Biomedical subjects
Publications and source records attributed to Lyle R Petersen.
We report 1-year follow-up data from a longitudinal prospective cohort study of patients with West Nile virus-associated paralysis. As in the 4-month follow-up, a variety of recovery patterns were observed, but persistent weakness was frequent. Respiratory involvement was associated with considerable illness and death.
West Nile virus (WNV) was first detected in the Western Hemisphere in 1999 in New York City. From 1999 through 2004, >16,600 cases of WNV-related illnesses were reported in the United States, of which >7,000 were neuroinvasive disease and >600 were fatal. Several approaches are under way to develop a human vaccine. Through simulations and sensitivity analysis that incorporated uncertainties regarding future transmission patterns of WNV and costs of health outcomes, we estimated that the range of values for the cost per case of WNV illness prevented by vaccination was US 20,000 dollars-59,000 dollars(mean 36,000 dollars). Cost-effectiveness was most sensitive to changes in the risk for infection, probability of symptomatic illness, and vaccination cost. Analysis indicated that universal vaccination against WNV disease would be unlikely to result in societal monetary savings unless disease incidence increases substantially over what has been seen in the past 6 years.
National blood donor screening for West Nile virus (WNV) RNA using minipool nucleic acid amplification testing (MP-NAT) was implemented in the United States in July 2003. We compiled national NAT yield data and performed WNV immunoglobulin M (IgM) testing in 1 WNV-epidemic region (North Dakota). State-specific MP-NAT yield, antibody seroprevalence, and the average time RNA is detectable by MP-NAT were used to estimate incident infections in 2003. WNV donor screening yielded 944 confirmed viremic donors. MP-NAT yield peaked in August with >0.5% of donations positive for WNV RNA in 4 states. Peak IgM seroprevalence for North Dakota was 5.2% in late September. The average time viremia is detectable by MP-NAT was 6.9 days (95% confidence interval [CI] 3.0-10.7). An estimated 735,000 (95% CI 322,000-1,147,000) infections occurred in 2003, with 256 (95% CI 112-401) infections per neuroinvasive case. In addition to preventing transfusion-transmitted WNV infection, donor screening can serve as a tool to monitor seasonal incidence in the general population.
BACKGROUND: The spread of West Nile virus across North America and evidence of transmission by transfusion prompted the U.S. Food and Drug Administration to encourage the development of methods to screen the blood supply. OBJECTIVE: To assess the cost-effectiveness of nucleic acid amplification testing for West Nile virus in the U.S. blood supply. DESIGN: Markov cohort simulation. DATA SOURCES: Outcome probabilities estimated from nucleic acid testing done for West Nile virus in 2003, data from the Centers for Disease Control and Prevention, and published literature. Costs were taken from an economic study of West Nile virus infection and from estimated test costs. TARGET POPULATIONS: Transfusion recipients, 60 years of age or older, with and without underlying immunocompromise. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTIONS: The authors compared 6 strategies, taking into consideration minipool (pools of 6 to 16 donations) versus individual donation testing, and the geographic and seasonal nature of West Nile virus activity. OUTCOME MEASURES: Costs and effects of each strategy based on the prevention of transfusion-transmitted West Nile virus. RESULTS OF BASE-CASE ANALYSIS: The cost-effectiveness of annual, national minipool testing was 483,000 dollars per quality-adjusted life-year (QALY), whereas the cost-effectiveness of annual, national individual donation testing was 897,000 dollars/QALY. The cost-effectiveness of targeted individual donation testing in an area experiencing an outbreak coupled with minipool testing elsewhere was 520,000 dollars/QALY. RESULTS OF SENSITIVITY ANALYSIS: In 1-way analyses, the most important influences were the prevalence of West Nile virus and the cost of minipool testing and individual donation testing. The 95% range of results from probabilistic sensitivity analysis for targeted individual donation testing was 256,000 dollars to 1,044,000 dollars/QALY. LIMITATIONS: The outcomes of West Nile virus infection were based on data from the general population rather than from the population who received transfusions. The results are most useful in the context of geographically focused outbreaks of West Nile virus infection. CONCLUSIONS: Using targeted individual donation testing to interdict blood donations that are positive for the West Nile virus is relatively cost-effective but is highly dependent on West Nile virus prevalence.
We characterized rash in 15 patients with West Nile virus (WNV) fever. Generalized, maculopapular rash typically occurred on days 5-12 of illness. Dysesthesia was reported by 27% of patients, and pruritus by 33% of patients. Because the rash was nonspecific and serologic test results were often negative for WNV at presentation, convalescent-phase testing was frequently required to diagnose WNV fever.
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The dengue, West Nile, Japanese encephalitis and yellow fever viruses are important mosquito-borne viruses whose epidemiology is shifting in response to changing societal factors, such as increasing commerce, urbanization of rural areas, and population growth. All four viruses are expanding geographically, as exemplified by the emergence of West Nile virus in the Americas and Japanese encephalitis virus in Australasia. The large, recent global outbreaks of severe neurological disease caused by West Nile virus, the increasing frequency of dengue hemorrhagic fever outbreaks in the Americas, and the emergence of yellow fever virus vaccination-associated viscerotropic disease, are new clinical epidemiologic trends. These worrisome epidemiologic trends will probably continue in coming decades, as a reversal of their societal and biological drivers is not in sight. Nevertheless, the substantial reductions in Japanese encephalitis virus incidence resulting from vaccination programs and economic development in some Asian countries provide some encouragement within this overall guarded outlook.
The causes and frequency of acute paralysis and respiratory failure with West Nile virus (WNV) infection are incompletely understood. During the summer and fall of 2003, we conducted a prospective, population-based study among residents of a 3-county area in Colorado, United States, with developing WNV-associated paralysis. Thirty-two patients with developing paralysis and acute WNV infection were identified. Causes included a poliomyelitislike syndrome in 27 (84%) patients and a Guillain-Barré-like syndrome in 4 (13%); 1 had brachial plexus involvement alone. The incidence of poliomyelitislike syndrome was 3.7/100,000. Twelve patients (38%), including 1 with Guillain-Barré-like syndrome, had acute respiratory failure that required endotracheal intubation. At 4 months, 3 patients with respiratory failure died, 2 remained intubated, 25 showed various degrees of improvement, and 2 were lost to followup. A poliomyelitislike syndrome likely involving spinal anterior horn cells is the most common mechanism of WNV-associated paralysis and is associated with significant short- and long-term illness and death.
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Mosquito-borne flaviviruses provide some of the most important examples of emerging and resurging diseases of global significance. Here, we describe three of them: the resurgence of dengue in tropical and subtropical areas of the world, and the spread and establishment of Japanese encephalitis and West Nile viruses in new habitats and environments. These three examples also illustrate the complexity of the various factors that contribute to their emergence, resurgence and spread. Whereas some of these factors are natural, such as bird migration, most are due to human activities, such as changes in land use, water impoundments and transportation, which result in changed epidemiological patterns. The three examples also show the ease with which mosquito-borne viruses can spread to and colonize new areas, and the need for continued international surveillance and improved public health infrastructure to meet future emerging disease threats.
A diagnostic algorithm was developed to differentiate between human infections of West Nile virus (WNV) and St. Louis encephalitis virus (SLEV) using positive-to-negative (P/N) ratios derived from the immunoglobulin M capture enzyme-linked immunosorbent assay (MAC-ELISA). To validate this algorithm, we tested 1,418 serum and cerebrospinal fluid (CSF) samples from confirmed WNV and SLEV infections collected during the WNV epidemic of 2002 in the United States. WNV P/N-to-SLEV P/N ratios (W/S ratios) were calculated and used to identify the infecting virus. These results were compared to results from the plaque reduction neutralization test (PRNT), which is currently the standard assay used to discriminate between closely related flavivirus infections. If the W/S ratio was > or =1, the predictive value positive (PNP) for WNV was 97.8%, where 95% of flavivirus cases were due to WNV infection and only 3.7% of specimens would require PRNT to differentiate WNV from SLEV infection. Use of the W/S ratio as part of the testing algorithm to interpret MAC-ELISA results generates reportable probable cases quickly, alleviating the need for PRNT in most instances.
West Nile virus (WNV), a mosquito-transmitted single-stranded RNA flavivirus, causes human disease of variable severity. We report clinical and pathologic findings of fatal encephalitis from the transmission of WNV from an organ donor to a kidney transplant recipient. The patient developed a febrile illness 18 days after transplantation, which progressed to encephalitis. Postmortem examination demonstrated extensive viral encephalopathic changes. Immunohistochemical studies highlighted WNV antigens within neurons, especially in the cerebellum and brainstem. Flavivirus virions were detected ultrastructurally within the cerebellum, and WNV was isolated from the brain and the brainstem. Thus, this case demonstrates the first death in the first solid organ transplant-associated transmission of WNV. Immunosuppression of the transplant recipient might have been responsible for the fulminant viral effects. The pathologic diagnosis helped guide subsequent epidemiologic and laboratory studies.
In 2001, an outbreak of acute respiratory disease occurred among persons working at a Native American archeological site at Dinosaur National Monument in northeastern Utah. Epidemiologic and environmental investigations were undertaken to determine the cause of the outbreak. A clinical case was defined by the presence of at least two of the following symptoms: self-reported fever, shortness of breath, or cough. Ten workers met the clinical case definition; 9 had serologic confirmation of coccidioidomycosis, and 8 were hospitalized. All 10 were present during sifting of dirt through screens on June 19; symptoms began 9-12 days later (median 10). Coccidioidomycosis also developed in a worker at the site in September 2001. A serosurvey among 40 other Dinosaur National Monument workers did not find serologic evidence of recent infection. This outbreak documents a new endemic focus of coccidioidomycosis, which extends northward its known geographic distribution in Utah by approximately 200 miles.
West Nile virus (WNV) is transmitted by mosquitoes and can cause illness in humans ranging from mild fever to encephalitis. In 2002, a total of 4,156 WNV cases were reported in the United States; 329 were in Louisiana. To estimate the economic impact of the 2002 WNV epidemic in Louisiana, we collected data from hospitals, a patient questionnaire, and public offices. Hospital charges were converted to economic costs by using Medicare cost-to-charge ratios. The estimated cost of the Louisiana epidemic was US 20.1 million dollars from June 2002 to February 2003, including a US 10.9 million dollars cost of illness (US 4.4 million dollars medical and US 6.5 million dollars nonmedical costs) and a US 9.2 million dollars cost of public health response. These data indicate a substantial short-term cost of the WNV disease epidemic in Louisiana.
We conducted a case-control study to investigate risk factors for acquiring autochthonous alveolar echinococcosis in Germany. Forty cases and 120 controls matched by age and residence were interviewed. Patients were more likely than controls to have owned dogs that killed game (odds ratio [OR] = 18.0), lived in a farmhouse (OR = 6.4), owned dogs that roamed outdoors unattended (OR = 6.1), collected wood (OR = 4.7), been farmers (OR = 4.7), chewed grass (OR = 4.4), lived in a dwelling close to fields (OR = 3.0), gone into forests for vocational reasons (OR = 2.8), grown leaf or root vegetables (OR = 2.5), owned cats that roamed outdoors unattended (OR = 2.3), and eaten unwashed strawberries (OR = 2.2). Sixty-five percent of cases were attributable to farming. Measures that prevent accidental swallowing of possibly contaminated material during farming or adequate deworming of pet animals might reduce the risk for alveolar echinococcosis.
BACKGROUND: During the 2002 West Nile virus epidemic in the United States, patients were identified whose West Nile virus illness was temporally associated with the receipt of transfused blood and blood components. METHODS: Patients with laboratory evidence of recent West Nile virus infection within four weeks after receipt of a blood component from a donor with viremia were considered to have a confirmed transfusion-related infection. We interviewed the donors of these components, asking them whether they had had symptoms compatible with the presence of a viral illness before or after their donation; blood specimens retained from the time of donation and collected at follow-up were tested for West Nile virus. RESULTS: Twenty-three patients were confirmed to have acquired West Nile virus through transfused leukoreduced and nonleukoreduced red cells, platelets, or fresh-frozen plasma. Of the 23 recipients, 10 (43 percent) were immunocompromised owing to transplantation or cancer and 8 (35 percent) were at least 70 years of age. Immunocompromised recipients tended to have longer incubation periods than nonimmunocompromised recipients and infected persons in mosquito-borne community outbreaks. Sixteen donors with evidence of viremia at donation were linked to the 23 infected recipients; of these donors, 9 reported viral symptoms before or after donation, 5 were asymptomatic, and 2 were lost to follow-up. Fever, new rash, and painful eyes were independently associated with being an implicated donor with viremia rather than a donor without viremia. All 16 donors were negative for West Nile virus-specific IgM antibody at donation. CONCLUSIONS: Transfused red cells, platelets, and fresh-frozen plasma can transmit West Nile virus. Screening of potential donors with the use of nucleic acid-based assays for West Nile virus may reduce this risk.
CONTEXT: The neurologic manifestations, laboratory findings, and outcome of patients with West Nile virus (WNV) infection have not been prospectively characterized. OBJECTIVE: To describe prospectively the clinical and laboratory features and long-term outcome of patients with neurologic manifestations of WNV infection. DESIGN, SETTING, AND PARTICIPANTS: From August 1 to September 2, 2002, a community-based, prospective case series was conducted in St Tammany Parish, La. Standardized clinical data were collected on patients with suspected WNV infection. Confirmed WNV-seropositive patients were reassessed at 8 months. MAIN OUTCOME MEASURES: Clinical, neurologic, and laboratory features at initial presentation, and long-term neurologic outcome. RESULTS: Sixteen (37%) of 39 suspected cases had antibodies against WNV; 5 had meningitis, 8 had encephalitis, and 3 had poliomyelitis-like acute flaccid paralysis. Movement disorders, including tremor (15 [94%]), myoclonus (5 [31%]), and parkinsonism (11 [69%]), were common among WNV-seropositive patients. One patient died. At 8-month follow-up, fatigue, headache, and myalgias were persistent symptoms; gait and movement disorders persisted in 6 patients. Patients with WNV meningitis or encephalitis had favorable outcomes, although patients with acute flaccid paralysis did not recover limb strength. CONCLUSIONS: Movement disorders, including tremor, myoclonus, and parkinsonism, may be present during acute illness with WNV infection. Some patients with WNV infection and meningitis or encephalitis ultimately may have good long-term outcome, although an irreversible poliomyelitis-like syndrome may result.