Epidemiology, = clinical manifestations, and diagnosis of swine H1N1 influenza A

TOPIC OUTLINE

INTRODUCTION=20
EPIDEMIOLOGY=20
- Historical=20 perspective=20
- 2009=20 outbreak
VIROLOGY=20
- Influenza=20 subtypes=20
- Role=20 of pigs=20
- Person-to-person=20 transmission=20
- Shedding=20
- Incubation=20 period
CLINICAL=20 MANIFESTATIONS=20
- Signs=20 and symptoms=20
  - Children=20
- Complications=20
- Mortality=20
DIAGNOSIS=20
- Specimens=20
- Recommended=20 tests=20
- Other=20 tests
CASE=20 DEFINITIONS=20
SUMMARY=20 AND RECOMMENDATIONS=20
- 2009=20 outbreak=20
- Clinical=20 manifestations=20
- Diagnosis=20
- Case=20 definitions
REFERENCES=20

RELATED TOPICS

Treatment and prevention of swine H1N1 influenza A=20
Antiviral drugs for the treatment of influenza in = adults=20
Antiviral drugs for the prevention of influenza in = adults=20
Treatment and prevention of avian influenza=20
Antiviral drugs for the prevention and treatment of = influenza in=20 children=20
Clinical manifestations and diagnosis of influenza in = adults=20
Clinical features and diagnosis of influenza in = children=20

Epidemiology, clinical=20 manifestations, and diagnosis of swine H1N1 influenza=20 A

Author Anna R Thorner, MD	Section Editor = Martin S Hirsch, MD	Deputy Editor = Barbara H McGovern,=20 MD

Last literature review version 17.1: = =E4=B8=80=E6=9C=88 2009=20 | This topic last updated: = =E4=BA=94=E6=9C=88 1, 2009=20 (More)=20

INTRODUCTION =E2=80=94 Swine = influenza viruses=20 usually infect pigs, but occasionally can cross species = barriers to=20 infect humans. In the past, cases of person-to-person = transmission=20 have been reported but have been confined to small outbreaks = [1,2].

In late March and early April 2009, an outbreak of swine = H1N1=20 influenza A virus infection was detected in Mexico, with = subsequent=20 cases observed in several other countries including the = United=20 States [1,3,4].

The epidemiology, clinical manifestations, and diagnosis = of swine=20 H1N1 influenza A virus infection will be reviewed here. The=20 treatment and prevention of swine H1N1 influenza A virus = infection,=20 and seasonal influenza and avian (H5N1) influenza virus = infections=20 are discussed separately. (See "Treatment and prevention of swine H1N1 = influenza=20 A" and see "Antiviral drugs for the treatment of = influenza=20 in adults" and see "Antiviral drugs for the prevention of = influenza=20 in adults" and see "Treatment and prevention of avian = influenza"=20 and see "Antiviral drugs for the prevention and = treatment=20 of influenza in children")and other topic reviews).

EPIDEMIOLOGY

Historical=20 perspective =E2=80=94 Illness with = influenza in pigs was=20 first recognized during the influenza pandemic of 1918 to = 1919, and=20 a swine influenza virus was first isolated from a human in = 1974 [2,5].=20 Between 1958 and 2005, 37 cases of swine influenza among = civilians=20 were reported [2].=20 Six cases (17 percent) resulted in death. Forty-four percent = of=20 infected individuals had known exposure to pigs. Cases were = reported=20 in the United States, former Czechoslovakia, the = Netherlands,=20 Russia, Switzerland, and Hong Kong.

In 1976, swine influenza virus caused a respiratory = illness with=20 one fatality among 13 soldiers in Fort Dix, New Jersey [6].=20 No exposure to pigs was found. A subsequent epidemiologic = study=20 showed that up to 230 soldiers had been infected with the = virus [2,7].

2009 = outbreak =E2=80=94 In=20 the spring of 2009, an outbreak of respiratory illnesses was = first=20 noted in three clusters in Mexico, which were eventually = identified=20 as being related to swine H1N1 influenza A [8,9].=20 As of May 1, 2009, over 150 laboratory-confirmed cases of = swine H1N1=20 influenza A infection have been reported in Mexico, = including 9=20 deaths [3].=20

As of May 1, 2009, over 140 confirmed cases of swine H1N1 = influenza A infection have been reported from several states = in the=20 United States [12].=20 The majority of cases in the US have been mild, although = some=20 patients have required hospitalization and at least one = patient has=20 died [12].=20 Cases have also been reported in many other countries [3,4].=20

Updated information on the number of confirmed cases can = be found=20 at the websites of the United States Centers for Disease = Control and=20 Prevention (http://www.cdc.gov/swineflu) and the = World Health=20 Organization (http://www.who.int/csr/disease/swineflu/en/index.html= ).

On April 29, 2009, the World Health Organization raised = its=20 pandemic alert level to phase 5, indicating that there is = sustained=20 person-to-person spread in at least two countries [12].=20 This designation implies that a pandemic is imminent and = that the=20 time to finalize the organization, communication, and = implementation=20 of the planned mitigation measures is short.

VIROLOGY

Influenza=20 subtypes =E2=80=94 Clinical influenza can = be caused by=20 several different swine influenza A subtypes, although H1N1 = is the=20 most common subtype implicated in both pig and human = infections [8].=20 Human cases of swine H3N2 influenza virus infection have = been=20 reported rarely [2].=20 Other subtypes that have circulated in pigs include H1N2, = H3N1, and=20 H3N2.

Role of = pigs =E2=80=94 =20 Pigs may play an important role in interspecies transmission = of=20 influenza virus. Susceptible pig cells possess receptors for = both=20 avian and human influenza strains, which allow for the = reassortment=20 of influenza viruses from different species if a pig cell is = infected with more than one strain [2,13,14].=20 The outbreak in the spring of 2009 was caused by an H1N1 = virus that=20 had not been recognized previously in pigs or humans [9].=20 This strain represents a genetic reassortment of swine, = human, and=20 avian strains of influenza [15].=20 It is not clear yet how this virus arose or was initially=20 transmitted to humans.

There is no risk of becoming infected with influenza = virus from=20 eating pork [3].=20

Person-to-person=20 transmission =E2=80=94 Influenza virus is = present in=20 respiratory secretions of infected persons. As a result, = influenza=20 virus can be transmitted through sneezing and coughing via=20 large-particle aerosols, as well as by contact with surfaces = that=20 have been contaminated with respiratory droplets [16].=20 (See "Clinical manifestations and diagnosis = of=20 influenza in adults", section on Transmission).

In contrast to previous outbreaks described above, the = outbreak=20 of swine H1N1 influenza A infection in the spring of 2009 = appears to=20 involve sustained human-to-human transmission, as suggested = by the=20 large numbers of patients with respiratory illnesses = identified=20 within a short period of time at various locations around = the world=20 [17].=20 Several of the isolates causing disease in the United States = have=20 been found to be nearly genetically identical to isolates in = Mexico,=20 supportive of person-to-person transmission [9,18].

Infection control and social distancing measures are = discussed=20 separately. (See "Treatment and prevention of swine H1N1 = influenza=20 A", section on Social distancing measures and section on = Infection control").

Shedding =E2=80=94 Since=20 the duration of shedding of swine H1N1 influenza A virus is=20 currently unclear, the estimated duration of shedding is = based upon=20 what is known for seasonal influenza virus [19].

Patients with swine H1N1 influenza A virus infection are=20 considered to be infectious from one day prior to the = development of=20 signs and symptoms until resolution of fever [19].=20 Individuals should be considered contagious until seven days = after=20 illness onset. Longer periods of shedding may occur in = children=20 (especially young infants), elderly adults, patients with = chronic=20 illnesses, and immunocompromised hosts. (See "Clinical manifestations and diagnosis = of=20 influenza in adults", section on Transmission and see "Clinical features and diagnosis of = influenza in=20 children", section on Transmission").

Incubation=20 period =E2=80=94 Although the precise = incubation period has=20 not been established for swine H1N1 influenza A infection, = it could=20 range from one to seven days, and most likely from one to = four days=20 [16].

CLINICAL = MANIFESTATIONS

Signs and=20 symptoms =E2=80=94 The signs and symptoms = of influenza=20 caused by swine H1N1 influenza A virus are similar to those = of=20 seasonal influenza [1].=20 Typical clinical manifestations include fever, headache, = cough, sore=20 throat, myalgias, chills, and fatigue. Diarrhea and vomiting = may=20 also occur.

During the 2009 outbreak, rapidly progressive pneumonia,=20 respiratory failure, and acute respiratory distress syndrome = have=20 been reported in some cases in Mexico [20].=20 In the United States, most described cases to date have been = mild as=20 of April 29, 2009 in the United States. (See "Clinical manifestations and diagnosis = of=20 influenza in adults").

Children =E2=80=94 Young=20 children are less likely to have the usual influenza signs = and=20 symptoms, such as fever and cough [21].=20 Infants may present with fever and lethargy, and may not = have cough=20 or other respiratory symptoms. Symptoms of severe disease in = infants=20 and young children may include apnea, tachypnea, dyspnea, = cyanosis,=20 dehydration, altered mental status, and extreme = irritability. (See "Clinical features and diagnosis of = influenza in=20 children").

Complications =E2=80=94 The = range of=20 complications of infection with the current strain of swine = H1N1=20 influenza A is not yet known, although fatal and non-fatal = cases of=20 pneumonia have occurred [16].

Young children (eg, <5 years of age), pregnant women, = and=20 those with comorbidities are at increased risk of influenza=20 complications [21,22].=20 Increased rates of spontaneous abortion and preterm birth = have also=20 been reported among pregnant women, especially those with = pneumonia=20 [22].

The complications of infection with swine H1N1 influenza = A are=20 likely to be similar to those of seasonal influenza, such as = [16]:

Exacerbation of underlying chronic medical conditions =

Upper respiratory tract disease (sinusitis, otitis = media,=20 croup)

Lower respiratory tract disease (pneumonia, = bronchiolitis,=20 status asthmaticus)

Cardiac (myocarditis, pericarditis)

Neurologic (Acute and post-infectious encephalopathy,=20 encephalitis, febrile seizures, status epilepticus) =

Toxic shock syndrome

Secondary bacterial pneumonia with or without sepsis =

The complications of seasonal influenza are discussed in = greater=20 detail separately. (See "Clinical manifestations and diagnosis = of=20 influenza in adults" and see "Clinical features and diagnosis of = influenza in=20 children").

Mortality =E2=80=94 =20 Seasonal influenza results in higher mortality rates among = patients=20 with certain chronic medical conditions, as well as in = pregnant=20 women, and those at the extremes of age. (See "Antiviral drugs for the prevention of = influenza=20 in adults", section on Definition of high risk and see "Antiviral drugs for the prevention and = treatment=20 of influenza in children", section on Target = groups).

As of May 1, 2009, over 150 deaths in Mexico have been = ascribed=20 to swine H1N1 influenza A, although only 9 of these deaths = have been=20 laboratory-confirmed to date [3,11].=20 Most of these deaths were related to respiratory failure. = Among more=20 than 140 cases in the United States, there has been one = death in a=20 23 month old child [12].

Variable severity of human infections with swine = influenza=20 viruses has been reported in several studies, as illustrated = by the=20 following findings [1]:

In a review of 37 cases of human infections with swine = influenza virus reported between 1958 and 2005, six cases = (17=20 percent) resulted in death, all of which were due to = pneumonia.=20 Influenza virus was the only pathogen identified from the = lungs in=20 four patients; in one individual, Streptococcus viridans,=20 Neisseria spp, and Klebsiella spp were also identified in = addition=20 to influenza virus [5,23-26].=20

Between 2005 and January 2009, 12 cases of human = infection=20 with swine influenza virus were detected in the United = States with=20 no fatalities [1].=20

An outbreak occurred among soldiers in Fort Dix, New = Jersey in=20 1976, which involved up to 230 individuals but resulted in = only=20 one death [1,2,6,7].=20

A fatal human infection with swine influenza virus = complicated by=20 pneumonia was also reported in a previously healthy pregnant = woman=20 in 1988 [1].

DIAGNOSIS =E2=80=94 Guidelines for the=20 diagnosis of swine H1N1 influenza A virus have been released = by the=20 United States Centers for Disease Control and Prevention = (CDC) [19].=20 Updated recommendations can be found at the CDC's website = (http://www.cdc.gov/swineflu/). = Clinicians in other=20 countries should consult their individual health ministries = for=20 information about recommended diagnostic testing.

Specimens =E2=80=94 When=20 swine H1N1 influenza A is suspected, an upper respiratory = sample=20 (nasopharyngeal swab/aspirate or nasal wash/aspirate) should = be=20 collected as soon as possible [19].=20 If these samples are not able to be obtained, a combined = nasal swab=20 with an oropharyngeal swab should be collected. In intubated = patients, an endotracheal aspirate should also be = obtained.

Swabs with a synthetic tip (eg, polyester or Dacron) and = an=20 aluminum or plastic shaft should be used. Swabs with cotton = tips and=20 wooden shafts are not recommended. Swabs made of calcium = alginate=20 are not acceptable. The collection vial in which the swab is = placed=20 should contain 3 mL of viral transport media.

Specimens should be placed in viral transport media and = placed on=20 ice (4=C2=BAC) or refrigerated immediately for = transportation to the=20 laboratory. Once the samples arrive in the laboratory, they = should=20 be stored either in a refrigerator at 4=C2=BAC or in a = -70=C2=BAC freezer. If=20 a -70=C2=BAC freezer is not available, they should be kept = refrigerated,=20 preferably for =E2=89=A41 week.

Specimens should be shipped on dry ice to the state = public health=20 laboratory in clearly labeled containers and should include = all=20 information requested by the state health laboratory.

State laboratories in the United States should will send = all=20 unsubtypable influenza A specimens to the CDC for further=20 testing.

Recommended=20 tests =E2=80=94 In the United States, the = recommended test=20 for suspected cases of swine H1N1 influenza A virus is = real-time=20 reverse transcriptase (RT)-PCR for influenza A, B, H1, and = H3 [19].=20 The strain of swine H1N1 influenza A virus associated with = the 2009=20 outbreak tests positive for influenza A and negative for H1 = and H3=20 by real-time RT-PCR. RT-PCR testing is generally performed = at a=20 state health department laboratory; confirmatory testing is=20 performed at the CDC. Case definitions of confirmed, = probable, and=20 suspected swine H1N1 influenza A virus infection are = discussed=20 below. (See=20 "Case definitions" belowSee=20 "Case definitions" below).

Other=20 tests =E2=80=94 Certain rapid influenza = antigen tests that=20 are commercially available can distinguish between influenza = A and B=20 viruses [19].=20 Thus, a patient with only influenza B virus infection would = not be=20 suspected of having swine H1N1 influenza A virus infection. = In=20 contrast, a patient with a positive rapid antigen test for = influenza=20 A may be considered a probable case if he or she meets the = other=20 criteria (see=20 "Case definitions" belowsee=20 "Case definitions" below). However, the sensitivity and=20 specificity of rapid antigen testing for swine H1N1 = influenza A=20 virus infection is unknown and poor sensitivity has already = been=20 demonstrated for seasonal influenza. A negative rapid = influenza test=20 does not exclude infection.

Direct of indirect immunofluorescent antibody testing = (DFA or=20 IFA) can distinguish between influenza A and B. Thus, a = patient with=20 a positive DFA or IFA may be considered a probable case if = he or she=20 meets the other criteria (see=20 "Case definitions" belowsee=20 "Case definitions" below). A negative DFA or IFA does = not=20 exclude swine H1N1 influenza A infection since these tests = have=20 unclear sensitivity to detect this virus.

Isolation of swine H1N1 influenza A virus using culture = is=20 diagnostic, but culture is usually too slow to help guide = clinical=20 management. A negative viral culture does not exclude swine = H1N1=20 influenza A infection.

The diagnostic tests for influenza are discussed in = greater=20 detail separately. (See "Clinical manifestations and diagnosis = of=20 influenza in adults" and see "Clinical features and diagnosis of = influenza in=20 children")

CASE=20 DEFINITIONS =E2=80=94 Definitions are = changing as we learn=20 more about this virus and the syndromes it causes. Updated=20 definitions can be found at the CDC's website (http://www.cdc.gov/swineflu/). Cases in = the United=20 States are confirmed by diagnostic testing at the Centers = for=20 Disease Control and Prevention [1,19,27].=20 (See=20 "Diagnosis" aboveSee=20 "Diagnosis" above).

The following current case definitions have been provided = by the=20 United States Centers for Disease and Prevention and are = current as=20 of April 29, 2009 [1,19,27]:

A confirmed case of swine H1N1 influenza A is defined = as an=20 individual with an acute febrile respiratory illness (a = measured=20 temperature of 37.8=C2=BAC [100.4=C2=BAF] and recent onset = of at least one=20 of the following: rhinorrhea or nasal congestion, sore = throat, or=20 cough) with laboratory-confirmed swine H1N1 influenza A = virus=20 detection by real-time reverse transcriptase (RT)-PCR or = culture.=20

A probable case of swine H1N1 influenza A is defined = as an=20 individual with an acute febrile respiratory illness who = is=20 positive for influenza A, but negative for H1 and H3 by = RT-PCR=20

A suspected case of swine H1N1 influenza A is defined = as an=20 individual with an acute febrile respiratory illness who: =

- Develops symptoms = within=20 seven days of close contact with a person who is a confirmed = case of=20 swine H1N1 influenza A virus infection or

- Develops symptoms = within=20 seven days of travel to a community either within the United = States=20 or internationally where there are one or more confirmed = swine H1N1=20 influenza A cases or

- Resides in a = community=20 where there are one or more confirmed swine H1N1 influenza A = cases=20 (See=20 "Epidemiology" above).

SUMMARY AND = RECOMMENDATIONS=20

2009 outbreak =

In late March and early April 2009, an outbreak of = swine H1N1=20 influenza A virus infection was detected in Mexico, with=20 subsequent cases observed in several other countries = including the=20 United States. (See=20 "Introduction" above and see=20 "Epidemiology" above).

The outbreak in the spring of 2009 was caused by an = H1N1 virus=20 that had not been recognized previously in pigs or humans. = This=20 strain represents a genetic reassortment of swine, human, = and=20 avian strains of influenza, and its origins are currently = unclear.=20 (See=20 "Virology" above).

Influenza virus can be transmitted through sneezing = and=20 coughing via large-particle aerosols, as well as by = contact with=20 surfaces that have been contaminated with respiratory = droplets.=20 (See=20 "Person-to-person transmission" above).

Patients with swine H1N1 influenza A virus infection = are=20 considered to be infectious from one day prior to the = development=20 of signs and symptoms until resolution of fever. = Individuals=20 should be considered contagious until seven days after = illness=20 onset. (See=20 "Shedding" above).

Although the incubation period has not been = established for=20 swine H1N1 influenza A infection, it could range from one = to seven=20 days, and most likely from one to four days. (See=20 "Incubation period" above).

Infection control and social distancing measures help = to limit=20 transmission of influenza viruses. (See "Treatment and prevention of swine = H1N1=20 influenza A", section on Infection control and section = on=20 Social distancing measures).

Clinical = manifestations

The signs and symptoms of swine H1N1 influenza A virus = infection are similar to those of seasonal influenza. = Typical=20 clinical manifestations include fever, headache, cough, = sore=20 throat, myalgias, chills, and fatigue. During the 2009 = outbreak,=20 rapidly progressive pneumonia, respiratory failure, and = acute=20 respiratory distress syndrome have been reported in some = cases.=20 (See=20 "Clinical manifestations" aboveSee=20 "Clinical manifestations" above).

Diagnosis =E2=80=94 Guidelines for the=20 diagnosis of swine H1N1 influenza A virus have been released = by the=20 United States Centers for Disease Control and Prevention = (CDC).=20 Updated recommendations can be found at the CDC's website = (http://www.cdc.gov/swineflu/).

The diagnosis of swine H1N1 influenza A virus = infection is=20 established either by real time reverse-transcriptase PCR = or viral=20 culture. Cases in the United States are confirmed by = diagnostic=20 testing at the Centers for Disease Control and Prevention. = (See=20 "Diagnosis" aboveSee=20 "Diagnosis" above).

In the United States, the recommended test for = suspected cases=20 is real-time reverse transcriptase (RT)-PCR for influenza = A, B,=20 H1, and H3, which is generally performed at a state health = department laboratory. (See=20 "Recommended tests" above).

When swine H1N1 influenza A virus is suspected, an = upper=20 respiratory sample (nasopharyngeal swab/aspirate or nasal=20 wash/aspirate) should be collected as soon as possible.=20 Appropriate swabs must be used and conditions observed for = optimal=20 specimen collection. (See=20 "Specimens" above).

Case definitions =

Case definitions of suspected, probable, and confirmed = swine=20 H1N1 influenza A virus infection are based on symptoms, = signs, and=20 epidemiologic information. (See=20 "Case definitions" aboveSee=20 "Case definitions" above).

Use of UpToDate is subject to the = Subscription and=20 License Agreement.

REFERENCES

United States Centers for Disease Control and=20 Prevention.Interim guidelines on antiviral recommendations = for=20 patients with confirmed or suspected swine influenza A = (H1N1)=20 virus infection and close contacts. = http://www.cdc.gov/swineflu=20 (Accessed April 29, 2009).=20
Myers, KP, Olsen, CW, Gray, GC. Cases of swine = influenza in=20 humans: a review of the literature. Clin Infect Dis 2007; = 44:1084.=20
World Health Organization. Swine influenza - update 3, = 27=20 April 2009.=20 http://www.who.int/csr/don/2009_04_27/en/index.html = (Accessed=20 April 27, 2009).=20
The New York Times. Mexico Limits Many Activities as = Flu=20 Alerts Are Increased.=20 = http://www.nytimes.com/2009/05/01/health/01flu.html?_r=3D1=20 & hp (Accessed April 30, 2009).=20
Smith, TF, Burgert, EO Jr, Dowdle, WR, et al. = Isolation of=20 swine influenza virus from autopsy lung tissue of man. N = Engl J=20 Med 1976; 294:708.=20
Gaydos, JC, Hodder, RA, Top, FH Jr, et al. Swine = influenza A=20 at Fort Dix, New Jersey (January-February 1976). I. Case = finding=20 and clinical study of cases. J Infect Dis 1977; 136 = Suppl:S356.=20
Gaydos, JC, Hodder, RA, Top, FH Jr, et al. Swine = influenza A=20 at Fort Dix, New Jersey (January-February 1976). II. = Transmission=20 and morbidity in units with cases. J Infect Dis 1977; 136=20 Suppl:S363.=20
World Health Organization. Swine flu illness in the = United=20 States and Mexico - update 2, 26 April 2009.=20 http://www.who.int/csr/don/2009_04_26/en/index.html = (Accessed=20 April 27, 2009).=20
World Health Organization. Influenza-like illness in = the=20 United States and Mexico, 24 April 2009.=20 http://www.who.int/csr/don/2009_04_24/en/index.html = (Accessed=20 April 27, 2009).=20
World Health Organization. Swine influenza - update 5, = 29=20 April 2009.=20 http://www.who.int/csr/don/2009_04_29/en/index.html = (Accessed=20 April 29, 2009).=20
Latin American Herald Tribune. Mexico Flu Deaths Rise = to 159.=20 http://www.laht.com/article.asp?ArticleId=3D333228 &=20 CategoryId=3D10718 (Accessed April 30, 2009).=20
United States Centers for Disease Control and = Prevention.=20 Swine influenza (flu). http://www.cdc.gov/swineflu/ = (Accessed=20 April 30, 2009).=20
Ito, T, Couceiro, JN, Kelm, S, et al. Molecular basis = for the=20 generation in pigs of influenza A viruses with pandemic = potential.=20 J Virol 1998; 72:7367.=20
Thacker, E, Janke, B. Swine influenza virus: zoonotic=20 potential and vaccination strategies for the control of = avian and=20 swine influenzas. J Infect Dis 2008; 197 Suppl 1:S19.=20
United States Centers for Disease Control and = Prevention. CDC=20 Briefing on Public Health Investigation of Human Cases of = Swine=20 Influenza, April 23, 2009.=20 http://www.cdc.gov/media/transcripts/2009/t090423.htm = (Accessed April 27, 2009).=20
United States Centers for Disease Control and = Prevention.=20 Interim Guidance for Clinicians on Identifying and Caring = for=20 Patients with Swine-origin Influenza A (H1N1) Virus = Infection=20 http://www.cdc.gov/swineflu/identifyingpatients.htm = (Accessed=20 April 29, 2009).=20
United States Centers for Disease Control and = Prevention.=20 Interim CDC Guidance for Nonpharmaceutical Community = Mitigation in=20 Response to Human Infections with Swine Influenza (H1N1) = Virus.=20 http://www.cdc.gov/swineflu/mitigation.htm (Accessed = April=20 27, 2009).=20
Update: Swine Influenza A (H1N1) infection--California = and=20 Texas, April 2009. MMWR Morb Mortal Wkly Rep 2009; 58:1.=20
United States Centers for Disease Control and = Prevention.=20 Interim Guidance on Specimen Collection and Processing for = Patients with Suspected Swine Influenza A (H1N1) Virus = Infection.=20 http://www.cdc.gov/swineflu/specimencollection.htm. = (Accessed=20 April 28, 2009).=20
United States Centers for Disease Control and = Prevention.=20 Interim Guidance on Case Definitions to be Used For = Investigations=20 of Swine Influenza A (H1N1) Cases.=20 http://www.cdc.gov/swineflu/casedef_swineflu.htm = (Accessed=20 April 27, 2009).=20
United States Centers for Disease Control and = Prevention.=20 Interim Guidance for Clinicians on the Prevention and = Treatment of=20 Swine-Origin Influenza Virus Infection in Young Children.=20 http://www.cdc.gov/swineflu/childrentreatment.htm = (Accessed=20 April 29, 2009).=20
United States Centers for Disease Control and = Prevention.=20 Interim Guidance =E2=80=94 Pregnant Women and Swine = Influenza:=20 Considerations for Clinicians.=20 http://www.cdc.gov/swineflu/clinician_pregnant.htm = (Accessed=20 April 29, 2009).=20
Patriarca, PA, Kendal, AP, Zakowski, PC, et al. Lack = of=20 significant person-to-person spread of swine = influenza-like virus=20 following fatal infection in an immunocompromised child. = Am J=20 Epidemiol 1984; 119:152.=20
McKinney, WP, Volkert, P, Kaufman, J. Fatal swine = influenza=20 pneumonia during late pregnancy. Arch Intern Med 1990; = 150:213.=20
Wentworth, DE, Thompson, BL, Xu, X, et al. An = influenza A=20 (H1N1) virus, closely related to swine influenza virus,=20 responsible for a fatal case of human influenza. J Virol = 1994;=20 68:2051.=20
Kimura, K, Adlakha, A, Simon, PM. Fatal case of swine=20 influenza virus in an immunocompetent host. Mayo Clin Proc = 1998;=20 73:243.=20
United States Centers for Disease Control and = Prevention.=20 Interim Guidance on Case Definitions to be Used For = Investigations=20 of Swine Influenza A (H1N1) Cases.=20 http://www.cdc.gov/swineflu/casedef_swineflu.htm = (Accessed=20 April 29, 2009).=20