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1.
WHO, 2023. WHO Guidelines for Malaria (WHO/UCN/GMP/2023.01.). Geneva, Switzerland: World Health Organization. Available at: https://www.ncbi.nlm.nih.gov/books/NBK588130/. Accessed May 29, 2024.
-
2.
WHO, 2019. Artemisinin Resistance and Artemisinin-Based Combination Therapy Efficacy. Geneva, Switzerland: World Health Organization. Available at: https://www.who.int/docs/default-source/documents/publications/gmp/who-cds-gmp-2019-17-eng.pdf?ua=1. Accessed June 2, 2024.
-
3.
WHO, 2022. Malaria: Artemisinin Partial Resistance. Geneva, Switzerland: World Health Organization. Available at: https://www.who.int/news-room/questions-and-answers/item/artemisinin-resistance. Accessed August 12, 2024.
-
4.
Sondén K, Wyss K, Jovel I, Vieira da Silva A, Pohanka A, Asghar M, Homann MV, Gustafsson LL, Hellgren U, Färnert A, 2017. High rate of treatment failures in nonimmune travelers treated with artemether–lumefantrine for uncomplicated Plasmodium falciparum malaria in Sweden: Retrospective comparative analysis of effectiveness and case series. Clin Infect Dis 64: 199–206.
-
5.
Abuaku B, Duah-Quashie NO, Quashie N, Gyasi A, Afriyie PO, Owusu-Antwi F, Ghansah A, Malm KL, Bart-Plange C, Koram KA, 2021. Trends and predictive factors for treatment failure following artemisinin-based combination therapy among children with uncomplicated malaria in Ghana: 2005–2018. BMC Infect Dis 21: 1255.
-
6.
Uwimana A et al., 2021. Association of Plasmodium falciparum kelch13 R561H genotypes with delayed parasite clearance in Rwanda: An open-label, single-arm, multicentre, therapeutic efficacy study. Lancet Infect Dis 21: 1120–1128.
-
7.
Conrad MD et al., 2023. Evolution of partial resistance to artemisinins in malaria parasites in Uganda. N Engl J Med 389: 722–732.
-
8.
Straimer J et al., 2015. Drug resistance. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates. Science 347: 428–431.
-
9.
Demas AR, Sharma AI, Wong W, Early AM, Redmond S, Bopp S, Neafsey DE, Volkman SK, Hartl DL, Wirth DF, 2018. Mutations in Plasmodium falciparum actin-binding protein coronin confer reduced artemisinin susceptibility. Proc Natl Acad Sci USA 115: 12799–12804.
-
10.
Laird VR et al., 2024. Plasmodium falciparum Multidrug Resistance 1 Gene Polymorphisms Associated with Outcomes after Antimalarial Treatment. Available at: https://doi.org/10.1101/2024.07.01.24309724. Accessed August 13, 2024.
-
11.
Watson OJ, Gao B, Nguyen TD, Tran TN, Penny MA, Smith DL, Okell L, Aguas R, Boni MF, 2022. Pre-existing partner-drug resistance to artemisinin combination therapies facilitates the emergence and spread of artemisinin resistance: A consensus modelling study. Lancet Microbe 3: e701–e710.
-
12.
Lim P et al., 2009. Pfmdr1 copy number and arteminisin derivatives combination therapy failure in falciparum malaria in Cambodia. Malar J 8: 11.
-
13.
Farnert A, Ursing J, Tolfvenstam T, Rono J, Karlsson L, Sparrelid E, Lindegardh N, 2012. Artemether–lumefantrine treatment failure despite adequate lumefantrine day 7 concentration in a traveller with Plasmodium falciparum malaria after returning from Tanzania. Malar J 11: 176.
-
14.
van Schalkwyk DA et al., 2024. Treatment failure in a UK malaria patient harboring genetically variant Plasmodium falciparum from Uganda with reduced in vitro susceptibility to artemisinin and lumefantrine. Clin Infect Dis 78: 445–452.
-
15.
Njiro BJ, Mutagonda RF, Chamani AT, Mwakyandile T, Sabas D, Bwire GM, 2022. Molecular surveillance of chloroquine-resistant Plasmodium falciparum in sub-Saharan African countries after withdrawal of chloroquine for treatment of uncomplicated malaria: A systematic review. J Infect Public Health 15: 550–557.
-
16.
Artimovich E et al., 2015. The effect of local variation in malaria transmission on the prevalence of sulfadoxine-pyrimethamine resistant haplotypes and selective sweep characteristics in Malawi. Malar J 14: 387.
-
17.
Ashley EA et al.; Tracking Resistance to Artemisinin Collaboration (TRAC), 2014. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 371: 411–423.
-
18.
Daily JP, Minuti A, Khan N, 2022. Diagnosis, treatment, and prevention of malaria in the US: A review. JAMA 328: 460–471.
-
19.
van der Pluijm RW et al.; Tracking Resistance to Artemisinin Collaboration, 2020. Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: A multicentre, open-label, randomised clinical trial. Lancet 395: 1345–1360.
-
20.
Kurth F et al., 2016. Hemolysis after oral artemisinin combination therapy for uncomplicated Plasmodium falciparum malaria. Emerg Infect Dis 22: 1381–1386.
| Past two years | Past Year | Past 30 Days | |
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| Abstract Views | 1786 | 1786 | 120 |
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Recurrent Plasmodium falciparum Malaria in U.S. Travelers Treated with Artemether–Lumefantrine
Hendrik Sy
hesy@montefiore.org
Hendrik Sy
Division of Infectious Diseases, Montefiore Medical Center/Albert Einstein College of Medicine, New York, New York;
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Sharan Yadav
Sharan Yadav
Division of Infectious Diseases, Weill Cornell Medicine, New York, New York;
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Peter Yangga
Peter Yangga
Division of Infectious Diseases, Montefiore Medical Center/Albert Einstein College of Medicine, New York, New York;
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Alexander Shaffer
Alexander Shaffer
Division of Infectious Diseases, Montefiore Medical Center/Albert Einstein College of Medicine, New York, New York;
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Amie John
Amie John
Division of Infectious Diseases, Montefiore Medical Center/Albert Einstein College of Medicine, New York, New York;
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Wesley Rogers
Wesley Rogers
Division of Infectious Diseases, Weill Cornell Medicine, New York, New York;
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Lars Westblade
Lars Westblade
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York;
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Rebecca Marrero Rolón
Rebecca Marrero Rolón
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York;
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Susan Madison-Antenucci
Susan Madison-Antenucci
Parasitology Laboratory, New York State Department of Health, Albany, New York;
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Phyu M. Thwe
Phyu M. Thwe
Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, New York, New York;
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Erika Orner
Erika Orner
Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, New York, New York;
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Kerry Murphy
Kerry Murphy
Division of Infectious Diseases, Montefiore Medical Center/Albert Einstein College of Medicine, New York, New York;
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Grace A. Maldarelli
Grace A. Maldarelli
Division of Infectious Diseases, Weill Cornell Medicine, New York, New York;
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Laura Kirkman
Laura Kirkman
Division of Infectious Diseases, Weill Cornell Medicine, New York, New York;
Department of Microbiology and Immunology, Weill Cornell Medicine, New York, New York
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Department of Microbiology and Immunology, Weill Cornell Medicine, New York, New York
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Johanna P. Daily
Johanna P. Daily
Division of Infectious Diseases, Montefiore Medical Center/Albert Einstein College of Medicine, New York, New York;
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ABSTRACT.
We report two cases of recurrent malaria in U.S. travelers returning from Africa (Ghana and Central African Republic) despite a full course of artemether–lumefantrine (AL). Both patients presented to New York City hospitals, received AL treatment, and clinically improved. Within 2 weeks, they presented with recurrent Plasmodium falciparum malaria. Parasite isolates were sequenced, and P. falciparum kelch 13 propeller domain mutations that are validated or candidate markers of artemisinin partial resistance were not identified. Parasites had mutations within the P. falciparum multidrug resistance protein 1 gene. It is crucial to remain vigilant for recurrent malaria in travelers, even from African regions where partial resistance to artemisinin-based combination therapy has only rarely been reported.
Author Notes
Financial support: The project described was supported by the
Disclosures: The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH.
Current contact information: Hendrik Sy, Division of Infectious Diseases, Montefiore Medical Center/Albert Einstein College of Medicine, New York, NY, E-mail: hesy@montefiore.org. Sharan Yadav, Wesley Rogers, and Grace A. Maldarelli, Division of Infectious Diseases, Weill Cornell Medicine, New York, NY, E-mails: ssy9009@nyp.org, wer9011@nyp.org, and gam9044@med.cornell.edu. Peter Yangga, Alexander Shaffer, Amie John, Kerry Murphy, and Johanna P. Daily, Division of Infectious Diseases, Montefiore Medical Center/Albert Einstein College of Medicine, New York, NY, E-mails: pyangga@montefiore.org, ashaffer@montefiore.org, amjohn@montefiore.org, kerry.murphy@einsteinmed.edu, and jdaily@montefiore.org. Lars Westblade and Rebecca Marrero Rolón, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, E-mails: law9067@med.cornell.edu and rmarrerorolon@pennstatehealth.psu.edu. Susan Madison-Antenucci, Parasitology Laboratory, New York State Department of Health, Albany, New York, NY, E-mail: s.antenucci@health.ny.gov. Phyu M. Thwe and Erika Orner, Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, New York, NY, E-mails: pthwe@montefiore.org and eorner@montefiore.org. Laura Kirkman, Division of Infectious Diseases and Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, E-mail: lak9015@med.cornell.edu.
ProCite
RefWorks
Reference Manager
BibTeX
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-
1.
WHO, 2023. WHO Guidelines for Malaria (WHO/UCN/GMP/2023.01.). Geneva, Switzerland: World Health Organization. Available at: https://www.ncbi.nlm.nih.gov/books/NBK588130/. Accessed May 29, 2024.
-
2.
WHO, 2019. Artemisinin Resistance and Artemisinin-Based Combination Therapy Efficacy. Geneva, Switzerland: World Health Organization. Available at: https://www.who.int/docs/default-source/documents/publications/gmp/who-cds-gmp-2019-17-eng.pdf?ua=1. Accessed June 2, 2024.
-
3.
WHO, 2022. Malaria: Artemisinin Partial Resistance. Geneva, Switzerland: World Health Organization. Available at: https://www.who.int/news-room/questions-and-answers/item/artemisinin-resistance. Accessed August 12, 2024.
-
4.
Sondén K, Wyss K, Jovel I, Vieira da Silva A, Pohanka A, Asghar M, Homann MV, Gustafsson LL, Hellgren U, Färnert A, 2017. High rate of treatment failures in nonimmune travelers treated with artemether–lumefantrine for uncomplicated Plasmodium falciparum malaria in Sweden: Retrospective comparative analysis of effectiveness and case series. Clin Infect Dis 64: 199–206.
-
5.
Abuaku B, Duah-Quashie NO, Quashie N, Gyasi A, Afriyie PO, Owusu-Antwi F, Ghansah A, Malm KL, Bart-Plange C, Koram KA, 2021. Trends and predictive factors for treatment failure following artemisinin-based combination therapy among children with uncomplicated malaria in Ghana: 2005–2018. BMC Infect Dis 21: 1255.
-
6.
Uwimana A et al., 2021. Association of Plasmodium falciparum kelch13 R561H genotypes with delayed parasite clearance in Rwanda: An open-label, single-arm, multicentre, therapeutic efficacy study. Lancet Infect Dis 21: 1120–1128.
-
7.
Conrad MD et al., 2023. Evolution of partial resistance to artemisinins in malaria parasites in Uganda. N Engl J Med 389: 722–732.
-
8.
Straimer J et al., 2015. Drug resistance. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates. Science 347: 428–431.
-
9.
Demas AR, Sharma AI, Wong W, Early AM, Redmond S, Bopp S, Neafsey DE, Volkman SK, Hartl DL, Wirth DF, 2018. Mutations in Plasmodium falciparum actin-binding protein coronin confer reduced artemisinin susceptibility. Proc Natl Acad Sci USA 115: 12799–12804.
-
10.
Laird VR et al., 2024. Plasmodium falciparum Multidrug Resistance 1 Gene Polymorphisms Associated with Outcomes after Antimalarial Treatment. Available at: https://doi.org/10.1101/2024.07.01.24309724. Accessed August 13, 2024.
-
11.
Watson OJ, Gao B, Nguyen TD, Tran TN, Penny MA, Smith DL, Okell L, Aguas R, Boni MF, 2022. Pre-existing partner-drug resistance to artemisinin combination therapies facilitates the emergence and spread of artemisinin resistance: A consensus modelling study. Lancet Microbe 3: e701–e710.
-
12.
Lim P et al., 2009. Pfmdr1 copy number and arteminisin derivatives combination therapy failure in falciparum malaria in Cambodia. Malar J 8: 11.
-
13.
Farnert A, Ursing J, Tolfvenstam T, Rono J, Karlsson L, Sparrelid E, Lindegardh N, 2012. Artemether–lumefantrine treatment failure despite adequate lumefantrine day 7 concentration in a traveller with Plasmodium falciparum malaria after returning from Tanzania. Malar J 11: 176.
-
14.
van Schalkwyk DA et al., 2024. Treatment failure in a UK malaria patient harboring genetically variant Plasmodium falciparum from Uganda with reduced in vitro susceptibility to artemisinin and lumefantrine. Clin Infect Dis 78: 445–452.
-
15.
Njiro BJ, Mutagonda RF, Chamani AT, Mwakyandile T, Sabas D, Bwire GM, 2022. Molecular surveillance of chloroquine-resistant Plasmodium falciparum in sub-Saharan African countries after withdrawal of chloroquine for treatment of uncomplicated malaria: A systematic review. J Infect Public Health 15: 550–557.
-
16.
Artimovich E et al., 2015. The effect of local variation in malaria transmission on the prevalence of sulfadoxine-pyrimethamine resistant haplotypes and selective sweep characteristics in Malawi. Malar J 14: 387.
-
17.
Ashley EA et al.; Tracking Resistance to Artemisinin Collaboration (TRAC), 2014. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 371: 411–423.
-
18.
Daily JP, Minuti A, Khan N, 2022. Diagnosis, treatment, and prevention of malaria in the US: A review. JAMA 328: 460–471.
-
19.
van der Pluijm RW et al.; Tracking Resistance to Artemisinin Collaboration, 2020. Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: A multicentre, open-label, randomised clinical trial. Lancet 395: 1345–1360.
-
20.
Kurth F et al., 2016. Hemolysis after oral artemisinin combination therapy for uncomplicated Plasmodium falciparum malaria. Emerg Infect Dis 22: 1381–1386.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 1786 | 1786 | 120 |
| Full Text Views | 77 | 77 | 19 |
| PDF Downloads | 105 | 105 | 34 |