Nicole P. Lindsey

Adverse event reports following yellow fever vaccination.

Yellow fever (YF) vaccine has been used for prevention of YF since 1937 with over 500 million doses administered. However, rare reports of severe adverse events following vaccination have raised concerns about the vaccines safety. We reviewed reports of adverse events following YF vaccination reported to the U.S. Vaccine Adverse Event Reporting System (VAERS) from 2000 to 2006. We used estimates of age and sex distribution of administered doses obtained from a 2006 survey of authorized vaccine providers to calculate age- and sex-specific reporting rates of all serious adverse events (SAE), anaphylaxis, YF vaccine-associated neurotropic disease, and YF vaccine-associated viscerotropic disease. Reporting rates of SAEs were substantially higher in males and in persons aged > or =60 years. These findings reinforce the generally acceptable safety profile of YF vaccine, but highlight the importance of physician and traveler education regarding the risks and benefits of YF vaccination, particularly for travelers > or =60 years of age. Vaccination should be limited to persons traveling to areas where the risk of YF is expected to exceed the risk of serious adverse events after vaccination, or if not medically contraindicated, where national regulations require proof of vaccination to prevent introduction of YF.

West Nile Virus Neuroinvasive Disease Incidence in the United States, 2002–2006

As the geographic range of reported human West Nile virus (WNV) disease has expanded across the United States, seasonal transmission and outbreaks have persisted over several years in many areas of the country. West Nile virus neuroinvasive disease (WNND) case reports from 2002 to 2006 were reviewed to determine which areas of the country have the highest reported cumulative incidence and whether those areas have had consistently high annual incidence. During the 5-year period examined, 9632 cases of WNND were reported nationwide. The cumulative incidence of WNND ranged from 0.2 to 32.2 per 100,000 population by state and from 0.1 to 241.2 per 100,000 population by county. States and counties with the highest cumulative incidence were primarily located in the northern Great Plains. States with consistently high annual incidence included South Dakota, North Dakota, Wyoming, New Mexico, Mississippi, Nebraska, Louisiana, and Colorado. All of these states, with the exception of New Mexico, were also among the states with the highest cumulative incidence. Counties with repeatedly high annual incidence were also primarily in the Great Plains and mid-South. The risk of WNND appears to be highest in areas where the primary WNV vectors are Culex tarsalis and Cx. quinquefasciatus mosquitoes.

West Nile Virus Disease in Children, United States, 1999–2007

BACKGROUND. Although West Nile virus (WNV) disease has occurred predominantly among adults in the United States, children are also susceptible. Epidemiological data describing WNV disease in children are limited. METHODS. We described the epidemiological features of WNV disease among children (<18 years of age) reported to the Centers for Disease Control and Prevention from 1999 through 2007 and compared features of pediatric and adult West Nile neuroinvasive disease (WNND). RESULTS. Of 1478 pediatric WNV cases reported from 1999 through 2007, 443 (30%) were classified as WNND, 1009 (68%) were classified as West Nile fever, and 26 (2%) were of unknown clinical presentation. Three WNND cases were fatal. The vast majority of reported case subjects (92%) had onset of illness between July and September. Children accounted for only 4% of all of the WNND case subjects reported from 1999 to 2007, with a median annual incidence of 0.07 case subjects per 100 000 children (range: 0.00–0.19 case subjects). In children and younger adults WNND most often manifested as meningitis, in contrast to the predominance of encephalitis among older adults with WNND. The geographic distribution and temporal trends were of pediatric and adult WNND. CONCLUSIONS. The epidemiological characteristics of WNV disease in children are similar to adult case subjects; however, WNND is more likely to manifest as meningitis in children than in older adults. WNV should be considered in the differential diagnosis for pediatric patients presenting with febrile illness, meningitis, encephalitis, or acute flaccid paralysis, particularly during seasonal outbreaks in endemic areas.

Medical Risk Factors for Severe West Nile Virus Disease, United States, 2008–2010

We conducted enhanced surveillance to identify medical risk factors for severe illness (i.e., hospitalization or death) and neuroinvasive disease (i.e., encephalitis or meningitis) among all West Nile virus disease cases reported from selected states from 2008 to 2010. Of the 1,090 case-patients included in the analysis, 708 (65%) case-patients were hospitalized, 641 (59%) case-patients had neuroinvasive disease, and 55 (5%) case-patients died. Chronic renal disease (adjusted odds ratio [aOR] = 4.1; 95% confidence interval [CI] = 1.4-12.1), history of cancer (aOR = 3.7; 95% CI = 1.8-7.5), history of alcohol abuse (aOR = 3.0; 95% CI = 1.3-6.7), diabetes (aOR = 2.2; 95% CI = 1.4-3.4), and hypertension (aOR = 1.5; 95% CI = 1.1-2.1) were independently associated with severe illness on multivariable analysis. Although the same medical conditions were independently associated with encephalitis, only hypertension was associated with meningitis. The only condition independently associated with death was immune suppression. Prevention messages should be targeted to persons with these conditions.

Neuroinvasive Arboviral Disease in the United States: 2003 to 2012

OBJECTIVE: To describe the epidemiologic and clinical syndromes associated with pediatric neuroinvasive arboviral infections among children in the United States from 2003 through 2012. METHODS: We reviewed data reported by state health departments to ArboNET, the national arboviral surveillance system, for 2003 through 2012. Children (<18 years) with neuroinvasive arboviral infections (eg, meningitis, encephalitis, or acute flaccid paralysis) were included. Demographic, clinical syndrome, outcome, geographic, and temporal data were analyzed for all cases. RESULTS: During the study period, 1217 cases and 22 deaths due to pediatric neuroinvasive arboviral infection were reported from the 48 contiguous states. La Crosse virus (665 cases; 55%) and West Nile virus (505 cases; 41%) were the most common etiologies identified. Although less common, Eastern equine encephalitis virus (30 cases; 2%) resulted in 10 pediatric deaths. La Crosse virus primarily affected younger children, whereas West Nile virus was more common in older children and adolescents. West Nile virus disease cases occurred throughout the country, whereas La Crosse and the other arboviruses were more focally distributed. CONCLUSIONS: Neuroinvasive arboviral infections were an important cause of pediatric disease from 2003 through 2012. Differences in the epidemiology and clinical disease result from complex interactions among virus, vector, host, and the environment. Decreasing the morbidity and mortality from these agents depends on vector control, personal protection to reduce mosquito and tick bites, and blood donor screening. Effective surveillance is critical to inform clinicians and public health officials about the epidemiologic features of these diseases and to direct prevention efforts.

West Nile Virus and Other Nationally Notifiable Arboviral Diseases - United States, 2015.

Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. The leading cause of domestically acquired arboviral disease in the United States is West Nile virus (WNV) (1). Other arboviruses, including La Crosse, St. Louis encephalitis, Jamestown Canyon, Powassan, and eastern equine encephalitis viruses, also cause sporadic cases and outbreaks. This report summarizes surveillance data reported to CDC in 2015 for nationally notifiable arboviruses. It excludes dengue, chikungunya, and Zika viruses, which are primarily nondomestic viruses typically acquired through travel (and are addressed in other CDC reports). In 2015, 45 states and the District of Columbia (DC) reported 2,282 cases of domestic arboviral disease. Among these cases, 2,175 (95%) were WNV disease and 1,455 (67%) of those were classified as neuroinvasive disease (meningitis, encephalitis, or acute flaccid paralysis). The national incidence of WNV neuroinvasive disease was 0.45 cases per 100,000 population. Because arboviral diseases continue to cause serious illness, maintaining surveillance is important to direct prevention activities such as reduction of vector populations and screening of blood donors.

Delayed Mortality in a Cohort of Persons Hospitalized with West Nile Virus Disease in Colorado in 2003

Most mortality associated with West Nile virus (WNV) disease occurs during the acute or early convalescent phases of illness. However, some reports suggest mortality may be elevated for months or longer after acute illness. The objective of this study was to assess the survival of a cohort of patients hospitalized with WNV disease in Colorado in 2003 up to 4 years after illness onset. We calculated age-adjusted standardized mortality ratios (SMRs) to evaluate excess mortality, evaluated reported causes of death in those who died, and analyzed potential covariates of delayed mortality. By 1 year after illness onset, 4% of the 201 patients had died (SMR, 2.7; 95% confidence interval [CI], 1.3-5.2), and 12% had died by 4 years after onset (SMR, 2.0; 95% CI, 1.3-3.0). Among those who had died, the most common immediate and contributory causes of death included pulmonary disease and cardiovascular disease; cancer, hepatic disease, and renal disease were mentioned less frequently. In multivariate analysis, age (hazard ratio [HR], 2.0 per 10-year increase; 95% CI, 1.4-2.7), autoimmune disease (HR, 3.0; 95% CI, 1.1-7.9), ever-use of tobacco (HR, 3.0; 95% CI, 1.3-7.0), encephalitis during acute WNV illness (HR, 2.6; 95% CI, 1.1-6.4), and endotracheal intubation during acute illness (HR 4.8; 95% CI, 1.9-12.1) were found to be independently associated with mortality. Our finding of an approximate twofold increase in mortality for up to 3 years after acute illness reinforces the need for prevention measures against WNV infection among at-risk groups to reduce acute as well as longer-term adverse outcomes.

Meteorological Conditions Associated with Increased Incidence of West Nile Virus Disease in the United States, 2004-2012

West Nile virus (WNV) is a leading cause of mosquito-borne disease in the United States. Annual seasonal outbreaks vary in size and location. Predicting where and when higher than normal WNV transmission will occur can help direct limited public health resources. We developed models for the contiguous United States to identify meteorological anomalies associated with above average incidence of WNV neuroinvasive disease from 2004 to 2012. We used county-level WNV data reported to ArboNET and meteorological data from the North American Land Data Assimilation System. As a result of geographic differences in WNV transmission, we divided the United States into East and West, and 10 climate regions. Above average annual temperature was associated with increased likelihood of higher than normal WNV disease incidence, nationally and in most regions. Lower than average annual total precipitation was associated with higher disease incidence in the eastern United States, but the opposite was true in most western regions. Although multiple factors influence WNV transmission, these findings show that anomalies in temperature and precipitation are associated with above average WNV disease incidence. Readily accessible meteorological data may be used to develop predictive models to forecast geographic areas with elevated WNV disease risk before the coming season.

Chikungunya Virus Infections Among Travelers–United States, 2010–2013

Chikungunya virus is an emerging threat to the United States because humans are amplifying hosts and competent mosquito vectors are present in many regions of the country. We identified laboratory-confirmed chikungunya virus infections with diagnostic testing performed in the United States from 2010 through 2013. We described the epidemiology of these cases and determined which were reported to ArboNET. From 2010 through 2013, 115 laboratory-confirmed chikungunya virus infections were identified. Among 55 cases with known travel history, 53 (96%) reported travel to Asia and 2 (4%) to Africa. No locally-acquired infections were identified. Six patients had detectable viremia after returning to the United States. Only 21% of identified cases were reported to ArboNET, with a median of 72 days between illness onset and reporting. Given the risk of introduction into the United States, healthcare providers and public health officials should be educated about the recognition, diagnosis, and timely reporting of chikungunya virus disease cases.

Primary causes of death in reported cases of fatal West Nile Fever, United States, 2002-2006.

Morbidity and mortality associated with human West Nile virus (WNV) infection is generally attributable to severe neurologic disease; most illness with WNV, however, is characterized by febrile illness. Although generally considered to be a benign, self-limited syndrome, some cases of West Nile Fever (WNF) have been reported as resulting in fatal outcome. We reviewed cause-of-death information for 35 cases of WNF reported as fatal to the Centers for Disease Control and Prevention between 2002 and 2006, to determine underlying primary causes of death and identify groups at highest risk for fatal WNF. Fifteen were determined to be misclassified neuroinvasive disease cases; one death was medically unrelated to WNV infection. Among the remaining 23 cases, the median age was 78 years (range: 54-92), and 78% were >70 years old; the median age for all 13,482 reported cases of WNF during this time period was 47 years (range: 1 month-97 years). Cardiac (8 cases, 35%) and pulmonary complications (6 cases, 25%) were the most common primary causes of death. Underlying medical conditions among fatal WNF cases included cardiovascular disease (13; 76%), hypertension (8; 47%), and diabetes mellitus (6; 35%). Our study suggests that in some individuals, especially persons of advanced age and those with underlying medical conditions, WNF may precipitate death. The elderly are at increased risk of death from both West Nile neuroinvasive disease and WNF, which emphasizes the importance of primary prevention of WNV infection and close monitoring for cardiac and pulmonary complications in elderly patients hospitalized for WNV disease.