SAN DIEGO, CALIFORNIA—Late on the afternoon of 16 April, 5 days before the public first learned about the current outbreak of swine flu, Michele Ginsberg received word from the U.S. Centers for Disease Control and Prevention (CDC) that a 10-year-old boy in San Diego County had tested positive for the rare infection. “I thought this could be the big one, honestly,” says Ginsberg, chief of community epidemiology for the San Diego County Health & Human Services Agency. By “big one,” Ginsberg meant the long-anticipated arrival of a new strain of influenza that humans had not seen before and could completely overwhelm the immune system, vaccinated or not.
Ginsberg says the first two cases that surfaced easily could have been missed, but novel research projects under way in the San Diego area, both connected to the Naval Health Research Center (NHRC) here, determined that something unusual was afoot. NHRC has developed sophisticated tests for influenza that can sort out whether the virus is strain A or B and then the specific subtype based on two proteins, hemagglutinin and neuraminidase, on the viral surface. “In the usual setting, they would have done a rapid test and found that they were both positive for influenza A, and that’s as far as it would have gone,” says Ginsberg. But the new tests couldn't identify the specific subtype, so the Navy forwarded the samples to CDC.
NHRC has received little attention for its critical role in uncovering the U.S. outbreak with what’s known as an H1N1 influenza A virus, so ScienceInsider asked for a detailed explanation of its influenza program and how these two cases came its way.
Answers after the jump.
Q: When did the NHRC increase its surveillance capabilities for influenza?
Our expansion was largely a result of an initiative by the Department of Defense’s (DOD's) Global Emerging Infectious System to intensify pandemic surveillance as a result of the avian influenza (H5N1) crisis. NHRC augmented existing febrile respiratory illness surveillance programs in military recruit trainees and ship-board populations and expanded into dependent populations in San Diego. Also, in a collaborative effort with the CDC, we developed surveillance on the Southern California-Mexico border, which was enhanced this year to deepen surveillance and augment diagnostic training of our Mexican collaborators via funding from the Department of State’s Biosecurity Engagement Program.
Q. How did these swine flu cases end up at NHRC?
The first case, a 10-year-old DOD dependent, was identified in a trial to evaluate a novel influenza diagnostic. On 1 April, a swab sample from the patient was tested on the diagnostic platform. The result suggested an influenza A but subtype negative virus. Our screening questionnaire deemed the patient at low-risk for an avian influenza infection. Per the study protocol, a second specimen was sent to a third-party lab in Wisconsin. This laboratory, along with the state laboratory, confirmed the influenza A/un-typed finding. The specimen and an isolated virus were then sent to the CDC for confirmation. The CDC determined the virus was an influenza A/swine/H1N1.
The second case, a 9-year-old female from Brawley, California, was sampled in the collaborative study with the CDC’s Border Infectious Disease Surveillance Project. What was thought to be a routine specimen was sent to our laboratory the first week in April. Our initial testing demonstrated an influenza A/untyped virus. Further testing on the Ibis T5000 platform, which infers H and N types from multiple genomic signatures, suggested an influenza A/swine/H1 virus. [Although most tests rely on known DNA sequence or antibodies to identify influenza isolates, the Ibis T5000 has a mass spectrometer and can identify unknown subtypes.] This was right about the time we received word from CDC about the first case. At that point we knew we were onto something significant. The CDC subsequently confirmed an influenza A/swine/H1N1 virus.
Q: What was the reaction of the researchers at NHRC?
The evasive nature of influenza viruses keeps us on our toes. Because of the obvious public health concern, we found it prudent to send the sample to CDC for confirmation.
Q: How many influenza specimens does NHRC process during flu season and has it increased since the discovery of this swine flu case?
NHRC regularly processes around 5500 specimens a year, about two-thirds of which come in during the influenza season from October to February. Normally, towards the end of the flu season, the number of specimens we process each week falls. In the 2008-2009 season, cases began to decrease in late January. This decline continued until last week when the number of cases and the sampling effort among our civilian populations was increased.
Q: Had you ever had specimens before that you could not type and sent to CDC?
This was the first.
Q: Does NHRC do surveillance only for San Diego County or for a larger area?
Our surveillance is quite expansive. NHRC is the Navy hub for the conduct of population-based surveillance at recruit centers involving the Army, Navy, Air Force, Marine Corps and Coast Guard. We also conduct surveillance onboard 20 large-deck U.S. Navy ships in three fleets, within the Pacific Rim, among deployed populations and of course along the U.S./Mexico border. We participate in surveillance during military exercises such as Cobra Gold, in Thailand, and also collaborate in febrile respiratory infection surveillance with the Singaporean military.
Q: Do you now have the capability to identify this strain of swine flu or must samples still be sent to the CDC?
We hope to have the reagents for the swine variant soon. We are in the process of developing our own reagents. At this time we can use advanced diagnostics such as the Ibis T5000 to detect swine viruses. That stated, it is important to share novel specimens with the CDC for the purpose of public health. Both institutes gain from this collaboration.