TY - JOUR
T1 - A review of the frequencies of Plasmodium falciparum Kelch 13 artemisinin resistance mutations in Africa
AU - Ndwiga, Leonard
AU - Kimenyi, Kelvin M.
AU - Wamae, Kevin
AU - Osoti, Victor
AU - Akinyi, Mercy
AU - Omedo, Irene
AU - Ishengoma, Deus S.
AU - Duah-Quashie, Nancy
AU - Andagalu, Ben
AU - Ghansah, Anita
AU - Amambua-Ngwa, Alfred
AU - Tukwasibwe, Stephen
AU - Tessema, Sofonias K.
AU - Karema, Corine
AU - Djimde, Abdoulaye A.
AU - Dondorp, Arjen M.
AU - Raman, Jaishree
AU - Snow, Robert W.
AU - Bejon, Philip
AU - Ochola-Oyier, Lynette Isabella
N1 - Funding Information: The DELTAS Africa Initiative (Grant No. DEL-15-003 ), an independent funding scheme of the African Academy of Sciences ( AAS ) Alliance for Accelerating Excellence in Science in Africa ( AESA ) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust and the UK government, DELGEME Grant 107740/Z/15/Z supports K.M.K and IDeAL Grant No. 107769/Z/10/Z supported K.W and M.A. The views expressed in this publication are those of the author(s) and not necessarily those of AAS, NEPAD Agency, Wellcome Trust or the UK government. RWS is supported as a Wellcome Trust Principal Fellow (# 212176 ). LN, KMK, KW, VO, MA, IO, RWS, PB and LIOO are grateful to the support of the Wellcome Trust to the Kenya Major Overseas Programme (# 203077). L.I.O–O and V.O. are supported by a Wellcome Trust Intermediate Fellowship (Grant No. 107568/Z/15/Z awarded to L.I.O–O). We also thank the Director of KEMRI for permission to publish this article. Funding Information: How to intergrate molecular surveillance and clinical effectiveness to support decision making by National Malaria Control Programmes needs defining and needs investment in order to stay ahead of the ART resistance curve. Taking lessons from historically successful networks, twenty years ago, the East African Network for Monitoring Antimalarial Treatment (EANMAT) served as a flagship collaboration between sub-regional research scientists and national ministry of health case-management implementing and policy staff (EANMAT, 2001; EANMAT, 2003). The network successfully lobbied governments and donors to switch to ACTs that were expected to last for a long time, in 2004, however EANMAT has been inactive since 2004. Re-establishing sentinel surveillance sites to formulate evidence-based antimalarial drug policies through sub-regional technical networks for monitoring antimalarial resistance such as EANMAT, West African Network for Monitoring Antimalarial Treatment (WANMAT) and Horn of Africa Network for Monitoring Antimalarial Treatment (HANMAT) (EANMAT, 2000; EANMAT, 2001; Talisuna et al., 2006; HANMAT Report 2013), would provide an effective framework to combine longitudinal, sentinel site surveillance and clinical therapeutic efficacy studies (TES). In addition, including the new recommendation of a change in drug policy if day 28 or day 42 efficacy falls below 90% in TES (WHO Report on antimalarial efficacy, 2020) to transform policy and provide a holistic view of antimalarial resistance in Africa.The DELTAS Africa Initiative (Grant No. DEL-15-003), an independent funding scheme of the African Academy of Sciences (AAS) Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust and the UK government, DELGEME Grant 107740/Z/15/Z supports K.M.K and IDeAL Grant No. 107769/Z/10/Z supported K.W and M.A. The views expressed in this publication are those of the author(s) and not necessarily those of AAS, NEPAD Agency, Wellcome Trust or the UK government. RWS is supported as a Wellcome Trust Principal Fellow (# 212176). LN, KMK, KW, VO, MA, IO, RWS, PB and LIOO are grateful to the support of the Wellcome Trust to the Kenya Major Overseas Programme (# 203077). L.I.O?O and V.O. are supported by a Wellcome Trust Intermediate Fellowship (Grant No. 107568/Z/15/Z awarded to L.I.O?O). We also thank the Director of KEMRI for permission to publish this article. Publisher Copyright: © 2021 The Authors
PY - 2021/8/1
Y1 - 2021/8/1
N2 - Artemisinin resistance (AR) emerged in South East Asia 13 years ago and the identification of the resistance conferring molecular marker, Plasmodium falciparum Kelch 13 (Pfk13), 7 years ago has provided an invaluable tool for monitoring AR in malaria endemic countries. Molecular Pfk13 surveillance revealed the resistance foci in the Greater Mekong Subregion, an independent emergence in Guyana, South America, and a low frequency of mutations in Africa. The recent identification of the R561H Pfk13 AR associated mutation in Tanzania, Uganda and in Rwanda, where it has been associated with delayed parasite clearance, should be a concern for the continent. In this review, we provide a summary of Pfk13 resistance associated propeller domain mutation frequencies across Africa from 2012 to 2020, to examine how many other countries have identified these mutations. Only four African countries reported a recent identification of the M476I, P553L, R561H, P574L, C580Y and A675V Pfk13 mutations at low frequencies and with no reports of clinical treatment failure, except for Rwanda. These mutations present a threat to malaria control across the continent, since the greatest burden of malaria remains in Africa. A rise in the frequency of these mutations and their spread would reverse the gains made in the reduction of malaria over the last 20 years, given the lack of new antimalarial treatments in the event artemisinin-based combination therapies fail. The review highlights the frequency of Pfk13 propeller domain mutations across Africa, providing an up-to-date perspective of Pfk13 mutations, and appeals for an urgent and concerted effort to monitoring antimalarial resistance markers in Africa and the efficacy of antimalarials by re-establishing sentinel surveillance systems.
AB - Artemisinin resistance (AR) emerged in South East Asia 13 years ago and the identification of the resistance conferring molecular marker, Plasmodium falciparum Kelch 13 (Pfk13), 7 years ago has provided an invaluable tool for monitoring AR in malaria endemic countries. Molecular Pfk13 surveillance revealed the resistance foci in the Greater Mekong Subregion, an independent emergence in Guyana, South America, and a low frequency of mutations in Africa. The recent identification of the R561H Pfk13 AR associated mutation in Tanzania, Uganda and in Rwanda, where it has been associated with delayed parasite clearance, should be a concern for the continent. In this review, we provide a summary of Pfk13 resistance associated propeller domain mutation frequencies across Africa from 2012 to 2020, to examine how many other countries have identified these mutations. Only four African countries reported a recent identification of the M476I, P553L, R561H, P574L, C580Y and A675V Pfk13 mutations at low frequencies and with no reports of clinical treatment failure, except for Rwanda. These mutations present a threat to malaria control across the continent, since the greatest burden of malaria remains in Africa. A rise in the frequency of these mutations and their spread would reverse the gains made in the reduction of malaria over the last 20 years, given the lack of new antimalarial treatments in the event artemisinin-based combination therapies fail. The review highlights the frequency of Pfk13 propeller domain mutations across Africa, providing an up-to-date perspective of Pfk13 mutations, and appeals for an urgent and concerted effort to monitoring antimalarial resistance markers in Africa and the efficacy of antimalarials by re-establishing sentinel surveillance systems.
KW - ACT
KW - Artemisinin resistance
KW - Molecular marker
KW - Pfk13
UR - http://www.scopus.com/inward/record.url?scp=85108099892&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ijpddr.2021.06.001
DO - https://doi.org/10.1016/j.ijpddr.2021.06.001
M3 - Review article
C2 - 34146993
SN - 2211-3207
VL - 16
SP - 155
EP - 161
JO - INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
JF - INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
ER -