The Ethiopian highlands were historically believed to be malaria-free, yet clinical cases are frequently observed in health centers at elevations above 2,000 m. The proportion of cases that recently returned from the lowlands where malaria is endemic, seasonal patterns, and risk factors for infection are poorly described. Febrile patients were enrolled from November 2019 to September 2020 in a health center in Gondar, Ethiopia, at an elevation of 2,100 m. Plasmodium falciparum and P. vivax were detected by microscopy conducted at the health center and by quantitative polymerase chain reaction (qPCR). A total of 183 P. falciparum infections were typed for hrp2 and hrp3 gene deletions ( hrp2 : 2.7%; hrp3 : 55.2%; dual: 21.9%), and 1,819 participants were enrolled. Test positivity by microscopy and qPCR was 58.1% and 64.1% for P. falciparum , and 41.8% and 35.9% for P. vivax ; 3.1% of individuals reported travel to the lowlands within 4 weeks prior to sample collection. Travel increased the odds of malaria infection by 4.1 times, but 92.4% of individuals who tested positive did not report travel. Adults 16 to 35 years of age accounted for 57% of individuals who presented for testing, and test positivity peaked in this age group ( P. falciparum : 27.3%; P. vivax : 10.9%). Most individuals who were malaria-positive had not traveled, suggesting that local transmission is occurring within the Ethiopian highlands. The concentration of infections in adult males points to a strong behavior-related risk of infection.
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