It happened in the area of Highway 65 and Avenue 196 near Strathmore just after 2:00 a.m. on Sunday.
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Officers say 24-year-old Jazmin Paramo was driving northbound in the southbound lane of Highway 65 when she crashed head-on into two motorcycles.
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CHP says the motorcycle riders, two men and two women in their forties, died at the scene. Their names have not been released by authorities.
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Paramo was transported to Kaweah Delta Medical Center with moderate injuries. Officers say she has been booked into the Tulare County Jail for suspicion of DUI.