The online version of this article (doi:10.1186/1475-2875-11-434) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
All authors have reviewed the final draft and agreed to its submission. CHVW initiated the research project, wrote the protocol, co-ordinated the research, collated the data, and composed most of the research report. JR contributed to study design, performed the PCR and molecular analysis, and assisted with editing of the manuscript. ER participated in the study design and supervised Malaria Control Personnel for the follow-up of non-returning patients. EI co-ordinated the recruitment of patients at local clinics, the collection of samples, and was responsible for overseeing clinical care of recruited patients. HR co-ordinated local recruitment of patients, collection of samples, and was responsible for overseeing clinical care of recruited patients. KG reviewed the study protocol, co-ordinated local recruitment of patients, and was responsible for overseeing clinical care of recruited patients. SK assisted with the development of the protocol and the write-up of the report of the research.
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.
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 (Coartem®) 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.
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.
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.
World Health Organization: Methods for surveillance of antimalarial efficacy. 2009, Geneva: WHO Press
World Health Organization: World Malaria Report 2011. 2011, Geneva: WHO Press
Barnes KI, Durrheim DN, Little F, Jackson A, Mehta U, Allen E, Dlamini SS, Tsoka J, Bredenkamp B, Mthembu DJ, White NJ, Sharp BL: Effect of artemether-lumefantrine policy and improved vector control on malaria burden in KwaZulu-Natal. South Africa. PLoS Med. 2005, 2: e330-10.1371/journal.pmed.0020330. PubMedCentralCrossRefPubMed
Vaughan Williams CH: Success of insecticide spraying in controlling malaria. S Afr Med J. 2003, 93: 160-
Herbst JM, Taylor LA, Joubert SM: In vitro chloroquine-resistant Plasmodium falciparum malaria in the Natal/Kwazulu area. S Afr Med J. 1985, 68: 749-750. PubMed
Freese JA, Sharp BL, Nxongo SN, Markus MB: In vitro confirmation of chloroquine-resistant Plasmodium falciparum malaria in KwaZulu. S Afr Med J. 1988, 74: 576-578. PubMed
Bredenkamp BL, Sharp BL, Mthembu SD, Durrheim DN, Barnes KI: Failure of sulphadoxine-pyrimethamine in treating Plasmodium falciparum malaria in KwaZulu-Natal. S Afr Med J. 2001, 91: 970-972. PubMed
Sharp BL, le Sueur D: Malaria in South Africa–the past, the present and selected implications for the future. S Afr Med J. 1996, 86: 83-89. PubMed
KZN MCP Malaria Cases for Years. 1996, [ http://www.kznhealth.gov.za/malaria1.pdf], -2004
World Health Organization: Guidelines for the treatment of Malaria - 2nd edition. 2010, Geneva: WHO Press
Vaughan Williams CH, La Cock C, Henry GFJ, Ross AJ: Audit of failure rate of Coartem™ at single fourteen-day follow-up. SA Fam Pract. 2002, 25: 8-12.
Vaughan Williams CH, La Cock C, Bredenkamp BLF: Audit of efficacy of Coartem™ to clear Plasmodium falciparum malaria parasitaemia at single forty-two day follow-up. SA Fam Pract. 2004, 46: 21-24.
Novatis Pharma AG: Novartis International Package Leaflet Coartem. 2012, Basel: Switzerland: Novartis Pharma AG
Borrmann S, Sallas WM, Machevo S, Gonzalez R, Bjorkman A, Martensson A, Hamel M, Juma E, Peshu J, Ogutu B, Djimde A, D'Alessandro U, Marrast AC, Lefevre G, Kern SE: The effect of food consumption on lumefantrine bioavailability in African children receiving artemether-lumefantrine crushed or dispersible tablets (Coartem) for acute uncomplicated Plasmodium falciparum malaria. Trop Med Int Health. 2010, 15: 434-441. PubMed
Hung T-Y, Davis TME, Ilett KF, Karunajeewa H, Hewitt S, Denis MB, Lim C, Socheat D: Population pharmacokinetics of piperaquine in adults and children with uncomplicated falciparum or vivax malaria. Br J Clin Pharmacol. 2003, 57: 253-262. 10.1046/j.1365-2125.2003.02004.x. CrossRef
Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, Lwin KM, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NP, Lindegardh N, Socheat D, White NJ: Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009, 361: 455-467. 10.1056/NEJMoa0808859. PubMedCentralCrossRefPubMed
Borrmann S, Sasi P, Mwai L, Bashraheil M, Abdallah A, Muriithi S, Fruhauf H, Schaub B, Pfeil J, Peshu J, Hanpithakpong W, Rippert A, Juma E, Tsofa B, Mosobo M, Lowe B, Osier F, Fegan G, Lindegardh N, Nzila A, Peshu N, Mackinnon M, Marsh K: Declining responsiveness of Plasmodium falciparum infections to artemisinin-based combination treatments on the Kenyan coast. PLoS One. 2011, 6: e26005-10.1371/journal.pone.0026005. PubMedCentralCrossRefPubMed
World Health Organization: Monitoring antimalarial drug resistance. 2002, Geneva: World Health Organization
Price RN, Uhlemann AC, van Vugt M, Brockman A, Hutagalung R, Nair S, Nash D, Singhasivanon P, Anderson TJ, Krishna S, White NJ, Nosten F: Molecular and pharmacological determinants of the therapeutic response to artemether-lumefantrine in multidrug-resistant Plasmodium falciparum malaria. Clin Infect Dis. 2006, 42: 1570-1577. 10.1086/503423. PubMedCentralCrossRefPubMed
World Health Organization: Assessment of therapeutic efficacy of antimalarial drugs for uncomplicated falciparum malaria in areas with intense transmission. 1996, Geneva: World Health Organization
DGM Microbiology working group: Standard Operating Procedure: Processing specimens for Malaria parasites. 2011, Johannesburg: South African National Health Laboratory Service
Department of Health Republic of South Africa: Guidelines for the treatment of malaria in South Africa. 2008, Pretoria: Department of Health
Mungthin M, Khositnithikul R, Sitthichot N, Suwandittakul N, Wattanaveeradej V, Ward SA, Na-Bangchang K: Association between the pfmdr1 gene and in vitro artemether and lumefantrine sensitivity in Thai isolates of Plasmodium falciparum. AmJTrop Med Hyg. 2010, 83: 1005-1009. 10.4269/ajtmh.2010.10-0339. CrossRef
African Union: Fight Malaria: Africa Goes from Control to Elimination by 2010. African Union Launch of the Africa Malaria Elimination Campaign during 3rd Session of AU Conference of Ministers of Health. 2007, Johannesburg, South Africa
- 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-Williams
- BioMed Central
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