Artemether-lumefantrine treatment failure of uncomplicated Plasmodium falciparum malaria in travellers coming from Angola and Mozambique
•Artemether-lumefantrine (AL) treatment failure of imported malaria in Portugal•AL treatment failure in the presence of wild-type pfk13 and pfmdr1•Is the standard 3-day course of AL sufficient to ensure parasite clearance?•AL increasing treatment failures urges closer immediate follow up of malaria...
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Published in | International journal of infectious diseases Vol. 110; pp. 151 - 154 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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01.09.2021
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Abstract | •Artemether-lumefantrine (AL) treatment failure of imported malaria in Portugal•AL treatment failure in the presence of wild-type pfk13 and pfmdr1•Is the standard 3-day course of AL sufficient to ensure parasite clearance?•AL increasing treatment failures urges closer immediate follow up of malaria patients
The failure of artemisinin combination therapy (ACT) in malaria patients returning from endemic regions may be driven by parasite resistance to this treatment. ACT is used globally as the first-line treatment for Plasmodium falciparum malaria. However, artemisinin-resistant strains of P. falciparum have emerged and spread across Southeast Asia, with the risk of reaching high malaria burden regions in Africa and elsewhere. Here, we report on two malaria imported cases from Africa with possible parasite resistance to the ACT artemether-lumefantrine (AL).
Case presentation: Two middle-aged males returning from Angola and Mozambique developed malaria symptoms in Portugal, where they were diagnosed and received treatment with AL as hospital inpatients. After apparent cure and discharge from hospital, these individuals returned to hospital showing signs of late clinical failure. Molecular analysis was performed across a number of drug resistance associated genes. No evidence of pfk13-mediated artemisinin resistance was found. Both subjects had complete parasite clearance after treatment with non-ACT antimalarials.
Conclusion: Our case-studies highlights the need for close monitoring of signs of unsatisfactory antimalarial efficacy among AL treated patients and the possible implication of other genes or mutations in the parasite response to ACTs. |
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AbstractList | •
Artemether-lumefantrine (AL) treatment failure of imported malaria in Portugal
•
AL treatment failure in the presence of wild-type pfk13 and pfmdr1
•
Is the standard 3-day course of AL sufficient to ensure parasite clearance?
•
AL increasing treatment failures urges closer immediate follow up of malaria patients
The failure of artemisinin combination therapy (ACT) in malaria patients returning from endemic regions may be driven by parasite resistance to this treatment. ACT is used globally as the first-line treatment for
Plasmodium falciparum
malaria. However, artemisinin-resistant strains of
P. falciparum
have emerged and spread across Southeast Asia, with the risk of reaching high malaria burden regions in Africa and elsewhere. Here, we report on two malaria imported cases from Africa with possible parasite resistance to the ACT artemether-lumefantrine (AL).
Case presentation: Two middle-aged males returning from Angola and Mozambique developed malaria symptoms in Portugal, where they were diagnosed and received treatment with AL as hospital inpatients. After apparent cure and discharge from hospital, these individuals returned to hospital showing signs of late clinical failure. Molecular analysis was performed across a number of drug resistance associated genes. No evidence of
pfk13
-mediated artemisinin resistance was found. Both subjects had complete parasite clearance after treatment with non-ACT antimalarials.
Conclusion: Our case-studies highlights the need for close monitoring of signs of unsatisfactory antimalarial efficacy among AL treated patients and the possible implication of other genes or mutations in the parasite response to ACTs. The failure of artemisinin combination therapy (ACT) in malaria patients returning from endemic regions may be driven by parasite resistance to this treatment. ACT is used globally as the first-line treatment for Plasmodium falciparum malaria. However, artemisinin-resistant strains of P. falciparum have emerged and spread across Southeast Asia, with the risk of reaching high malaria burden regions in Africa and elsewhere. Here, we report on two malaria imported cases from Africa with possible parasite resistance to the ACT artemether-lumefantrine (AL).Case presentation: Two middle-aged males returning from Angola and Mozambique developed malaria symptoms in Portugal, where they were diagnosed and received treatment with AL as hospital inpatients. After apparent cure and discharge from hospital, these individuals returned to hospital showing signs of late clinical failure. Molecular analysis was performed across a number of drug resistance associated genes. No evidence of pfk13-mediated artemisinin resistance was found. Both subjects had complete parasite clearance after treatment with non-ACT antimalarials.Conclusion: Our case-studies highlights the need for close monitoring of signs of unsatisfactory antimalarial efficacy among AL treated patients and the possible implication of other genes or mutations in the parasite response to ACTs. •Artemether-lumefantrine (AL) treatment failure of imported malaria in Portugal•AL treatment failure in the presence of wild-type pfk13 and pfmdr1•Is the standard 3-day course of AL sufficient to ensure parasite clearance?•AL increasing treatment failures urges closer immediate follow up of malaria patients The failure of artemisinin combination therapy (ACT) in malaria patients returning from endemic regions may be driven by parasite resistance to this treatment. ACT is used globally as the first-line treatment for Plasmodium falciparum malaria. However, artemisinin-resistant strains of P. falciparum have emerged and spread across Southeast Asia, with the risk of reaching high malaria burden regions in Africa and elsewhere. Here, we report on two malaria imported cases from Africa with possible parasite resistance to the ACT artemether-lumefantrine (AL). Case presentation: Two middle-aged males returning from Angola and Mozambique developed malaria symptoms in Portugal, where they were diagnosed and received treatment with AL as hospital inpatients. After apparent cure and discharge from hospital, these individuals returned to hospital showing signs of late clinical failure. Molecular analysis was performed across a number of drug resistance associated genes. No evidence of pfk13-mediated artemisinin resistance was found. Both subjects had complete parasite clearance after treatment with non-ACT antimalarials. Conclusion: Our case-studies highlights the need for close monitoring of signs of unsatisfactory antimalarial efficacy among AL treated patients and the possible implication of other genes or mutations in the parasite response to ACTs. |
Author | Mansinho, Kamal Cardoso, Margarida Domingos, João Toscano, Cristina Campino, Susana Conceição, Cláudia Clark, Taane G. Baptista-Fernandes, Teresa Reis, Ana Nogueira, Fatima Caldas, João Paulo Silva-Pinto, André Benavente, Ernest Diez |
Author_xml | – sequence: 1 givenname: André surname: Silva-Pinto fullname: Silva-Pinto, André email: u011354@chsj.min-saude.pt organization: Infectious Diseases Department, Centro Hospitalar Universitário de São João e Faculdade de Medicina da Universidade do Porto, Porto, Portugal – sequence: 2 givenname: João surname: Domingos fullname: Domingos, João email: jdomingos@chlo.min-saude.pt organization: Infectious Diseases Department, Centro Hospitalar Lisboa Ocidental, Lisboa, Portugal – sequence: 3 givenname: Margarida surname: Cardoso fullname: Cardoso, Margarida email: amrcardoso@chlo.min-saude.pt organization: Infectious Diseases Department, Centro Hospitalar Lisboa Ocidental, Lisboa, Portugal – sequence: 4 givenname: Ana surname: Reis fullname: Reis, Ana email: anareis@ihmt.unl.pt organization: Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, Portugal – sequence: 5 givenname: Ernest Diez surname: Benavente fullname: Benavente, Ernest Diez email: Ernest.DiezBenavente@lshtm.ac.uk organization: Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom – sequence: 6 givenname: João Paulo surname: Caldas fullname: Caldas, João Paulo email: joao.paulo.caldas@chsj.min-saude.pt organization: Infectious Diseases Department, Centro Hospitalar Universitário de São João e Faculdade de Medicina da Universidade do Porto, Porto, Portugal – sequence: 7 givenname: Cláudia surname: Conceição fullname: Conceição, Cláudia email: claudiaconceicao@ihmt.unl.pt organization: Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, Portugal – sequence: 8 givenname: Cristina surname: Toscano fullname: Toscano, Cristina email: ctoscano@chlo.min-saude.pt organization: Laboratório de Microbiologia Clínica e Biologia Molecular do Serviço de Patologia Clínica do CHLO – sequence: 9 givenname: Teresa surname: Baptista-Fernandes fullname: Baptista-Fernandes, Teresa email: tmfernandes@chlo.min-saude.pt organization: Laboratório de Microbiologia Clínica e Biologia Molecular do Serviço de Patologia Clínica do CHLO – sequence: 10 givenname: Taane G. surname: Clark fullname: Clark, Taane G. email: Taane.clark@lshtm.ac.uk organization: Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom – sequence: 11 givenname: Kamal surname: Mansinho fullname: Mansinho, Kamal email: kmansinho@chlo.min-saude.pt organization: Infectious Diseases Department, Centro Hospitalar Lisboa Ocidental, Lisboa, Portugal – sequence: 12 givenname: Susana surname: Campino fullname: Campino, Susana email: Susana.campino@lshtm.ac.uk organization: Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, Portugal – sequence: 13 givenname: Fatima surname: Nogueira fullname: Nogueira, Fatima email: fnogueira@ihmt.unl.pt organization: Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, Portugal |
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CitedBy_id | crossref_primary_10_1016_j_ijpddr_2024_100532 crossref_primary_10_1007_s11908_023_00805_9 crossref_primary_10_3390_toxins15060375 crossref_primary_10_1016_j_ijantimicag_2021_106482 crossref_primary_10_1093_jtm_taad114 crossref_primary_10_1002_cmdc_202200709 crossref_primary_10_1186_s12936_023_04587_2 crossref_primary_10_1016_j_pt_2022_03_005 crossref_primary_10_1093_cid_ciac527 |
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Keywords | Therapeutic failure Plasmodium falciparum Artemether-Lumefantrine |
Language | English |
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United Kingdom publication-title: Antimicrob Agents Chemother doi: 10.1128/AAC.02382-16 contributor: fullname: Sutherland – volume: 18 year: 2019 ident: 10.1016/j.ijid.2021.07.008_bib0011 article-title: Persistence of chloroquine resistance alleles in malaria endemic countries: A systematic review of burden and risk factors publication-title: Malar J doi: 10.1186/s12936-019-2716-z contributor: fullname: Ocan – volume: 112 year: 2013 ident: 10.1016/j.ijid.2021.07.008_bib0007 article-title: Pharmacokinetic modelling of the anti-malarial drug artesunate and its active metabolite dihydroartemisinin publication-title: Comput Methods Programs Biomed doi: 10.1016/j.cmpb.2013.05.010 contributor: fullname: Hall – volume: 64 year: 2020 ident: 10.1016/j.ijid.2021.07.008_bib0008 article-title: Modification of pfap2μ and pfubp1 Markedly Reduces Ring-Stage Susceptibility of Plasmodium falciparum to Artemisinin in Vitro publication-title: Antimicrob Agents Chemother contributor: fullname: Henrici |
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Snippet | •Artemether-lumefantrine (AL) treatment failure of imported malaria in Portugal•AL treatment failure in the presence of wild-type pfk13 and pfmdr1•Is the... • Artemether-lumefantrine (AL) treatment failure of imported malaria in Portugal • AL treatment failure in the presence of wild-type pfk13 and pfmdr1 • Is the... The failure of artemisinin combination therapy (ACT) in malaria patients returning from endemic regions may be driven by parasite resistance to this treatment.... |
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SubjectTerms | Artemether-Lumefantrine Case Report Plasmodium falciparum Therapeutic failure |
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Title | Artemether-lumefantrine treatment failure of uncomplicated Plasmodium falciparum malaria in travellers coming from Angola and Mozambique |
URI | https://dx.doi.org/10.1016/j.ijid.2021.07.008 https://pubmed.ncbi.nlm.nih.gov/PMC8461077 https://doaj.org/article/f2be4b7c651a42a58a793eebc87d73fb |
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