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New Test Tells a Patient's Flu Type–and Subtype–in Minutes, Not Days

Dr. Kelly Henrickson
Dr. Kelly Henrickson.

Dr. Kelly Henrickson is a pediatric infectious disease specialist at the Children’s Hospital of Wisconsin, a Professor of Pediatrics and Microbiology, and the Director of the Midwest Respiratory Virus Program (MRVP) at the Medical College of Wisconsin. He is in charge of the molecular diagnostic laboratory at the MRVP, where he and his colleagues develop clinical diagnostic tests for respiratory viruses like influenza. It was here that Dr. Henrickson’s team developed a specific test that could not only diagnose influenza, but unlike other diagnostics, could also identify the type and subtype of the virus. This new test was in a late stage of development when the 2009 H1N1 influenza outbreak began in late April, and was quickly put to use at exactly the right time.

We spoke with Dr. Henrickson about his work and about the role his lab played in responding to the Milwaukee area’s 2009 H1N1 outbreak.

Question: How did you get started in respiratory disease research?

Answer: I’ve been focusing on molecular diagnostic research for most of my medical career. I started out at the University of Washington School of Medicine in Seattle, followed by fellowships in Molecular Virology and Clinical Infectious Disease at St. Jude Children’s Research Hospital. After training in Pediatrics at Strong Memorial Hospital at the University of Rochester New York, I started my professorship at the Medical College of Wisconsin. I also began working in a basic science lab, first studying paramyxoviruses then moving on to molecular diagnostic research at the MRVP.

Q: How did you get involved in diagnosing cases of H1N1?

A: My lab was in contact with our Wisconsin State Laboratory of Hygiene (WSLH) right away when we heard about the influenza outbreak. We knew there were many cases of this novel influenza virus circulating in the population and we had the capacity to help with diagnosis. The WSLH’s protocol to diagnose probable cases of H1N1 was to send the patients’ respiratory samples to the Centers for Disease Control and Prevention (CDC) in Atlanta and then wait about 10 days for results. But we had a fast and accurate test that was close to home, so we knew we could help with this process. The WSLH worked very quickly to validate our diagnostic assay and then announced that it was approved with 100% correlation with the CDC assays. By getting started so quickly, we diagnosed the first case of H1N1 in Milwaukee County and have reported about 44% of all pandemic H1N1 cases in Wisconsin since then.

Q: Why is your diagnostic test such an important contribution to influenza diagnosis?

A: My lab has developed a number of diagnostic assays with funding from both the National Institutes of Health (NIH) and the Centers for Diseases Control and Prevention (CDC). However, this test is different from other tests because it is a broad multiplex assay, or a test that can identify both an influenza virus itself, and also identify the type of influenza virus. Most tests can distinguish influenza viruses from other types of viruses, and differentiate between Type A and Type B influenza. Our assay was also able to tell the difference between human and animal viruses, and was able to tell that the neuraminidase (the ‘N’ part of H1N1) was of swine origin, therefore differentiating this virus from other strains of influenza that circulate seasonally and are of human origin. This is important because different types of influenza need to be treated differently; some may need different antiviral medications. It’s important to know what type of virus you’re dealing with before deciding the best way to care for the patient.

Q: How did you feel when you diagnosed the first case of H1N1 in Wisconsin? Were you worried that this could turn into a pandemic?

A: My first reaction was a sense of urgency to help the community. I knew we had the equipment and the knowledge to help the state of Wisconsin quickly determine whether this was a novel virus. For the first five weeks of the outbreak, we subtyped many samples at no charge to the patient because we knew how critical it was to assist in any way that we could. Subtyping was really important because there was also a human-origin influenza circulating in the population at the same time as this swine-origin virus, and these two different strains needed to be treated differently. I didn’t worry about how big or small the outbreak was, I tried to focus on the role my lab could play in order to be the most beneficial for the state of Wisconsin and the country.

Q: What lessons have you or the research community as a whole learned from this outbreak that could help in similar situations in the future?

A: I think we learned a major lesson in preparedness. Luckily, our diagnostic assay was ready to detect this H1N1 strain so we were almost immediately prepared to offer our services. Although a lot of good fortune was involved in the timing, the NIH also had the foresight to voice the need for a multiplex assay that could subtype many different strains of influenza. In situations like this H1N1 outbreak, it is easy to see why preparedness is so vital in the field of public health.

Our story also shows how forward-thinking the NIH has to be in order to really make a difference in science and medicine. Although it is not always obvious as to how certain research topics are relevant at the time, it is important to think about the future and try to plan for the unexpected outbreaks like this one.

Q: How has this experience changed your work?

A: Before the outbreak, we were working on creating a test that could diagnose animal influenza, which many people thought was an irrelevant activity. Then, when the outbreak started, we were suddenly in a different role – one of a major contributor to the public health response.

Part of creating a diagnostic test is to assess the ability of that test to perform, and there is no better way than to test a diagnostic assay under fire! We were able to continue our research goals by showing just how well this test could work in a real outbreak situation, so although our work was shifted into a higher gear, we were able to stay on track. This has been a very hectic time, but it has been a very positive and productive experience because we were able to combine our research with helping the community.

Q: If the outbreak continues in the fall, would you be willing do this all over again?

A: Yes, definitely. Our Midwest Respiratory Virus Program has its own clinical lab and we have established a relationship with the local hospitals over the last year. Collaboration between our lab and the children’s hospital, adult hospital, and a few other laboratories allowed us to diagnose 2009 H1N1 cases quickly and efficiently. Our lab’s relationship with the hospitals has been strengthened by this experience, so hopefully we will be even more prepared next time. This was a positive experience and if the state laboratories need my lab again, I will definitely be here to help. 

Q: What are you working on now?

A: We have about 2500 clinical samples of the virus, which is probably one of the largest collections in the world. There will be a lot of useful information that we can gather from these isolates, so we have a number of studies in progress. We recently published three papers that chronicle the first five weeks of the H1N1 outbreak in Milwaukee and also describe some of the assays we developed and used. We are also studying the pathogenesis of the disease and continue to investigate the genomics of the H1N1 virus. There are quite a few questions we’re asking in our research, and hopefully the answers will increase our understanding of this influenza strain. In turn, we hope the information that comes out of our studies will help the public health community plan for other outbreaks and pandemics, and help to better prevent and treat the disease.

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Last Updated October 26, 2009