» Articles » PMID: 34242769

Artemether-lumefantrine Treatment Failure of Uncomplicated Plasmodium Falciparum Malaria in Travellers Coming from Angola and Mozambique

Abstract

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.

Citing Articles

Low prevalence of copy number variation in pfmdr1 and pfpm2 in Plasmodium falciparum isolates from southern Angola.

Duarte D, Manuel F, Dias A, Sacato E, Taleingue E, Daniel E Malar J. 2025; 24(1):5.

PMID: 39794826 PMC: 11720348. DOI: 10.1186/s12936-024-05240-2.


Temporal genomics in Southern Zambia shows rising prevalence of Plasmodium falciparum mutations linked to delayed clearance after artemisinin-lumefantrine treatment.

Fola A, Kobayashi T, Hamapumbu H, Musonda M, Katowa B, Matoba J Sci Rep. 2024; 14(1):26789.

PMID: 39500918 PMC: 11538544. DOI: 10.1038/s41598-024-76442-6.


Genetic surveillance reveals low, sustained malaria transmission with clonal replacement in Sao Tome and Principe.

Chen Y, Ng P, Garcia D, Elliot A, Palmer B, Carvalho R medRxiv. 2024; .

PMID: 39072035 PMC: 11275696. DOI: 10.1101/2024.07.15.24309968.


Temporal genomic analysis of reveals increased prevalence of mutations associated with delayed clearance following treatment with artemisinin-lumefantrine in Choma District, Southern Province, Zambia.

Fola A, Kobayashi T, Shields T, Hamapumbu H, Musonda M, Katowa B medRxiv. 2024; .

PMID: 38883763 PMC: 11178023. DOI: 10.1101/2024.06.05.24308497.


Effects of the G-quadruplex-binding drugs quarfloxin and CX-5461 on the malaria parasite Plasmodium falciparum.

Craven H, Nettesheim G, Cicuta P, Blagborough A, Merrick C Int J Parasitol Drugs Drug Resist. 2023; 23:106-119.

PMID: 38041930 PMC: 10711401. DOI: 10.1016/j.ijpddr.2023.11.007.


References
1.
Bretscher M, Dahal P, Griffin J, Stepniewska K, Bassat Q, Baudin E . The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: a meta-analysis of individual patient data. BMC Med. 2020; 18(1):47. PMC: 7043031. DOI: 10.1186/s12916-020-1494-3. View

2.
Henrici R, van Schalkwyk D, Sutherland C . Modification of and Markedly Reduces Ring-Stage Susceptibility of Plasmodium falciparum to Artemisinin . Antimicrob Agents Chemother. 2019; 64(1). PMC: 7187599. DOI: 10.1128/AAC.01542-19. View

3.
Dogovski C, Xie S, Burgio G, Bridgford J, Mok S, McCaw J . Targeting the cell stress response of Plasmodium falciparum to overcome artemisinin resistance. PLoS Biol. 2015; 13(4):e1002132. PMC: 4406523. DOI: 10.1371/journal.pbio.1002132. View

4.
Adamu A, Jada M, Haruna H, Yakubu B, Ibrahim M, Balogun E . Plasmodium falciparum multidrug resistance gene-1 polymorphisms in Northern Nigeria: implications for the continued use of artemether-lumefantrine in the region. Malar J. 2020; 19(1):439. PMC: 7708160. DOI: 10.1186/s12936-020-03506-z. View

5.
Ocan M, Akena D, Nsobya S, Kamya M, Senono R, Kinengyere A . Persistence of chloroquine resistance alleles in malaria endemic countries: a systematic review of burden and risk factors. Malar J. 2019; 18(1):76. PMC: 6419488. DOI: 10.1186/s12936-019-2716-z. View