Uncomplicated Clinical Malaria Features, the Efficacy of Artesunate-Amodiaquine and Their Relation with Multiplicity of Infection in the Democratic Republic of Congo.
BACKGROUND
In the Democratic Republic of Congo, artesunate-amodiaquine (ASAQ) is the first-line medication recommended for uncomplicated malaria treatment. We conducted a study in Kinshasa to describe the clinical features of the disease and assess the efficacy of ASAQ and its impact on the multiplicity of infection in children with uncomplicated malaria.


METHODS
Children aged 12 to 59 months with uncomplicated P. falciparum malaria were treated with ASAQ and followed up passively for 42 days. To distinguish new infections from recrudescent parasites, samples were genotyped using a stepwise strategy with three molecular markers (GLURP, MSP2 and MSP1). We then assessed PCR-corrected and -uncorrected day-42 cure rates and multiplicity of infection (MOI).


RESULTS
In total, 2,796 patients were screened and 865 enrolled in the study. Clinical features were characterized by history of fever (100%), coryza (59.9%) and weakness (59.4%). The crude and PCR-corrected efficacies of ASAQ were 55.3% (95%CI: 51.8-58.8) and 92.8% (95%CI: 91.0-94.6) respectively, as 83.6% (95%CI: 79.1-87.2) of the recurrences were new infections. Compared to monoclonal infections, polyclonal infections were more frequent at enrollment (88.1%) and in recurrences (80.1%; p = 0.005; OR: 1.8, 95%CI: 1.20-2.8). The median MOI at enrollment (MOI = 3.7; IQR: 0.7-6.7) decreased to 3 (IQR: 1-5) in the recurrent samples (p<0.001). Patients infected with a single haplotype on day 0 had no recrudescence; the risk of recrudescence increased by 28% with each additional haplotype (HR: 1.3, 95%CI: 1.24-1.44).


CONCLUSIONS
The PCR-corrected efficacy of ASAQ at day 42 was 92.8%, but crude efficacy was relatively poor due to high reinfection rates. Treatment outcomes were positively correlated with MOI. Continued monitoring of the efficacy of ACTs-ASAQ, in this case-is paramount.


BACKGROUND
ClinicalTrials.gov NCT01374581.
Tropical Medicine Department, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of Congo.|Global Health Institute, University of Antwerp, Antwerp, Belgium.
Hypolite
H
Muhindo Mavoko
Outpatients Department, Lisungi Health Center, Kinshasa, Democratic Republic of Congo.
Marion
M
Kalabuanga
Global Health Institute, University of Antwerp, Antwerp, Belgium.
Christopher
C
Delgado-Ratto
Tropical Medicine Department, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of Congo.|Global Health Institute, University of Antwerp, Antwerp, Belgium.
Vivi
V
Maketa
Tropical Medicine Department, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of Congo.
Rodin
R
Mukele
Outpatients Department, Lisungi Health Center, Kinshasa, Democratic Republic of Congo.
Blaise
B
Fungula
Global Health Institute, University of Antwerp, Antwerp, Belgium.
Raquel
R
Inocêncio da Luz
Institute of Tropical Medicine, Antwerp, Belgium.
Anna
A
Rosanas-Urgell
Tropical Medicine Department, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of Congo.
Pascal
P
Lutumba
Global Health Institute, University of Antwerp, Antwerp, Belgium.
Jean-Pierre
JP
Van Geertruyden
D000655:Amodiaquine / Q000627:therapeutic use*; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D002675:Child, Preschool; D015023:Democratic Republic of the Congo / Q000453:epidemiology; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology*; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000472:pathogenicity; D016896:Treatment Outcome
D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; C515299:amodiaquine, artesunate drug combination; D000655:Amodiaquine