N Engl J Med. Emergence of a Novel Swine-Origin Influenza A (H1N1) Virus in Humans.

[Giuseppe]

NEJM -- Emergence of a Novel Swine-Origin Influenza A (H1N1) Virus in Humans

Published at www.nejm.org May 7, 2009 (10.1056/NEJMoa0903810)

Emergence of a Novel Swine-Origin Influenza A (H1N1) Virus in Humans

Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team


ABSTRACT

Background
On April 15 and April 17, 2009, novel swine-origin influenza A (H1N1) virus (S-OIV) was identified in specimens obtained from two epidemiologically unlinked patients in the United States. The same strain of the virus was identified in Mexico, Canada, and elsewhere. We describe 642 confirmed cases of human S-OIV infection identified from the rapidly evolving U.S. outbreak.

Methods
Enhanced surveillance was implemented in the United States for human infection with influenza A viruses that could not be subtyped. Specimens were sent to the Centers for Disease Control and Prevention for real-time reverse-transcriptase?polymerase-chain-reaction confirmatory testing for S-OIV.

Results
From April 15 through May 5, a total of 642 confirmed cases of S-OIV infection were identified in 41 states. The ages of patients ranged from 3 months to 81 years; 60% of patients were 18 years of age or younger. Of patients with available data, 18% had recently traveled to Mexico, and 16% were identified from school outbreaks of S-OIV infection. The most common presenting symptoms were fever (94% of patients), cough (92%), and sore throat (66%); 25% of patients had diarrhea, and 25% had vomiting. Of the 399 patients for whom hospitalization status was known, 36 (9%) required hospitalization. Of 22 hospitalized patients with available data, 12 had characteristics that conferred an increased risk of severe seasonal influenza, 11 had pneumonia, 8 required admission to an intensive care unit, 4 had respiratory failure, and 2 died. The S-OIV was determined to have a unique genome composition that had not been identified previously.

Conclusions
A novel swine-origin influenza A virus was identified as the cause of outbreaks of febrile respiratory infection ranging from self-limited to severe illness. It is likely that the number of confirmed cases underestimates the number of cases that have occurred.
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<cite cite="http://content.nejm.org/cgi/content/full/NEJMoa0903810?query=TOC">NEJM -- Emergence of a Novel Swine-Origin Influenza A (H1N1) Virus in Humans</cite>

 

[sharon sanders]

Re: N Engl J Med. Emergence of a Novel Swine-Origin Influenza A (H1N1) Virus in Humans.

Continued identification of new cases in the United States andelsewhere indicates sustained human-to-human transmission ofthis novel influenza A virus. The modes of transmission of influenzaviruses in humans, including S-OIV, are not known but are thoughtto occur mainly through the dissemination of large dropletsand possibly small-particle droplet nuclei⁸ expelled when aninfected person coughs.



There is also potential for transmissionthrough contact with fomites that are contaminated with respiratoryor gastrointestinal material.⁹^,¹⁰ Since many patients with S-OIVinfection have had diarrhea, the potential for fecal viral sheddingand subsequent fecal?oral transmission should be consideredand investigated. Until further data are available, all potentialroutes of transmission and sources of viral shedding shouldbe considered.

The incubation period for S-OIV infection appears to range from2 to 7 days; however, additional information is needed. On thebasis of data regarding viral shedding from studies of seasonalinfluenza, most patients with S-OIV infection might shed virusfrom 1 day before the onset of symptoms through 5 to 7 daysafter the onset of symptoms or until symptoms resolve; in youngchildren and in immunocompromised or severely ill patients,the infectious period might be longer.¹¹ Studies of viral sheddingto define the infectious period are under way. The potentialfor persons with asymptomatic infection to be the source ofinfection to others is unknown but should be investigated.


The clinical spectrum of novel S-OIV infection is still beingdefined, but both self-limited illness and severe outcomes,including respiratory failure and death, have been observedamong identified patients ? a wide clinical spectrum similarto that seen among persons infected with earlier strains ofswine-origin influenza viruses³ and seasonal influenza viruses.¹²The severe illness and deaths associated with seasonal influenzaepidemics are in large part the result of secondary complications,including primary viral pneumonia, secondary bacterial pneumonia(particularly with group A streptococcus, Staphylococcus aureus,and Streptococcus pneumoniae),¹³^,¹⁴^,¹⁵ and exacerbations ofunderlying chronic conditions.¹⁶ These same complications mayoccur with S-OIV infection.



Patients who are at highest riskfor severe complications of S-OIV infection are likely to includebut may not be limited to groups at highest risk for severeseasonal influenza: children under the age of 5 years, adults65 years of age or older, children and adults of any age withunderlying chronic medical conditions, and pregnant women.¹⁷^,¹⁸Of the 22 hospitalized patients with confirmed S-OIV infectionwho have been identified thus far and for whom data are available,12 had characteristics (pregnancy, chronic medical conditions,or an age of less than 5 years) that conferred an increasedrisk of severe seasonal influenza, although none of the patientswere 65 years of age or older.


Human infection with novel S-OIV emerged in the United Statesat a time when seasonal influenza A and B virus activity wasdecreasing. The cocirculation of human influenza A (H1N1) virus,influenza A (H3N2) virus, or influenza B virus in areas wherehuman cases of S-OIV infection are being identified presentsdiagnostic and treatment challenges for clinicians.


Cliniciansshould consider the diagnosis of S-OIV infection in patientswith febrile respiratory illness seeking care in affected areasor in those who have traveled to affected areas. The CDC hasdeveloped a Swine Influenza Virus Real-Time RT-PCR DetectionPanel. Under the Project Bioshield Act of 2004, the FDA hasissued an emergency-use authorization, allowing for the useof this assay by state public health laboratories to respondto the current outbreak.¹⁹ If S-OIV infection is suspected anddiagnostic testing is indicated, clinicians should obtain anasopharyngeal specimen, notify their local public health department,and arrange for specimens to be tested for S-OIV by Swine InfluenzaVirus Real-Time RT-PCR Detection Panel, according to local andstate public health guidance and after consideration of locallaboratory capacity for diagnostic testing.


Two classes of antiviral medication are available for the treatmentof seasonal human influenza: neuraminidase inhibitors (oseltamivirand zanamivir) and adamantanes (rimantadine and amantadine).During the 2008?2009 influenza season, almost all circulatinghuman influenza A (H1N1) viruses in the United States were resistantto oseltamivir.²⁰ However, genetic and phenotypic analyses indicatethat S-OIV is susceptible to oseltamivir and zanamivir but resistantto the adamantanes.²¹ At this time, the clinical effectivenessof antiviral treatment of S-OIV is unknown. As of May 5, 2009,the CDC has recommended that given the severity of illness observedamong some patients with S-OIV infection, therapy with neuraminidaseinhibitors should be prioritized for hospitalized patients withsuspected or confirmed S-OIV infection and for patients whoare at high risk for complications from seasonal influenza.As recommendations are updated, they will be posted on the CDC'sWeb site at www.cdc.gov/h1n1flu/recommendations.htm. The FDAhas issued an emergency-use authorization that approves theuse of oseltamivir to treat influenza in infants under the ageof 1 year (treatment that is normally approved for those 1 yearof age or older) and for chemoprophylaxis in infants older than3 months of age (chemoprophylaxis that is normally approvedfor children 1 year of age or older).¹⁹

Prevention and control measures for S-OIV are based on our understandingof seasonal human influenza²² and consideration of potentialmodes of transmission.


As of May 5, 2009, the CDC has recommendedthat health care workers who provide direct care for patientswith known or suspected S-OIV infection should observe contactand droplet precautions, including the use of gowns, gloves,eye protection, face masks, and fit-tested, disposable N95 respirators.



In addition, patients with confirmed or suspected S-OIV infectionshould be placed in a single-patient room with the door keptclosed, and airborne-infection isolation rooms with negative-pressurehandling should be used whenever an aerosol-generating procedureis being performed.


Frequent hand washing with soap and watermay reduce the risk of infection and transmission.²³



As recommendationsare updated, they will be posted at www.cdc.gov/h1n1flu/guidelines_infection_control.htm.Because the novel S-OIV strain is antigenically distinct fromthe influenza A (H1N1) strain represented in the 2008?2009influenza vaccine, seasonal influenza vaccination during the2008?2009 influenza season is not anticipated to provideprotection against novel S-OIV infection. A strain of S-OIVhas been identified as a potential egg-derived candidate strainfor S-OIV vaccine development and has been sent to partner laboratoriesfor evaluation and further development.


Given the rapidly evolving nature of this outbreak, the CDC'srecommendations are likely to change as more information becomesavailable. Clinicians are advised to monitor the H1N1 Influenza Center(NEJM.org) and the CDC Web site (www.cdc.gov/h1n1flu/) for changesin guidance for testing, treatment, and infection control.


In conclusion, we report an outbreak of human infection witha novel influenza A (H1N1) virus of swine origin in the UnitedStates, which is spreading through sustained human-to-humantransmission in multiple countries. The identification of humanS-OIV infection in geographically dispersed countries and acrosscontinents demonstrates the ease with which infection can bespread and facilitated by air and land travel and communitynetworks and gatherings. As enhanced surveillance for S-OIVinfection is implemented globally, additional cases are expectedto be identified. The cases of infection with S-OIV describedin this report may provide guidance for clinicians with respectto presenting symptoms and outcomes of infection with this novelvirus.