You will be shown a paragraph from a biomedical research paper, followed by a question about the paper. Please extract text from the paragraph to answer the question. Do not include any text in your repsonse other than the answer.

Paragraph: Subsequent research indicates that descendants of the 1918
Virus still persists enzootically in pigs. They probably also
circulated continuously in humans, undergoing gradual
antigenic drift and causing annual epidemics, until the
1950s. With the appearance of a new H2N2 pandemic
strain in 1957 (“Asian ﬂu”), the direct H1N1 Viral descen-
dants 0f the 1918 pandemic strain disappeared from human
circulation entirely, although the related lineage persisted
enzootically in pigs.  But in 1977, human H1N1 Viruses
suddenly “reemerged” from a laboratory freezer (9). They
continue to circulate endemically and epidemically. Thus in 2006, 2 major descendant lineages of the 1918
H1N1 Virus, as well as 2 additional reassortant lineages,
persist naturally: a human epidemic/endemic H1N1 line-
age, a porcine enzootic H1N1 lineage (so-called classic
swine ﬂu), and the reassorted human H3N2 Virus lineage,
which like the human H1N1 Virus, has led to a porcine
H3N2 lineage. None of these Viral descendants, however,
approaches the pathogenicity of the 1918 parent Virus. Apparently, the porcine H1N1 and H3N2 lineages uncom-
monly infect humans, and the human H1N1 and H3N2 lin-
eages have both been associated with substantially lower
rates ofillness and death than the virus of 1918. In fact, cur-
rent H1N1 death rates are even lower than those for H3N2
lineage strains (prevalent from 1968 until the present). H1N1 Viruses descended from the 1918 strain, as well as 
H3N2 Viruses, have now been cocirculating worldwide for
29 years and show little evidence of imminent extinction. Trying To Understand What Happened

By the early 1990s, 75 years of research had failed to
answer a most basic question about the 1918 pandemic:
why was it so fatal? No Virus from 1918 had been isolated,
but all of its apparent descendants caused substantially
milder human disease. Moreover, examination of mortality
data from the 1920s suggests that within a few years after
1918, inﬂuenza epidemics had settled into a pattern of
annual epidemicity associated with strain drifting and sub-
stantially lowered death rates. Did some critical Viral genet-
ic event produce a 1918 Virus of remarkable pathogenicity
and then another critical genetic event occur soon after the
1918 pandemic to produce an attenuated H1N1 Virus? In 1995, a scientiﬁc team identiﬁed archival inﬂuenza
autopsy materials collected in the autumn of 1918 and
began the slow process of sequencing small Viral RNA
fragments to determine the genomic structure of the
causative inﬂuenza Virus (10). These efforts have now
determined the complete genomic sequence of 1 Virus and
partial sequences from 4 others. The primary data from the
above studies (11717) and a number of reviews covering
different aspects of the 1918 pandemic have recently been
published ([8720) and conﬁrm that the 1918 Virus is the
likely ancestor of all 4 of the human and swine H1N1 and
H3N2 lineages, as well as the “extinct” H2N2 lineage. No
known mutations correlated with high pathogenicity in
other human or animal inﬂuenza Viruses have been found
in the 1918 genome, but ongoing studies to map Virulence
factors are yielding interesting results. The 1918 sequence
data, however, leave unanswered questions about the ori-
gin of the Virus (19) and about the epidemiology of the
pandemic. When and Where Did the 1918 Inﬂuenza
Pandemic Arise? Before and after 1918, most inﬂuenza pandemics
developed in Asia and spread from there to the rest of the
world. Confounding deﬁnite assignment of a geographic
point of origin, the 1918 pandemic spread more or less
simultaneously in 3 distinct waves during an z12-month
period in 191871919, in Europe, Asia, and North America
(the ﬁrst wave was best described in the United States in
March 1918). Historical and epidemiologic data are inade-
quate to identify the geographic origin of the Virus (21),
and recent phylogenetic analysis of the 1918 Viral genome
does not place the Virus in any geographic context ([9). Although in 1918 inﬂuenza was not a nationally
reportable disease and diagnostic criteria for inﬂuenza and
pneumonia were vague, death rates from inﬂuenza and
pneumonia in the United States had risen sharply in 1915
and 1916 because of a major respiratory disease epidemic
beginning in December 1915 (22). Death rates then dipped
slightly in 1917. The ﬁrst pandemic inﬂuenza wave
appeared in the spring of 1918, followed in rapid succes-
sion by much more fatal second and third waves in the fall
and winter of 191871919, respectively (Figure 1). Is it pos-
sible that a poorly-adapted H1N1 Virus was already begin-
ning to spread in 1915, causing some serious illnesses but
not yet sufﬁciently ﬁt to initiate a pandemic? Data consis-
tent with this possibility were reported at the time from
European military camps (23), but a counter argument is
that if a strain with a new hemagglutinin (HA) was caus-
ing enough illness to affect the US national death rates
from pneumonia and inﬂuenza, it should have caused a
pandemic sooner, and when it eventually did, in 1918,
many people should have been immune or at least partial-
ly immunoprotected. “Herald” events in 1915, 1916, and
possibly even in early 1918, if they occurred, would be dif-
ﬁcult to identify. The 1918 inﬂuenza pandemic had another unique fea-
ture, the simultaneous (or nearly simultaneous) infection
of humans and swine. The Virus of the 1918 pandemic like-
ly expressed an antigenically novel subtype to which most
humans and swine were immunologically naive in 1918
(12,20). Recently published sequence and phylogenetic
analyses suggest that the genes encoding the HA and neu-
raminidase (NA) surface proteins of the 1918 Virus were
derived from an avianlike inﬂuenza Virus shortly before
the start of the pandemic and that the precursor Virus had
not circulated widely in humans or swine in the few
decades before (12,15, 24). More recent analyses of the
other gene segments of the Virus also support this conclu-
sion. Regression analyses of human and swine inﬂuenza
sequences obtained from 1930 to the present place the ini-
tial circulation of the 1918 precursor Virus in humans at
approximately 191571918 (20). Thus, the precursor was
probably not circulating widely in humans until shortly
before 1918, nor did it appear to have jumped directly
from any species of bird studied to date (19). In summary,
its origin remains puzzling. Were the 3 Waves in 1918—1 919 Caused
by the Same Virus? If So, How and Why? Historical records since the 16th century suggest that
new inﬂuenza pandemics may appear at any time of year,
not necessarily in the familiar annual winter patterns of
interpandemic years, presumably because newly shifted
inﬂuenza Viruses behave differently when they ﬁnd a uni-
versal or highly susceptible human population. Thereafter,
confronted by the selection pressures of population immu-
nity, these pandemic Viruses begin to drift genetically and
eventually settle into a pattern of annual epidemic recur-
rences caused by the drifted Virus variants. Figure 1. Three pandemic waves: weekly combined inﬂuenza and
pneumonia mortality, United Kingdom, 1918—1919 (21). In the 1918-1919 pandemic, a ﬁrst or spring wave
began in March 1918 and spread unevenly through the
United States, Europe, and possibly Asia over the next 6
months (Figure 1). Illness rates were high, but death rates
in most locales were not appreciably above normal. A sec-
ond or fall wave spread globally from September to
November 1918 and was highly fatal. In many nations, a
third wave occurred in early 1919 (21). Clinical similari-
ties led contemporary observers to conclude initially that
they were observing the same disease in the successive
waves. The milder forms of illness in all 3 waves were
identical and typical of inﬂuenza seen in the 1889 pandem-
ic and in prior interpandemic years. In retrospect, even the
rapid progressions from uncomplicated inﬂuenza infec-
tions to fatal pneumonia, a hallmark of the 191871919 fall
and winter waves, had been noted in the relatively few
severe spring wave cases. The differences between the
waves thus seemed to be primarily in the much higher fre-
quency of complicated, severe, and fatal cases in the last 2
waves. But 3 extensive pandemic waves of inﬂuenza within 1
year, occurring in rapid succession, with only the briefest
of quiescent intervals between them, was unprecedented. The occurrence, and to some extent the severity, of recur-
rent annual outbreaks, are driven by Viral antigenic drift,
with an antigenic variant Virus emerging to become domi-
nant approximately every 2 to 3 years. Without such drift,
circulating human inﬂuenza Viruses would presumably
disappear once herd immunity had reached a critical
threshold at which further Virus spread was sufﬁciently
limited. The timing and spacing of inﬂuenza epidemics in
interpandemic years have been subjects of speculation for
decades. Factors believed to be responsible include partial
herd immunity limiting Virus spread in all but the most
favorable circumstances, which include lower environ-
mental temperatures and human nasal temperatures (bene-
ﬁcial to thermolabile Viruses such as inﬂuenza), optimal
humidity, increased crowding indoors, and imperfect ven-
tilation due to closed windows and suboptimal airﬂow. However, such factors cannot explain the 3 pandemic
waves of 1918-1919, which occurred in the spring-sum-
mer, summer—fall, and winter (of the Northern
Hemisphere), respectively. The ﬁrst 2 waves occurred at a
time of year normally unfavorable to inﬂuenza Virus
spread. The second wave caused simultaneous outbreaks
in the Northern and Southern Hemispheres from
September to November. Furthermore, the interwave peri-
ods were so brief as to be almost undetectable in some
locales. Reconciling epidemiologically the steep drop in
cases in the ﬁrst and second waves with the sharp rises in
cases of the second and third waves is difﬁcult. Assuming
even transient postinfection immunity, how could suscep-
tible persons be too few to sustain transmission at 1 point,
and yet enough to start a new explosive pandemic wave a
few weeks later? Could the Virus have mutated profoundly
and almost simultaneously around the world, in the short
periods between the successive waves? Acquiring Viral
drift sufﬁcient to produce new inﬂuenza strains capable of
escaping population immunity is believed to take years of
global circulation, not weeks of local circulation. And hav-
ing occurred, such mutated Viruses normally take months
to spread around the world. At the beginning of other “off season” inﬂuenza pan-
demics, successive distinct waves within a year have not
been reported. The 1889 pandemic, for example, began in
the late spring of 1889 and took several months to spread
throughout the world, peaking in northern Europe and the
United States late in 1889 or early in 1890. The second
recurrence peaked in late spring 1891 (more than a year
after the ﬁrst pandemic appearance) and the third in early
1892 (21 ). As was true for the 1918 pandemic, the second
1891 recurrence produced of the most deaths. The 3 recur-
rences in 1889-1892, however, were spread over >3 years,
in contrast to 191871919, when the sequential waves seen
in individual countries were typically compressed into
z879 months. What gave the 1918 Virus the unprecedented ability to
generate rapidly successive pandemic waves is unclear. Because the only 1918 pandemic Virus samples we have
yet identiﬁed are from second-wave patients ([6), nothing
can yet be said about whether the ﬁrst (spring) wave, or for
that matter, the third wave, represented circulation of the
same Virus or variants of it. Data from 1918 suggest that
persons infected in the second wave may have been pro-
tected from inﬂuenza in the third wave. But the few data
bearing on protection during the second and third waves
after infection in the ﬁrst wave are inconclusive and do lit-
tle to resolve the question of whether the ﬁrst wave was
caused by the same Virus or whether major genetic evolu-
tionary events were occurring even as the pandemic
exploded and progressed. Only inﬂuenza RNAipositive
human samples from before 1918, and from all 3 waves,
can answer this question. What Was the Animal Host
Origin of the Pandemic Virus? Viral sequence data now suggest that the entire 1918
Virus was novel to humans in, or shortly before, 1918, and
that it thus was not a reassortant Virus produced from old
existing strains that acquired 1 or more new genes, such as
those causing the 1957 and 1968 pandemics.

Question: Did the Spanish Influenza or Swine flu or the H1N1 virus disappear in humans for some time?
descendants of the 1918
Virus still persists enzootically in pigs. They probably also
circulated continuously in humans, undergoing gradual
antigenic drift and causing annual epidemics, until the
1950s. With the appearance of a new H2N2 pandemic
strain in 1957 (“Asian ﬂu”), the direct H1N1 Viral descen-
dants 0f the 1918 pandemic strain disappeared from human
circulation entirely, although the related lineage persisted
enzootically in pigs.