Effective case management of malaria is hampered by the spread of parasite resistance to nonartemisinin
antimalarials. To counteract the impact of drug resistance, the World Health
Organization (WHO) has endorsed artemisinin-based combination therapy (ACT) as the first-line
treatment for uncomplicated Plasmodium falciparum malaria. Currently recommended
ACTs are artemether-lumefantrine, artesunate plus amodiaquine, artesunate plus mefloquine,
artesunate plus sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine.
This study sought to review evidence of the efficacy and safety of different non-artemisinin
antimalarials in combination with artesunate, artemether or dihydroartemisinin for the
treatment of uncomplicated P. falciparum malaria in non-pregnant adults and children. The
search for randomized controlled trials (RCTs) was conducted in the Cochrane Central
Register for Controlled Trials (CENTRAL), MEDLINE, EMBASE and in ClinicalTrials.gov
in January 2009. The eligibility and the methodological quality of trials were assessed and
data were extracted, using standard forms. Data were captured and analyzed in Review
Manager Software, versions 4.2 and 5.0. The outcomes assessed were: treatment failure, fever
and parasite clearance time, calculating the relative risk (RR) and a weighted mean difference
(WMD) with a 95% confidence interval and p-values, indicating statistical significance at
0.05.
Thirty-seven trials with 6862 participants were included. Artesunate combined with
amodiaquine had a statistically significant lower risk of treatment failure compared to the
combination of artesunate with sulfadoxine-pyrimethamine (RR=0.57, 95% CI [0.33, 0.97],
p=0.04, seven trials, N=1341). In addition, treatment with artesunate plus mefloquine was
significantly associated with a lower risk of treatment failure compared to artesunate plus
azithromycin (RR=0.04, 95% CI [0.00, 0.64], p=0.02, one trial, N=54). There was no
significant difference when either mefloquine or atovaquone-proguanil were combination
partners with artesunate (RR=2.6, 95% CI [0.93; 7.24], p=0.07, one trial, N=1066). When
artesunate was combined with chloroquine, primaquine or azithromycin and compared with
artesunate monotherapy, there was no statistically significant difference in the risk of
unadjusted treatment failure. Each of these comparisons had one trial each. Artesunate plus
chloroquine was quicker at clearing fever compared to artesunate plus sulfadoxinepyrimethamine
(WMD= -7.20, 95% CI [-12.53, -1.87], one trial, N=132).
Few trials adequately reported adverse events. There was no significant difference observed in
the risk of adverse events between artesunate plus amodiaquine compared with artesunate
monotherapy, however, adverse events were significantly less in artesunate plus amodiaquine
compared to artesunate plus methylene-blue. Artesunate plus amodiaquine on the other hand
had significantly more adverse events reported compared to artesunate plus sulfadoxine-pyrimethamine.
The findings of this study support the implementation of artemisinin-based combination
therapy for the treatment of uncomplicated malaria. Most crucially, this review found a greater
advantage of combining amodiaquine with artesunate compared to sulfadoxine-pyrimethamine.
The efficacy of artesunate plus mefloquine was superior to that of artesunate
plus azithromycin. Furthermore, the combination of artemisinins with chloroquine, primaquine
and azithromycin has shown very low efficacy and these combination therapies should not be
recommended. The reporting of efficacy was not standardized as many trials did not
differentiate between re-infections and recrudescences. Adverse events were also not
adequately reported. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2011.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:ukzn/oai:http://researchspace.ukzn.ac.za:10413/10009 |
| Date | 15 November 2013 |
| Creators | Zani, Babalwa. |
| Contributors | Goldring, J. P. Dean. |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | English |
| Type | Thesis |
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