HISTORICAL PERSPECTIVE pptx

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HISTORICAL PERSPECTIVE — The pandemic that began in March 2009 was

caused by an H1N1 influenza A virus that represents a quadruple reassortment of

two swine strains, one human strain, 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 recognized 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 caused a respiratory illness with one

fatality 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 infected with the virus [4,8].

Between 1958 and 2005, 37 cases of swine influenza among civilians 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.

EPIDEMIOLOGY OF THE 2009-2010 PANDEMIC — In March 2009, an

outbreak of respiratory illnesses was first noted in Mexico, which was eventually

identified as being related to H1N1 influenza A [1]. The outbreak spread rapidly

to the United States, Canada, and throughout the world as a result of airline

travel [9]. On June 11, 2009, the World Health Organization (WHO) raised its

pandemic alert level to the highest level, phase 6, indicating widespread

community transmission on at least two continents [3].

Reported cases — During the 2009-2010 H1N1 influenza A pandemic, over 99

percent of subtyped influenza A isolates in Europe and the US were pandemic

H1N1 influenza A [10,11].

In the US, the first wave of pandemic H1N1 influenza A occurred in the spring of

2009 and was followed by a second wave in the subsequent fall [12]. Influenza

activity peaked in October 2009, and then declined rapidly to below baseline

levels in January 2010.

More than 214 countries and territories have reported laboratory-confirmed cases

of pandemic H1N1 influenza A [13].

The WHO has reported the following patterns as of early June 2010 [13]:

• Although disease activity is low in most regions, including the US, active

but declining transmission of pandemic H1N1 influenza A persists in certain areas

of the tropics, particularly in Southeast Asia and the Caribbean.

• In the temperate southern hemisphere where winter is beginning, only

sporadic influenza activity has been detected, except in Chile and Uruguay, where

small numbers of cases of pandemic H1N1 influenza A have been reported.

• Since late February 2010, seasonal influenza B viruses have been the

predominant type of influenza virus circulating worldwide, but there have been

increasing but low levels of detection of seasonal H3N2 influenza A viruses,

especially in South America and East Africa.

Further details regarding disease activity in specific regions can be found

at: http://www.who.int/csr/disease/swineflu/en/index.html.

Since early July 2009, the World Health Organization has ceased closely tracking

the number of cases, since it has become difficult for countries to continue such

monitoring in the setting of widespread community transmission [14].

Furthermore, even with close tracking, the true numbers of cases are many fold

higher than the numbers of confirmed cases [15].

Estimated cases — A modeling study suggested that by late July 2009, the

number of individuals infected with pandemic H1N1 influenza A in the United

States may have been up to 140 times greater than the reported number of

confirmed cases [15]. Using the same methodology, the US Centers for Disease

Control and Prevention estimated that between April 2009 and April 10, 2010,

approximately 61 million cases of pandemic H1N1 influenza occurred, including

approximately 274,000 hospitalizations, and 12,470 deaths [12].

Rates of infection by age — The rate of infection in the United States has been

highest among individuals ≤24 years of age [16-19]. Between April 2009 and

April 10, 2010, the following estimates of cases in the US by age group were

[12]:

• 0 to 17 years — 20 million cases

• 18 to 64 years — 35 million cases

• 65 years and older — 6 million cases

• Total — 61 million cases

Similar patterns have been noted in England; a cross-sectional serologic survey

that compared serum samples from 2008 and September of 2009 demonstrated

that approximately one in three children had acquired pandemic H1N1 influenza A

infection; these rates were 10 times higher than estimates based on clinical

surveillance [20].

To date, pandemic H1N1 influenza A infections are uncommon in persons older

than 65 years, possibly as a result of preexisting immunity against antigenically

similar influenza viruses that circulated prior to 1957 [20-22]. For example, in a

study of more than 1400 serum samples taken in 2008, pre-existing cross￾reactive antibodies to the 2009 pandemic H1N1 influenza A virus were found in

1.8 percent of children <4 years of age compared with 31 percent among adults

≥80 years of age [20].

TRANSMISSION

Person-to-person transmission — Influenza virus can be transmitted through

sneezing and coughing via large-particle droplets [23]. In addition to respiratory

secretions, certain other bodily fluids (eg, diarrheal stool) should also be

considered potentially infectious.

In contrast to previous outbreaks of swine influenza viruses described above, the

pandemic of H1N1 influenza A infection has demonstrated sustained human-to￾human transmission, as suggested by the large numbers of patients with

respiratory illnesses identified within a short period of time at various locations

around the world [24]. Several of the isolates causing disease in the United

States have been found to be nearly genetically identical to isolates in Mexico,

supportive of person-to-person transmission [2,25]. Nosocomial transmission has

also been observed among hospitalized patients [26].

Viral shedding — Influenza shedding begins the day prior to symptom onset and

often persists for five to seven days or longer in immunocompetent individuals

[23,27-29]. Even longer periods of shedding may occur in children (especially

young infants), elderly adults, patients with chronic illnesses, and

immunocompromised hosts. Delayed clearance of virus from the nasopharynx has

also been observed in patients who developed acute respiratory distress

syndrome or who had fatal disease [30]. The amount of virus shed is greatest

during the first two to three days of illness.

Various findings related to viral shedding have been observed among patients

infected with pandemic H1N1 influenza A, as illustrated by the following studies:

• Although it is thought that immunocompetent 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, longer periods

of shedding were detected in a study of US air force academy cadets with

confirmed or suspected pandemic H1N1 influenza A infection [27]. Of 29 samples

that were obtained seven days following illness onset, seven (24 percent)

contained viable H1N1 influenza virus.

• In a study that included 426 patients in China who were quarantined with

pandemic H1N1 influenza A virus infection, the average duration of viral shedding

was six days based upon real-time reverse transcriptase PCR (rRT-PCR) [28]. The

median interval from resolution of fever to a negative rRT-PCR result was three

days, with negative results occurring within seven days in 96 percent of patients.

However, PCR techniques detect viral RNA, and not infectious virus, and may

continue to be positive after viral cultures become negative.

• In a study of 70 patients treated for pandemic H1N1 influenza A, most of

whom had no comorbidities, the duration of viral shedding was reduced in

patients who initiated oseltamivir therapy during the first 3 days of illness

compared with those who began therapy on day 4 or later [29]. The mean

duration of shedding from illness onset was five days among patients who began

oseltamivir therapy during the first 3 days of illness, compared with 7 days

among those who began therapy on day 4 of illness, and 8.5 days among those

who began therapy on day 5 of illness or later [29].

Studies of shedding of seasonal influenza viruses are reviewed separately.

(See "Clinical manifestations and diagnosis of seasonal influenza in adults",

section on 'Transmission'.)

Incubation period — The estimated median incubation period is approximately

1.5 to 3 days [28,31-34].

Secondary attack rates — Outbreaks of pandemic H1N1 influenza infection

have been documented in daycare centers, camps, schools, universities, and

among military personnel [31,35-37]. In a study from Singapore, seroconversion

rates were substantially higher among military personnel (29 percent) than

community members (14 percent) or hospital staff (7 percent) [37]. The younger

age of the military cohort compared with the other cohorts may have been at

least partially responsible for this difference. (See 'Rates of infection by

age' above.)