Expansion of artemisinin partial resistance mutations and lack of histidine rich protein-2 and -3 deletions in Plasmodium falciparum infections from Rukara, Rwanda
Abstract Background Emerging artemisinin partial resistance and diagnostic resistance are a threat to malaria control in Africa. Plasmodium falciparum kelch13 (k13) propeller-domain mutations that confer artemisinin partial resistance have emerged in Africa. k13-561H was initially described at a fre...
Published in: | Malaria Journal |
---|---|
Main Authors: | , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
BMC
2024
|
Subjects: | |
Online Access: | https://doi.org/10.1186/s12936-024-04981-4 https://doaj.org/article/4261890500dc4fec81162e753d47366e |
id |
ftdoajarticles:oai:doaj.org/article:4261890500dc4fec81162e753d47366e |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:4261890500dc4fec81162e753d47366e 2024-09-09T19:28:18+00:00 Expansion of artemisinin partial resistance mutations and lack of histidine rich protein-2 and -3 deletions in Plasmodium falciparum infections from Rukara, Rwanda Cecile Schreidah David Giesbrecht Pierre Gashema Neeva Wernsman Young Tharcisse Munyaneza Claude Mambo Muvunyi Kyaw Thwai Jean-Baptiste Mazarati Jeffrey A. Bailey Jonathan J. Juliano Corine Karema 2024-05-01T00:00:00Z https://doi.org/10.1186/s12936-024-04981-4 https://doaj.org/article/4261890500dc4fec81162e753d47366e EN eng BMC https://doi.org/10.1186/s12936-024-04981-4 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-024-04981-4 1475-2875 https://doaj.org/article/4261890500dc4fec81162e753d47366e Malaria Journal, Vol 23, Iss 1, Pp 1-9 (2024) Artemisinin kelch13 K13 R561H Rukara Rwanda Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2024 ftdoajarticles https://doi.org/10.1186/s12936-024-04981-4 2024-08-05T17:49:22Z Abstract Background Emerging artemisinin partial resistance and diagnostic resistance are a threat to malaria control in Africa. Plasmodium falciparum kelch13 (k13) propeller-domain mutations that confer artemisinin partial resistance have emerged in Africa. k13-561H was initially described at a frequency of 7.4% from Masaka in 2014–2015, but not present in nearby Rukara. By 2018, 19.6% of isolates in Masaka and 22% of isolates in Rukara contained the mutation. Longitudinal monitoring is essential to inform control efforts. In Rukara, an assessment was conducted to evaluate recent k13-561H prevalence changes, as well as other key mutations. Prevalence of hrp2/3 deletions was also assessed. Methods Samples collected in Rukara in 2021 were genotyped for key artemisinin and partner drug resistance mutations using molecular inversion probe assays and for hrp2/3 deletions using qPCR. Results Clinically validated k13 artemisinin partial resistance mutations continue to increase in prevalence with the overall level of mutant infections reaching 32% in Rwanda. The increase appears to be due to the rapid emergence of k13-675V (6.4%, 6/94 infections), previously not observed, rather than continued expansion of 561H (23.5% 20/85). Mutations to partner drugs and other anti-malarials were variable, with high levels of multidrug resistance 1 (mdr1) N86 (95.5%) associated with lumefantrine decreased susceptibility and dihydrofolate reductase (dhfr) 164L (24.7%) associated with a high level of antifolate resistance, but low levels of amodiaquine resistance polymorphisms with chloroquine resistance transporter (crt) 76T: at 6.1% prevalence. No hrp2 or hrp3 gene deletions associated with diagnostic resistance were found. Conclusions Increasing prevalence of artemisinin partial resistance due to k13-561H and the rapid expansion of k13-675V is concerning for the longevity of artemisinin effectiveness in the region. False negative RDT results do not appear to be an issue with no hrp2 or hpr3 deletions detected. Continued molecular ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 23 1 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Artemisinin kelch13 K13 R561H Rukara Rwanda Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Artemisinin kelch13 K13 R561H Rukara Rwanda Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Cecile Schreidah David Giesbrecht Pierre Gashema Neeva Wernsman Young Tharcisse Munyaneza Claude Mambo Muvunyi Kyaw Thwai Jean-Baptiste Mazarati Jeffrey A. Bailey Jonathan J. Juliano Corine Karema Expansion of artemisinin partial resistance mutations and lack of histidine rich protein-2 and -3 deletions in Plasmodium falciparum infections from Rukara, Rwanda |
topic_facet |
Artemisinin kelch13 K13 R561H Rukara Rwanda Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Emerging artemisinin partial resistance and diagnostic resistance are a threat to malaria control in Africa. Plasmodium falciparum kelch13 (k13) propeller-domain mutations that confer artemisinin partial resistance have emerged in Africa. k13-561H was initially described at a frequency of 7.4% from Masaka in 2014–2015, but not present in nearby Rukara. By 2018, 19.6% of isolates in Masaka and 22% of isolates in Rukara contained the mutation. Longitudinal monitoring is essential to inform control efforts. In Rukara, an assessment was conducted to evaluate recent k13-561H prevalence changes, as well as other key mutations. Prevalence of hrp2/3 deletions was also assessed. Methods Samples collected in Rukara in 2021 were genotyped for key artemisinin and partner drug resistance mutations using molecular inversion probe assays and for hrp2/3 deletions using qPCR. Results Clinically validated k13 artemisinin partial resistance mutations continue to increase in prevalence with the overall level of mutant infections reaching 32% in Rwanda. The increase appears to be due to the rapid emergence of k13-675V (6.4%, 6/94 infections), previously not observed, rather than continued expansion of 561H (23.5% 20/85). Mutations to partner drugs and other anti-malarials were variable, with high levels of multidrug resistance 1 (mdr1) N86 (95.5%) associated with lumefantrine decreased susceptibility and dihydrofolate reductase (dhfr) 164L (24.7%) associated with a high level of antifolate resistance, but low levels of amodiaquine resistance polymorphisms with chloroquine resistance transporter (crt) 76T: at 6.1% prevalence. No hrp2 or hrp3 gene deletions associated with diagnostic resistance were found. Conclusions Increasing prevalence of artemisinin partial resistance due to k13-561H and the rapid expansion of k13-675V is concerning for the longevity of artemisinin effectiveness in the region. False negative RDT results do not appear to be an issue with no hrp2 or hpr3 deletions detected. Continued molecular ... |
format |
Article in Journal/Newspaper |
author |
Cecile Schreidah David Giesbrecht Pierre Gashema Neeva Wernsman Young Tharcisse Munyaneza Claude Mambo Muvunyi Kyaw Thwai Jean-Baptiste Mazarati Jeffrey A. Bailey Jonathan J. Juliano Corine Karema |
author_facet |
Cecile Schreidah David Giesbrecht Pierre Gashema Neeva Wernsman Young Tharcisse Munyaneza Claude Mambo Muvunyi Kyaw Thwai Jean-Baptiste Mazarati Jeffrey A. Bailey Jonathan J. Juliano Corine Karema |
author_sort |
Cecile Schreidah |
title |
Expansion of artemisinin partial resistance mutations and lack of histidine rich protein-2 and -3 deletions in Plasmodium falciparum infections from Rukara, Rwanda |
title_short |
Expansion of artemisinin partial resistance mutations and lack of histidine rich protein-2 and -3 deletions in Plasmodium falciparum infections from Rukara, Rwanda |
title_full |
Expansion of artemisinin partial resistance mutations and lack of histidine rich protein-2 and -3 deletions in Plasmodium falciparum infections from Rukara, Rwanda |
title_fullStr |
Expansion of artemisinin partial resistance mutations and lack of histidine rich protein-2 and -3 deletions in Plasmodium falciparum infections from Rukara, Rwanda |
title_full_unstemmed |
Expansion of artemisinin partial resistance mutations and lack of histidine rich protein-2 and -3 deletions in Plasmodium falciparum infections from Rukara, Rwanda |
title_sort |
expansion of artemisinin partial resistance mutations and lack of histidine rich protein-2 and -3 deletions in plasmodium falciparum infections from rukara, rwanda |
publisher |
BMC |
publishDate |
2024 |
url |
https://doi.org/10.1186/s12936-024-04981-4 https://doaj.org/article/4261890500dc4fec81162e753d47366e |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 23, Iss 1, Pp 1-9 (2024) |
op_relation |
https://doi.org/10.1186/s12936-024-04981-4 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-024-04981-4 1475-2875 https://doaj.org/article/4261890500dc4fec81162e753d47366e |
op_doi |
https://doi.org/10.1186/s12936-024-04981-4 |
container_title |
Malaria Journal |
container_volume |
23 |
container_issue |
1 |
_version_ |
1809897560766152704 |