Jay M. Lieberman, MD

By Kurt Woock

Jay M. Lieberman, MD, an expert in infectious diseases and emerging infectious diseases, is medical director of infectious diseases for Quest Diagnostics, Madison, NJ, and medical and laboratory director for Focus Diagnostics. He is based at the Focus Diagnostics’ laboratory in Cypress, Calif. Focus Diagnostics provides the majority of test kits for West Nile virus in the United States, and was the first laboratory company to introduce testing services in the United States for a number of emerging infectious diseases, such as West Nile virus, chikungunya virus, and SARS. Focus Diagnostics also launched the first commercial H1N1 flu test in the United States. CLP spoke with him about the West Nile virus outbreak.

CLP: Please update us on the latest stats from the Centers for Disease Control and Prevention (CDC) on the West Nile virus outbreak.
Jay M. Lieberman, MD: Everyone was caught by surprise by the magnitude of the West Nile virus outbreak this summer. West Nile virus emerged in the United States in 1999 in New York and over the next few years, there was a very clear spread to the south and the west. By 2002-2003, West Nile had caused the largest arboviral encephalitis outbreaks in the history of the United States. Then, things seemed to have subsided somewhat. Cases continued to occur every year, but the magnitude had dramatically lessened. A lot of that was attributed to strong public health and vector control measures.

There are a couple things that have happened to make West Nile virus a major area of health concern this year. First, there’s been a clear increase in the number of West Nile virus infections. Most neuroinvasive cases, such as encephalitis and meningitis, get diagnosed because the clinical presentation is so clear-cut. Clinicians are used to looking for West Nile. Then, with the media attention, you start seeing more cases diagnosed, including atypical neurologic cases and nonneurologic cases, and public health increases surveillance of birds, mosquitoes, etc. It wouldn’t be surprising for cases to continue to rise in the next few weeks, some of which would be a consequence of more testing. To see what’s really happening, look at the neuroinvasive cases, which show the real impact the virus is having in people.

On September 12, the CDC provided an update on this year’s outbreak. A total of 2,636 cases of West Nile virus disease in people, including 118 deaths, have been reported to CDC. Of these, 1,405 (53%) were classified as neuroinvasive disease and 1,231 (47%) were classified as nonneuroinvasive disease. By way of comparison, there were a total of 486 infections and 43 deaths reported in all of 2011.
The 2,636 cases reported to date is the highest number of cases reported to CDC through the second week in September since 2003.

CLP: How many infected people show symptoms, and what risk do they carry to others?
Lieberman: Most people infected with West Nile (approximately 80%) are asymptomatic. They are well, but the risk they pose is that if they donate blood, transfusion recipients can be infected. That sounds like it would be a rare event. But in 2002, it was first recognized that some blood transfusion recipients developed West Nile disease, and routine screening of the blood supply for West Nile virus began in 2003. To date, 385 potentially viremic blood donors have been identified this year because of screening.

CLP: What are the different tests performed by clinical labs for West Nile?
Lieberman: For West Nile Virus, it’s predominantly antibody testing. Measuring IgM and IgG antibody from serum and CSF when available is the way you make a diagnosis in the majority of cases. That’s in contrast to other cases of encephalitis, where clinicians have learned over the years to use molecular tests to diagnose HSV or enteroviral infection, for example. For West Nile, molecular testing plays a lesser role. That’s because by the time most patients present clinically, the virus is at a low or undetectable level in the bloodstream, and fewer than half of patients have virus detectable by PCR in the CSF. Molecular testing has a role for patients early in the disease course, for immunocompromised patients, and as a tool for screening the blood supply. But the cornerstone of testing is antibody testing. So, every patient should have serum and CSF, if available, sent for IgM and IgG antibody testing. The caveat is that serum collected fewer than 7 days after symptom onset may not have detectable IgM, so if you’re within the first week and it’s negative, that does not rule out infection. Also, IgM antibodies can persist for more than a year in some patients so their presence in a patient who also has IgG antibodies could indicate infection during the previous year.

In addition, there can be false-positives due to other flavivirus infections. For most people in the United States, it’s not an issue as they’ve not had dengue fever or Japanese encephalitis. But for people born in other countries, they could have cross-reactive antibodies

CLP: Could you describe the spectrum of West Nile infection in patients, and also, the probably health outcomes for people who test positive for infection but show no symptoms?
Lieberman: Approximately, 20% of people infected develop West Nile Fever, which presents as a flu-like illness with fever, headaches, muscle aches, fatigue, and sometimes swollen lymph nodes, vomiting, and diarrhea. These patients generally recover in a week or so, although some patients are sick for a month or longer. They don’t feel well, but the vast majority are going to recover. One in every 150 infected patients develops central nervous system manifestations. Most commonly, it’s encephalitis or meningitis, but a polio-like flaccid paralysis also occurs. Certain populations are at higher risk for severe disease, such as persons older than 50 years of age and underlying conditions like diabetes or cancer. Approximately 10% of patients with neuroinvasive disease die, and survivors often suffer sequelae of their infection, with three-quarters of those with encephalitis needing assisted living.

CLP: How are kit manufacturers handling the increased demand?
Lieberman: At Focus, we take great pride in being a leader in the diagnosis of emerging infectious diseases. We were the first commercial lab to offer testing for West Nile Virus, and we produce the great majority of West Nile virus test kits used by laboratories in the United States. .

This year, we are seeing an unprecedented demand for testing. In August, we experienced approximately seven times the demand for test kits as compared to the same month last year. Manufacturing the test kits is a time-consuming process that includes growing the antigen in cell culture and can take weeks. When we got the first inkling that West Nile seemed to be up this year, we started to ramp up production, and for weeks now, we have been working around the clock to get kits out to help laboratories meet the demand for testing.

CLP: Do you believe the West Nile outbreak may be a precursor of other mosquito-borne, emerging infectious diseases (such as dengue and chikungunya) that could affect this country and its labs in the future? If so, what is the risk of future outbreaks, and how can overburdened public health resources and laboratorians ensure they are equipped to handle potential future testing demands?
Lieberman: The ecology of mosquitoes of mosquito-borne illness is complex. I’d emphasize that the mosquitoes that carry West Nile virus are different than the mosquitoes that carry dengue and chikungunya viruses. But we have those mosquitoes in the US as well, as their geographic range has spread over the last several decades. Chikungunya virus was primarily limited to Africa and transmitted by the Yellow Fever mosquito until a single-point genetic mutation enhanced the abililty of the Asian Tiger mosquito to carry it. What we’ve seen over the past several years are local outbreaks of this virus in areas like northern Italy and southeastern France. Those outbreaks were sparked when a traveler to an area where chikungunya is common was bitten and infected, returned to his or her home, was then bitten by a local mosquito while viremic, which started a local transmission cycle of the virus.

CLP: What factors lead to the spread of these diseases?
Lieberman: Climate change, international travel, genetic mutations in the viruses, and reductions in public health and vector control funding. I hope that this current West Nile virus outbreak reemphasizes the value of public health and vector control. We also need clinicians to be aware of the clinical presentations of these viruses and order the appropriate tests in order to recognize when an outbreak is occurring.

CLP: As the West Nile Virus season is still ongoing, what can people do to avoid infection?
Lieberman: I think they need to know what’s happening locally. We’re certainly not done with West Nile season, and it could get worse before it gets better.

Individuals play a role in controlling mosquitoes in their local area (by eliminating standing water in backyards that serve as breeding grounds for mosquitoes) and also can take measures to reduce the chance of being bitten by a mosquito.

Kurt Woock is associate editor for CLP. CLP’s Editor Judy O’Rourke contributed to this article.

On September 11, CLP spoke with Irina Lutinger, MPH, MASCP, H(ASCP)DLM, FACHE, ASCP, about impacts of the West Nile outbreak on labs. [removed]Click here[/removed] to read.