title: Efficacy of artemether-lumefantrine in treatment of malaria among under-fives and prevalence of drug resistance markers in Igombe-Mwanza, north-western Tanzania.
abstract: BACKGROUND
  Drug resistance to anti-malarials is a major public health problem worldwide. This study aimed at establishing the efficacy of artemether-lumefantrine (ACT) in Igombe-Mwanza, north-western Tanzania after a few years of ACT use, and establish the prevalence of mutations in key targets for artemisinin, chloroquine and sulphadoxine/pyrimetamine (SP) drugs.
  
  
  METHODS
  A prospective single cohort study was conducted at Igombe health centre using artemether-lumefantrine combination therapy between February 2010 and March 2011. The follow-up period was 28 days and outcome measures were according to WHO guidelines. Blood was collected on Whatman filter paper for DNA analysis. DNA extraction was done using TRIS-EDTA method, and mutations in Pfcrt, Pfmdr1, Pfdhfr, Pfdhps and Pfatp6 were detected using PCR-RFLP methods established previously.
  
  
  RESULTS
  A total of 103 patients completed the 28 days follow-up. The mean haemoglobin was 8.9 g/dl (range 5.0 to 14.5 g/dl) and mean parasite density was 5,608 parasites/μl. Average parasite clearance time was 34.7 hours and all patients cleared the parasites by day 3. There was no early treatment failure in this study. Late clinical failure was seen in three (2.9%) patients and late parasitological failure (LPF) was seen in two (1.9%). PCR-corrected LPF was 1% and adequate clinical and parasitological response was 96%. The majority of parasites have wild type alleles on pfcrt 76 and pfmdr1 86 positions being 87.8% and 93.7% respectively. Mutant parasites predominated at pfdhfr gene at the main three positions 108, 51 and 59 with prevalence of 94.8%, 75.3% and 82.5% respectively. Post-treatment parasites had more wild types of pfdhps at position 437 and 540 than pre-treatment parasites. No mutation was seen in pfatp6 769 in re-infecting or recrudescing parasites.
  
  
  CONCLUSIONS
  The efficacy of artemether-lumefantrine for treatment of uncomplicated malaria is still high in the study area although the rate of re-infection is higher than previously reported. Parasite clearance after 48 hours was lower compared to previous studies. The prevalence of wild type allele pfcrt 76 K and pfmdr1 86 N was high in the study area while markers for SP resistance is still high. Artemether-lumefantrine may be selecting for wild type alleles on both positions (437 and 540) of pfdhps.
authors.affiliation: Weill-Bugando University College of Health Sciences, Mwanza, Tanzania. erasmuskamugisha@yahoo.com
authors.forename: Erasmus
authors.initials: E
authors.lastname: Kamugisha
authors.forename: Sun
authors.initials: S
authors.lastname: Jing
authors.forename: Mercy
authors.initials: M
authors.lastname: Minde
authors.forename: Johaness
authors.initials: J
authors.lastname: Kataraihya
authors.forename: Gilbert
authors.initials: G
authors.lastname: Kongola
authors.forename: Fred
authors.initials: F
authors.lastname: Kironde
authors.forename: Göte
authors.initials: G
authors.lastname: Swedberg
mesh_terms: D000953:Antigens, Protozoan / Q000235:genetics; D000962:Antimalarials / Q000008:administration & dosage*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage*; D001769:Blood / Q000469:parasitology; D002675:Child, Preschool; D015331:Cohort Studies; D016172:DNA Fingerprinting; D016054:DNA, Protozoan / Q000235:genetics / Q000302:isolation & purification; D004338:Drug Combinations; D004351:Drug Resistance; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage*; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D008288:Malaria / Q000188:drug therapy* / Q000453:epidemiology*; D008297:Male; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D011446:Prospective Studies; D013636:Tanzania / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000953:Antigens, Protozoan; D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D016054:DNA, Protozoan; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes