Skip to main content
Top
Published in: Malaria Journal 1/2017

Open Access 01-12-2017 | Research

Artemether-lumefantrine and liver enzyme abnormalities in non-severe Plasmodium falciparum malaria in returned travellers: a retrospective comparative study with quinine-doxycycline in a Portuguese centre

Authors: André Silva-Pinto, Rogério Ruas, Francisco Almeida, Raquel Duro, André Silva, Cândida Abreu, António Sarmento

Published in: Malaria Journal | Issue 1/2017

Login to get access

Abstract

Background

Artemisinin-based therapy is the current standard treatment for non-severe malaria due to Plasmodium falciparum. The potential for asymptomatic liver toxicity of this therapy and its implication in clinical practice is currently unknown. The aim of this study is to assess the hepatic function in patients treated with a standard three-day artemisinin-based regimen and to compare it with the quinine-doxycycline regimen.

Methods

Retrospective and comparative study of returned adult travellers admitted with non-severe P. falciparum malaria. Fifty-seven patients were included: 19 treated with artemisinin-based therapy and 38 with quinine-doxycycline therapy.

Results

During treatment, when compared with quinine-doxycycline group, the artemisinin-lumefantrine group presented a higher proportion of significant liver enzyme abnormalities (42 vs. 5%, p < 0.01) and a higher peak value of aspartate aminotransferase (131 vs. 64 U/L, p < 0.01) and alanine aminotransferase (99 vs. 75 U/L, p = 0.05). None of the patients was symptomatic, there were no treatment interruptions and all patients achieved clinical cure.

Conclusions

Treatment of uncomplicated falciparum malaria with artemisinin-based therapy might cause asymptomatic liver enzyme abnormalities in the first days of treatment. Nevertheless, these liver enzyme abnormalities seem to be harmless, asymptomatic and self-limited.
Literature
1.
go back to reference WHO. Guidelines for the treatment of malaria. 3rd ed. Geneva: World Health Organization; 2015. WHO. Guidelines for the treatment of malaria. 3rd ed. Geneva: World Health Organization; 2015.
2.
go back to reference WHO. Antimalarial drug combination therapy. Report of a WHO Technical Consultation. World Health Organization, 2001. WHO. Antimalarial drug combination therapy. Report of a WHO Technical Consultation. World Health Organization, 2001.
3.
go back to reference McIntosh HM, Olliaro P. Artemisinin derivatives for treating severe malaria. Cochrane Database Syst Rev. 2000;(2):CD000527. McIntosh HM, Olliaro P. Artemisinin derivatives for treating severe malaria. Cochrane Database Syst Rev. 2000;(2):CD000527.
4.
go back to reference Achan J, Talisuna AO, Erhart A, Yeka A, Tibenderana JK, Baliraine FN, et al. Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria. Malar J. 2011;10:144.CrossRefPubMedPubMedCentral Achan J, Talisuna AO, Erhart A, Yeka A, Tibenderana JK, Baliraine FN, et al. Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria. Malar J. 2011;10:144.CrossRefPubMedPubMedCentral
5.
go back to reference Omotuyi IO, Nwangwu SC, Okugbo OT, Okoye OT, Ojieh GC, Wogu DM. Hepatotoxic and hemolytic effects of acute exposure of rats to artesunate overdose. Afr J Biochem Res. 2008;2:107–10. Omotuyi IO, Nwangwu SC, Okugbo OT, Okoye OT, Ojieh GC, Wogu DM. Hepatotoxic and hemolytic effects of acute exposure of rats to artesunate overdose. Afr J Biochem Res. 2008;2:107–10.
6.
go back to reference Owumi SE, Gbadegesin MA, Odunola OA, Adegoke AM, Uwaifo AO. Toxicity associated with repeated administration of artemether–lumefantrine in rats. Environ Toxicol. 2015;30:301–7.CrossRefPubMed Owumi SE, Gbadegesin MA, Odunola OA, Adegoke AM, Uwaifo AO. Toxicity associated with repeated administration of artemether–lumefantrine in rats. Environ Toxicol. 2015;30:301–7.CrossRefPubMed
7.
go back to reference Yin JY, Wang HM, Wang QJ, Dong YS, Han G, Guan YB, et al. Subchronic toxicological study of two artemisinin derivatives in dogs. PLoS One. 2014;9:e94034.CrossRefPubMedPubMedCentral Yin JY, Wang HM, Wang QJ, Dong YS, Han G, Guan YB, et al. Subchronic toxicological study of two artemisinin derivatives in dogs. PLoS One. 2014;9:e94034.CrossRefPubMedPubMedCentral
8.
go back to reference Ribeiro IR, Olliaro P. Safety of artemisinin and its derivatives: a review of published and unpublished clinical trials. Med Trop (Mars). 1998;58:50–3.PubMed Ribeiro IR, Olliaro P. Safety of artemisinin and its derivatives: a review of published and unpublished clinical trials. Med Trop (Mars). 1998;58:50–3.PubMed
10.
go back to reference Heaton PC, Fenwick SR, Brewer DE. Association between tetracycline or doxycycline and hepatotoxicity: a population based case-control study. J Clin Pharm Ther. 2007;32:483–7.CrossRefPubMed Heaton PC, Fenwick SR, Brewer DE. Association between tetracycline or doxycycline and hepatotoxicity: a population based case-control study. J Clin Pharm Ther. 2007;32:483–7.CrossRefPubMed
11.
go back to reference Punukollu RC, Kumar S, Mullen KD. Quinine hepatotoxicity. An underrecognized or rare phenomenon? Arch Intern Med. 1990;150:1112–3.CrossRefPubMed Punukollu RC, Kumar S, Mullen KD. Quinine hepatotoxicity. An underrecognized or rare phenomenon? Arch Intern Med. 1990;150:1112–3.CrossRefPubMed
12.
go back to reference Bakshi R, Hermeling-Fritz I, Gathmann I, Alteri E. An integrated assessment of the clinical safety of artemether–lumefantrine: a new oral fixed-dose combination antimalarial drug. Trans R Soc Trop Med Hyg. 2000;94:419–24.CrossRefPubMed Bakshi R, Hermeling-Fritz I, Gathmann I, Alteri E. An integrated assessment of the clinical safety of artemether–lumefantrine: a new oral fixed-dose combination antimalarial drug. Trans R Soc Trop Med Hyg. 2000;94:419–24.CrossRefPubMed
13.
go back to reference Makanga M, Bassat Q, Falade CO, Premji ZG, Krudsood S, Hunt P, et al. Efficacy and safety of artemether–lumefantrine in the treatment of acute, uncomplicated Plasmodium falciparum malaria: a pooled analysis. Am J Trop Med Hyg. 2011;85:793–804.CrossRefPubMedPubMedCentral Makanga M, Bassat Q, Falade CO, Premji ZG, Krudsood S, Hunt P, et al. Efficacy and safety of artemether–lumefantrine in the treatment of acute, uncomplicated Plasmodium falciparum malaria: a pooled analysis. Am J Trop Med Hyg. 2011;85:793–804.CrossRefPubMedPubMedCentral
14.
go back to reference Angus B. Novel anti-malarial combinations and their toxicity. Expert Rev Clin Pharmacol. 2014;7:299–316.CrossRefPubMed Angus B. Novel anti-malarial combinations and their toxicity. Expert Rev Clin Pharmacol. 2014;7:299–316.CrossRefPubMed
15.
go back to reference Efferth T, Kaina B. Toxicity of the antimalarial artemisinin and its dervatives. Crit Rev Toxicol. 2010;40:405–21.CrossRefPubMed Efferth T, Kaina B. Toxicity of the antimalarial artemisinin and its dervatives. Crit Rev Toxicol. 2010;40:405–21.CrossRefPubMed
16.
go back to reference Gordi T, Lepist EI. Artemisinin derivatives: toxic for laboratory animals, safe for humans? Toxicol Lett. 2004;147:99–107.CrossRefPubMed Gordi T, Lepist EI. Artemisinin derivatives: toxic for laboratory animals, safe for humans? Toxicol Lett. 2004;147:99–107.CrossRefPubMed
17.
go back to reference Adaramoye OA, Osaimoje DO, Akinsanya AM, Nneji CM, Fafunso MA, Ademowo OG. Changes in antioxidant status and biochemical indices after acute administration of artemether, artemether–lumefantrine and halofantrine in rats. Basic Clin Pharmacol Toxicol. 2008;102:412–8.CrossRefPubMed Adaramoye OA, Osaimoje DO, Akinsanya AM, Nneji CM, Fafunso MA, Ademowo OG. Changes in antioxidant status and biochemical indices after acute administration of artemether, artemether–lumefantrine and halofantrine in rats. Basic Clin Pharmacol Toxicol. 2008;102:412–8.CrossRefPubMed
19.
go back to reference Kurth F, Belard S, Basra A, Ramharter M. Pyronaridine-artesunate combination therapy for the treatment of malaria. Curr Opin Infect Dis. 2011;24:564–9.CrossRefPubMed Kurth F, Belard S, Basra A, Ramharter M. Pyronaridine-artesunate combination therapy for the treatment of malaria. Curr Opin Infect Dis. 2011;24:564–9.CrossRefPubMed
20.
go back to reference Adjuik M, Babiker A, Garner P, Olliaro P, Taylor W, White N, et al. Artesunate combinations for treatment of malaria: meta-analysis. Lancet. 2004;363:9–17.CrossRefPubMed Adjuik M, Babiker A, Garner P, Olliaro P, Taylor W, White N, et al. Artesunate combinations for treatment of malaria: meta-analysis. Lancet. 2004;363:9–17.CrossRefPubMed
Metadata
Title
Artemether-lumefantrine and liver enzyme abnormalities in non-severe Plasmodium falciparum malaria in returned travellers: a retrospective comparative study with quinine-doxycycline in a Portuguese centre
Authors
André Silva-Pinto
Rogério Ruas
Francisco Almeida
Raquel Duro
André Silva
Cândida Abreu
António Sarmento
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2017
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-017-1698-y

Other articles of this Issue 1/2017

Malaria Journal 1/2017 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.