Deciphering the etiology of the 2024 outbreak of undiagnosed febrile illness in Panzi, Democratic Republic of the Congo.

In late 2024, an outbreak of over 400 cases of undiagnosed febrile illness, predominantly presenting as fever and cough, was reported in Panzi Health Zone, southwestern Democratic Republic of the Congo. Here we conducted an epidemiological and laboratory investigation to determine the etiology of the outbreak. Clinical data and specimens were prospectively collected from 108 individuals, of whom 59/108 (54.6%) were female. Children aged <5 years were the most affected (47/108, 43.5%); 14/32 (43.7%) were malnourished. Oro/nasopharyngeal swabs from 96/108 individuals were PCR tested; 26 blood samples were sequenced. Plasmodium falciparum was detected in 56/108 (51.8%) individuals. Co-infections were also detected, with influenza A(H1N1)pdm09 virus in 16/56 (28.6%) and severe acute respiratory syndrome coronavirus 2 in 10/56 (17.9%) individuals. No novel pathogens were detected via metagenomics. Our findings suggest that the outbreak was primarily associated with a surge in malaria cases, with concurrent viral respiratory infections. Increasing decentralized laboratory capacity and strengthening broader health systems remain crucial for faster outbreak detection and investigation.