Efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated malaria in Papua New Guinea

Tavul, Livingstone, Hetzel, Manuel W., Teliki, Albina, Walsh, Dorish, Kiniboro, Benson, Rare, Lawrence, Pulford, Justin ORCID: https://orcid.org/0000-0003-4756-8480, Siba, Peter M., Karl, Stephan, Makita, Leo, Robinson, Leanne, Kattenberg, Johanna H., Laman, Moses, Oswyn, Gilchrist and Mueller, Ivo (2018) 'Efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated malaria in Papua New Guinea'. Malaria Journal, Vol 17, Issue 1, e350.

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Abstract

Background: In 2009, the Papua New Guinea (PNG) Department of Health adopted artemether–lumefantrine (AL)
and dihydroartemisinin–piperaquine (DHA-PPQ) as the first- and second-line treatments for uncomplicated malaria,
respectively. This study was conducted to assess the efficacy of both drugs following adoption of the new policy.
Methods: Between June 2012 and September 2014, a therapeutic efficacy study was conducted in East Sepik and
Milne Bay Provinces of PNG in accordance with the standard World Health Organization (WHO) protocol for surveillance
of anti-malarial drug efficacy. Patients ≥ 6 months of age with microscopy confirmed Plasmodium falciparum
or Plasmodium vivax mono-infections were enrolled, treated with AL or DHA-PPQ, and followed up for 42 days. Study
endpoints were adequate clinical and parasitological response (ACPR) on days 28 and 42. The in vitro efficacy of antimalarials
and the prevalence of selected molecular markers of resistance were also determined.
Results: A total of 274 P. falciparum and 70 P. vivax cases were enrolled. The day-42 PCR-corrected ACPR for P. falciparum
was 98.1% (104/106) for AL and 100% (135/135) for DHA-PPQ. The day-42 PCR-corrected ACPR for P. vivax was
79.0% (15/19) for AL and 92.3% (36/39) for DHA-PPQ. Day 3 parasite clearance of P. falciparum was 99.2% with AL and
100% with DHA-PPQ. In vitro testing of 96 samples revealed low susceptibility to chloroquine (34% of samples above
IC50
threshold) but not to lumefantrine (0%). Molecular markers assessed in a sub-set of the study population indicated
high rates of chloroquine resistance in P. falciparum (pfcrt SVMNT: 94.2%, n = 104) and in P. vivax (pvmdr1 Y976F:
64.8%, n = 54).
Conclusions: AL and DHA-PPQ were efficacious as first- and second-line treatments for uncomplicated malaria in
PNG. Continued in vivo efficacy monitoring is warranted considering the threat of resistance to artemisinin and partner
drugs in the region and scale-up of artemisinin-based combination therapy in PNG.
Keywords: Efficacy, Artemether–lumefantrine, Dihydroartemisinin–piperaquine, Plasmodium falciparum, Plasmodium
vivax, Malaria, In vivo, In vitro

Item Type:	Article
Subjects:	QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 256 Antimalarials QX Parasitology > Protozoa > QX 135 Plasmodia WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department:	Clinical Sciences & International Health > International Public Health Department
Digital Object Identifer (DOI):	https://doi.org/10.1186/s12936-018-2494-z
Depositing User:	Stacy Murtagh
Date Deposited:	11 Oct 2018 10:43
Last Modified:	13 Sep 2019 14:48
URI:	https://archive.lstmed.ac.uk/id/eprint/9444

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