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Ex vivo susceptibility of Plasmodium falciparum to antimalarial drugs in Northern Uganda.

Authors
  • Fukuda, Naoyuki1
  • Tachibana, Shin-Ichiro1
  • Ikeda, Mie1
  • Sakurai-Yatsushiro, Miki2
  • Balikagala, Betty1
  • Katuro, Osbert T3
  • Yamauchi, Masato1
  • Emoto, Sakurako1
  • Hashimoto, Muneaki4
  • Yatsushiro, Shouki4
  • Sekihara, Makoto1
  • Mori, Toshiyuki1
  • Hirai, Makoto1
  • Opio, Walter5
  • Obwoya, Paul S5
  • Auma, Mary A5
  • Anywar, Denis A6
  • Kataoka, Masatoshi4
  • Palacpac, Nirianne M Q7
  • Odongo-Aginya, Emmanuel I6
  • And 4 more
  • 1 Department of Tropical Medicine and Parasitology, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. , (Japan)
  • 2 Department of International Affairs and Tropical Medicine, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. , (Japan)
  • 3 Mildmay Uganda, Nazibwa Hill, Lweza, P.O. Box 24985, Kampala, Uganda. , (Uganda)
  • 4 Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 2217-14, Hayashi-cho, Takamatsu, Kagawa, 761-0301, Japan. , (Japan)
  • 5 St. Mary's Hospital Lacor, P.O. Box 180, Gulu, Uganda. , (Uganda)
  • 6 Faculty of Medicine, Gulu University, P.O. Box 166, Gulu, Uganda. , (Uganda)
  • 7 Department of Malaria Vaccine Development, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. , (Japan)
  • 8 School of Tropical Medicine and Global Health, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, Nagasaki 852-8523, Japan. , (Japan)
  • 9 Department of Tropical Medicine and Parasitology, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: [email protected] , (Japan)
Type
Published Article
Journal
Parasitology international
Publication Date
Dec 25, 2020
Volume
81
Pages
102277–102277
Identifiers
DOI: 10.1016/j.parint.2020.102277
PMID: 33370608
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.

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