Swine Influenza A (H1N1) Infection in Two Children --- = Southern=20 California, March--April 2009

On April 21, this report was posted as an MMWR Early = Release=20 on the MMWR website (http://www.cdc.gov/mmwr).

On April 17, 2009, CDC determined that two cases of febrile = respiratory=20 illness occurring in children who resided in adjacent counties in = southern=20 California were caused by infection with a swine influenza A = (H1N1) virus.=20 The viruses from the two cases are closely related genetically, = resistant=20 to amantadine and rimantadine, and contain a unique combination of = gene=20 segments that previously has not been reported among swine or = human=20 influenza viruses in the United States or elsewhere. Neither child = had=20 contact with pigs; the source of the infection is unknown. = Investigations=20 to identify the source of infection and to determine whether = additional=20 persons have been ill from infection with similar swine influenza = viruses=20 are ongoing. This report briefly describes the two cases and the=20 investigations currently under way. Although this is not a new = subtype of=20 influenza A in humans, concern exists that this new strain of = swine=20 influenza A (H1N1) is substantially different from human influenza = A=20 (H1N1) viruses, that a large proportion of the population might be = susceptible to infection, and that the seasonal influenza vaccine = H1N1=20 strain might not provide protection. The lack of known exposure to = pigs in=20 the two cases increases the possibility that human-to-human = transmission=20 of this new influenza virus has occurred. Clinicians should = consider=20 animal as well as seasonal influenza virus infections in their=20 differential diagnosis of patients who have febrile respiratory = illness=20 and who 1) live in San Diego and Imperial counties or 2) traveled = to these=20 counties or were in contact with ill persons from these counties = in the 7=20 days preceding their illness onset, or 3) had recent exposure to = pigs.=20 Clinicians who suspect swine influenza virus infections in a = patient=20 should obtain a respiratory specimen and contact their state or = local=20 health department to facilitate testing at a state public health=20 laboratory.

Case Reports

Patient A. On April 13, 2009, CDC was = notified=20 of a case of respiratory illness in a boy aged 10 years who lives = in San=20 Diego County, California. The patient had onset of fever, cough, = and=20 vomiting on March 30, 2009. He was taken to an outpatient clinic, = and a=20 nasopharyngeal swab was collected for testing as part of a = clinical study.=20 The boy received symptomatic treatment, and all his symptoms = resolved=20 uneventfully within approximately 1 week. The child had not = received=20 influenza vaccine during this influenza season. Initial testing at = the=20 clinic using an investigational diagnostic device identified an = influenza=20 A virus, but the test was negative for human influenza subtypes = H1N1,=20 H3N2, and H5N1. The San Diego County Health Department was = notified, and=20 per protocol, the specimen was sent for further confirmatory = testing to=20 reference laboratories, where the sample was verified to be an=20 unsubtypable influenza A strain. On April 14, 2009, CDC received = clinical=20 specimens and determined that the virus was swine influenza A = (H1N1). The=20 boy and his family reported that the child had had no exposure to = pigs.=20 Investigation of potential animal exposures among the boy's = contacts is=20 continuing. The patient's mother had respiratory symptoms without = fever in=20 the first few days of April 2009, and a brother aged 8 years had a = respiratory illness 2 weeks before illness onset in the patient = and had a=20 second illness with cough, fever, and rhinorrhea on April 11, = 2009.=20 However, no respiratory specimens were collected from either the = mother or=20 brother during their acute illnesses. = Public=20 health officials are conducting case and contact investigations to = determine whether illness has occurred among other relatives and = contacts=20 in California, and during the family's travel to Texas on April 3, = 2009.

Patient B. CDC received an influenza = specimen=20 on April 17, 2009, that had been forwarded as an unsubtypable = influenza A=20 virus from the Naval Health Research Center in San Diego, = California. CDC=20 identified this specimen as a swine influenza A (H1N1) virus on = April 17,=20 2009, and notified the California Department of Public Health. The = source=20 of the specimen, patient B, is a girl aged 9 years who resides in = Imperial=20 County, California, adjacent to San Diego County. On March 28, = 2009, she=20 had onset of cough and fever (104.3=C2=B0F [40.2=C2=B0C]). She was = taken to an=20 outpatient facility that was participating in an influenza = surveillance=20 project, treated with amoxicillin/clavulanate potassium and an=20 antihistamine, and has since recovered uneventfully. The child had = not=20 received influenza vaccine during this influenza season. The = patient and=20 her parents reported no exposure to pigs, although the girl did = attend an=20 agricultural fair where pigs were exhibited approximately 4 weeks = before=20 illness onset. She reported that she did not see pigs at the fair = and went=20 only to the amusement section of the fair. The Imperial County = Public=20 Health Department and the California Department of Public Health = are now=20 conducting an investigation to determine possible sources of = infection and=20 to identify any additional human cases. The patient's brother aged = 13=20 years had influenza-like symptoms on April 1, 2009, and a male = cousin aged=20 13 years living in the home had influenza-like symptoms on March = 25, 2009,=20 3 days before onset of the patient's symptoms. The brother and = cousin were=20 not tested for influenza at the time of their illnesses.

Epidemiologic and = Laboratory=20 Investigations

As of April 21, 2009, no epidemiologic link between patients A = and B=20 had been identified, and no additional cases of infection with the = identified strain of swine influenza A (H1N1) had been identified. = Surveillance data from Imperial and San Diego counties, and from=20 California overall, showed declining influenza activity at the = time of the=20 two patients' illnesses. Case and contact investigations by the = county and=20 state departments of health in California and Texas are ongoing. = Enhanced=20 surveillance for possible additional cases is being implemented in = the=20 area.

Preliminary genetic characterization of the influenza viruses = has=20 identified them as swine influenza A (H1N1) viruses. The viruses = are=20 similar to each other, and the majority of their genes, including = the=20 hemagglutinin (HA) gene, are similar to those of swine influenza = viruses=20 that have circulated among U.S. pigs since approximately 1999; = however,=20 two genes coding for the neuraminidase (NA) and matrix (M) = proteins are=20 similar to corresponding genes of swine influenza viruses of the = Eurasian=20 lineage (1). This particular genetic combination of swine = influenza=20 virus segments has not been recognized previously among swine or = human=20 isolates in the United States, or elsewhere based on analyses of = influenza=20 genomic sequences available on GenBank.*=20 Viruses with this combination of genes are not known to be = circulating=20 among swine in the United States; however, no formal national = surveillance=20 system exists to determine what viruses are prevalent in the U.S. = swine=20 population. Recent collaboration between the U.S. Department of=20 Agriculture and CDC has led to development of a pilot swine = influenza=20 virus surveillance program to better understand the epidemiology = and=20 ecology of swine influenza virus infections in swine and = humans.

The viruses in these two patients demonstrate antiviral=20 resistance to amantadine and rimantadine, and testing to determine = susceptibility to the neuraminidase inhibitor drugs oseltamivir = and=20 zanamivir is under way. Because these viruses carry a unique = combination=20 of genes, no information currently is available regarding the = efficiency=20 of transmission in swine or in humans. Investigations to = understand=20 transmission of this virus are ongoing.

Reported by: M Ginsberg, MD, J Hopkins, = MPH, A=20 Maroufi, MPH, G Dunne, DVM, DR Sunega, J Giessick, P McVay, MD, = San Diego=20 County Health and Human Svcs; K Lopez, MD, P Kriner, MPH, K Lopez, = S=20 Munday, MD, Imperial County Public Health Dept; K Harriman, = PhD, B=20 Sun, DVM, G Chavez, MD, D Hatch, MD, R Schechter, MD, D Vugia, MD, = J=20 Louie, MD, California Dept of Public Health. W Chung, MD, Dallas = County=20 Health and Human Svcs; N Pascoe, S Penfield, MD, J Zoretic, MD, V = Fonseca,=20 MD, Texas Dept of State Health Svcs. P Blair, PhD, D Faix, PhD, = Naval=20 Health Research Center; J Tueller, MD, Navy Medical Center, San = Diego,=20 California. T Gomez, DVM, Animal and Plant Health Inspection Svc, = US Dept=20 of Agriculture. F Averhoff, MD, F Alavrado-Ramy, MD, S Waterman, = MD, J=20 Neatherlin, MPH, Div of Global Migration and Quarantine; L = Finelli, DrPH,=20 S Jain, MD, L Brammer, MPH, J Bresee, MD, C Bridges, MD, S Doshi, = MD, R=20 Donis, PhD, R Garten, PhD, J Katz, PhD, S Klimov, PhD, D Jernigan, = MD, S=20 Lindstrom, PhD, B Shu, MD, T Uyeki, MD, X Xu, MD, N Cox, PhD, = Influenza=20 Div, National Center for Infectious and Respiratory Diseases, = CDC.

Editorial Note:

In the past, CDC has received reports of approximately one = human swine=20 influenza virus infection every 1--2 years in the United States=20 (2,3). However, during December=20 2005--January 2009, 12 cases of human infection with swine = influenza were=20 reported; five of these 12 cases occurred in patients who had = direct=20 exposure to pigs, six in patients reported being near pigs, and = the=20 exposure in one case was unknown (1,4,5). In the United = States,=20 novel influenza A virus infections in humans, including swine = influenza=20 infections, have been nationally notifiable conditions since 2007. = The=20 recent increased reporting might be, in part, a result of = increased=20 influenza testing capabilities in public health laboratories, but = genetic=20 changes in swine influenza viruses and other factors also might be = a=20 factor (1,4,5). Although the vast majority of human = infections with=20 animal influenza viruses do not result in human-to-human = transmission=20 (2,3), each case should be fully investigated to be certain = that=20 such viruses are not spreading among humans and to limit further = exposure=20 of humans to infected animals, if infected animals are identified. = Such=20 investigations should include close collaboration between state = and local=20 public health officials with animal health officials.

The lack of known exposure to pigs in the two cases described = in this=20 report increases the possibility that human-to-human transmission = of this=20 new influenza virus has occurred. Clinicians should consider = animal as=20 well as seasonal influenza virus infections in the differential = diagnosis=20 of patients with febrile respiratory illness who live in San Diego = and=20 Imperial counties or have traveled to these areas or been in = contact with=20 ill persons from these areas in the 7 days before their illness = onset. In=20 addition, clinicians should consider animal influenza infections = among=20 persons with febrile respiratory illness who have been near pigs, = such as=20 attending fairs or other places where pigs might be displayed. = Clinicians=20 who suspect swine influenza virus infections in humans should = obtain a=20 nasopharyngeal swab from the patient, place the swab in a viral = transport=20 medium, and contact their state or local health department to = facilitate=20 transport and timely diagnosis at a state public health = laboratory. CDC=20 requests that state public health laboratories send all influenza = A=20 specimens that cannot be subtyped to the CDC, Influenza Division, = Virus=20 Surveillance and Diagnostics Branch Laboratory.

Interim guidance on infection control, treatment, and = chemoprophylaxis=20 for swine influenza is available at http://www.cdc.= gov/flu/swine/recommendations.htm.=20 Additional information about swine influenza is available at http://www.cdc.gov/flu/sw= ine/index.htm.

References

Vincent AL, Ma W, Lager KM, Janke BH, Richt JA. Swine = influenza=20 viruses: a North American perspective. Adv Virus Res = 2008;72:127--54.=20
Myers KP, Olsen CW, Gray GC. Cases of swine influenza in = humans: a=20 review of the literature. Clin Infect Dis 2007;44:1084--8.=20
Wells DL, Hopfensperger DJ, Arden NH, et al. Swine influenza = virus=20 infections. Transmission from ill pigs to humans at a Wisconsin=20 agricultural fair and subsequent probable person-to-person = transmission.=20 JAMA 1991;265:478--81.=20
Vincent AL, Swenson SL, Lager KM, Gauger PC, Loiacono C, = Zhang Y.=20 Characterization of an influenza A virus isolated from pigs = during an=20 outbreak of respiratory disease in swine and people during a = county fair=20 in the United States. Vet Microbiol 2009;online publication = ahead of=20 print.=20
Newman AP, Reisdorf E, Beinemann J, et al. Human case of = swine=20 influenza A (H1N1) triple reassortant virus infection, = Wisconsin. Emerg Infect Dis 2008;14:1470--2.

* Available at http://www.ncbi.nlm.nih.gov/= Genbank.

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Date last=20 reviewed: 4/22/2009