Closing the Brief Case: A 10-Year-Old Girl with Meningoencephalitis

ANSWERS TO SELF-ASSESSMENT QUESTIONS

1. Infection with JCV may result in serologic cross-reactivity with which of the following viruses?

   1. La Crosse virus
   2. Cytomegalovirus
   3. Enterovirus
   4. Powassan virus

Answer: A. La Crosse virus. Patients infected with Jamestown Canyon virus may show serologic cross-reactivity with other viruses in the California serogroup, such as La Crosse virus. Due to this cross-reactivity, plaque reduction neutralization testing (PRNT) is required to confirm a diagnosis of JCV, with a 4-fold (or greater) difference in endpoint titer between tests allowing for a diagnosis to be established. No serologic cross-reactivity would be expected with viruses in the Herpesviridae family (e.g., cytomegalovirus), enteroviruses, or flaviviruses, including Powassan virus.

1. Which of the following statements about JCV is true?

   1. Infections most commonly occur between October and March in the United States
   2. Transmission has been documented by several different species of mosquito vectors
   3. Laboratory diagnosis of JCV is most commonly made by real-time PCR with confirmation requiring growth of the virus in cell culture
   4. Vaccination for JCV is recommended in the United States for all adults 18 to 65 years of age

Answer: B. Transmission has been documented for several different species of mosquito vectors. Jamestown Canyon virus is transmitted through the bite of infected mosquitoes, most commonly during the months of April to September in the United States. Currently, no vaccine or specific antiviral therapy is available, and patients with JCV disease are managed with supportive care. Nucleic acid amplification tests or viral culture are not usually performed as part of the diagnostic workup for JCV.

1. Which of the following methods is used to confirm a diagnosis of JCV infection?

   1. IgM enzyme immunoassay
   2. Plaque reduction neutralization test
   3. IgM immunofluorescence assay
   4. NS1 antigen

Answer: B. Plaque reduction neutralization test. PRNT is used to confirm JCV infection following a positive or equivocal result for IgM-class antibodies by enzyme immunoassay or immunofluorescence assay. PRNT is also used to compare the endpoint neutralizing antibody titers between closely related viruses, with the infectious virus most frequently identified as the one with at least a 4-fold or higher endpoint titer compared to the other tested viruses. This is especially helpful if serologic testing is positive for more than one virus in the California serogroup, which occurs frequently due to the cross-reactivity of these assays.

TAKE-HOME POINTS

• Jamestown Canyon virus is an arboviral infection that is spread through the bite of infected mosquitoes. Infection may result in a nonspecific febrile illness and, in ∼50% of cases, central nervous system disease.

• Jamestown Canyon virus is a bunyavirus within the California serogroup and is closely related to La Crosse encephalitis virus.

• The diagnosis of Jamestown Canyon virus is most frequently made through serologic testing; however, there is significant cross-reactivity with other members of the California serogroup of viruses, including La Crosse, California encephalitis, and snowshoe hare viruses.

• PRNT is required to confirm the diagnosis of Jamestown Canyon virus, with PRNT endpoint titers for Jamestown Canyon virus being at least 4-fold higher than PRNT endpoint titers for other viruses.

See https://doi.org/10.1128/JCM.00254-18 in this issue for case presentation and discussion.