Artemisinin and partner drug resistance markers in Plasmodium falciparum from Tanzanian paediatric malaria patients, 2016–2022
Abstract Background Plasmodium falciparum malaria remains a significant public health concern in Tanzania, particularly among children under 5 years of age. The emergence and spread of partial artemisinin resistance in East Africa add to this concern. Specific mutations in the P. falciparum kelch-13...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
|
| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12936-025-05447-x |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849402775799070720 |
|---|---|
| author | Aveline Assey Silvia Scialabba Maria Mgella Zinga Philip Koliopoulos Welmoed van Loon Caroline A. Minja Britta Groendahl Johannes Plett Stephan Gehring Mariam M. Mirambo Neema Kayange Frank P. Mockenhaupt Stephen E. Mshana |
| author_facet | Aveline Assey Silvia Scialabba Maria Mgella Zinga Philip Koliopoulos Welmoed van Loon Caroline A. Minja Britta Groendahl Johannes Plett Stephan Gehring Mariam M. Mirambo Neema Kayange Frank P. Mockenhaupt Stephen E. Mshana |
| author_sort | Aveline Assey |
| collection | DOAJ |
| description | Abstract Background Plasmodium falciparum malaria remains a significant public health concern in Tanzania, particularly among children under 5 years of age. The emergence and spread of partial artemisinin resistance in East Africa add to this concern. Specific mutations in the P. falciparum kelch-13 (Pfk13) and multidrug drug resistance 1 (Pfmdr1) genes are associated with artemisinin resistance and lumefantrine tolerance, respectively. The emergence of antimalarial drug resistance may be associated with unstable transmission in sub-Saharan Africa (SSA). Time-trends of Pfk13 and Pfmdr1 mutations as well as the multiplicity of infection (MOI) as a proxy for transmission intensity were investigated. Methods Between 2016 and 2022, 173 P. falciparum PCR-positive samples were collected from febrile inpatient and outpatient children aged 3 months to 18 years at selected health facilities in Mwanza, Tanzania. Pfk13 and Pfmdr1 were amplified by PCR and Sanger-sequenced. Polymorphic Pfmsp1 and Pfmsp2 allelic markers were genotyped by nested PCR in 168 samples to assess MOI. Results Among 143 samples successfully sequenced for Pfk13, 7.0% (10/143) exhibited non-synonymous mutations including the WHO-validated artemisinin resistance marker R561H in 1.4% (2 patients, 2022). As for Pfmdr1, the wild-type N86 allele was observed in 100% (97/97) of isolates, and about half (55/97) carried the wild-type Y184 allele. The mean multiplicity of infection (MOI) was 1.5, and did not change significantly over time. Single-genotype and polyclonal infections were observed in 59.3% (80/135), and 40.7% (55/135) respectively. Conclusion This study from Mwanza, Tanzania demonstrates the presence of a validated artemisinin resistance marker Pfk13 R561H in 2022 and suggests increased lumefantrine tolerance. MOI as a proxy marker of endemicity was low and stable over the six years of observation. The detection of these resistance markers reinforces the need for continuous genetic surveillance to sustain the efficacy of antimalarial therapies in paediatric patients. |
| format | Article |
| id | doaj-art-18671d1bee7a4cb69a787b856425ae48 |
| institution | Kabale University |
| issn | 1475-2875 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj-art-18671d1bee7a4cb69a787b856425ae482025-08-20T03:37:28ZengBMCMalaria Journal1475-28752025-07-012411810.1186/s12936-025-05447-xArtemisinin and partner drug resistance markers in Plasmodium falciparum from Tanzanian paediatric malaria patients, 2016–2022Aveline Assey0Silvia Scialabba1Maria Mgella Zinga2Philip Koliopoulos3Welmoed van Loon4Caroline A. Minja5Britta Groendahl6Johannes Plett7Stephan Gehring8Mariam M. Mirambo9Neema Kayange10Frank P. Mockenhaupt11Stephen E. Mshana12Department of Parasitology and Entomology, Catholic University of Health and Allied SciencesCentre of Paediatric and Adolescent Medicine, University Medical CenterDepartment of Parasitology and Entomology, Catholic University of Health and Allied SciencesCentre of Paediatric and Adolescent Medicine, University Medical CenterCharité—Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität Zu Berlin, Charité Center for Global Health, Institute of International HealthDepartment of Biochemistry and Molecular Biology, Catholic University of Health and Allied SciencesCentre of Paediatric and Adolescent Medicine, University Medical CenterCentre of Paediatric and Adolescent Medicine, University Medical CenterCentre of Paediatric and Adolescent Medicine, University Medical CenterDepartment of Microbiology and Immunology, Catholic University of Health and Allied SciencesDepartment of Paediatrics, Catholic University of Health and Allied SciencesCharité—Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität Zu Berlin, Charité Center for Global Health, Institute of International HealthDepartment of Microbiology and Immunology, Catholic University of Health and Allied SciencesAbstract Background Plasmodium falciparum malaria remains a significant public health concern in Tanzania, particularly among children under 5 years of age. The emergence and spread of partial artemisinin resistance in East Africa add to this concern. Specific mutations in the P. falciparum kelch-13 (Pfk13) and multidrug drug resistance 1 (Pfmdr1) genes are associated with artemisinin resistance and lumefantrine tolerance, respectively. The emergence of antimalarial drug resistance may be associated with unstable transmission in sub-Saharan Africa (SSA). Time-trends of Pfk13 and Pfmdr1 mutations as well as the multiplicity of infection (MOI) as a proxy for transmission intensity were investigated. Methods Between 2016 and 2022, 173 P. falciparum PCR-positive samples were collected from febrile inpatient and outpatient children aged 3 months to 18 years at selected health facilities in Mwanza, Tanzania. Pfk13 and Pfmdr1 were amplified by PCR and Sanger-sequenced. Polymorphic Pfmsp1 and Pfmsp2 allelic markers were genotyped by nested PCR in 168 samples to assess MOI. Results Among 143 samples successfully sequenced for Pfk13, 7.0% (10/143) exhibited non-synonymous mutations including the WHO-validated artemisinin resistance marker R561H in 1.4% (2 patients, 2022). As for Pfmdr1, the wild-type N86 allele was observed in 100% (97/97) of isolates, and about half (55/97) carried the wild-type Y184 allele. The mean multiplicity of infection (MOI) was 1.5, and did not change significantly over time. Single-genotype and polyclonal infections were observed in 59.3% (80/135), and 40.7% (55/135) respectively. Conclusion This study from Mwanza, Tanzania demonstrates the presence of a validated artemisinin resistance marker Pfk13 R561H in 2022 and suggests increased lumefantrine tolerance. MOI as a proxy marker of endemicity was low and stable over the six years of observation. The detection of these resistance markers reinforces the need for continuous genetic surveillance to sustain the efficacy of antimalarial therapies in paediatric patients.https://doi.org/10.1186/s12936-025-05447-xPlasmodium falciparumPfmsp1Pfmsp2Genetic diversityMultiplicity of infectionPfk13 |
| spellingShingle | Aveline Assey Silvia Scialabba Maria Mgella Zinga Philip Koliopoulos Welmoed van Loon Caroline A. Minja Britta Groendahl Johannes Plett Stephan Gehring Mariam M. Mirambo Neema Kayange Frank P. Mockenhaupt Stephen E. Mshana Artemisinin and partner drug resistance markers in Plasmodium falciparum from Tanzanian paediatric malaria patients, 2016–2022 Malaria Journal Plasmodium falciparum Pfmsp1 Pfmsp2 Genetic diversity Multiplicity of infection Pfk13 |
| title | Artemisinin and partner drug resistance markers in Plasmodium falciparum from Tanzanian paediatric malaria patients, 2016–2022 |
| title_full | Artemisinin and partner drug resistance markers in Plasmodium falciparum from Tanzanian paediatric malaria patients, 2016–2022 |
| title_fullStr | Artemisinin and partner drug resistance markers in Plasmodium falciparum from Tanzanian paediatric malaria patients, 2016–2022 |
| title_full_unstemmed | Artemisinin and partner drug resistance markers in Plasmodium falciparum from Tanzanian paediatric malaria patients, 2016–2022 |
| title_short | Artemisinin and partner drug resistance markers in Plasmodium falciparum from Tanzanian paediatric malaria patients, 2016–2022 |
| title_sort | artemisinin and partner drug resistance markers in plasmodium falciparum from tanzanian paediatric malaria patients 2016 2022 |
| topic | Plasmodium falciparum Pfmsp1 Pfmsp2 Genetic diversity Multiplicity of infection Pfk13 |
| url | https://doi.org/10.1186/s12936-025-05447-x |
| work_keys_str_mv | AT avelineassey artemisininandpartnerdrugresistancemarkersinplasmodiumfalciparumfromtanzanianpaediatricmalariapatients20162022 AT silviascialabba artemisininandpartnerdrugresistancemarkersinplasmodiumfalciparumfromtanzanianpaediatricmalariapatients20162022 AT mariamgellazinga artemisininandpartnerdrugresistancemarkersinplasmodiumfalciparumfromtanzanianpaediatricmalariapatients20162022 AT philipkoliopoulos artemisininandpartnerdrugresistancemarkersinplasmodiumfalciparumfromtanzanianpaediatricmalariapatients20162022 AT welmoedvanloon artemisininandpartnerdrugresistancemarkersinplasmodiumfalciparumfromtanzanianpaediatricmalariapatients20162022 AT carolineaminja artemisininandpartnerdrugresistancemarkersinplasmodiumfalciparumfromtanzanianpaediatricmalariapatients20162022 AT brittagroendahl artemisininandpartnerdrugresistancemarkersinplasmodiumfalciparumfromtanzanianpaediatricmalariapatients20162022 AT johannesplett artemisininandpartnerdrugresistancemarkersinplasmodiumfalciparumfromtanzanianpaediatricmalariapatients20162022 AT stephangehring artemisininandpartnerdrugresistancemarkersinplasmodiumfalciparumfromtanzanianpaediatricmalariapatients20162022 AT mariammmirambo artemisininandpartnerdrugresistancemarkersinplasmodiumfalciparumfromtanzanianpaediatricmalariapatients20162022 AT neemakayange artemisininandpartnerdrugresistancemarkersinplasmodiumfalciparumfromtanzanianpaediatricmalariapatients20162022 AT frankpmockenhaupt artemisininandpartnerdrugresistancemarkersinplasmodiumfalciparumfromtanzanianpaediatricmalariapatients20162022 AT stephenemshana artemisininandpartnerdrugresistancemarkersinplasmodiumfalciparumfromtanzanianpaediatricmalariapatients20162022 |