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Ex vivo susceptibility of Plasmodium falciparum to antimalarial drugs in Northern Uganda. 2021
Naoyuki Fukuda, and
Shin-Ichiro Tachibana, and
Mie Ikeda, and
Miki Sakurai-Yatsushiro, and
Betty Balikagala, and
Osbert T Katuro, and
Masato Yamauchi, and
Sakurako Emoto, and
Muneaki Hashimoto, and
Shouki Yatsushiro, and
Makoto Sekihara, and
Toshiyuki Mori, and
Makoto Hirai, and
Walter Opio, and
Paul S Obwoya, and
Mary A Auma, and
Denis A Anywar, and
Masatoshi Kataoka, and
Nirianne M Q Palacpac, and
Emmanuel I Odongo-Aginya, and
Eisaku Kimura, and
Martin Ogwang, and
Toshihiro Horii, and
Toshihiro Mita
Department of Tropical Medicine and Parasitology, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
In Uganda, artemether-lumefantrine was introduced as an artemisinin-based combination therapy (ACT) for malaria in 2006. We have previously reported a moderate decrease in ex vivo efficacy of lumefantrine in Northern Uganda, where we also detected ex vivo artemisinin-resistant Plasmodium falciparum. Therefore, it is necessary to search for candidate partner alternatives for ACT. Here, we investigated ex vivo susceptibility to four ACT partner drugs as well as quinine and chloroquine, in 321 cases between 2013 and 2018. Drug-resistant mutations in pfcrt and pfmdr1 were also determined. Ex vivo susceptibility to amodiaquine, quinine, and chloroquine was well preserved, whereas resistance to mefloquine was found in 45.8%. There were few cases of multi-drug resistance. Reduced sensitivity to mefloquine and lumefantrine was significantly associated with the pfcrt K76 wild-type allele, in contrast to the association between chloroquine resistance and the K76T allele. Pfmdr1 duplication was not detected in any of the cases. Amodiaquine, a widely used partner drug for ACT in African countries, may be the first promising alternative in case lumefantrine resistance emerges. Therapeutic use of mefloquine may not be recommended in this area. This study also emphasizes the need for sustained monitoring of antimalarial susceptibility in Northern Uganda to develop proper treatment strategies.
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