Multiplicity of Plasmodium falciparum infection predicts antimalarial treatment outcome in Ugandan children.
BACKGROUND
In areas with intense malaria transmission, individuals are often simultaneously infected with multiple parasite strains. This study assessed the effect of multiple infections on treatment response in Ugandan children with uncomplicated malaria.


METHODS
Four hundred and seventy six blood specimens were analysed for parasite genetic diversity. The P.falciparum merozoite surface protein-2 (msp-2) was analysed to establish multiplicity of infection for pre and post treatment specimens.


RESULTS
There were 32 different msp-2 alleles, 15 corresponding to the IC/3D7 and 17 to the FC27 allelic family. The majority of the isolates (343, 72 %) were multiple infections resulting into an overall mean multiplicity of infection of 2.15 (SD+/-1.02). Children infected with multiple strains had nearly a 3-fold increase in treatment failure (Hazard Ratio = 2.8, 95 % CI: 1.5-5.3) compared to their age mates infected with a single strain.


CONCLUSIONS
Multiple-strain infection reduced response to antimalarial therapy. Strategies that reduce multiple-strain infections (intermitted presumptive treatment, indoor residual spraying, insecticide treated nets and efficacious drugs) are likely to improve antimalarial drug efficacy and reduce rate of spread of drug resistance.
Kyabayinze
Daniel J
DJ
College of Health Sciences, Makerere University, Kampala, Uganda. drdjkyabayinze@yahoo.com
Karamagi
Charles
C
Kiggundu
Moses
M
Kamya
Moses R
MR
Wabwire-Mangen
Fred
F
Kironde
Fred
F
Talisuna
Ambrose
A
D000483:Alleles; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism; D000962:Antimalarials / Q000627:therapeutic use*; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000469:parasitology; D008297:Male; D010963:Plasmodium falciparum / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D016896:Treatment Outcome; D014454:Uganda / Q000453:epidemiology
D000953:Antigens, Protozoan; D000962:Antimalarials; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium