Plasmodium falciparum resistant to artemisinin and diagnostics have emerged in Ethiopia

• Published in: Nature microbiology Vol. 8; no. 10; pp. 1911 - 1919
• Main Authors: Fola, Abebe A., Feleke, Sindew M., Mohammed, Hussein, Brhane, Bokretsion G., Hennelly, Christopher M., Assefa, Ashenafi, Crudal, Rebecca M., Reichert, Emily, Juliano, Jonathan J., Cunningham, Jane, Mamo, Hassen, Solomon, Hiwot, Tasew, Geremew, Petros, Beyene, Parr, Jonathan B., Bailey, Jeffrey A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2023; Nature Publishing Group
• Subjects: 45; 45/22; 45/23; 45/41; 45/77; 631/326/2521; 631/326/417/2551; Analysis; Antimalarials - pharmacology; Artemisinin; Artemisinins - pharmacology; Biomedical and Life Sciences; Drug resistance; Ethiopia - epidemiology; Genomes; Histidine; Humans; Infectious Diseases; Life Sciences; Malaria; Malaria, Falciparum - diagnosis; Malaria, Falciparum - drug therapy; Malaria, Falciparum - epidemiology; Medical Microbiology; Microbiology; Mutation; Parasite resistance; Parasites; Parasitology; Plasmodium falciparum; Plasmodium falciparum - metabolism; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Virology; Ethiopia
• ISSN: 2058-5276; 2058-5276
• DOI: 10.1038/s41564-023-01461-4

Diagnosis and treatment of Plasmodium falciparum infections are required for effective malaria control and are pre-requisites for malaria elimination efforts; hence we need to monitor emergence, evolution and spread of drug- and diagnostics-resistant parasites. We deep sequenced key drug-resistance mutations and 1,832 SNPs in the parasite genomes of 609 malaria cases collected during a diagnostic-resistance surveillance study in Ethiopia. We found that 8.0% (95% CI 7.0–9.0) of malaria cases were caused by P. falciparum carrying the candidate artemisinin partial-resistance kelch13 ( K13 ) 622I mutation, which was less common in diagnostic-resistant parasites mediated by histidine-rich proteins 2 and 3 ( pfhrp2/3 ) deletions than in wild-type parasites ( P  = 0.03). Identity-by-descent analyses showed that K13 622I parasites were significantly more related to each other than to wild type ( P  < 0.001), consistent with recent expansion and spread of this mutation. Pfhrp2/3- deleted parasites were also highly related, with evidence of clonal transmissions at the district level. Of concern, 8.2% of K13 622I parasites also carried the pfhrp2/3 deletions. Close monitoring of the spread of combined drug- and diagnostic-resistant parasites is needed. Plasmodium falciparum candidate artemisinin partial-resistance Kelch13 622I mutation co-occurs with pfhrp2/3 deletions in Ethiopia.