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

Livingstone Tavul; Manuel W. Hetzel; Albina Teliki; Dorish Walsh; Benson Kiniboro; Lawrence Rare; Justin Pulford; Peter M. Siba; Stephan Karl; Leo Makita; Leanne Robinson; Johanna H. Kattenberg; Moses Laman; Gilchrist Oswyn; Ivo Mueller

doi:10.1186/s12936-018-2494-z

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

Livingstone Tavul
, Manuel W. Hetzel
, Albina Teliki
, Dorish Walsh
, Benson Kiniboro
, Lawrence Rare
, Justin Pulford
, Peter M. Siba
, Stephan Karl
, Leo Makita
, Leanne Robinson
, Johanna H. Kattenberg
, Moses Laman
, Gilchrist Oswyn
, Ivo Mueller

International Public Health

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

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

Original language	English
Article number	350
Pages (from-to)	e350
Journal	Malaria Journal
Volume	17
Issue number	1
Early online date	5 Oct 2018
DOIs	https://doi.org/10.1186/s12936-018-2494-z
Publication status	E-pub ahead of print - 5 Oct 2018

Keywords

Artemether-lumefantrine
Dihydroartemisinin-piperaquine
Efficacy
In vitro
In vivo
Malaria
Plasmodium falciparum
Plasmodium vivax

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

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S12936-018-2494-z - JustinFinal published version, 1.35 MBLicence: CC BY

Cite this

Tavul, L., Hetzel, M. W., Teliki, A., Walsh, D., Kiniboro, B., Rare, L., Pulford, J., Siba, P. M., Karl, S., Makita, L., Robinson, L., Kattenberg, J. H., Laman, M., Oswyn, G., & Mueller, I. (2018). Efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated malaria in Papua New Guinea. Malaria Journal, 17(1), e350. Article 350. Advance online publication. https://doi.org/10.1186/s12936-018-2494-z

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

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 andMilne Bay Provinces of PNG in accordance with the standard World Health Organization (WHO) protocol for surveillanceof anti-malarial drug efficacy. Patients ≥ 6 months of age with microscopy confirmed Plasmodium falciparumor Plasmodium vivax mono-infections were enrolled, treated with AL or DHA-PPQ, and followed up for 42 days. Studyendpoints were adequate clinical and parasitological response (ACPR) on days 28 and 42. The in vitro efficacy of antimalarialsand 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. falciparumwas 98.1\% (104/106) for AL and 100\% (135/135) for DHA-PPQ. The day-42 PCR-corrected ACPR for P. vivax was79.0\% (15/19) for AL and 92.3\% (36/39) for DHA-PPQ. Day 3 parasite clearance of P. falciparum was 99.2\% with AL and100\% with DHA-PPQ. In vitro testing of 96 samples revealed low susceptibility to chloroquine (34\% of samples aboveIC50threshold) but not to lumefantrine (0\%). Molecular markers assessed in a sub-set of the study population indicatedhigh 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 inPNG. Continued in vivo efficacy monitoring is warranted considering the threat of resistance to artemisinin and partnerdrugs in the region and scale-up of artemisinin-based combination therapy in PNG.Keywords: Efficacy, Artemether–lumefantrine, Dihydroartemisinin–piperaquine, Plasmodium falciparum, Plasmodiumvivax, Malaria, In vivo, In vitro",

keywords = "Artemether-lumefantrine, Dihydroartemisinin-piperaquine, Efficacy, In vitro, In vivo, Malaria, Plasmodium falciparum, Plasmodium vivax",

author = "Livingstone Tavul and Hetzel, \{Manuel W.\} and Albina Teliki and Dorish Walsh and Benson Kiniboro and Lawrence Rare and Justin Pulford and Siba, \{Peter M.\} and Stephan Karl and Leo Makita and Leanne Robinson and Kattenberg, \{Johanna H.\} and Moses Laman and Gilchrist Oswyn and Ivo Mueller",

year = "2018",

month = oct,

day = "5",

doi = "10.1186/s12936-018-2494-z",

language = "English",

volume = "17",

pages = "e350",

journal = "Malaria Journal",

issn = "1475-2875",

publisher = "BioMed Central Ltd",

number = "1",

}

Tavul, L, Hetzel, MW, Teliki, A, Walsh, D, Kiniboro, B, Rare, L, Pulford, J, Siba, PM, Karl, S, Makita, L, Robinson, L, Kattenberg, JH, Laman, M, Oswyn, G & Mueller, I 2018, 'Efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated malaria in Papua New Guinea', Malaria Journal, vol. 17, no. 1, 350, pp. e350. https://doi.org/10.1186/s12936-018-2494-z

TY - JOUR

T1 - Efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated malaria in Papua New Guinea

AU - Tavul, Livingstone

AU - Hetzel, Manuel W.

AU - Teliki, Albina

AU - Walsh, Dorish

AU - Kiniboro, Benson

AU - Rare, Lawrence

AU - Pulford, Justin

AU - Siba, Peter M.

AU - Karl, Stephan

AU - Makita, Leo

AU - Robinson, Leanne

AU - Kattenberg, Johanna H.

AU - Laman, Moses

AU - Oswyn, Gilchrist

AU - Mueller, Ivo

PY - 2018/10/5

Y1 - 2018/10/5

N2 - 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 andMilne Bay Provinces of PNG in accordance with the standard World Health Organization (WHO) protocol for surveillanceof anti-malarial drug efficacy. Patients ≥ 6 months of age with microscopy confirmed Plasmodium falciparumor Plasmodium vivax mono-infections were enrolled, treated with AL or DHA-PPQ, and followed up for 42 days. Studyendpoints were adequate clinical and parasitological response (ACPR) on days 28 and 42. The in vitro efficacy of antimalarialsand 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. falciparumwas 98.1% (104/106) for AL and 100% (135/135) for DHA-PPQ. The day-42 PCR-corrected ACPR for P. vivax was79.0% (15/19) for AL and 92.3% (36/39) for DHA-PPQ. Day 3 parasite clearance of P. falciparum was 99.2% with AL and100% with DHA-PPQ. In vitro testing of 96 samples revealed low susceptibility to chloroquine (34% of samples aboveIC50threshold) but not to lumefantrine (0%). Molecular markers assessed in a sub-set of the study population indicatedhigh 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 inPNG. Continued in vivo efficacy monitoring is warranted considering the threat of resistance to artemisinin and partnerdrugs in the region and scale-up of artemisinin-based combination therapy in PNG.Keywords: Efficacy, Artemether–lumefantrine, Dihydroartemisinin–piperaquine, Plasmodium falciparum, Plasmodiumvivax, Malaria, In vivo, In vitro

AB - 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 andMilne Bay Provinces of PNG in accordance with the standard World Health Organization (WHO) protocol for surveillanceof anti-malarial drug efficacy. Patients ≥ 6 months of age with microscopy confirmed Plasmodium falciparumor Plasmodium vivax mono-infections were enrolled, treated with AL or DHA-PPQ, and followed up for 42 days. Studyendpoints were adequate clinical and parasitological response (ACPR) on days 28 and 42. The in vitro efficacy of antimalarialsand 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. falciparumwas 98.1% (104/106) for AL and 100% (135/135) for DHA-PPQ. The day-42 PCR-corrected ACPR for P. vivax was79.0% (15/19) for AL and 92.3% (36/39) for DHA-PPQ. Day 3 parasite clearance of P. falciparum was 99.2% with AL and100% with DHA-PPQ. In vitro testing of 96 samples revealed low susceptibility to chloroquine (34% of samples aboveIC50threshold) but not to lumefantrine (0%). Molecular markers assessed in a sub-set of the study population indicatedhigh 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 inPNG. Continued in vivo efficacy monitoring is warranted considering the threat of resistance to artemisinin and partnerdrugs in the region and scale-up of artemisinin-based combination therapy in PNG.Keywords: Efficacy, Artemether–lumefantrine, Dihydroartemisinin–piperaquine, Plasmodium falciparum, Plasmodiumvivax, Malaria, In vivo, In vitro

KW - Artemether-lumefantrine

KW - Dihydroartemisinin-piperaquine

KW - Efficacy

KW - In vitro

KW - In vivo

KW - Malaria

KW - Plasmodium falciparum

KW - Plasmodium vivax

U2 - 10.1186/s12936-018-2494-z

DO - 10.1186/s12936-018-2494-z

M3 - Article

SN - 1475-2875

VL - 17

SP - e350

JO - Malaria Journal

JF - Malaria Journal

IS - 1

M1 - 350

ER -

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

Abstract

Keywords

UN SDGs

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