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Open Access Research

Assessment of the therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal: an observational cohort study

Charles H Vaughan-Williams17*, Jaishree Raman2, Eric Raswiswi3, Etienne Immelman4, Holger Reichel5, Kelly Gate6 and Steve Knight7

Author Affiliations

1 Umkhanyakude Health District Office, Jozini, KwaZulu-Natal, 3969, South Africa

2 Malaria Research Unit, South African Medical Research Council, Durban, KwaZulu-Natal, 4001, South Africa

3 Umkhanyakude Health District Office, Jozini, KwaZulu-Natal, 3969, South Africa

4 Manguzi Hospital, Private Bag X301, KwaNgwanase, KwaZulu-Natal, 3793, South Africa

5 Mosvold Hospital, Private Bag X2211, Ingwavuma, KwaZulu-Natal, 3968, South Africa

6 Bethesda Hospital, Private Bag X605, Ubombo, KwaZulu-Natal, 3970, South Africa

7 Department of Public Health Medicine, University of KwaZulu-Natal, 236 George Campbell Building, Howard College Campus, King George V Avenue, Durban, KwaZulu-Natal, 4041, South Africa

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Malaria Journal 2012, 11:434  doi:10.1186/1475-2875-11-434

Published: 28 December 2012

Abstract

Background

Recent malaria epidemics in KwaZulu-Natal indicate that effective anti-malarial therapy is essential for malaria control. Although artemether-lumefantrine has been used as first-line treatment for uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal since 2001, its efficacy has not been assessed since 2002. The objectives of this study were to quantify the proportion of patients treated for uncomplicated P. falciparum malaria with artemether-lumefantrine who failed treatment after 28 days, and to determine the prevalence of molecular markers associated with artemether-lumefantrine and chloroquine resistance.

Methods

An observational cohort of 49 symptomatic patients, diagnosed with uncomplicated P. falciparum malaria by rapid diagnostic test, had blood taken for malaria blood films and P. falciparum DNA polymerase chain reaction (PCR). Following diagnosis, patients were treated with artemether-lumefantrine (CoartemĀ®) and invited to return to the health facility after 28 days for repeat blood film and PCR. All PCR P. falciparum positive samples were analysed for molecular markers of lumefantrine and chloroquine resistance.

Results

Of 49 patients recruited on the basis of a positive rapid diagnostic test, only 16 were confirmed to have P. falciparum by PCR. At follow-up, 14 were PCR-negative for malaria, one was lost to follow-up and one blood specimen had insufficient blood for a PCR analysis. All 16 with PCR-confirmed malaria carried a single copy of the multi-drug resistant (mdr1) gene, and the wild type asparagine allele mdr1 codon 86 (mdr1 86N). Ten of the 16 samples carried the wild type haplotype (CVMNK) at codons 72-76 of the chloroquine resistance transporter gene (pfcrt); three samples carried the resistant CVIET allele; one carried both the resistant and wild type, and in two samples the allele could not be analysed.

Conclusions

The absence of mdr1 gene copy number variation detected in this study suggests lumefantrine resistance has yet to emerge in KwaZulu-Natal. In addition, data from this investigation implies the possible re-emergence of chloroquine-sensitive parasites. Results from this study must be viewed with caution, given the extremely small sample size. A larger study is needed to accurately determine therapeutic efficacy of artemether-lumefantrine and resistance marker prevalence. The high proportion of rapid diagnostic test false-positive results requires further investigation.

Keywords:
Plasmodium falciparum malaria; Artemether; Lumefantrine; Therapeutic efficacy; Resistance markers; KwaZulu-Natal