Swine flu: more on the cases

Late yesterday The New England Journal of Medicine published a number of papers on the recent swine flu outbreak. The first paper, "Emergence of a Novel Swine-Origin Influenza A (H1N1) Virus in Humans" by large federal-state team of epidemiologists describes 642 confirmed cases in 41 states as of May 5, 2009, two days before publication. What I find remarkable is the speed the problem was recognized -- literally days. Identification of the virus was first made in the CDC laboratory on April 15, just 3 weeks ago. Now we are already reading scientific papers providing a wealth of detail.

Among those details is a fuller account of the two epidemiologically unlinked US index cases, first reported in MMWR on April 21 and the subject of a post here shortly thereafter. This was just before it was determined the same virus was circulating in Mexico and causing substantial morbidity and worrying mortality:

On March 30, 2009, in San Diego County, California, a 10-year-old boy with asthma (Patient 1) had an onset of fever, cough, and vomiting. On April 1, he was evaluated in an urgent care clinic, where he received treatment for his symptoms. He recovered from the illness within approximately 1 week. An influenza A virus that could not be sub-typed was identified from a nasopharyngeal specimen that was collected from Patient 1 as part of a clinical trial to evaluate an experimental diagnostic test. As specified by the study protocol, the specimen was then sent to a reference laboratory for further testing and was found to be positive for influenza A virus but negative for both human H1 and H3 subtypes, with the use of real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing. On April 15, the CDC received the clinical specimen and identified a novel influenza A (H1N1) virus of swine origin. On the same day, the CDC notified the California Department of Public Health, and an epidemiologic investigation was initiated by state and local health department officials and animal health officials. A viral isolate was found to contain genes from triple-reassortant swine influenza viruses that were known to circulate among swine herds in North America and two genes encoding the neuraminidase and matrix proteins that were most closely related to genes of viruses obtained from ill pigs in Eurasia, according to results available in GenBank.

On March 28, 2009, in Imperial County, California, a 9-year-old girl (Patient 2) without an epidemiologic link to Patient 1 had an onset of cough and fever. Two days later, she was taken to an outpatient clinic that was participating in an influenza surveillance project. A nasopharyngeal swab was collected at the clinic. Patient 2 was treated with amoxicillin-clavulanate, and she had an uneventful recovery. The nasopharyngeal specimen was sent to the Naval Health Research Center in San Diego, where an influenza A virus that could not be subtyped was identified. The specimen was shipped to the CDC, where it was received on April 17, and a novel influenza A (H1N1) virus of swine origin was identified. The genotype of the virus was similar to that of the virus isolated from the sample obtained from Patient 1. On April 17, both cases were reported to the World Health Organization (WHO), according to the provisions of the International Health Regulations.

Epidemiologic investigation of Patients 1 and 2 revealed that neither patient had a recent history of exposure to swine. According to protocol, the identification of these two epidemiologically unlinked patients with novel S-OIV infection prompted the CDC to notify state and local health departments, which initiated case investigations and implemented enhanced surveillance for influenza A viruses that could not be subtyped. The CDC issued recommendations to clinicians, asking that they consider the diagnosis of S-OIV infection in patients with an acute febrile respiratory illness who met the following criteria: residence in an area where confirmed cases of human infection with S-OIV had been identified, a history of travel to such areas, or contact with ill persons from these areas in the 7 days before the onset of illness. If S-OIV infection was suspected in a patient, clinicians were asked to obtain a nasopharyngeal swab from the patient and to contact their state and local health departments in order to facilitate initial testing of the specimen by RT-PCR assay at the state public health laboratory. State public health laboratories were asked to send all specimens identified as influenza A viruses that could not be subtyped to the CDC for further investigation. Additional cases were identified with the use of a nationally standardized case definition of confirmed swine influenza A (H1N1) virus infection, which was defined as an acute febrile respiratory illness with the presence of S-OIV confirmed by real-time RT-PCR, viral culture, or both. (Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team, New England Journal of Medicine)

There were some lucky breaks in all this, including the enhanced surveillance in the border area, the evaluation of a new diagnostic test, and the fact that CDC had recently prepared PCR primers for swine influenza requiring only minor modification to identify the new strain. While both children recovered uneventfully, it is clear patient 1 was a pretty sick little boy. 60% of the cases reported in this paper were under 18 years of age. 18% had recently traveled to Mexico, although in yesterday's CDC briefing it was said that the travel associated cases are now only 10% of the US total as sustained person to person transmission begins to take hold on US soil. The most common presenting symptom was fever (94%) followed by cough (92%) and sore throat (66%). Unusually for respiratory influenza, 25% had diarrhea and 25% vomiting.

Hospitalization status was known for 399 of the cases and amounted to 36 in the series (it has since increased). While this 9% prevalence is high, it is likely that more serious cases were preferentially tested, so we have yet to get a good fix on the severity of illness caused by this virus. Sufficient information on 22 hospitalized patients showed that 12, or about half, had underlying medical conditions that might have increased risk, but half did not, that is, they were previously healthy individuals, many of them young. There were 11 cases of pneumonia among the hospitalized. 8 wound up in intensive care, 4 had respiratory failure and 2 died.

All of these things happen with seasonal influenza, too, so it doesn't mean this is an especially virulent version of flu. It may well qualify for the much used term, "mild," in that regard, because real seasonal influenza is an inherently nasty illness.

But for these patients, half of them previously healthy and on average quite young, "mild" won't cut it as a description of what they went through. Something to keep in mind.