Emergence of a Novel Swine-Origin Influenza A (H1N1) Virus in Humans
N Engl J Med
vol. 361, ePub - ahead of print, 2009
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.
Commentary
= Top Article
Articles that are within the top 10% of all articles published annually and are of critical importance to physicians. These articles will have a lasting impact on medical practice.
C: Evidence that is in the form of a consensus viewpoint or expert opinion.
Global swine influenza A (H1N1) outbreak, Spring 2009. Around mid-April 2009, the United States Centers for Disease Control and Prevention (CDC) identified a novel strain of swine influenza virus (H1N1) in respiratory specimens obtained from 2 separate individuals in San Diego County, California. In the following weeks, this new strain of swine-origin influenza virus (S-OIV) rapidly spread through Mexico, forcing the Government of Mexico to close schools, and disrupting usual businesses. As the epidemic started spreading in the United States, the federal government announced a public health emergency, and the World Health Organization (WHO) raised their pandemic influenza alert to level 5.
A timely article published by the CDC's Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team gives a very nice summary of how this investigation was initiated, and how the epidemic was traced electronically during the initial 3 weeks. They analyzed data obtained from 642 cases confirmed by real-time RT-PCR (reverse transcriptase PCR), which showed that most of the infections occurred in children and adolescents below 18 years old. The clinical features were similar to the regular seasonal influenza A infection, including fever, cough, and sore throat, but about 25% of patients also reported vomiting and diarrhea. Hospital admission was necessary in only 9% of confirmed cases who had severe influenza, pneumonia, or respiratory failure. Death occurred in only 2 of the 642 confirmed cases—1 child with myasthenia gravis and 1 pregnant female. Although much higher morbidity and mortality were reported from Mexico, these data for United States patients do not seem to be in excess of what is expected during a regular influenza season.
The other interesting aspect of this article is the work by the group on the nucleotide sequencing and phylogenetic analysis of this novel strain of swine influenza A virus, named as A/California/04/2009. Their analyses showed that this virus is closely related to the triple-reassortant influenza A (H1) virus (human, swine, and avian influenza), which was first identified in 1998, and 12 cases were identified by CDC between 2005 and 2009. The novel S-OIV (A/California/04/2009) also showed genetic homology with Eurasian lineage and North American swine influenza viruses, indicating that a probable triple-reassortment may have occurred again.
The authors also performed genetic and phenotypic analyses, which indicated that the virus was susceptible only to the neuraminidase inhibitors (oseltamivir and zanamivir), but resistant to the adamantanes (amantadine and rimantadine).
As of May 13, 2009, WHO reported 5728 laboratory confirmed cases in 33 countries and 56 deaths, including 3009 cases and 3 deaths in the United States. Although the epidemic appears to be milder at present, based on the experience of 1918 swine flu pandemic, it is important to be prepared for a possible second wave with more severe morbidity and mortality in the fall and winter of 2009.
