The online version of this article (doi:10.1186/1475-2875-11-240) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
TE coordinated the clinical study in Ethiopia, participated in the molecular genetic studies and helped draft the manuscript. NA, KB and SF participated in and carried out the clinical studies. AW and MP established the QT-NASBA technology, carried out the gametocyte analysis and revised the manuscript. TL participated in study design and coordination and drafted the manuscript. NB-R designed the study protocol, was PI of the study, carried out the molecular genetic studies as well as the sequence alignments, conducted the statistical analysis and drafted the manuscript. All authors read and approved the final manuscript.
In Jimma Zone, Ethiopia, the first-line treatment of uncomplicated falciparum malaria has been changed from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (AL) in 2006. The objective of this study was to assess the effectiveness of AL in Jimma Zone two to three years after its broad introduction.
An open-label, single-arm, 42-day study of AL against falciparum malaria was conducted in four areas with moderate transmission in Jimma Zone between November 2008 and January 2009 and between August and December 2009. Patients (one-81 years) with uncomplicated Plasmodium falciparum mono-infection were consecutively enrolled. Follow-up visits were at day 2, 3, 7, 28 and 42 or any other day if symptoms reoccurred. Primary and secondary endpoints were PCR-corrected and uncorrected cure rates (molecular differentiation between recrudescence and re-infection) on days 28 and 42. Other secondary endpoints were gametocytaemia at day 7 and day 28, parasitaemia at day 2 and 3, and re-infection rates at day 28 and day 42.
Of 348 enrolled patients, 313 and 301 completed follow-up at day 28 and at day 42, respectively. No early treatment failure occurred. For per protocol analysis, PCR-uncorrected cure rates at day 28 and 42 were 99.1% (95% CI 98.0-100.0) and 91.1% (95% CI 87.9-94.3), respectively. PCR-corrected cure rates at day 28 and 42 were 99.4% (95% CI 98.5-100.0) and 94.7% (95% CI 92.2-97.2), respectively. PCR-corrected cure rate at day 42 for children ≤5 years was 90.6% (95% CI 82.4-98.7) only. Adverse events were in general mild to moderate. Incidence of new infections was 3.4% during 42 days, no new infections with Plasmodium vivax were observed. Microscopically detected gametocytaemia was reduced by 80% between day 0 and day 7.
In general, AL was effective and well tolerated in Jimma Zone, Ethiopia. However, the PCR-corrected recrudescence rate per-protocol at day 42 for children ≤5 years was 9.4%. Therefore, further development should be monitored on a regular basis as recommended by WHO.
Additional file 1: Outcome at day 42 stratified in age groups. Description: The table shows the outcome at day 42 stratified in the age groups > 5 years and ≤ 5 years. The cure rates are in general lower for the under five years old children but the difference is not significant. (DOC 38 KB)12936_2012_2160_MOESM1_ESM.doc
Additional file 2: Association with outcome recrudescence (ACPR & Recrudescences, n = 302). Description: The data show a multi-variate analysis with the outcome recrudescences as dependent variable and independent variables like parasitaemia at day 0, gametocytaemia over time, and parasite clearance, controlled for age and gender. Delayed clearance and gametocytaemie at day 28 were associated with recrudescences. There was evidence for a strong association (P ≤ 0.01) but confidence intervals were wide. (DOC 44 KB)12936_2012_2160_MOESM2_ESM.doc
Additional file 3: Clearance of microscopically detected gametocytes over time. Description: Clearance of microscopically detected gametocytes during follow-up in both age groups and overall. Clearance in older patients seemed to be faster than in children below 6 years of age. (TIFF 78 KB)12936_2012_2160_MOESM3_ESM.tiff
Additional file 4: Symptoms at recruitment (n = 348). Description: The data show all symptoms presented at admission with absolute and relative frequencies and duration. Fever, headache and shivering were the leading symptoms. (DOC 38 KB)12936_2012_2160_MOESM4_ESM.doc
Additional file 5: Adverse events (AE) during follow-up. Description: The table presents all adverse events reported until day 7. Abdominal pain was the most reported AE. Prevalence was overall low. (DOC 33 KB)12936_2012_2160_MOESM5_ESM.doc
Authors’ original file for figure 112936_2012_2160_MOESM6_ESM.tiff
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- Open-label trial with artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria three years after its broad introduction in Jimma Zone, Ethiopia
Kunuz H Bedru
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