Our CRISPR diagnostic can also detect clinically relevant levels of parasitemia in 40 min or less from unextracted blood samples (10-min S-PREP followed by 30-min SHERLOCK) with better sensitivity than existing POC antigen-based RDTs, filling an important clinical diagnostic gap for hrp2 deletion P. falciparum and nonfalciparum malaria. Here, HDGFL2 is linked to parasitic infectious disease.