Recovery and stable persistence of chloroquine sensitivity in Plasmodium falciparum parasites after its discontinued use in Northern Uganda
Abstract Background Usage of chloroquine was discontinued from the treatment of Plasmodium falciparum infection in almost all endemic regions because of global spread of resistant parasites. Since the first report in Malawi, numerous epidemiological studies have demonstrated that the discontinuance...
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BMC
2020-02-01
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| Series: | Malaria Journal |
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| Online Access: | http://link.springer.com/article/10.1186/s12936-020-03157-0 |
| _version_ | 1819092830684971008 |
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| author | Betty Balikagala Miki Sakurai-Yatsushiro Shin-Ichiro Tachibana Mie Ikeda Masato Yamauchi Osbert T. Katuro Edward H. Ntege Makoto Sekihara Naoyuki Fukuda Nobuyuki Takahashi Shouki Yatsushiro Toshiyuki Mori Makoto Hirai Walter Opio Paul S. Obwoya Denis A. Anywar Mary A. Auma Nirianne M. Q. Palacpac Takafumi Tsuboi Emmanuel I. Odongo-Aginya Eisaku Kimura Martin Ogwang Toshihiro Horii Toshihiro Mita |
| author_facet | Betty Balikagala Miki Sakurai-Yatsushiro Shin-Ichiro Tachibana Mie Ikeda Masato Yamauchi Osbert T. Katuro Edward H. Ntege Makoto Sekihara Naoyuki Fukuda Nobuyuki Takahashi Shouki Yatsushiro Toshiyuki Mori Makoto Hirai Walter Opio Paul S. Obwoya Denis A. Anywar Mary A. Auma Nirianne M. Q. Palacpac Takafumi Tsuboi Emmanuel I. Odongo-Aginya Eisaku Kimura Martin Ogwang Toshihiro Horii Toshihiro Mita |
| author_sort | Betty Balikagala |
| collection | DOAJ |
| description | Abstract Background Usage of chloroquine was discontinued from the treatment of Plasmodium falciparum infection in almost all endemic regions because of global spread of resistant parasites. Since the first report in Malawi, numerous epidemiological studies have demonstrated that the discontinuance led to re-emergence of chloroquine-susceptible P. falciparum, suggesting a possible role in future malaria control. However, most studies were cross-sectional, with few studies looking at the persistence of chloroquine recovery in long term. This study fills the gap by providing, for a period of at least 6 years, proof of persistent re-emergence/stable recovery of susceptible parasite populations using both molecular and phenotypic methods. Methods Ex vivo drug-susceptibility assays to chloroquine (n = 319) and lumefantrine (n = 335) were performed from 2013 to 2018 in Gulu, Northern Uganda, where chloroquine had been removed from the official malaria treatment regimen since 2006. Genotyping of pfcrt and pfmdr1 was also performed. Results Chloroquine resistance (≥ 100 nM) was observed in only 3 (1.3%) samples. Average IC50 values for chloroquine were persistently low throughout the study period (17.4–24.9 nM). Parasites harbouring pfcrt K76 alleles showed significantly lower IC50s to chloroquine than the parasites harbouring K76T alleles (21.4 nM vs. 43.1 nM, p-value = 3.9 × 10−8). Prevalence of K76 alleles gradually increased from 71% in 2013 to 100% in 2018. Conclusion This study found evidence of stable persistence of chloroquine susceptibility with the fixation of pfcrt K76 in Northern Uganda after discontinuation of chloroquine in the region. Accumulation of similar evidence in other endemic areas in Uganda could open channels for possible future re-use of chloroquine as an option for malaria treatment or prevention. |
| first_indexed | 2024-12-21T23:01:51Z |
| format | Article |
| id | doaj.art-a30e9925e11f4df196431e86b981ef3e |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-21T23:01:51Z |
| publishDate | 2020-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-a30e9925e11f4df196431e86b981ef3e2022-12-21T18:47:16ZengBMCMalaria Journal1475-28752020-02-0119111210.1186/s12936-020-03157-0Recovery and stable persistence of chloroquine sensitivity in Plasmodium falciparum parasites after its discontinued use in Northern UgandaBetty Balikagala0Miki Sakurai-Yatsushiro1Shin-Ichiro Tachibana2Mie Ikeda3Masato Yamauchi4Osbert T. Katuro5Edward H. Ntege6Makoto Sekihara7Naoyuki Fukuda8Nobuyuki Takahashi9Shouki Yatsushiro10Toshiyuki Mori11Makoto Hirai12Walter Opio13Paul S. Obwoya14Denis A. Anywar15Mary A. Auma16Nirianne M. Q. Palacpac17Takafumi Tsuboi18Emmanuel I. Odongo-Aginya19Eisaku Kimura20Martin Ogwang21Toshihiro Horii22Toshihiro Mita23Department of Tropical Medicine and Parasitology, School of Medicine, Juntendo UniversityDepartment of International Affairs and Tropical Medicine, School of Medicine, Tokyo Women’s Medical UniversityDepartment of Tropical Medicine and Parasitology, School of Medicine, Juntendo UniversityDepartment of Tropical Medicine and Parasitology, School of Medicine, Juntendo UniversityDepartment of Tropical Medicine and Parasitology, School of Medicine, Juntendo UniversityMildmay UgandaDivision of Malaria Research, Proteo-Science Center, Ehime UniversityDepartment of Tropical Medicine and Parasitology, School of Medicine, Juntendo UniversityDepartment of Tropical Medicine and Parasitology, School of Medicine, Juntendo UniversityDepartment of International Affairs and Tropical Medicine, School of Medicine, Tokyo Women’s Medical UniversityHealth Research Institute, National Institute of Advanced Industrial Science and Technology (AIST)Department of Tropical Medicine and Parasitology, School of Medicine, Juntendo UniversityDepartment of Tropical Medicine and Parasitology, School of Medicine, Juntendo UniversitySt. Mary’s Hospital LacorSt. Mary’s Hospital LacorFaculty of Science, Gulu UniversitySt. Mary’s Hospital LacorDepartment of Malaria Vaccine Development, Research Institute for Microbial Diseases, Osaka UniversityDivision of Malaria Research, Proteo-Science Center, Ehime UniversityFaculty of Science, Gulu UniversityInstitute of Tropical Medicine, Nagasaki UniversitySt. Mary’s Hospital LacorDepartment of Malaria Vaccine Development, Research Institute for Microbial Diseases, Osaka UniversityDepartment of Tropical Medicine and Parasitology, School of Medicine, Juntendo UniversityAbstract Background Usage of chloroquine was discontinued from the treatment of Plasmodium falciparum infection in almost all endemic regions because of global spread of resistant parasites. Since the first report in Malawi, numerous epidemiological studies have demonstrated that the discontinuance led to re-emergence of chloroquine-susceptible P. falciparum, suggesting a possible role in future malaria control. However, most studies were cross-sectional, with few studies looking at the persistence of chloroquine recovery in long term. This study fills the gap by providing, for a period of at least 6 years, proof of persistent re-emergence/stable recovery of susceptible parasite populations using both molecular and phenotypic methods. Methods Ex vivo drug-susceptibility assays to chloroquine (n = 319) and lumefantrine (n = 335) were performed from 2013 to 2018 in Gulu, Northern Uganda, where chloroquine had been removed from the official malaria treatment regimen since 2006. Genotyping of pfcrt and pfmdr1 was also performed. Results Chloroquine resistance (≥ 100 nM) was observed in only 3 (1.3%) samples. Average IC50 values for chloroquine were persistently low throughout the study period (17.4–24.9 nM). Parasites harbouring pfcrt K76 alleles showed significantly lower IC50s to chloroquine than the parasites harbouring K76T alleles (21.4 nM vs. 43.1 nM, p-value = 3.9 × 10−8). Prevalence of K76 alleles gradually increased from 71% in 2013 to 100% in 2018. Conclusion This study found evidence of stable persistence of chloroquine susceptibility with the fixation of pfcrt K76 in Northern Uganda after discontinuation of chloroquine in the region. Accumulation of similar evidence in other endemic areas in Uganda could open channels for possible future re-use of chloroquine as an option for malaria treatment or prevention.http://link.springer.com/article/10.1186/s12936-020-03157-0Chloroquine sensitivityPersistent recoveryPlasmodium falciparumUganda |
| spellingShingle | Betty Balikagala Miki Sakurai-Yatsushiro Shin-Ichiro Tachibana Mie Ikeda Masato Yamauchi Osbert T. Katuro Edward H. Ntege Makoto Sekihara Naoyuki Fukuda Nobuyuki Takahashi Shouki Yatsushiro Toshiyuki Mori Makoto Hirai Walter Opio Paul S. Obwoya Denis A. Anywar Mary A. Auma Nirianne M. Q. Palacpac Takafumi Tsuboi Emmanuel I. Odongo-Aginya Eisaku Kimura Martin Ogwang Toshihiro Horii Toshihiro Mita Recovery and stable persistence of chloroquine sensitivity in Plasmodium falciparum parasites after its discontinued use in Northern Uganda Malaria Journal Chloroquine sensitivity Persistent recovery Plasmodium falciparum Uganda |
| title | Recovery and stable persistence of chloroquine sensitivity in Plasmodium falciparum parasites after its discontinued use in Northern Uganda |
| title_full | Recovery and stable persistence of chloroquine sensitivity in Plasmodium falciparum parasites after its discontinued use in Northern Uganda |
| title_fullStr | Recovery and stable persistence of chloroquine sensitivity in Plasmodium falciparum parasites after its discontinued use in Northern Uganda |
| title_full_unstemmed | Recovery and stable persistence of chloroquine sensitivity in Plasmodium falciparum parasites after its discontinued use in Northern Uganda |
| title_short | Recovery and stable persistence of chloroquine sensitivity in Plasmodium falciparum parasites after its discontinued use in Northern Uganda |
| title_sort | recovery and stable persistence of chloroquine sensitivity in plasmodium falciparum parasites after its discontinued use in northern uganda |
| topic | Chloroquine sensitivity Persistent recovery Plasmodium falciparum Uganda |
| url | http://link.springer.com/article/10.1186/s12936-020-03157-0 |
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