Uncomplicated Clinical Malaria Features, the Efficacy of Artesunate-Amodiaquine and Their Relation with Multiplicity of Infection in the Democratic Republic of Congo.

Hypolite Muhindo Mavoko,Jean-Pierre Van Geertruyden,Pascal Lutumba,Vivi Maketa,Blaise Fungula,Raquel Inocêncio Da Luz,Christopher Delgado-Ratto,Rodin Mukele,Marion Kalabuanga,Anna Rosanas-Urgell

doi:10.1371/journal.pone.0157074

Hypolite Muhindo Mavoko, Jean-Pierre Van Geertruyden + Show 8 more

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https://doi.org/10.1371/journal.pone.0157074

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Abstract

BackgroundIn 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.MethodsChildren 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).ResultsIn 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).ConclusionThe 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.Trial RegistrationClinicalTrials.gov NCT01374581

Highlights

The Democratic Republic of Congo (DR Congo) is considered to be one of the countries most severely affected by malaria [1]
We considered late treatment failure to be any failure occurring from day 14 onwards, as this was the threshold for recruitment in the randomized clinical trial (RCT) phase
ASAQ remains a suitable treatment for uncomplicated malaria in Kinshasa, with a PCR-corrected efficacy of 92.8% after 42 days of follow-up

Summary

Introduction

The Democratic Republic of Congo (DR Congo) is considered to be one of the countries most severely affected by malaria [1]. Due to widespread chloroquine resistance, the Congolese National Malaria Control Program (NMCP) introduced sulfadoxine-pyrimethamine (SP) in 2001 as the first-line drug for uncomplicated malaria. After observing an increase in treatment failure rates with SP, the NMCP turned to artemisinin-based combination therapy (ACT) in 2005, in particular artesunate-amodiaquine (ASAQ), to replace SP. In 2010, the NMCP selected artemether-lumefantrine (AL) as an alternative first-line treatment, alongside ASAQ [5]. 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

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