Skip to main content
Top
Published in: Malaria Journal 1/2016

Open Access 01-12-2016 | Case report

Failure of dihydroartemisinin-piperaquine treatment of uncomplicated Plasmodium falciparum malaria in a traveller coming from Ethiopia

Authors: Federico Gobbi, Dora Buonfrate, Michela Menegon, Gianluigi Lunardi, Andrea Angheben, Carlo Severini, Stefania Gori, Zeno Bisoffi

Published in: Malaria Journal | Issue 1/2016

Login to get access

Abstract

Background

Artemisinin combination therapy (ACT) is used worldwide as the first-line treatment against uncomplicated Plasmodium falciparum malaria. Despite the success of ACT in reducing the global burden of malaria, the emerging of resistance to artemisinin threatens its use.

Case report

This report describes the first case of failure of dihydroartemisinin-piperaquine (DHA-PPQ) for the treatment of P. falciparum malaria diagnosed in Europe. It occurred in an Italian tourist returned from Ethiopia. She completely recovered after the DHA-PPQ treatment but 32 days after the end of therapy she had a recrudescence. The retrospective analysis indicated a correct DHA-PPQ absorption and genotyping demonstrated that the same P. falciparum strain was responsible for the both episodes.

Conclusion

In consideration of the growing number of cases of resistance to ACT, it is important to consider a possible recrudescence, that can manifest also several weeks after treatment.
Literature
1.
go back to reference Nguyen TD, Olliaro P, Dondorp AM, Baird JK, Lam HM, Farrar J, et al. Optimum population-level use of artemisinin combination therapies: a modelling study. Lancet Glob Health. 2015;3:e758–66.CrossRefPubMedPubMedCentral Nguyen TD, Olliaro P, Dondorp AM, Baird JK, Lam HM, Farrar J, et al. Optimum population-level use of artemisinin combination therapies: a modelling study. Lancet Glob Health. 2015;3:e758–66.CrossRefPubMedPubMedCentral
2.
go back to reference Pfeil J, Borrmann S, Bassat Q, Mulenga M, Talisuna A, Tozan Y. An economic evaluation of the posttreatment prophylactic effect of dihydroartemisinin-piperaquine versus artemether-lumefantrine for first-line treatment of Plasmodium falciparum malaria across different transmission settings in Africa. Am J Trop Med Hyg. 2015;93:961–6.CrossRefPubMed Pfeil J, Borrmann S, Bassat Q, Mulenga M, Talisuna A, Tozan Y. An economic evaluation of the posttreatment prophylactic effect of dihydroartemisinin-piperaquine versus artemether-lumefantrine for first-line treatment of Plasmodium falciparum malaria across different transmission settings in Africa. Am J Trop Med Hyg. 2015;93:961–6.CrossRefPubMed
3.
go back to reference Saunders DL, Vanachayangkul P, Lon C. Dihydroartemisinin-piperaquine failure in Cambodia. N Engl J Med. 2014;371:484–5.CrossRefPubMed Saunders DL, Vanachayangkul P, Lon C. Dihydroartemisinin-piperaquine failure in Cambodia. N Engl J Med. 2014;371:484–5.CrossRefPubMed
4.
go back to reference Amaratunga C, Lim P, Suon S, Sreng S, Mao S, Sopha C, et al. Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study. Lancet Infect Dis. 2016;16:357–65.CrossRefPubMed Amaratunga C, Lim P, Suon S, Sreng S, Mao S, Sopha C, et al. Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study. Lancet Infect Dis. 2016;16:357–65.CrossRefPubMed
5.
go back to reference Tun KM, Jeeyapant A, Imwong M, Thein M, Aung SS, Hlaing TM, et al. Parasite clearance rates in Upper Myanmar indicate a distinctive artemisinin resistance phenotype: a therapeutic efficacy study. Malar J. 2016;15:185.CrossRefPubMedPubMedCentral Tun KM, Jeeyapant A, Imwong M, Thein M, Aung SS, Hlaing TM, et al. Parasite clearance rates in Upper Myanmar indicate a distinctive artemisinin resistance phenotype: a therapeutic efficacy study. Malar J. 2016;15:185.CrossRefPubMedPubMedCentral
6.
go back to reference Grande T, Bernasconi A, Erhart A, Gamboa D, Casapia M, Delgado C, et al. A randomised controlled trial to assess the efficacy of dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Peru. PLoS ONE. 2007;2:e1101.CrossRefPubMedPubMedCentral Grande T, Bernasconi A, Erhart A, Gamboa D, Casapia M, Delgado C, et al. A randomised controlled trial to assess the efficacy of dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Peru. PLoS ONE. 2007;2:e1101.CrossRefPubMedPubMedCentral
7.
go back to reference Zongo I, Somé FA, Somda SA, Parikh S, Rouamba N, Rosenthal PJ, et al. Efficacy and day 7 plasma piperaquine concentrations in African children treated for uncomplicated malaria with dihydroartemisinin-piperaquine. PLoS ONE. 2014;9:e103200.CrossRefPubMedPubMedCentral Zongo I, Somé FA, Somda SA, Parikh S, Rouamba N, Rosenthal PJ, et al. Efficacy and day 7 plasma piperaquine concentrations in African children treated for uncomplicated malaria with dihydroartemisinin-piperaquine. PLoS ONE. 2014;9:e103200.CrossRefPubMedPubMedCentral
8.
go back to reference Agarwal A, McMorrow M, Onyango P, Otieno K, Odero C, Williamson J, et al. A randomized trial of artemether-lumefantrine and dihydroartemisinin-piperaquine in the treatment of uncomplicated malaria among children in western Kenya. Malar J. 2013;12:254.CrossRefPubMedPubMedCentral Agarwal A, McMorrow M, Onyango P, Otieno K, Odero C, Williamson J, et al. A randomized trial of artemether-lumefantrine and dihydroartemisinin-piperaquine in the treatment of uncomplicated malaria among children in western Kenya. Malar J. 2013;12:254.CrossRefPubMedPubMedCentral
9.
go back to reference Plucinski MM, Talundzic E, Morton L, Dimbu PR, Macaia AP, Fortes F, et al. Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for treatment of uncomplicated malaria in children in Zaire and Uíge provinces, Angola. Antimicrob Agents Chemother. 2015;59:437–43.CrossRefPubMed Plucinski MM, Talundzic E, Morton L, Dimbu PR, Macaia AP, Fortes F, et al. Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for treatment of uncomplicated malaria in children in Zaire and Uíge provinces, Angola. Antimicrob Agents Chemother. 2015;59:437–43.CrossRefPubMed
10.
go back to reference Nguyen DV, Nguyen QP, Nguyen ND, Le TT, Nguyen TD, Dinh DN, et al. Pharmacokinetics and ex vivo pharmacodynamics antimalarial activity of dihydroartemisinin-piperaquine in patients with uncomplicated falciparum malaria in Vietnam. Antimicrob Agents Chemother. 2009;53:3534–7.CrossRefPubMedPubMedCentral Nguyen DV, Nguyen QP, Nguyen ND, Le TT, Nguyen TD, Dinh DN, et al. Pharmacokinetics and ex vivo pharmacodynamics antimalarial activity of dihydroartemisinin-piperaquine in patients with uncomplicated falciparum malaria in Vietnam. Antimicrob Agents Chemother. 2009;53:3534–7.CrossRefPubMedPubMedCentral
11.
go back to reference Price RN, Hasugian AR, Ratcliff A, Siswantoro H, Purba HL, Kenangalem E, et al. Clinical and pharmacological determinants of the therapeutic response to dihydroartemisinin-piperaquine for drug-resistant malaria. Antimicrob Agents Chemother. 2007;51:4090–7.CrossRefPubMedPubMedCentral Price RN, Hasugian AR, Ratcliff A, Siswantoro H, Purba HL, Kenangalem E, et al. Clinical and pharmacological determinants of the therapeutic response to dihydroartemisinin-piperaquine for drug-resistant malaria. Antimicrob Agents Chemother. 2007;51:4090–7.CrossRefPubMedPubMedCentral
12.
go back to reference Wooden J, Kyes S, Sibley CH. PCR and strain identification in Plasmodium falciparum. Parasitol Today. 1993;9:303–5.CrossRefPubMed Wooden J, Kyes S, Sibley CH. PCR and strain identification in Plasmodium falciparum. Parasitol Today. 1993;9:303–5.CrossRefPubMed
13.
go back to reference Viriyakosol S, Siripoon N, Petcharapirat C, Petcharapirat P, Jarra W, Thaithong S, et al. Genotyping of Plasmodium falciparum isolates by the polymerase chain reaction and potential uses in epidemiological studies. Bull World Health Organ. 1995;73:85–95.PubMedPubMedCentral Viriyakosol S, Siripoon N, Petcharapirat C, Petcharapirat P, Jarra W, Thaithong S, et al. Genotyping of Plasmodium falciparum isolates by the polymerase chain reaction and potential uses in epidemiological studies. Bull World Health Organ. 1995;73:85–95.PubMedPubMedCentral
14.
go back to reference Taylor SM, Parobek CM, DeConti DK, Kayentao K, Coulibaly SO, Greenwood BM, et al. Absence of putative artemisinin resistance mutations among Plasmodium falciparum in sub-Saharan Africa: a molecular epidemiologic study. J Infect Dis. 2015;211:680–8.CrossRefPubMed Taylor SM, Parobek CM, DeConti DK, Kayentao K, Coulibaly SO, Greenwood BM, et al. Absence of putative artemisinin resistance mutations among Plasmodium falciparum in sub-Saharan Africa: a molecular epidemiologic study. J Infect Dis. 2015;211:680–8.CrossRefPubMed
15.
go back to reference Menegon M, Pearce RJ, Inojosa WO, Pisani V, Abel PM, Matondo A, et al. Monitoring for multidrug-resistant Plasmodium falciparum isolates and analysis of pyrimethamine resistance evolution in Uige province, Angola. Trop Med Int Health. 2009;14:1251–7.CrossRefPubMed Menegon M, Pearce RJ, Inojosa WO, Pisani V, Abel PM, Matondo A, et al. Monitoring for multidrug-resistant Plasmodium falciparum isolates and analysis of pyrimethamine resistance evolution in Uige province, Angola. Trop Med Int Health. 2009;14:1251–7.CrossRefPubMed
16.
go back to reference Duraisingh MT, Jones P, Sambou I, von Seidlein L, Pinder M, Warhurst DC. The tyrosine-86 allele of the pfmdr1 gene of Plasmodium falciparum is associated with increased sensitivity to the anti-malarials mefloquine and artemisinin. Mol Biochem Parasitol. 2000;108:13–23.CrossRefPubMed Duraisingh MT, Jones P, Sambou I, von Seidlein L, Pinder M, Warhurst DC. The tyrosine-86 allele of the pfmdr1 gene of Plasmodium falciparum is associated with increased sensitivity to the anti-malarials mefloquine and artemisinin. Mol Biochem Parasitol. 2000;108:13–23.CrossRefPubMed
17.
go back to reference Palmieri F, Petrosillo N, Paglia MG, Conte A, Goletti D, Pucillo LP, et al. Genetic confirmation of quinine-resistant Plasmodium falciparum malaria followed by postmalaria neurological syndrome in a traveler from Mozambique. J Clin Microbiol. 2004;42:5424–6.CrossRefPubMedPubMedCentral Palmieri F, Petrosillo N, Paglia MG, Conte A, Goletti D, Pucillo LP, et al. Genetic confirmation of quinine-resistant Plasmodium falciparum malaria followed by postmalaria neurological syndrome in a traveler from Mozambique. J Clin Microbiol. 2004;42:5424–6.CrossRefPubMedPubMedCentral
18.
go back to reference Korsinczky M, Chen N, Kotecka B, Saul A, Rieckmann K, Cheng Q. Mutations in Plasmodium falciparum cytochrome b that are associated with atovaquone resistance are located at a putative drug-binding site. Antimicrob Agents Chemother. 2000;44:2100–8.CrossRefPubMedPubMedCentral Korsinczky M, Chen N, Kotecka B, Saul A, Rieckmann K, Cheng Q. Mutations in Plasmodium falciparum cytochrome b that are associated with atovaquone resistance are located at a putative drug-binding site. Antimicrob Agents Chemother. 2000;44:2100–8.CrossRefPubMedPubMedCentral
19.
go back to reference Duru V, Khim N, Leang R, Kim S, Domergue A, Kloeung N, et al. Plasmodium falciparum dihydroartemisinin-piperaquine failures in Cambodia are associated with mutant K13 parasites presenting high survival rates in novel piperaquine in vitro assays: retrospective and prospective investigations. BMC Med. 2015;13:305.CrossRefPubMedPubMedCentral Duru V, Khim N, Leang R, Kim S, Domergue A, Kloeung N, et al. Plasmodium falciparum dihydroartemisinin-piperaquine failures in Cambodia are associated with mutant K13 parasites presenting high survival rates in novel piperaquine in vitro assays: retrospective and prospective investigations. BMC Med. 2015;13:305.CrossRefPubMedPubMedCentral
Metadata
Title
Failure of dihydroartemisinin-piperaquine treatment of uncomplicated Plasmodium falciparum malaria in a traveller coming from Ethiopia
Authors
Federico Gobbi
Dora Buonfrate
Michela Menegon
Gianluigi Lunardi
Andrea Angheben
Carlo Severini
Stefania Gori
Zeno Bisoffi
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2016
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-016-1572-3

Other articles of this Issue 1/2016

Malaria Journal 1/2016 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.