When infection is more severe the person may experience headache, high fever, neck stiffness, stupor, disorientation, coma, tremors, occasional convulsions and spastic paralysis.

A recent evolutionary study[9] based on 23 new full open reading frame sequences (near-complete genomes) found that the North American strains belonged to a single clade.

Positive selection was statistically detected only at one single codon coding for amino acids belonging to the hypothesized N-linked glycosylation site of the envelope protein.

In an independent study[8] 14 out of 106 examined envelope gene sequences were found not to contain a specific codon at position 156 coding for this glycosylation site (Ser→Phe/Tyr).

There are no vaccines or any other treatments specifically for Saint Louis encephalitis virus, although one study showed that early use of interferon alfa-2b may decrease the severity of complications.

In temperate areas of the United States, Saint Louis encephalitis cases occur primarily in the late summer or early fall.