and the age groupings available, we calculatedthe risk ratio (20) of <45 to 45 excess death rates to providea single measure of relative risk of influenza-related deathby age during the influenza periods identified by the model.

We obtained annual P&I mortality rates by age group for1915-1917 to look for the typical "U-shaped" mortality curve(increased rates at the extremes of age) and for 1918 to lookfor the "W-shaped" curve characteristic of the pandemic (highestannual mortality rates among young children, young adults, andthe elderly). To provide an alternative measure of the age-specificimpact on interpandemic and pandemic influenza-related deaths,excess mortality rates were plotted by age and compared forthe severe 1915/1916 influenza season, the March and April 1918epidemic months, and the 1918/1919 pandemic season. As donerecently to characterize mortality age patterns for the 1968pandemic (31), we calculated the age-specific ratio of pandemicto interpandemic excess rates to estimate age-specific relativerisk by using 45 years of age as the cutoff.

Results
Excess Mortality.

Severe epidemic mortality occurred in 5 ofthe 10 influenza seasons during 1911-1921.

The 1911/1912 influenzaseason was reported by the health department as distinctly freeof epidemic influenza, and the 1915/1916 influenza epidemicwas noted at the time as the worst to date that century (4).

During the 1915-1920 epidemic seasons, the temporal patternand peaks in all-cause and P&I deaths coincided (Fig. 1 A and B).Epidemic period estimates for all ages in the 1915/1916and 1916/1917 seasons were 2,100 and 2,800 excess all-causedeaths, respectively (Table 1). Excess all-cause deaths in the1918/1919 pandemic and 1919/1920 recrudescence were 29,200 and8,200, respectively (Table 1). An estimated 4,600 excess all-causedeaths occurred during the 1917/1918 influenza season (Table 1);epidemic mortality in this season occurred in two peaks,in January and March 1918 (Fig. 1 A and B, arrowheads).

[IMG]file:///C:/DOCUME%7E1/STOCKD%7E1/LOCALS%7E1/Temp/moz-screenshot.jpg[/IMG][IMG]file:///C:/DOCUME%7E1/STOCKD%7E1/LOCALS%7E1/Temp/moz-screenshot-1.jpg[/IMG]



Fig. 1. All-cause and P&I monthly mortality rates for all ages (A and B) and all-cause mortality rates by age group (C-H) are calculated per 10,000 population. Observed rates are days-per-month adjusted. Expected model baselines (solid lines) are derived from each series of nonepidemic months. Epidemic thresholds (dashed lines) are the upper 95% confidence limit above each baseline. The major epidemic influenza season months are indicated (shaded). Two 1917/1918 influenza season peaks (arrowheads) show excess mortality primarily confined to the 65-years age group in January (C), and to the groups <45 years old in March 1918 (E-H). Other severe mortality events are evident: summer diarrheal disease epidemics were confined to young children (H), the 1916 polio epidemic to all children (G and H), and the summer 1917 heat wave and diarrheal disease epidemic among the youngest and oldest age groups (C and H)

Table 1. Influenza season excess deaths <table border="0"><tbody><tr><td><table cellpadding="0" cellspacing="10" width="100%"> <tbody><tr><td colspan="9"><hr noshade="noshade" size="1"></td></tr><tr> <td align="left" valign="bottom">
</td> <td colspan="4" align="center" valign="bottom"> Number of excess deaths (rate per 10,000 population)
<hr noshade="noshade" size="1"></td> <td rowspan="2" align="center" valign="bottom"> Risk ratio <45:45
<hr noshade="noshade" size="1"></td> </tr> <tr> <td align="left" valign="bottom"> Epidemic period^*
<hr noshade="noshade" size="1"></td> <td align="center" valign="bottom"> AC
<hr noshade="noshade" size="1"></td> <td align="center" valign="bottom"> P&I
<hr noshade="noshade" size="1"></td> <td align="center" valign="bottom"> AC<45
<hr noshade="noshade" size="1"></td> <td align="center" valign="bottom"> AC45
<hr noshade="noshade" size="1"></td> </tr> <tr> <td align="left" valign="bottom"> December 1915-February 1916 </td> <td align="center" valign="bottom"> 2,100 (4.0) </td> <td align="center" valign="bottom"> 1,600 (3.0) </td> <td align="center" valign="bottom"> 600 (1.3) </td> <td align="center" valign="bottom"> 1,400 (14.9) </td> <td align="center" valign="bottom"> 0.1 </td> </tr> <tr> <td align="left" valign="bottom"> December 1916-February 1917 </td> <td align="center" valign="bottom"> 2,800 (5.3) </td> <td align="center" valign="bottom"> 1,600 (3.0) </td> <td align="center" valign="bottom"> 800 (1.8) </td> <td align="center" valign="bottom"> 2,100 (21.2) </td> <td align="center" valign="bottom"> 0.1 </td> </tr> <tr> <td align="left" valign="bottom"> December 1917 and January 1918 </td> <td align="center" valign="bottom"> 1,500 (2.8) </td> <td align="center" valign="bottom"> 600 (1.1) </td> <td align="center" valign="bottom"> 1,000 (2.3) </td> <td align="center" valign="bottom"> 400 (3.9) </td> <td align="center" valign="bottom"> 0.6 </td> </tr> <tr> <td align="left" valign="bottom"> February 1918 </td> <td align="center" valign="bottom"> 400 (0.7) </td> <td align="center" valign="bottom"> 200 (0.5) </td> <td align="center" valign="bottom"> 400 (0.8) </td> <td align="center" valign="bottom"> 100 (0.6) </td> <td align="center" valign="bottom"> 1.3 </td> </tr> <tr> <td align="left" valign="bottom"> March and April 1918 </td> <td align="center" valign="bottom"> 2,700 (4.9) </td> <td align="center" valign="bottom"> 1,900 (3.5) </td> <td align="center" valign="bottom"> 2,500 (5.6) </td> <td align="center" valign="bottom"> 200 (2.1) </td> <td align="center" valign="bottom"> 2.6 </td> </tr> <tr> <td align="left" valign="bottom"> September 1918-April 1919 </td> <td align="center" valign="bottom"> 29,200 (53.0) </td> <td align="center" valign="bottom"> 28,600 (51.8) </td> <td align="center" valign="bottom"> 26,200 (58.7) </td> <td align="center" valign="bottom"> 2,100 (20.3) </td> <td align="center" valign="bottom"> 2.9 </td> </tr> <tr> <td align="left" valign="bottom"> January-March 1920
<hr noshade="noshade" size="1"></td> <td align="center" valign="bottom"> 8,200 (14.6)
<hr noshade="noshade" size="1"></td> <td align="center" valign="bottom"> 6,000 (10.7)
<hr noshade="noshade" size="1"></td> <td align="center" valign="bottom"> 5,400 (11.8)
<hr noshade="noshade" size="1"></td> <td align="center" valign="bottom"> 1,800 (16.5)
<hr noshade="noshade" size="1"></td> <td align="center" valign="bottom"> 0.7
<hr noshade="noshade" size="1"></td> </tr> </tbody></table></td></tr></tbody></table>
<!-- tblfn -->^* Epidemic periods are consecutive months when P&I mortality exceeded the arbitrarily defined threshold. The 1917/1918 influenza season is broken down by period to illustrate the changing age distribution.
<!-- tblfn --> Excess total all-cause (AC) and P&I mortality estimates are derived from the total population data. Excess AC<45 and AC45 mortality estimates are derived from the <45 and the 45 age groups. The difference between total all-cause and the sum of age-specificall-cause values was due to rounding and variation between the total and age-stratified analyses.
<!-- tblfn --> The risk ratio is derived from the AC<45 and AC45 excess mortality rates.

Age-Specific Analyses.

The age pattern of mortality shiftedprofoundly during the 1917/1918 season.

In the 1915/1916 and1916/1917 influenza seasons and in January 1918, excess mortalityincidence was greatest in those 65 years old (Fig. 1 C).

DuringFebruary-April 1918 and the 1918/1919 season, those 65 yearsold experienced little or no excess mortality (Fig. 1C), whereasthose aged 15-24 and 25-44 years experienced sharply elevateddeath rates (Fig. 1 E and F). Mortality data for children <5and 5-14 years old did not exhibit winter peaks before the 1917/1918season (Fig. 1 G and H). Before 1918, children experienced mortalitypeaks from summer diarrheal disease epidemics, a severe polioepidemic in the summer of 1916 (Fig. 1 G and H), and a coincidentdiarrheal epidemic and heat wave in the summer of 1917Fig.1H). (

Because of the striking contrast in mortality impact by ageduring the 1918/1919 pandemic season, we calculated the ratioof <45 to 45 years epidemic period excess death rates (Table 1).The ratio of age-specific epidemic deaths shifted abruptlyin February 1918 and reached values >20-fold higher in Marchand April 1918 and in the 1918/1919 season than in the 1915/1916and 1916/1917 epidemic seasons (Table 1). The age-specific ratioin the 1919/1920 season was closer to prepandemic levels (Table 1);however, the total burden of excess deaths among people<45 years old remained extremely high, compared with theinterpandemic period (Fig. 1 E-H).

The W-Shaped Curve.

Average annual P&I death rates by agefor 1915-1917 showed the classic U-shaped mortality patterncharacteristic of influenza epidemic years (Fig. 2A). For calendaryear 1918, the age-specific mortality pattern showed the classicW-shaped distribution of the pandemic (Fig. 2 A).

In contrast,when we plotted seasonal age-specific excess mortality rates(specifically representing influenza-related mortality), a strikinglydifferent pattern emerged.

For the 1915/1916 interpandemic season,the U pattern is flattened on one end because children <5years had little excess epidemic-period impact, whereas theU pattern was elevated on the other, because the greatest increasein epidemic period mortality was among the elderly (Fig. 2B).<sup>

</sup>For the 1918/1919 pandemic season, mortality rates in youngchildren and young adults were sharply higher than for the 1915/1916epidemic, whereas mortality rates were lowest among the oldestage group, presenting an age pattern resembling an attenuatedW shape (Fig. 2B).




Fig. 2. Annual and epidemic period mortality rates by age group. (A) Average age-specific calendar year P&I death rates are plotted in a U-shaped age distribution for 1915-1917 (), and in the characteristic W-shaped distribution for the pandemic year 1918 (). (B) Influenza-season-attributable excess deaths are plotted for the 1915/1916 epidemic influenza season (), the epidemic months March and April 1918 (), and the pandemic season from September 1918 through April 1919 (). (C) The excess rates are plotted on a log₁₀ scale. (D) Relative risk of death is plotted by age group on a log₁₀ scale for the March and April 1918 epidemic period () and the pandemic from September 1918 through April 1919 () relative to the severe 1915/1916 epidemic season.



The age pattern of excess epidemic death rates in early 1918,when the risk ratio shifted toward younger ages (Table 1), isnot immediately apparent as plotted (Fig. 2B). However, on alogarithmic scale, the relative pattern appears strikingly similarto the 1918/1919 pandemic period, and the 1915/1916 epidemicpattern clearly was different from both the early 1918 epidemicand the 1918/1919 season (Fig. 2C). To further illustrate theage pattern as a measure of mortality risk, the ratio of theearly 1918 epidemic and 1918/1919 pandemic periods relativeto the 1915/1916 epidemic are plotted (relative risk, Fig. 2D);this graph underscores that the oldest age groups fared betterduring these periods than during a typical severe influenzaepidemic season such as 1915/1916. <!-- null -->




Discussion
In the absence of virological evidence of an early wave of the1918 pandemic, we have alternatively pursued an epidemiologicalapproach based on previously unexploited age-detailed mortalitydata from New York City, which at the time comprised >5%of the entire U.S. population.

In this study, we have characterizedthe age-specific impact of influenza epidemics on mortalityfor 1911-1921 to identify and determine the timing of a "signature"age shift previously shown to distinguish pandemic from epidemicinfluenza periods (19).

We have demonstrated that a distinctshift in the age distribution of excess deaths occurred duringthe 1917/1918 season in a pattern suggestive of a herald waveof pandemic mortality.

A prevailing hypothesis of the 1918 pandemic'sorigin has been that it emerged in a mild wave in the springof 1918 from the central United States (11-15); however, theoriginal data supporting this argument have never been rigorouslyevaluated.

The data we present for New York City suggest thatprepandemic activity was occurring before spring 1918, and thatthe impact was far from mild.

These findings are inconsistentwith the prevailing hypothesis of a spring 1918 Kansas origin,and they reopen the possibility that the virus had spread fromEurope to New York City in the context of troop movement duringWorld War I.

The severe wave of mortality from February to April 1918 inNew York City caused more than one-tenth the number of excessall-cause deaths as occurred during the subsequent pandemicseason. The impact of the early wave on young adults was extreme,with a peak associated with a doubling of all-cause deaths among15- to 24-year-olds (Fig. 1F), and the impact on the oldestage group was typical of nonepidemic period winter mortality(Fig. 1C). If the 1918/1919 pandemic season had never occurred,the age-specific impact of the early 1918 epidemic would remainan unprecedented event in the history of New York City municipalmortality statistics. With the exception of the 1918/1919 pandemicseason, no reported influenza-like respiratory disease epidemic,other than the proposed herald wave that we report, has evercaused such an extreme increase in young adult deaths whilecausing little or no impact among older adults. The relativeimpact on the young and the lack of impact on the oldest agegroup present similar patterns for both the herald and pandemicwaves, compared with surrounding epidemic seasons (Fig. 2D).

Based on calendar-year data, the age pattern of the 1918 pandemichas typically been described as W-shaped, with high mortalityrates in three age groups: very young children, young adults,and the elderly (Fig. 2A).

Our study, which attempts to providean estimate of epidemic influenza-attributable deaths, specificallyshows that during pandemic months, the oldest age group experiencedlittle increase in mortality, thus attenuating the older endof the W curve (Fig. 2B). Other studies have similarly shownthis lack of impact in older age groups, based on quarterly(32) and annual (33) data. And other studies have shown a similarpandemic shift in age-specific relative risk, in the case ofthe 1968 A/H3N2 pandemic (31), consistent with serological evidenceof previous exposure to a similar antigenic subtype virus amongthose 77 years old (34). The relative sparing of the oldestage groups in our study is consistent with the hypothesis ofprotection due to the recycling of a similar virus subtype ahalf-century earlier (34) and also with the hypothesis thatantibody-dependent enhancement led to extreme virulence, specificallyin younger adults (35). We could not address these possibilitiesfurther with the data at hand, and we did not have the age detailto further characterize the age cutoff among the middle agegroups that would separate those affected from those not affectedby this influenza pandemic.

Furthermore, we did not have thespatial and temporal detail necessary to further characterizeprecisely when and where the pandemic mortality herald wavebegan. A shift in the relative distribution of mortality towardyounger ages occurred in each of the three major pandemics ofthe 20th century (19, 20). Whether and to what degree earlyevidence of the 1918 pandemic shift can be identified in othercities remains an important test of our hypothesis. Althoughour approach can detect only a significant mortality impactand would miss any sporadic pandemic activity, the magnitudeand age specificity of the early 1918 epidemic that we describesuggest that such an early wave may be identifiable in muchsmaller regional data sets. However, the recovery of A/H1N1influenza virus RNA from human tissue from this period remainsthe gold standard for identifying a precursor epidemic wave.

Since the original confirmation that an A/H1N1 influenza viruscaused the 1918 pandemic (5), further phylogenetic characterizationof the virus (6, 7, 36) and elucidation of its hemagglutininstructure (37, 38) have presented a complex and inconclusiveevolutionary story of an avian-like mammalian-adapted virus,more like the H5N1 avian influenza viruses that have been isolatedsince 1997 than the pandemic reassortments of either 1957 or1968 (39, 40).

Our epidemiological approach cannot provide insightinto the specific genetic characteristics of the virus thatcaused the observed early 1918 epidemic. However, the most parsimoniousexplanation is that the virus that caused the early wave wassimilar to that which caused the catastrophic wave that explodedglobally in the autumn of 1918.

We believe that the magnitudeof the increase in young-adult deaths accompanied by the lackof impact among older age groups provides compelling evidenceof an early phase or herald wave of the 1918 pandemic.

Further analysis of age-detailed historical mortality data fromother regions and periods may continue to provide insight intothe epidemiology of past influenza pandemics and may help toinform current preparedness planning efforts for future pandemics(41).

The historical-epidemiological evidence of the precursorwave that we present, along with a recent study of transmissibilityin the pandemic wave of autumn 1918 (42), suggest that if eventssimilar to those preceding autumn 1918 were to occur again,strengthened surveillance and increased capacity for rapid publichealth intervention could possibly prove critical in limitingthe emergence and impact of the next pandemic.

The speed withwhich human-to-human transmissibility of a highly pathogenicmammalian adapted avian influenza virus develops cannot currentlybe predicted.

Nevertheless, the historical precedent of 20th-centuryinfluenza pandemics suggests that theoretically controllabletransmissibility and a herald wave may occur before the onsetof a catastrophic pandemic wave, leaving a critical window ofopportunity for production and distribution of pandemic vaccinesand antivirals.

Acknowledgements
We thank D. S. Fedson, J. K. Taubenberger, and C. Viboud fortheir critical input and stimulating discussions during thedevelopment of this study, and R. J. Taylor for help in editingthe manuscript. S.S.M. is supported by Centers for Disease Controland Prevention Cooperative Agreements A1013-21/21 and U90/CCU224241and by the Arts and Letters and Achelis Foundations. <!-- null -->
<table bgcolor="#e1e1e1" cellpadding="0" cellspacing="0" width="100%"> <tbody><tr><td align="left" bgcolor="#ffffff" valign="middle" width="5%"></td> <th align="left" valign="middle" width="95%"> Footnotes </th></tr></tbody></table>
<!-- null --> Author contributions: D.R.O., L.S., and S.S.M. designed research;D.R.O. performed research; and D.R.O., L.S., P.J.E., and S.S.M.analyzed data and wrote the paper.
<!-- null --> This paper was submitted directly (Track II) to the PNAS office.
<!-- null --> Abbreviation: P&I, pneumonia and influenza.
<!-- null --> 
? 2005 by The National Academy of Sciences of the USA
<!-- null -->
<table bgcolor="#e1e1e1" cellpadding="0" cellspacing="0" width="100%"> <tbody><tr><td align="left" bgcolor="#ffffff" valign="middle" width="5%"></td> <th align="left" valign="middle" width="95%"> References </th></tr></tbody></table>

1. <!-- null -->
2. Glezen, W. P. (1996) Epidemiol. Rev. 18, 64-76.<!-- HIGHWIRE ID="102:31:11059:1" --><nobr>[Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
3. Johnson, N. P. A. S. & M?ller, J. (2002) Bull. Hist. Med. 76, 105-115.<!-- HIGHWIRE ID="102:31:11059:2" -->[ISI][Medline] <!-- /HIGHWIRE --><!-- null -->
4. Reid, A. H. & Taubenberger, J. K. (2003) J. Gen. Virol. 84, 2285-2292.<!-- HIGHWIRE ID="102:31:11059:3" --><nobr>[Abstract/Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
5. Jordan, E. O. (1927) Epidemic Influenza: A Survey (Am. Med. Assoc., Chicago).<!-- HIGHWIRE ID="102:31:11059:4" --><!-- /HIGHWIRE --><!-- null -->
6. Taubenberger, J. K., Reid, A. H., Krafft, A. E., Bijwaard, K. E. & Fanning, T. G. (1997) Science 275, 1793-1796.<!-- HIGHWIRE ID="102:31:11059:5" --><nobr>[Abstract/Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
7. Reid, A. H., Fanning, T. G., Hultin, J. V. & Taubenberger, J. K. (1999) Proc. Natl. Acad. Sci. USA 96, 1651-1656.<!-- HIGHWIRE ID="102:31:11059:6" --><nobr>[Abstract/Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
8. Reid, A. H., Janczewski, T. A., Lourens, R. M., Elliot, A. J., Daniels, R. S., Berry, C. L., Oxford, J. S. & Taubenberger, J. K. (2003) Emerg. Infect. Dis. 9, 1249-1253.<!-- HIGHWIRE ID="102:31:11059:7" -->[ISI][Medline] <!-- /HIGHWIRE --><!-- null -->
9. Oxford, J. S., Lambkin, R., Sefton, A., Daniels, R., Elliot, A., Brown, R. & Gill, D. (2005) Vaccine 23, 940-945.<!-- HIGHWIRE ID="102:31:11059:8" -->[CrossRef][ISI][Medline] <!-- /HIGHWIRE --><!-- null -->
10. Soper, G. A. (1918) Science 48, 451-456.<!-- HIGHWIRE ID="102:31:11059:9" --><nobr>[Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
11. Frost, W. H. (1919) J. Am. Med. Assoc. 73, 313-318.<!-- HIGHWIRE ID="102:31:11059:10" --><!-- /HIGHWIRE --><!-- null -->
12. Vaughn, W. T. (1921) Influenza: An Epidemiological Study (Am. J. Hyg., Baltimore), Monograph 1.<!-- HIGHWIRE ID="102:31:11059:11" --><!-- /HIGHWIRE --><!-- null -->
13. Crosby, A. W. (1989) America's Forgotten Pandemic: The Influenza of 1918 (Cambridge Univ. Press, New York).<!-- HIGHWIRE ID="102:31:11059:12" --><!-- /HIGHWIRE --><!-- null -->
14. Patterson, K. D. & Pyle, G. F. (1991) Bull. Hist. Med. 65, 4-21.<!-- HIGHWIRE ID="102:31:11059:13" -->[ISI][Medline] <!-- /HIGHWIRE --><!-- null -->
15. Phillips, H. & Killingray, D. (2003) in The Spanish Influenza Pandemic of 1918-1919: New Perspectives, eds. Phillips, H. & Killingray, D. (Routledge, New York), pp. 1-25.<!-- HIGHWIRE ID="102:31:11059:14" --><!-- /HIGHWIRE --><!-- null -->
16. Barry, J. M. (2004) The Great Influenza: The Epic Story of the Deadliest Plague in History (Viking, New York).<!-- HIGHWIRE ID="102:31:11059:15" --><!-- /HIGHWIRE --><!-- null -->
17. Kilbourne, E. D. (2003) in The Spanish Influenza Pandemic of 1918-1919: New Perspectives, eds. Phillips, H. & Killingray, D. (Routledge, New York), pp. 29-38.<!-- HIGHWIRE ID="102:31:11059:16" --><!-- /HIGHWIRE --><!-- null -->
18. Schoenbaum, S. C. (2003) in The Spanish Influenza Pandemic of 1918-1919: New Perspectives, eds. Phillips, H. & Killingray, D. (Routledge, New York), pp. 241-251.<!-- HIGHWIRE ID="102:31:11059:17" --><!-- /HIGHWIRE --><!-- null -->
19. Knobler, S. L., Mack, A., Mahmoud, A. & Lemon, S. M., eds. (2005) The Threat of Pandemic Influenza: Are We Ready? A Workshop Summary (Natl. Acad. Press, Washington, DC).<!-- HIGHWIRE ID="102:31:11059:18" --><!-- /HIGHWIRE --><!-- null -->
20. Simonsen, L., Clarke, M. J., Schonberger, L. B., Arden, N. H., Cox, N. J. & Fukuda, K. (1998) J. Infect. Dis. 178, 53-60.<!-- HIGHWIRE ID="102:31:11059:19" -->[ISI][Medline] <!-- /HIGHWIRE --><!-- null -->
21. Dauer, C. C. & Serfling, R. E. (1961) Am. Rev. Resp. Dis. 83, 15-28.<!-- HIGHWIRE ID="102:31:11059:20" -->[ISI]<!-- /HIGHWIRE --><!-- null -->
22. Eickhoff, T. C., Sherman, I. L. & Serfling, R. E. (1961) J. Am. Med. Assoc. 176, 776-782.<!-- HIGHWIRE ID="102:31:11059:21" -->[ISI][Medline] <!-- /HIGHWIRE --><!-- null -->
23. Serfling R. E. (1963) Public Health Rep. 78, 494-506.<!-- HIGHWIRE ID="102:31:11059:22" -->[ISI]<!-- /HIGHWIRE --><!-- null -->
24. Serfling, R. E., Sherman, I. L. & Houseworth, W. J. (1967) Am. J. Epidemiol. 86, 433-441.<!-- HIGHWIRE ID="102:31:11059:23" --><nobr>[Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
25. Choi, K. & Thacker, S. B. (1981) Am. J. Epidemiol. 113, 215-226.<!-- HIGHWIRE ID="102:31:11059:24" --><nobr>[Abstract/Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
26. Thompson, W. W., Shay, D. K., Weintraub, E., Brammer, L., Cox, N., Anderson, L. J. & Fukuda, K. (2003) J. Am. Med. Assoc. 289, 179-186.<!-- HIGHWIRE ID="102:31:11059:25" --><nobr>[Abstract/Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
27. Reichert, T. A., Simonsen, L., Sharma, A., Pardo, S.A., Fedson, D.S. & Miller, M.A. (2004) Am. J. Epidemiol. 160, 492-502.<!-- HIGHWIRE ID="102:31:11059:26" --><nobr>[Abstract/Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
28. Housworth, J. & Langmuir, A. D. (1974) Am. J. Epidemiol. 100, 40-48.<!-- HIGHWIRE ID="102:31:11059:27" --><nobr>[Abstract/Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
29. Lui, K. J. & Kendal, A. P. (1987) Am. J. Pub. Health 77, 712-716.<!-- HIGHWIRE ID="102:31:11059:28" -->[Abstract]<!-- /HIGHWIRE --><!-- null -->
30. Simonsen, L., Clarke, M. J., Williamson, G. D., Stroup, D. F., Arden, N. H. & Schonberger, L. B. (1997) Am. J. Pub. Health 87, 1944-1950.<!-- HIGHWIRE ID="102:31:11059:29" -->[Abstract]<!-- /HIGHWIRE --><!-- null -->
31. Viboud, C., Boelle, P. Y., Pakdaman, K., Carrat, F., Valleron, A. J. & Flahault, A. (2004) Emerg. Infect. Dis. 10, 32-39.<!-- HIGHWIRE ID="102:31:11059:30" -->[ISI][Medline] <!-- /HIGHWIRE --><!-- null -->
32. Simonsen, L., Reichert, T. A. & Miller, M. (2004) in Options for the Control of Influenza V, International Congress Series 1263, ed. Kawaoka, Y. (Elsevier, Okinawa, Japan), Vol. ICS 1263, pp. 791-794.<!-- HIGHWIRE ID="102:31:11059:31" --><!-- /HIGHWIRE --><!-- null -->
33. Nguyen-Van-Tam, J. S. & Hampson, A. W. (2003) Vaccine 21, 1762-1768.<!-- HIGHWIRE ID="102:31:11059:32" -->[CrossRef][ISI][Medline] <!-- /HIGHWIRE --><!-- null -->
34. Luk, J., Gross, P. & Thompson, W. W. (2001) Clin. Infect. Dis. 33, 1375-1378.<!-- HIGHWIRE ID="102:31:11059:33" -->[CrossRef][ISI][Medline] <!-- /HIGHWIRE --><!-- null -->
35. Schoenbaum, S. C., Coleman, M. T., Dowdle, W. R. & Mostow, S. R. (1976) Am. J. Epidemiol. 103, 166-173.<!-- HIGHWIRE ID="102:31:11059:34" --><nobr>[Abstract/Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
36. Morens, D. M. (1994) Clin. Infect. Dis. 19, 500-512.<!-- HIGHWIRE ID="102:31:11059:35" -->[ISI][Medline] <!-- /HIGHWIRE --><!-- null -->
37. Reid, A. H., Fanning, T. G., Janczewski, T. A., Lourens, R. M. & Taubenberger, J. K. (2004) J. Virol. 78, 12462-12470.<!-- HIGHWIRE ID="102:31:11059:36" --><nobr>[Abstract/Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
38. Gamblin, S. J., Haire, L. F., Russell, R. J., Stevens, D. J., Xiao, B., Ha, Y., Vasisht, N., Steinhauer, D. A., Daniels, R. S., Elliot, A., et al. (2004) Science 303, 1838-1842.<!-- HIGHWIRE ID="102:31:11059:37" --><nobr>[Abstract/Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
39. Stevens, J., Corper, A. L., Basler, C. F., Taubenberger, J. K., Palese, P. & Wilson, I. A. (2004) Science 303, 1866-1870.<!-- HIGHWIRE ID="102:31:11059:38" --><nobr>[Abstract/Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
40. Webster, R. G. (2001) Science 293, 1773-1775.<!-- HIGHWIRE ID="102:31:11059:39" --><nobr>[Free Full Text]</nobr><!-- /HIGHWIRE --><!-- null -->
41. Reid, A. H., Taubenberger, J. K. & Fanning, T. G. (2004) Nat. Rev. Microbiol. 2, 909-914.<!-- HIGHWIRE ID="102:31:11059:40" -->[CrossRef][ISI][Medline] <!-- /HIGHWIRE --><!-- null -->
42. Simonsen, L., Olson, D. R., Viboud, C. Heiman, E., Taylor, R. J., Miller, M. A. & Reichert, T. A. (2005) in The Threat of Pandemic Influenza: Are We Ready? A Workshop Summary, eds. Knobler, S. L., Mack, A., Mahmoud, A. & Lemon, S. M. (Natl. Acad. Press, Washington, DC), pp. 89-114.<!-- HIGHWIRE ID="102:31:11059:41" --><!-- /HIGHWIRE --><!-- null -->
43. Mills, C. E., Robins, J. M. & Lipsitch, M. (2004) Nature 432, 904-906.<!-- HIGHWIRE ID="102:31:11059:42" -->[CrossRef][ISI][Medline]

 
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[aNewDawn]

Re: Epidemiological evidence of an early wave of the 1918 influenza pandemic in New York

Thanks for posting this informative study, Snowy Owl !

It's probably at the top of everyone's list to try and discern just when to 'duckandcover' or to implement your own pan-plan ...

(Hmmm, I kinda like that term ... "Like, hey man... What's your Pan-Plan??" I think I'll start using "pan-plan" when I talk about prepping. Kinda catchy, if I say so myself! Easy to say; sounds do-able. .....From sleep-deprivation comes inspiration ...Can I get an "amen!"?? )

But.... back to the subject ... SnowyOwl, you consistently emphasized 1917 in red bold. To what date are you correlating 1917 in our time frame?? To last spring? Now in Indo? ???

Seems to me that the 1917-1918 season sorta relates to our 2005-2006 scenario. I consider every day just a gift of borrowed time. I'd appreciate your input, please.

Dawn

[Snowy Owl]

Re: Epidemiological evidence of an early wave of the 1918 influenza pandemic in New Y

Hi NewDawn,

Yes I am surprise by similarities of the actual increases in virulence of many bugs and its effects on animals and humans.

I am in a research since a couple of weeks now to compare 1916/1918 events with the 2004/2006 events.

There is more to come, specifically the Heat Wave of 1917 and its effects on many diseases and the rise of our temperature now.

The weather seems link to the increases of the numbers of human infections, at least the ones caused by mosquitoes.

There are other similarities and I shall post them as soon as I find corroborations.

SO

[LMonty]

Re: Epidemiological evidence of an early wave of the 1918 influenza pandemic in New Y

some search engines color the searched terms int he documents they turn up- that might be the etiology of the words heats and 1917 being colored red. Perhaps the formatting preserved when copied in here, I've seen it happen before. Just a guess


I really like Pan-Plan too, very catchy!

[Snowy Owl]

Re: Epidemiological evidence of an early wave of the 1918 influenza pandemic in New York

Compare new datas from Copenhagen at

Roskilde University, Denmark - Historical records suggest that an early pandemic wave struck Europe during the summer of 1918

Snowy

[colormyquilt]

Re: Epidemiological evidence of an early wave of the 1918 influenza pandemic in New York

Bump this.

[tropical]

Re: Epidemiological evidence of an early wave of the 1918 influenza pandemic in New York

At CNN a few minutes ago an brief report from the CDC,
Dr. Gupta interview of Dr. Shaw, CDC:

~"We have never seen before such kind of virus in humans nor in animals."

~"This virus could fizzled out soon, but it will came back in autumn"

#1:
"At the peak of the catastrophic wave in the autumn of 1918,<SUP> </SUP>
<SUP>an influenza-like epidemic the preceding spring was retrospectively described as an early wave of the pandemic (</SUP><SUP>9</SUP><SUP>).
At the end of the 1918/1919 season, an epidemiological study suggested that this early precursor wave had caused epidemic mortality in Atlantic seaboard cities before central and western U.S. cities (</SUP><SUP>10</SUP><SUP>). A limited collection of eyewitness case and outbreak reports, however, led to the consensus view that the pandemic emerged in a mild wave in the spring of 1918 from an isolated rural region in the central United States (</SUP><SUP>11</SUP><SUP>). This view became widely accepted (</SUP><SUP>12</SUP><SUP>-</SUP><SUP>15</SUP><SUP>), without rigorous reevaluation of the original evidence"
</SUP>