INTRODUCTION — In late March and early April 2009, an outbreak of H1N1 influenza A virus infec tion

was detected in Mexic o, with subsequent c ases observed in many other c ountries inc luding the United
States [1,2]. On June 11, 2009, t he World Healt h Organizat ion raised it s pandemic alert level t o t he
highest level, phase 6, indicating widespread community transmission on at least two continents [3].
The pandemic that began in March 2009 was caused by an H1N1 influenza A virus that represents a
quadruple reassort ment of t wo swine st rains, one human st rain, and one avian st rain of influenza. (See
"Genetic and antigenic characterization" below).
The epidemiology, c linic al manifestations, and diagnosis of pandemic H1N1 influenza A virus infec tion will
be reviewed here. The treatment and prevention of pandemic H1N1 influenza A virus infection are
discussed separately; seasonal and avian (H5N1) influenza viruses are also reviewed elsewhere. (See
"Prevention of pandemic H1N1 influenza ('swine influenza')" and see "Epidemiology of influenza" and see
"Epidemiology; transmission; and pathogenesis of avian influenza" and see "Clinic al manifestations and
diagnosis of influenza in adults" and see "Clinical features and diagnosis of influenza in children" and see
"Clinic al manifestations and diagnosis of avian influenza").
EPIDEMIOLOGY
Historical perspective — The pandemic that began in Marc h 2009 was c aused by an H1N1 influenza A
virus t hat represent s a quadruple reassort ment of t wo swine st rains, one human st rain, and one avian
strain of influenza; the largest proportion of genes comes from swine influenza viruses. (See "Genetic
and antigenic characterization" below).
Illness with influenza in pigs was first rec ognized during the influenza pandemic of 1918 to 1919, and a
swine influenza virus was first isolated from a human in 1974 [4-6]. In 1976, swine influenza virus
c aused a respirat ory illness wit h one fat alit y among 13 soldiers in Fort Dix, New Jersey [7]. No exposure
to pigs was found. A subsequent epidemiologic study showed that up to 230 soldiers had been infec ted
wit h t he virus [4,8].
Between 1958 and 2005, 37 c ases of swine influenza among c ivilians were reported [4]. Six cases (17
percent) resulted in death. Forty-four percent of infected individuals had known exposure to pigs. Cases
were reported in the United States, former Czechoslovakia, the Netherlands, Russia, Switzerland, and
Hong Kong.
2009 pandemic — In Marc h and April 2009, an outbreak of respiratory illnesses was first noted in
Mexic o, whic h was event ually ident ified as being relat ed t o H1N1 influenza A [1]. The out break spread
rapidly to the United States, Canada, and throughout the world as a result of airline travel [9].
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online5.hsls.pitt.edu:6552/…/topic.do?… 1/14Reported c ases — As of July 31, 2009, over 162,000 laboratory-c onfirmed c
ases had been reported in
over 160 c ountries [2]. Since early July, the World Health Organization has ceased closely tracking the
number of c ases, sinc e it has bec ome extremely diffic ult for c ountries to c ontinue suc h monitoring in the
setting of widespread community transmission [10]. Furt hermore, even wit h c lose t rac king, t he t rue
numbers of cases are many fold higher than the numbers of confirmed cases [11]. The focus has shifted
to following trends of illness rather than individual cases in countries with widespread disease, and to
c lose monitoring of c ases only in newly affec ted c ountries.
Over 10,200 laboratory-c onfirmed c ases of pandemic H1N1 influenza A infec tion had been reported in
Mexic o by July 6, 2009, with 119 deaths [12]. The World Healt h Organizat ion report ed in early June 2009
that the outbreak likely peaked in Mexico in late April, although cases have continued to be detected
since then [13].
In the United States, as of July 24, 2009, over 43,000 c onfirmed c ases had been reported from 55
states and territories, but reporting of case counts has since been discontinued [14]. The majority of
c ases in the US have been mild, although some patients have required hospitalization and some deaths
have oc c urred [14,15]. (See "Mort alit y" below).
Updated information can be found at the websites of the World Health Organization
(http://www.who.int/csr/disease/swineflu/en/index.html) and the United States Centers for Disease
Control and Prevention (http://www.cdc.gov/h1n1flu/update.htm).
Age distribution — A typical feature of newly emergent pandemic influenza strains is that severe
infection occurs disproportionately in individuals who are not at the extremes of age. In contrast,
seasonal influenza is more likely to cause severe disease in infants, young children, and elderly
individuals. From lat e Marc h t o lat e April 2009 in Mexic o, 87 perc ent of deat hs and 71 perc ent of c ases
of severe pneumonia occurred in patients between the ages of 5 and 59 years; by comparison, an
average of 17 percent of deaths and 32 percent of severe pneumonia were attributed to influenza
infec t ion during earlier influenza epidemic s [16].
In c ontrast, among 532 c ases of pandemic H1N1 influenza A in the United States, 318 (60 perc ent)
occurred in individuals 18 years of age or younger (range 3 months to 81 years), which is similar to the
age distribution that occurs with seasonal influenza [17,18].
Pandemic alert level — On June 11, 2009, the World Health Organization raised its pandemic alert level
t o t he highest level, phase 6, indic at ing widespread c ommunit y t ransmission on at least t wo c ont inent s
[3].
VIROLOGY
Influenza subtypes — Clinical influenza can be caused by several different influenza subtypes,
although H1N1 is the most common subtype implicated in both swine and human infections [19]. Human
c ases of swine H3N2 influenza A virus infec t ion have been report ed rarely [4]. Other subtypes that have
c irculated in pigs include H1N2, H3N1, and H3N2.
Genetic and antigenic characterization — The pandemic that began in Marc h 2009 was c aused by an
H1N1 influenza A virus that had not been recognized previously in pigs or humans, although six of its
eight gene segments were similar to ones previously detected in triple reassortant swine influenza
viruses in pigs in Nort h Americ a [20]. This st rain represent s a quadruple reassort ment of t wo swine
strains, one human strain, and one avian strain of influenza (show figure 1) [17,21-23]. The largest
proportion of genes comes from swine influenza viruses (30.6 percent from North American swine
influenza strains, 17.5 percent from Eurasian swine influenza strains), followed by North American avian
influenza strains (34.4 perc ent) and human influenza strains (17.5 perc ent) [24].
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online5.hsls.pitt.edu:6552/…/topic.do?… 2/14Analysis of the antigenic and genetic characteristics of the pandemic H1N1
influenza A virus
demonstrated that its gene segments have been circulating for many years, suggesting that lack of
surveillanc e in swine is t he reason t hat t his st rain had not been rec ognized previously [21,22,25]. One of
the swine influenza viruses that contributed gene segments to the strain causing the 2009 pandemic is
thought to have derived from the strain that c aused the 1918 influenza pandemic [21,26].
Among the 2009 pandemic H1N1 influenza A viruses sequenc ed, eac h gene segment had high sequenc e
ident it y (99.9 perc ent ), suggest ing t hat int roduc t ion int o humans was eit her a single event or mult iple
event s of genet ic ally similar viruses [21]. Furthermore, the H1N1 influenza A viruses c ausing the 2009
pandemic were found to be antigenic ally homogeneous. Phylogenetic analysis has suggested that initial
t ransmission t o humans oc c urred several mont hs before t he out break was rec ognized [25].
Sequence analysis of isolates from the United States and Mexico did not identify molecular features
known t o c onfer inc reased t ransmissibilit y or virulenc e [21].
TRANSMISSION
Person-to-person transmission — Influenza virus is present in respiratory secretions of infected
persons. As a result, influenza virus c an be transmitted through sneezing and c oughing via large-partic le
droplets [27,28]. Transmission via contact with surfaces that have been contaminated with respiratory
droplet s or by aerosolized small- part ic le droplet s may also oc c ur, alt hough t hese modes of t ransmission
have not been proven [27]. In addition to respiratory secretions, certain other bodily fluids (eg, diarrheal
st ool) should also be c onsidered pot ent ially infec t ious [27]. (See "Clinical manifestations and diagnosis of
influenza in adults", section on Transmission).
In c ontrast to previous outbreaks of swine influenza viruses desc ribed above, the pandemic of H1N1
influenza A infec tion that began in Marc h 2009 appears to involve sustained human-to-human
t ransmission, as suggest ed by t he large numbers of pat ient s wit h respirat ory illnesses ident ified wit hin a
short period of time at various locations around the world [29]. Several of t he isolat es c ausing disease in
the United States have been found to be nearly genetically identical to isolates in Mexico, supportive of
person-to-person transmission [20,30].
Based on analysis by the World Health Organization using early data from the outbreak in Mexico and
other countries, transmissibility appears substantially higher compared with seasonal influenza [31]. The
sec ondary at t ac k rat e of t he st rain c ausing t his pandemic is est imat ed t o be 22 t o 33 perc ent ,
compared with 5 to 15 percent for seasonal influenza [32]. However, the United States Centers for
Disease Control and Prevention subsequently reported that the attack rate observed in the US is similar
to that in seasonal influenza [33].
Infection control and social distancing measures are discussed in detail separately. (See "Prevention of
pandemic H1N1 influenza ('swine influenza')", section on Social distancing measures and section on
Infec t ion c ont rol).
Incubation period — Although the precise incubation period has not been established for pandemic
H1N1 influenza A infection, it could range from one to seven days, and most likely from one to four days
[28].
Shedding — Sinc e the duration of shedding of pandemic H1N1 influenza A virus is c urrently unc lear, the
estimated duration of shedding is based upon what is known for seasonal influenza virus [34].
Patients with pandemic H1N1 influenza A virus infection are likely to be contagious from one day prior to
the development of signs and symptoms until resolution of fever [34]. However, because the duration of
shedding has not been established, individuals should be c onsidered c ontagious until seven days after
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online5.hsls.pitt.edu:6552/…/topic.do?… 3/14illness onset . Longer periods of shedding may oc c ur in c hildren (espec ially
young infant s), elderly adult s,
patients with chronic illnesses, and immunocompromised hosts. (See "Clinic al manifestations and
diagnosis of influenza in adults", sec t ion on Transmission and see "Clinical features and diagnosis of
influenza in c hildren", sec t ion on Transmission).
Role of pigs — Pigs play an important role in interspecies transmission of influenza virus. Susceptible pig
c ells possess rec eptors for both avian (alpha 2-3-linked sialic ac ids) and human influenza strains (alpha
2- 6- linked sialic ac ids), whic h allow for t he reassort ment of influenza virus genes from different spec ies
if a pig c ell is infec t ed wit h more t han one st rain [4,35-37]. (See "Epidemiology, transmission, and
pathogenesis of avian influenza", section on Pathogenesis).
Sinc e the late 1990s, triple reassortant swine influenza A viruses c ontaining genes from swine, human,
and avian strains of influenza have been detec ted among swine herds in North Americ a [16,38,39].
Eleven sporadic cases of triple reassortant swine H1 influenza A viruses were detected in the United
States between Dec ember 2005 and February 2009 [16]. Nine patients had exposure to pigs.
It is not c lear yet how this virus arose or was initially transmitted to humans. On May 2, 2009, the
Canadian government reported the identification of pandemic H1N1 influenza A from a swine herd in
Alberta, Canada [12]. It is suspected that the pigs became infected following exposure to a farm worker
who had recently visited Mexico and had developed an influenza-like illness.
There is no risk of becoming infected with influenza virus from eating pork [12].
CLINICAL MANIFESTATIONS — The signs and symptoms of influenza caused by pandemic H1N1
influenza A virus are similar to those of seasonal influenza, although gastrointestinal manifestations
appear to be more common with pandemic H1N1 influenza A [1,21,33,49]. The severity appears to be
less than what was observed during the influenza pandemic of 1918 to 1919 [50]. (See "Epidemiology of
influenza").
Signs and symptoms — The most c ommon c linic al findings of the 2009 H1N1 influenza A pandemic
have been fever, c ough, sore throat, malaise, and headac he; vomiting and diarrhea have also been
common, both of which are unusual features of seasonal influenza [21,33,49]. Other frequent findings
have inc luded c hills, myalgias, and art hralgias [21,49].
In New York City, 95 percent of patients with pandemic H1N1 influenza A have met the case definition
for influenza- like illness (subjec t ive fever plus c ough and/or sore t hroat ) [21]. In contrast, approximately
one third of patients seen at two hospitals in Mexico had no fever at presentation [34]. (See "Clinical
manifestations and diagnosis of influenza in adults").
Certain groups, suc h as infants, elderly individuals, and immunocompromised hosts, may have atypical
presentations.
The full range of complications of infection with pandemic H1N1 influenza A is not yet known, although
fatal and non-fatal c ases of pneumonia have oc c urred. (See "Complic at ions" below).
Children — Young c hildren are less likely to have the usual influenza signs and symptoms, suc h as fever
and cough [35]. Infants may present with fever and lethargy, and may not have c ough or other
respiratory symptoms. Symptoms of severe disease in infants and young c hildren may inc lude apnea,
tachypnea, dyspnea, cyanosis, dehydration, altered mental status, and extreme irritability. (See "Clinical
features and diagnosis of influenza in children").
Young children (eg, <5 years of age) are at increased risk for influenza complications [35,36]. (See
"Complic at ions" below and see "Treatment of pandemic H1N1 influenza ('swine influenza')", section on
High risk groups).
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online5.hsls.pitt.edu:6552/…/topic.do?… 4/14High risk adults — Among 553 patients with confirmed or probable pandemic
H1N1 influenza A in
California, t he most c ommon risk fac t ors for influenza c omplic at ions were c hronic lung disease (ast hma
or c hronic obstructive pulmonary disease, 37 perc ent), immunosuppressive conditions (17 perc ent),
c ardiac disease (17 percent), pregnancy (17 percent), diabetes mellitus (13 percent), and obesity (13
percent) [37]. (See "Complic at ions" below and see "Treatment of pandemic H1N1 influenza ('swine
influenza')", section on High risk groups).
Although elderly patients are considered to be at an increased risk for complications of influenza,
pandemic H1N1 influenza A infections in such individuals have been uncommon to date possibly as a
result of preexisting immunity against antigenic ally similar influenza viruses that c irc ulated prior to 1957
[26]. A study of antibody responses to pandemic H1N1 influenza A in stored sera showed that 33
percent of individuals over age 60 had microneutralization titers ≥160 c ompared with 6 perc ent of
individuals aged 18 to 40, and 9 perc ent of individuals aged 18 to 64 [38]. Microneutralization titers
≥160 often correlate with at least a 50 percent decrease in risk for influenza infection or disease, but
whether these titers offer partial protection against pandemic H1N1 influenza A virus infection or disease
is unc lear.
Laboratory findings — Both leukocytosis and leukopenia have been observed among hospitalized
patients [33]. In Mexico, many hospitalized patients have had leukopenia, elevated aminotransferases,
elevated lactate dehydrogenase, and elevated creatinine phosphokinase. Some patients have also had
renal insuffic ienc y.
Complications
Range of complications — Approximately 2 to 5 percent of c onfirmed cases in the United States and
Canada have required hospit alizat ion c ompared wit h 6 perc ent in Mexic o [11,33,37]. However, since the
number of cases of mild illness is almost certainly under-reported, the true percentage of cases requiring
hospit alizat ion is muc h lower; it has been est imat ed t o be 0.3 perc ent of c ases in t he Unit ed St at es
[51]. The most common reasons for admission were pneumonia and dehydration [37].
During the 2009 pandemic, rapidly progressive pneumonia, respiratory failure, and ac ute respiratory
dist ress syndrome have been report ed in some c ases in Mexic o [33,39,52,53]. Between late March and
late April 2009, 2155 c ases of severe pneumonia, inc luding 821 hospitalizations and 100 deaths, were
report ed t o t he epidemiologic surveillanc e net work in Mexic o [52]. In contrast to the experience in
Mexico, pneumonia has been uncommon among patients with pandemic H1N1 influenza A in the United
States [49].
Among 18 pat ient s in Mexic o requiring hospit alizat ion for pneumonia due t o pandemic H1N1 influenza, all
had fever, cough, dyspnea or respiratory distress, increased serum lactate dehydrogenase levels, and
bilat eral pat c hy pneumonia [53]. Inc reased c reatine kinase levels and lymphopenia were also c ommon
findings, occ urring in 62 and 61 perc ent of patients, respec tively. Twelve patients required mechanical
ventilation and seven died.
Few bacterial infections have been detected in patients with pandemic H1N1 influenza A; these include
empyema, necrotizing pneumonia and bacterial c oinfec tion, as well as ventilator-associated pneumonia
[33,51].
Four c hildren in Texas with pandemic H1N1 influenza A have had seizures, three of whom also had
abnormal electroencephalograms [54]. All four rec overed fully. Anot her report ed c omplic at ion among
patients with severe pandemic H1N1 influenza A pneumonia and ARDS has been multiple pulmonary
emboli [51].
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online5.hsls.pitt.edu:6552/…/topic.do?… 5/14Among 30 hospit alized pat ient s in California, 19 (64 perc ent ) had
underlying medic al c ondit ions, five
were pregnant (17 perc ent), six (20 perc ent) required intensive c are unit admission, and four (13
perc ent ) had respirat ory failure [37]. Of the 25 patients who had chest radiographs, 15 (60 percent)
showed evidence of pneumonia. None had microbiologic evidence of secondary bac terial pneumonia. No
deat hs oc c urred.
The range of c omplic ations of infec tion with pandemic H1N1 influenza A are likely to be similar to those
of seasonal influenza, such as [21]:
Exac erbation of underlying c hronic medic al c onditions
Upper respirat ory t rac t disease (sinusit is, ot it is media, c roup)
Lower respirat ory t rac t disease (pneumonia, bronc hiolit is, st at us ast hmat ic us)
Cardiac (myoc ardit is, peric ardit is)
Neurologic (Ac ute and post-infectious enc ephalopathy, encephalitis, febrile seizures, status
epilepticus)
T oxic shoc k syndrome
Sec ondary bac t erial pneumonia wit h or wit hout sepsis
The c omplic at ions of seasonal influenza are disc ussed in great er det ail separat ely. (See "Clinical
manifestations and diagnosis of influenza in adults" and see "Clinical features and diagnosis of influenza
in c hildren").
Pregnant women — During seasonal influenza epidemic s and prior pandemic s, pregnant women have
had inc reased morbidity and mortality [36,55]. In the United States during the 2009 H1N1 influenza A
pandemic, increased rates of hospitalization have been observed among pregnant women compared with
the general population [56]. In addition, six influenza-related deaths in pregnant women were reported
to the US Centers of Disease Control and Prevention between April 15 and June 16, 2009; all deaths
oc c urred in women who developed pneumonia and ac ut e respirat ory dist ress syndrome requiring
mechanical ventilation. Other countries have also reported an increased risk of severe influenza among
pregnant women during the 2009 pandemic , partic ularly during the sec ond and third trimesters [51,57].
During previous influenza pandemic s, inc reased rates of spontaneous abortion and preterm birth have
been reported among pregnant women, espec ially those with pneumonia [36]. Of five pregnant women
requiring hospit alizat ion for pandemic H1N1 influenza A, t wo developed c omplic at ions inc luding
spontaneous abortion (at 13 weeks of gestation) and premature rupture of membranes (at 35 weeks of
gestation) [37].
Mortality — Seasonal influenza results in higher mortality rates among patients with certain chronic
medical conditions, as well as in pregnant women and those at the extremes of age. A similar pattern
has been observed with pandemic H1N1 influenza A, although few elderly individuals have been affected.
This may be due to some degree of preexisting immunity in older individuals against antigenically similar
influenza viruses that c irc ulated prior to 1957 [26]. (See "Antiviral drugs for the prevention of influenza
in adult s", section on Definition of high risk and see "Ant iviral drugs for t he prevent ion and t reat ment of
influenza in c hildren", section on Target groups).
As of July 31, 2009, there have been 162,380 laboratory-c onfirmed c ases of pandemic H1N1 influenza A
worldwide, inc luding 1154 deaths [58]. In Mexic o, 119 of 10,262 laboratory-c onfirmed c ases (1.2
percent) have been fatal [59]. Most of these deaths were related to respiratory failure resulting from
severe pneumonia with multifocal infiltrates and acute respiratory distress syndrome [33]. In addition to
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online5.hsls.pitt.edu:6552/…/topic.do?… 6/14respirat ory failure, renal or mult iorgan failure oc c urred in 24 perc ent of c
ases in Mexic o. As of July 24,
2009, among 43,771 c ases reported in the United States, there have been 302 deaths (0.7 perc ent)
[60]. In Argentina, 60 of 2485 cases (2.4 percent) have been fatal [59]. A few fatal cases have
oc c urred in ot her c ount ries. The World Healt h Organizat ion and Unit ed St at es Cent ers for Disease
Control and Prevention c eased c losely trac king the number of c ases in July 2009 [60,61].
Of 45 fatal cases in Mexico, 24 (54 percent) occurred in previously healthy individuals, most of whom
were between the ages of 20 and 59 [33]. Most of the deaths outside of Mexico occurred in individuals
with underlying health problems and in those aged 40 or older [11,40,49,51,60]. One death in Mexico
and one deat h in t he US oc c urred in women who were in t he t hird t rimest er of pregnanc y when t hey
bec ame ill [33,41].
Variable severity of human infections with swine influenza viruses isolated before the 2009 pandemic has
been reported in several studies, as illustrated by the following findings [1]:
In a review of 37 cases of human infections with swine influenza virus reported between 1958
and 2005, six c ases (17 perc ent) resulted in death, all of whic h were due to pneumonia.
Influenza virus was the only pathogen identified from the lungs in four patients; in one
individual, Streptoc occus viridans, Neisseria spp, and Klebsiella spp were also identified in
addit ion t o influenza virus [6,42-45].
Between 2005 and January 2009, 12 c ases of human infec tion with swine influenza virus were
detected in the United States with no fatalities [1].
An out break oc c urred among soldiers in Fort Dix, New Jersey in 1976, whic h involved up t o
230 individuals but resulted in only one death [1,2,7,8].
A fatal human infec tion with swine influenza virus c omplic ated by pneumonia was also
reported in a previously healthy pregnant woman in 1988 [1].
DIAGNOSIS — Guidelines for the diagnosis of pandemic H1N1 influenza A virus have been released by
the United States Centers for Disease Control and Prevention (CDC) [21,27]. Updated recommendations
c an be found at the CDC's website (http://www.cdc.gov/swineflu/). Clinic ians in other c ountries should
c onsult t heir individual healt h minist ries for informat ion about rec ommended diagnost ic t est ing.
Whom to test — Test ing for pandemic H1N1 influenza A should be c onsidered in individuals wit h an
ac ute febrile respiratory illness (a measured temperature of 100ºF or higher and rec ent onset of at least
one of the following: rhinorrhea, nasal congestion, sore throat, or cough) or sepsis-like syndrome [21].
Priority for testing should be given to [21]:
Those who require hospitalization and
Those who are at high risk for severe c omplic at ions (see "Treatment of pandemic H1N1
influenza ('swine influenza')", section on High risk groups).
Not all individuals with suspec ted pandemic H1N1 influenza A need to have the diagnosis c onfirmed,
part ic ularly if t he illness is mild or t he person resides in an area wit h c onfirmed c ases. Rec ommendat ions
on whom to test may differ by state or community.
Specimens — To establish the diagnosis of pandemic H1N1 influenza A, an upper respiratory sample
(nasopharyngeal swab, nasal swab, throat swab, combined oropharyngeal/nasopharyngeal swab, or
nasal aspirat e) should be c ollec t ed [27]. In intubated patients, an endotracheal aspirate should also be
obtained.
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online5.hsls.pitt.edu:6552/…/topic.do?… 7/14Swabs with a synthetic tip (eg, polyester or Dacron) and an aluminum or
plastic shaft should be used.
Swabs with cotton tips and wooden shafts are not recommended. Swabs made of calcium alginate are
not acceptable. The collection vial in which the swab is placed should contain 1 to 3 mL of viral
t ransport media.
Specimens should be placed in viral transport media and placed on ice (4ºC) or refrigerated immediately
for t ransport at ion t o t he laborat ory. Onc e t he samples arrive in t he laborat ory, t hey should be st ored
either in a refrigerator at 4ºC or in a -70ºC freezer. If a -70ºC freezer is not available, they should be
kept refrigerated, preferably for ≤1 week.
Specimens should be shipped on dry ice to the state public health laboratory in clearly labeled
containers and should include all information requested by the state health laboratory.
Recommended tests — In t he Unit ed St at es, t he rec ommended t est t o c onfirm t he diagnosis of
pandemic H1N1 influenza A virus is real- t ime reverse t ransc ript ase (RT)- PCR for influenza A, B, H1, and
H3 [27]. However, in some regions of t he c ount ry, RT- PCR is performed only when t he result s will
substantially impact clinic al management or when there is a rec ognized public health benefit [46].
The strain of H1N1 influenza A virus assoc iated with the 2009 pandemic tests positive for influenza A
and negative for H1 and H3 by real-time RT-PCR. RT-PCR testing is generally performed at a state health
department laboratory; confirmatory testing is performed at the CDC. Case definitions of c onfirmed,
probable, and suspected pandemic H1N1 influenza A virus infection are discussed below. (See "Case
definitions" below).
Isolation of pandemic H1N1 influenza A virus using c ulture is diagnostic , but c ulture is usually too slow to
help guide c linic al management. A negative viral c ulture does not exc lude pandemic H1N1 influenza A
infec t ion.
Rapid antigen tests — Clinic ians may c onsider using rapid influenza ant igen t est s as part of t heir
evaluation of patients suspected of having pandemic H1N1 influenza A, but results should be interpreted
with caution [62]. Confirmat ion of pandemic H1N1 influenza A infec t ion c an only be made by real- t ime
reverse- t ransc ript ase (RT)- PCR or c ult ure. (See "Recommended tests" above).
The sensit ivit y and spec ific it y of rapid ant igen t est ing for pandemic H1N1 influenza A virus infec t ion have
not been established, and poor sensitivity has already been demonstrated for seasonal influenza. Based
on limit ed dat a, t he sensit ivit y of rapid ant igen t est ing for det ec t ing pandemic H1N1 influenza is probably
similar t o, or lower t han, t he sensit ivit y for det ec t ing seasonal influenza [62-65].
Among 39 patients with pandemic H1N1 influenza A c onfirmed by RT-PCR, 20 had a positive rapid antigen
test using the Quic kVue Influenza A+B (Quidel) assay (sensitivity 51 perc ent) [63]. Twelve of 19
patients who had seasonal H1N1 influenza confirmed by RT-PCR had a positive rapid antigen test
(sensit ivit y 63 perc ent ). In t he same st udy, t he spec ific it y of rapid ant igen t est ing was 99 perc ent for
patients with either the pandemic strain or a seasonal strain of H1N1 influenza A. (See "Clinical
manifestations and diagnosis of influenza in adults").
Certain rapid influenza antigen tests that are commercially available can distinguish between influenza A
and B viruses [27,62]. Thus, a patient with only influenza B virus infec tion would not be suspec ted of
having pandemic H1N1 influenza A virus infection. In contrast, a patient with a positive rapid antigen
test for influenza A may be considered a probable case if he or she meets the other criteria (see "Case
definitions" below). A negative rapid influenza test does not exc lude infec tion.
Immunofluorescent antibody testing — Direc t or indirec t immunofluoresc ent ant ibody t est ing (DFA or
IFA) can distinguish between influenza A and B [27]. T hus, a pat ient wit h a posit ive DFA or IFA may be
22/08/2009 Epidemiology, clinical manifestations, …
online5.hsls.pitt.edu:6552/…/topic.do?… 8/14considered a probable case if he or she meets the other criteria (see "Case
definitions" below). A
negative DFA or IFA does not exc lude pandemic H1N1 influenza A infec tion sinc e these tests have
unc lear sensit ivit y t o det ec t t his virus.
The diagnostic tests for influenza are discussed in greater detail separately. (See "Clinic al manifestations
and diagnosis of influenza in adults" and see "Clinic al features and diagnosis of influenza in c hildren").
DEFINITIONS
Case definitions — Definitions are changing as we learn more about this virus and the syndromes it
c auses. Cases in t he Unit ed St at es are c onfirmed by diagnost ic t est ing at t he Cent ers for Disease
Control and Prevention [1,27,48]. (See "Diagnosis" above).
Influenza-like illness (ILI) is defined as fever (temperature of 100ºF [37.8ºC] or greater) with c ough or
sore throat in the absence of a known cause other than influenza [48].
The following case definitions have been provided by the United States Centers for Disease Control and
Prevention [48]:
A confirmed case of pandemic H1N1 influenza A is defined as an individual with an ILI with
laborat ory- c onfirmed H1N1 influenza A virus det ec t ion by real- t ime reverse t ransc ript ase
(RT)-PCR or culture.
A probable case of pandemic H1N1 influenza A is defined as an individual with an ILI who is
positive for influenza A, but negative for H1 and H3 by RT-PCR
Pandemic H1N1 influenza A may be suspec ted in an individual who does not meet the definitions of
c onfirmed or probable pandemic H1N1 influenza A, but has an ILI and an epidemiologic link (eg, likely
exposure to a confirmed or probable case within the past seven days). Full case definitions can be found
at the CDC's website (http://www.c dc .gov/swineflu/).
High risk groups — Individuals with certain medical conditions, those at the extremes of age, and
pregnant women are at increased risk of influenza complications. (See "Complications" above and see
"Treatment of pandemic H1N1 influenza ('swine influenza')", sec tion on High risk groups).
Close contacts — The definitions of close contacts are presented separately. (See "Treatment of
pandemic H1N1 influenza ('swine influenza')", sec t ion on Close c ont ac t s).
SUMMARY AND RECOMMENDATIONS
Pandemic in 2009
In March and April 2009, an outbreak of H1N1 influenza A virus infection was detected in
Mexic o, with subsequent c ases observed in many other c ountries inc luding the United States.
On June 11, 2009, the World Health Organization raised its pandemic alert level to the highest
level, phase 6, indic at ing widespread c ommunit y t ransmission on at least t wo c ont inent s.
(See "Introduc tion" above and see "Epidemiology" above).
The 2009 H1N1 influenza A pandemic was c aused by an H1N1 virus that had not been
recognized previously in pigs or humans. This strain represents a genetic reassortment of
swine, human, and avian st rains of influenza. (See "Genetic and antigenic characterization"
above).
Influenza virus c an be transmitted through sneezing and c oughing via large-partic le aerosols,
as well as by contact with surfaces that have been contaminated with respiratory droplets.
22/08/2009 Epidemiology, clinical manifestations, …
online5.hsls.pitt.edu:6552/…/topic.do?… 9/14(See "Person-to-person transmission" above).
Patients with pandemic H1N1 influenza A virus infection are likely to be contagious from one
day prior to the development of signs and symptoms until resolution of fever. However,
bec ause the duration of shedding has not been established, individuals should be c onsidered
c ont agious unt il seven days aft er illness onset . (See "Shedding" above).
Although the incubation period has not been established for pandemic H1N1 influenza A
infection, it could range from one to seven days, and most likely from one to four days. (See
"Inc ubation period" above).
Infec tion c ontrol and soc ial distanc ing measures help to limit transmission of influenza viruses.
(See "Prevention of pandemic H1N1 influenza ('swine influenza')", sec t ion on Infec t ion c ont rol
and section on Social distancing measures).
Clinical findings
Typical clinical manifestations include fever, headache, cough, sore throat, myalgias, chills,
and fatigue; vomiting and diarrhea have also been c ommon, both of whic h are unusual
features of seasonal influenza. During the 2009 pandemic , rapidly progressive pneumonia,
respirat ory failure, and ac ut e respirat ory dist ress syndrome have been report ed in some
cases. (See "Clinic al manifestations" above).
Diagnostic testing — Guidelines for the diagnosis of pandemic H1N1 influenza A virus have been
released by the United States Centers for Disease Control and Prevention (CDC). Updated
recommendations can be found at the CDC's website (http://www.cdc.gov/swineflu/).
Not all individuals with suspected pandemic H1N1 influenza A need to have the diagnosis
c onfirmed, part ic ularly if t he illness is mild or t he person resides in an area wit h c onfirmed
cases. Recommendations on whom to test may differ by state or community. (See "Whom to
t est " above).
In the United States, the recommended test for suspected cases is real-time reverse
transcriptase (RT)-PCR for influenza A, B, H1, and H3, which is generally performed at a state
healt h depart ment laborat ory. (See "Recommended tests" above).
To establish the diagnosis of pandemic H1N1 influenza A, an upper respiratory sample
(nasopharyngeal swab, nasal swab, throat swab, c ombined oropharyngeal/nasopharyngeal
swab, or nasal aspirate) should be collected. Appropriate swabs must be used and conditions
observed for opt imal spec imen c ollec t ion. (See "Spec imens" above).
Case definitions of pandemic H1N1 influenza A
Case definitions of suspec ted, probable, and c onfirmed pandemic H1N1 influenza A virus
infection are based on symptoms, signs, and epidemiologic information. (See "Case definitions"
above).
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