Medically important alphaviruses in the United States and how to test for them

Alphaviruses are arthropod-borne viruses (i.e. arboviruses) transmitted by mosquitos that are classically divided into two groups that infect humans: encephalitic and arthralgia-associated. While the encephalitic alphaviruses are primarily endemic in North and South America, alphaviruses associated with arthralgia are distributed globally. Given the overlapping clinical manifestations of alphaviruses with other arboviruses, diagnosis is dependent on both exposure history and laboratory testing. In the United States, diagnostic approaches largely rely on detection of host antibodies against these viruses via enzyme-linked immunosorbent assays (ELISAs) or indirect immunofluorescence assays (IFAs) in serum and/or cerebrospinal fluid. Positive results can be confirmed by plaque reduction neutralization testing (PRNT), which remains the reference standard method for anti-alphavirus antibody detection. Increasingly, select public health and reference laboratories are also offering molecular testing for certain alphaviruses, including chikungunya virus and Eastern equine encephalitis virus. Molecular testing, however, is most useful in acutely ill, viremic patients who present within the first week of symptom onset. There are no targeted antivirals for treatment, and prevention relies on protection from mosquito bites.