Surveillance of the Efficacy of Artemisinin-Piperaquine in the Treatment of Uncomplicated Plasmodium falciparum Malaria Among Children Under 5 Years of Age in Est-Mono District, Togo, in 2017

Abstract

Background: Malaria is a major public health concern in Togo. The Est-Mono district of Togo has a population of 150,000. Accordingly, the Guangzhou University of Chinese Medicine, China and the Ministry of Health and Social Security, Togo launched a nationwide Mass Drug Administration Project with artemisinin-piperaquine (AP) in Est-Mono. Before launching this project, the sensitivity test of AP was conducted in a general clinic in Elawagnon, Togo. With this background, we evaluated the efficacy and safety of AP for the treatment of uncomplicated falciparum malaria in children under the age of 5 years.

Methods: Children aged 6-59 months with uncomplicated falciparum malaria were enrolled in this study. The selected patients were treated with a combination regime of artemisinin-piperaquine. The patients were followed up for 28 days, during which signs of the following were observed for: the duration for fever clearance, parasitemia density, gametophyte generation, cure rate, hemoglobin level, and merozoite surface protein-2 (msp-2) polymorphism. The primary end point was a 28-day cure rate and polymerase chain reaction (PCR)-corrected reinfection and recrudescence. This research followed the standardized World Health Organization (WHO) protocol for the assessment of the efficacy of antimalarial drugs.

Results: A total of 91 children with uncomplicated falciparum malaria were enrolled in this study. Adequate clinical and parasitological responses (ACPRs) before and after PCR-correction were 66 (73%) and 90 (99%), respectively. The average hemoglobin level in the patient increased by 0.05 g/dl per day (p < 0.0001) after the treatment. The gametophyte generation did not decline at the beginning of the treatment; however, after 14 days, it declined (day 21: p < 0.05; day 28: p < 0.01). In the msp-2 polymorphism study of 24 children treated for parasite infection, one case of msp-2 with 3D7 haplotype and FC27 haplotype was noted, indicating its recrudescence, with a frequency of 4%. The remaining 23 cases could have been of reinfection, with a frequency of 96%. No serious adverse reactions occurred, and AP was well-tolerated by all patients.

Conclusion: Artemisinin-piperaquine was found to be an effective combination for treating uncomplicated falciparum malaria in children aged <5 years in Togo, and the drugs were well-tolerated. In Togo, Plasmodium falciparum remains sensitive to artemisinin-piperaquine, necessitating its trial in this region.

Clinical trial registration: Trial registration: ECGPHCM No. B2017-054-01; MHSST AVIS N° 0001/2016/CBRS du 07 janvier 2016. Registered 17 March 2014, http://www.chinadrugtrials.org.cn/eap/main.

Keywords: Plasmodium falciparum; Togo; artemisinin–piperaquine; gametophyte; merozoite surface protein-2.

Figure 1

Patient flow chart in the clinical trial. ACPR, adequate clinical and parasitological response; ETF, early treatment failure; LCF, late clinical failure; LPF, late parasitological failure; TF, treatment failure; P.f, Plasmodium falciparum; P.m, Plasmodium malariae; P.o, Plasmodium ovale.

Figure 2

Body temperature and parasitemia across days after treatment. Y axis represents the temperature (A) and parasitemia (B) in patients. The significance levels are shown as significant (****: p < 0.0001) and nonsignificant (NS). All data were analyzed with one-way ANOVA and multiple comparisons. Error bars show the standard error of the mean (SEM).

Figure 3

Gametocytemia (A), mean gametocytemia (B), and hemoglobin level (C) of patients from day 0 to day 28. The significance levels are shown as significant (****: p < 0.0001; **: p < 0. 01; *: p < 0. 05) and nonsignificant (NS). The gametocytemia and hemoglobin level of different groups were analyzed with one-way ANOVA and multiple comparisons. Error bars show the standard error of the mean (SEM).

Figure 4

White blood cells (A), parasitemia (B), and gametocytemia (C) of 24 patients with positive parasite detection after treatment on D0 and D28. The significance levels are shown as: significant (***: p < 0. 001; **: p < 0. 01; *: p < 0. 05) and nonsignificant (NS). White blood cells and parasitemia of 24 patients were analyzed with one-way ANOVA, and gametocytemia was analyzed with one-way ANOVA and multiple comparisons. Error bars show the standard error of the mean (SEM).