Factors contributing to delay in parasite clearance in uncomplicated falciparum malaria in children.
BACKGROUND
Drug resistance in Plasmodium falciparum is common in many endemic and other settings but there is no clear recommendation on when to change therapy when there is delay in parasite clearance after initiation of therapy in African children.


METHODS
The factors contributing to delay in parasite clearance, defined as a clearance time > 2 d, in falciparum malaria were characterized in 2,752 prospectively studied children treated with anti-malarial drugs between 1996 and 2008.


RESULTS
1,237 of 2,752 children (45%) had delay in parasite clearance. Overall 211 children (17%) with delay in clearance subsequently failed therapy and they constituted 72% of those who had drug failure, i.e., 211 of 291 children. The following were independent risk factors for delay in parasite clearance at enrolment: age less than or equal to 2 years (Adjusted odds ratio [AOR] = 2.13, 95% confidence interval [CI]1.44-3.15, P < 0.0001), presence of fever (AOR = 1.33, 95% CI = 1.04-1.69, P = 0.019), parasitaemia >50,000/ul (AOR = 2.21, 95% CI = 1.77-2.75, P < 0.0001), and enrolment before year 2000 (AOR= 1.55, 95% CI = 1.22-1.96, P < 0.0001). Following treatment, a body temperature >or= 38 degrees C and parasitaemia > 20000/microl a day after treatment began, were independent risk factors for delay in clearance. Non-artemisinin monotherapies were associated with delay in clearance and treatment failures, and in those treated with chloroquine or amodiaquine, with pfmdr 1/pfcrt mutants. Delay in clearance significantly increased gametocyte carriage (P < 0.0001).


CONCLUSIONS
Delay in parasite clearance is multifactorial, is related to drug resistance and treatment failure in uncomplicated malaria and has implications for malaria control efforts in sub-Saharan Africa.
Sowunmi
Akintunde
A
Department of Pharmacology & Therapeutics, University of Ibadan, Ibadan, Nigeria. akinsowunmi@hotmail.com
Adewoye
Elsie O
EO
Gbotsho
Grace O
GO
Happi
Christian T
CT
Sijuade
Abayomi
A
Folarin
Onikepe A
OA
Okuboyejo
Titilope M
TM
Michael
Obaro S
OS
D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology; D008297:Male; D026901:Membrane Transport Proteins / Q000097:blood; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000097:blood; D018512:Parasitemia / Q000188:drug therapy*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000302:isolation & purification*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D015800:Protozoan Proteins / Q000097:blood; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D000962:Antimalarials; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum