A new study by a research team from the Centers for Disease Control and Prevention (CDC) finds has determined that costs associated with West Nile virus (WNV) disease have been substantially underestimated. The study, “Initial and Long-Term Costs of Patients Hospitalized with West Nile Virus Disease,” was published online before print on Monday, February 10 by the American Journal of Tropical Medicine and Hygiene (AJTMH)
The report, co-authored by J. Erin Staples, Manjunath Shankar, James J. Sejvar, Martin I. Meltzer, and Marc Fischer — variously of the Arboviral Diseases Branch, Centers for Disease Control and Prevention, Fort Collins, Colorado; the Prion and Health Office, Centers for Disease Control and Prevention; and the Division of Preparedness and Emerging Infections, Centers for Disease Control and Prevention, Atlanta, Georgia, determines that West Nile virus-related hospitalizations and follow-ups in the United States cost a cumulative $778 million in health care expenses and lost productivity, or about about $56 million annually over the 14 years from 1999 when the virus was first detected in the Western Hemisphere at New York, through 2012, a much higher figure than had been previously estimated.
In the report abstract, the researchers note that there are no published data on the economic burden for specific West Nile virus (WNV) clinical syndromes (i.e., fever, meningitis, encephalitis, and acute flaccid paralysis [AFP]). They estimated initial hospital and lost-productivity costs from 80 patients hospitalized with WNV disease in Colorado during 2003; 38 of whom were tracked for five years to determine long-term medical and lost-productivity costs.
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Initial costs were found to be highest for patients with AFP (median $25,117; range $5,385–$283,381) and encephalitis (median $20,105; range $3,965–$324,167). Long-term costs were highest for patients with AFP (median $22,628; range $624–$439,945) and meningitis (median $10,556; range $0–$260,748).
Extrapolating from this small cohort to national surveillance data, the researchers estimated the total cumulative costs of reported WNV hospitalized cases from 1999 to 2012 to be $778 million (95% confidence interval $673 million–$1.01 billion), and affirm that they can be used in assessing the cost-effectiveness of interventions to prevent WNV disease.
This study found that both acute and long-term costs varied between the different clinical presentations of WNV disease. Overall, a substantial proportion of case-patients in our long-term follow-up cohort incurred additional medical or lost productivity costs in the 5 years after their hospitalization. We estimate that tens of millions of dollars are spent each year on WNV hospitalized cases and deaths.
To date, an estimated 18,775 non-hospitalized cases of WNV disease have been reported to CDC. If the cost estimate of a fever case (cost of one healthcare provider office visit, one diagnostic test, and five days off work) is applied and adjusted to 2012 USD, the estimated total costs of non-hospitalized cases from 1999 to 2012 would be $28 million or 3.6% of the total direct or indirect medical costs incurred by WNV disease cases.
However, the annual cost of WNV disease varies substantially as the number of WNV disease cases has ranged from 21 cases in 2000 to 9,862 cases in 2003. The CDC researchers’ estimate of WNV costs is conservative as it does not account for costs incurred by non-hospitalized WNV cases or make any adjustment for the under diagnosis or underreporting of WNV disease cases.
West Nile virus first entered the North American lexicon in 1999 when the first news reports of serious infection and deaths from the virus first emerged. Until then, West Nile virus—which is spread to humans by the bite of an infected mosquito—had not been detected outside of the Eastern Hemisphere. Annual outbreaks have continued to occur across the United States, such as the large outbreak in Dallas in 2012. Over 37,000 WNV disease cases have been reported to CDC since 1999, and this number likely underestimates the total number of infections that occurred in the United States.
The report notes that West Nile virus (WNV), a mosquito-borne flavivirus, has over the past 14 years become the leading cause of domestically acquired arboviral disease in the United States and is responsible for seasonal outbreaks of disease affecting all regions of the country. Approximately 80% of WNV infections are asymptomatic, and most persons presenting with symptoms experience an acute systemic febrile illness, known as West Nile fever or non-neuroinvasive disease, characterized by headache, myalgia, arthralgia, or rash. Fewer than than one percent of infected persons develop neuroinvasive disease, which typically manifests as encephalitis, meningitis, or acute flaccid paralysis (AFP). Most patients with WNV meningitis or non-neuroinvasive disease recover completely, but fatigue and malaise can linger for weeks or months. Patients who recover from WNV encephalitis or AFP often have residual neurologic deficits. Among patients with neuroinvasive disease, the overall case-fatality ratio is approximately ten percent, but mortality is notably higher for patients with WNV encephalitis and AFP.
The researchers found that From 1999 to 2012, over 36,000 cases and 1,500 deaths caused by WNV disease were reported to the Centers for Disease Control and Prevention (CDC), and despite the large number of cases over the last 14 years, only two studies have estimated the initial cost of WNV disease, and there are no published data on the economic burden of the specific clinical syndromes seen with WNV infections or the longer term costs of WNV disease incurred several years after the initial illness.
In addressing that data gap, the CDC research team presents data on both initial hospital costs and five years of follow-up care costs for persons hospitalized with different clinical presentations of WNV disease. They then use the data to estimate the total costs of hospitalized WNV disease cases and deaths reported to CDC — data that can be used in assessing the cost-effectiveness of various interventions designed to lower WNV disease risk.
An American Society of Tropical Medicine and Hygiene (ASTMH) release notes that about 1 in 5 people who are infected with the virus will develop a fever with other symptoms such as headache and joint pains, but about one in 150 of those infected develop a serious nervous system illness such as encephalitis or meningitis that typically requires hospitalization.
Little is known about the longer-term health needs of individuals affected by WNV disease or the economic cost of the disease to the nation. The study looked at the costs of initial hospitalization of WNV patients and long-term direct and indirect costs in the five years following their hospitalization—from follow-up doctor visits and medications to how much job or school time was missed.
“We believe that previous costs associated with West Nile virus disease have been underestimated because they’ve predominantly focused on the costs of the initial illness,” says J. Erin Staples, MD, PhD, a medical epidemiologist at CDC in Fort Collins, Colorado, and the study’s lead author in the release. “Many hospitalized patients will incur additional medical and indirect costs, and these need to be figured into the burden of WNV disease. Only with accurate figures can public health, academic, and industry officials determine the cost effectiveness of local mosquito control measures or of developing new drugs and vaccines.”
The report is the first published study to calculate costs for the four specific “clinical syndromes” of the disease: fever, meningitis, encephalitis and acute flaccid paralysis, the more severe of which can lead to death or long-term disability.
The ASTMH notes that 7,088 WNV disease cases reported to CDC from 1999 through 2012 included more than 16,000 patients with neurologic disease, over 18,000 patients who required hospitalization, and over 1,500 deaths. According to the CDC, individuals over 50 years of age are more likely to develop severe neurologic disease if infected.
The researchers found that short-term and long-term costs for individuals hospitalized with WNV disease varied widely and depended on the clinical syndrome encountered.
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“We broke down costs by clinical syndrome and were surprised by what we found. While patients with meningitis had shorter hospital stays than others with neurological syndromes, they were also younger and more likely to miss work, which translated to a higher economic cost in lost productivity,” Dr. Staples comments. “Encephalitis patients tended to be older, with many of them retired, so the cost associated with lost productivity was lower.” Among patients in the study, the average age at initial diagnosis was 55 years, and one-fourth of patients were over 65 years of age. Hospitalized patients were absent from work or school for a median 42 days due to their illness.
The CDC researchers were able to make national cost estimates due to the efforts of physicians and state public health officials who report confirmed WNV disease cases to the CDC ArboNET – a surveillance system. CDC uses ArboNET to track the incidence of WNV disease as well as other diseases caused by arthropod-borne viruses (arboviruses) transmitted by mosquitoes or ticks such as dengue, La Crosse, eastern equine encephalitis, and Powassan viruses.
“National surveillance efforts are critical to determining where and when outbreaks of mosquito or tick-borne diseases occur,” Dr. Staples observes. “Being able to react quickly to an outbreak and put in place preventive measures such as emptying outdoor water containers, wearing insect repellant and potentially beginning community-wide insecticide spraying is essential to limiting both the public health threat and the long-term economic cost of vector-borne infectious diseases.”
The researchers conclude that long-term costs need to be figured into the cost of WNV disease, and say additional studies are warranted among larger cohorts of both hospitalized and non-hospitalized persons with various clinical WNV disease syndromes to better understand and estimate the long-term effects and costs associated with WNV disease.
In an accompanying AJTMH editorial, Alan D. T. Barrett, PhD, a tropical viral disease specialist at the University of Texas Medical Branch, Galveston, Texas, writes that studies such as this “are critical to assessing cost-effectiveness of prevention and therapeutic countermeasures and various intervention strategies, and are important in helping guide public health decisions.” There are a number of candidate vaccines and antiviral drugs in development, and the figures for economic burden reported in this paper will aid policy makers and pharma to assess the economics of vaccine and drug development.”
Dr. Barrett’s laboratory at UTMB is undertaking basic research on the development of vaccines against the flavivirus diseases, including West Nile, Japanese encephalitis, yellow fever and dengue. In addition, recombinant DNA technology and infectious clone technology/reverse genetics are being used to identify molecular determinants of virulence of yellow fever, West Nile and Japanese encephalitis viruses with the aim of mutating these virulence determinants to develop candidate attenuated vaccine strains. We also investigate the molecular epidemiology of various flaviviruses (yellow fever, West Nile, Japanese encephalitis, and St Louis encephalitis viruses).
It is believed that West Nile virus most likely entered the United States through animals or mosquitoes imported from Europe or the Middle East. After human infections were first identified in New York City in late summer 1999, the virus spread across the entire continental United States in less than five years, and recent outbreaks confirm that WNV is firmly entrenched in the United States, and that seasonal outbreaks can be expected to recur annually. Several potential vaccines for WNV are being tested, but none are yet available to vaccinate the general public.
“Understanding the economic impact of disease is an increasingly important data point for the public health community and policy makers,” says Alan J. Magill, MD, FASTMH, president of the American Society of Tropical Medicine and Hygiene, which publishes the journal. “As we all strive for the most efficient and effective use of scarce resources, studies like this offer decision makers facts that will help them make sound funding and policy decisions.”
The American Society of Tropical Medicine and Hygiene, founded in 1903, is a worldwide organization of scientists, clinicians and program professionals whose mission is to promote global health through the prevention and control of infectious and other diseases that disproportionately afflict the global poor.
The American Journal of Tropical Medicine and Hygiene has been continuously published since 1921, AJTMH is the peer-reviewed journal of the American Society of Tropical Medicine and Hygiene, and the world’s leading voice in the fields of tropical medicine and global health. AJTMH disseminates new knowledge in fundamental, translational, clinical and public health sciences focusing on improving global health.
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