Diagnosis of VEEV infection is based on clinical suspicion, history, and physical examination, with laboratory testing to confirm diagnosis. The clinical spectrum of disease overlaps with that caused by other viral infections. As a consequence, the differential diagnosis is broad and includes herpes encephalitis, dengue, Zika, and chikungunya virus infection.

A high index of suspicion is necessary to diagnose VEEV infection since cases tend to be sporadic. Although VEEV infections are generally confined to endemic regions (i.e., Central and South America), there have been numerous reports of infection in regions where VEEV is not traditionally endemic, which has led to delays in the diagnosis. 

The diagnosis of VEEV infection is suggested by the presence of clinical features (e.g., acute onset of fever, headache, myalgia, mental status changes, and gastrointestinal [GI] bleeding) in conjunction with epidemiological criteria (e.g., recent history of travelling, working, or residing in endemic regions, particularly tropical and rural regions where risk of exposure to mosquitoes is high). Other epidemiological and environmental factors that should raise suspicion include peak mosquito season, a recent period of high rainfall, or a concurrent epizootic outbreak in horses. Confirmation of the diagnosis requires laboratory investigations, consisting of serology or detection of the virus by reverse transcription-polymerase chain reaction (RT-PCR) or viral isolation. 

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