La Crosse Virus Neuroinvasive Disease --- Missouri, 2009

La Crosse virus (LACV), a California serogroup bunyavirus, is a leading cause of pediatric arboviral encephalitis in the United States and is transmitted primarily by the eastern treehole mosquito (Aedes triseriatus) (1). On August 7, 2009, the Missouri Department of Health and Senior Services (MDHSS) was notified of suspected LACV neuroinvasive disease in a boy aged 8 years from northwest Missouri. Laboratory testing at CDC confirmed LACV infection. An environmental inspection identified multiple vector habitats, including tree holes and discarded tires within a 300-foot radius of the patient's home. Although a median of 67 (range: 29--167) California serogroup virus neuroinvasive disease cases have been reported annually in the United States since 1964, mostly from upper Midwestern and mid-Atlantic states (2), this is the first reported case of LACV neuroinvasive disease in Missouri since 2002. Ae. triseriatus is found throughout Missouri and as far west as central Kansas and eastern Nebraska. Health-care providers serving this region should maintain a high clinical suspicion for LACV among patients with unexplained meningoencephalitis occurring during summer and fall.

Case Report

On July 29, 2009, a previously healthy boy aged 8 years, who lived in Kansas City, Missouri, arrived at a local emergency department with headache, fatigue, nausea, vomiting, and abdominal pain. He was prescribed amoxicillin for presumed streptococcal pharyngitis. During the next 48 hours, he continued to have vomiting and developed fever and worsening headache, prompting a second emergency department visit on July 31. Physical examination revealed no focal neurologic signs, and a noncontrasted computed tomography of the head was unremarkable. Because of the child's fever, severe headache, and intractable vomiting, the physician transferred the patient to a pediatric hospital for admission on August 1 because of concerns about possible acute meningitis.

On examination at the pediatric hospital, the child's temperature was 104°F (40°C), with photophobia noted and neck pain with flexion. Neurologic examination, including mental status testing, was normal. Blood counts were remarkable for leukocytosis of 22,000/mm3 with neutrophil predominance (89%). Cerebrospinal fluid (CSF) obtained through lumbar puncture revealed an elevated white blood cell count (182 cells/mm3 [43% neutrophils, 40% lymphocytes, and 17% monocytes]), normal protein (31 mg/dL), and normal glucose (61 mg/dL). Polymerase chain reaction for enterovirus on CSF was negative. Vancomycin and ceftriaxone were initiated after lumbar puncture for possible bacterial meningitis.

Blood and CSF bacterial cultures remained negative. On August 3, the patient's serum and CSF were submitted to a referral laboratory for immunofluorescence assay (IFA) for antibodies against West Nile, eastern equine encephalitis, western equine encephalitis, St. Louis encephalitis, and California serogroup viruses. On August 7, results showed positive immunoglobulin M (IgM) and immunoglobulin G (IgG) against California serogroup viruses in serum and CSF. Because LACV is the most prevalent member of California serogroup viruses,* a presumptive diagnosis of LACV neuroinvasive disease was made. Antibiotics were discontinued. The patient's headache, neck pain, and abdominal pain improved during the course of admission, and he was discharged home on August 7. The patient remained healthy, and no neurologic abnormalities were detected through medical follow-up.

Public Health and Laboratory Investigations

MDHSS was notified of the case on August 7. The patient's parents were interviewed on August 13. The patient was the only child in this family, which lived in a house that had an air conditioner but no window screens. The mother reported that the patient had received multiple mosquito bites while playing in the woods near his home the week before symptom onset. He had no recent travel out of northwest Missouri. None of his family members were ill.

The patient's acute serum samples were not available from the hospital, and the parents did not consent to another blood draw. A sample of CSF collected during hospitalization was sent to CDC on September 3 and was reported positive by CDC on September 23 for LACV neutralizing antibodies. A titer of 1:128 was reported based on results of a plaque-reduction neutralization test (PRNT) with a 90% cutoff value (PRNT90). Convalescent serum collected on October 2 was reported positive by CDC on November 2 for LACV-specific IgM and IgG by capture enzyme-linked immunosorbent assay and for LACV neutralizing antibodies by PRNT. CDC tested the same serum sample for neutralizing antibodies against the closely related Jamestown Canyon virus by PRNT90 to rule out potential cross-reactivity; the titers for LACV were 1:10,240, whereas the titers for Jamestown Canyon virus were 1:40. LACV infection was confirmed.

On November 11, an examination was conducted in a 300-foot radius around the patient's home to locate and count containers that might serve as habitats for mosquito larvae; 14 tree holes and eight discarded tires, one of which contained water and mosquito larvae, were identified.

Reported by

S Patrick, PhD, G Turabelidze, MD, K Yates, MS, Missouri Dept of Health and Senior Svcs; A Myers, MD, Children's Mercy Hospitals and Clinics, Kansas City, and School of Medicine, Univ of Missouri-Kansas City, Missouri. R Nasci, PhD, Div of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases; KB Gibney, MBBS, YC Lo, MD, EIS officers, CDC.

Editorial Note

Before the case reported here, LACV neuroinvasive disease was last reported in Missouri in 2002 (in a girl aged 10 years from northeastern Missouri) and 13 cases were reported in the state during 1973--2001. LACV neuroinvasive disease has never been reported in Kansas or Nebraska. However, identification of this LACV case in northwest Missouri, near the border with Kansas, increases concern that LACV disease might have been underrecognized and underreported in this region. Because Ae. triseriatus is found throughout Missouri and as far west as central Kansas and eastern Nebraska, health-care providers serving this region should maintain a high clinical suspicion for LACV among patients with unexplained meningoencephalitis during summer and fall, when mosquitoes are active.

This investigation identified two characteristic Ae. triseriatus habitats, tree holes and discarded tires, near the patient's home. Holes in trees near areas in which persons live are a risk factor for LACV neuroinvasive disease (3,4). The holes can collect water and become breeding sites for mosquitoes. Similarly, manufactured containers (e.g., tires and buckets) might increase the risk for LACV transmission by increasing local mosquito density around the residence (3).

LACV neuroinvasive disease was first described from La Crosse County, Wisconsin, after isolation of the virus in 1964 from brain tissue of a girl aged 4 years who had died of encephalitis in 1960 (5,6). The incubation period in humans ranges from 5 to 15 days. Common reservoirs of LACV are small mammals such as chipmunks and squirrels. LACV passes from the female Ae. triseriatus mosquito to the eggs she lays, survives in dormant eggs through the winter, and results in infectious adult mosquitoes in the spring. LACV causes an illness that often includes fever, headache, nausea, vomiting, seizures, and disorientation (7). Severe neuroinvasive disease occurs most frequently among children. Neurologic sequelae, including epilepsy, hemiparesis, and cognitive and neurobehavioral abnormalities, have been reported in 6%−15% of all diagnosed cases (1).

California serogroup virus neuroinvasive disease has been nationally notifiable since 1995; however, CDC has been collecting data on the etiologic agents of arboviral neuroinvasive disease, including California serogroup viruses, since 1964. The highest number of California serogroup virus cases was reported in 2002; during 2003--2007, a total of 412 cases were reported (range: 50--113 cases per year). During 2003--2007, 407 (99%) of the 412 California serogroup virus neuroinvasive disease cases reported to CDC were LACV; of the 398 LACV cases for which outcome was known, seven (2%) were fatal (8). The disease is likely underdiagnosed because it mimics other viral encephalitides (e.g., enteroviral and herpes virus encephalitides) (1,9).

During the 1960s and 1970s, most cases of LACV neuroinvasive disease were reported from states in the upper Midwest (Illinois, Indiana, Iowa, Minnesota, Ohio, and Wisconsin). Since the mid-1980s, more cases have been reported from mid-Atlantic states (North Carolina, Tennessee, Virginia, and West Virginia). The reason for the increase in cases reported outside the upper Midwest is unclear but might be related to changes in diagnosis, reporting, or the ecology of the vectors (10).

This report indicates that LACV neuroinvasive disease still can occur in Missouri. CDC recommendations to reduce the risk for LACV infection include using mosquito repellents; wearing long sleeves, long pants, and socks; installing and repairing screens; filling tree holes; and removing standing water from containers. When LACV disease is suspected or confirmed, health-care providers should promptly report the case to the state and local public health departments. A Food and Drug Administration (FDA)-cleared and commercially available kit providing indirect IFA to detect IgM and IgG antibodies against California serogroup viruses can be useful in making a presumptive diagnosis. The FDA-cleared, commercially available test was validated for use with serum samples only. Currently, no FDA-cleared immunoassays are available for detection of LACV-specific IgM or IgG antibodies in serum or CSF. Confirmatory serologic testing by PRNT performed in a public health reference laboratory is recommended to differentiate LACV from other California serogroup viruses (1). Testing for LACV and other arboviruses can be performed at certain state public health laboratories and at CDC's Arboviral Diseases Branch (telephone: 970-221-6400). More information is available from CDC at http://www.cdc.gov/lac/index.html.

Acknowledgments

This report is based, in part, on data contributed by the Independence City Health Dept and the Kansas City Health Dept; P Franklin, H Marx, and J Bauer, Missouri Dept of Health and Senior Svcs; T Sheffer, Dept of Pathology and Laboratory Medicine, Children's Mercy Hospitals and Clinics, Kansas City, Missouri; R Houseman, PhD, Div of Plant Sciences, Univ of Missouri-Columbia; and R Lanciotti, PhD, Div of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, CDC.

References

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10. Haddow AD, Odoi A. The incidence risk, clustering, and clinical presentation of La Crosse virus infections in the eastern United States, 2003--2007. PLoS ONE 2009;4:e6145. Available at http://www.plosone.org/article/info%3adoi%2f10.1371%2fjournal.pone.0006145. Accessed July 21, 2010.

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