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 firstline
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 (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.
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.
ii
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.
Recommendations
A larger study is needed to accurately determine therapeutic efficacy of artemetherlumefantrine
and resistance marker prevalence. The high proportion of rapid diagnostic
test false-positive results requires further investigation. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Durban, 2013.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:ukzn/oai:http://researchspace.ukzn.ac.za:10413/11064 |
| Date | January 2013 |
| Creators | Vaughan-Williams, Charles Hervey. |
| Contributors | Knight, Stephen. |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | English |
| Type | Thesis |
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