Parasite reduction ratio one day after initiation of artemisinin-based combination therapies and its relationship with parasite clearance time in acutely malarious children

Abstract

BackgroundIn acute falciparum malaria, asexual parasite reduction ratio two days post-treatment initiation (PRRD2) ≥ 10 000 per cycle has been used as a measure of the rapid clearance of parasitaemia and efficacy of artemisinin derivatives. However, there is little evaluation of alternative measures; for example, parasite reduction ratio one day after treatment initiation (PRRD1) and its relationship with parasite clearance time (PCT) or PRRD2. This study evaluated the use of PRRD1 as a measure of responsiveness to antimalarial drugs.MethodsIn acutely malarious children treated with artesunate-amodiaquine (AA), artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DHP), the relationships between PRRD1 or PRRD2 and PCT, and between PRRD1 and PRRD2 were evaluated using linear regression. Agreement between estimates of PCT using PRRD1 and PRRD2 linear regression equations was evaluated using the Bland-Altman analysis. Predictors of PRRD1 > 5000 per half cycle and PRRD2 ≥ 10 000 per cycle were evaluated using stepwise multiple logistic regression models. Using the linear regression equation of the relationship between PRRD1 and PCT previously generated in half of the DHP-treated children during the early study phase, PCT estimates were compared in a prospective blinded manner with PCTs determined by microscopy during the later study phase in the remaining half.ResultsIn 919 malarious children, PRRD1 was significantly higher in DHP- and AA-treated compared with AL-treated children (P < 0.0001). PRRD1 or PRRD2 values correlated significantly negatively with PCT values (P < 0.0001 for each) and significantly positively with each other (P < 0.0001). PCT estimates from linear regression equations for PRRD1 and PRRD2 showed insignificant bias on the Bland-Altman plot (P = 0.7) indicating the estimates can be used interchangeably. At presentation, age > 15 months, parasitaemia > 10 000/μl and DHP treatment independently predicted PRRD1 > 5000 per half cycle, while age > 30 months, haematocrit ≥31%, body temperature > 37.4 °C, parasitaemia > 100 000/μl, PRRD1 value > 1000 and no gametocytaemia independently predicted PRRD2 ≥ 10 000 per cycle. Using the linear regression equation generated during the early phase in 166 DHP-treated children, PCT estimates and PCTs determined by microscopy in the 155 children in the later phase were similar in the same patients.ConclusionsPRRD1 and estimates of PCT using PRRD1 linear regression equation of PRRD1 and PCT can be used in therapeutic efficacy studies.Trial registrationPan African Clinical Trial Registration PACTR201709002064150, 1 March 2017, http://www.pactr.org

APDDD: Animal parasitic diseases and drugs database

“…(Man et al, 2022)For example, anti-malarial drugs are ineffective against other parasites except to few apicomplexans (Flannery et al, 2013). Therefore, it is di cult for a single drug to provide comprehensive control of all parasitic diseases (Akano et al, 2018). The current drugs utilized for the treatment of these diseases have numerous limitations and outdated origins, and particularly, over time, many parasites have developed resistance to some common drugs, making treatment more di cult (Légaré and Ouellette, 2017;Sibley and Hunt, 2003).…”

“…Combination treatments are widely recognized for their ability to prevent the development of parasite drug resistance. However, due to the lack of comprehensive antiparasitic drugs information, researchers are currently faced with challenges in accessing the necessary information on available drugs for the treatment of parasitic diseases (Akano et al, 2018). Despite some efforts, there remains a signi cant shortage of animal parasitic diseases and drugs databases.…”

Genetic features of P. falciparum parasites collected in 2012-2016 and anti-malaria resistance along China-Myanmar border

“…treatment for P.falciparum malaria since 2000s [1][2]. Recently, it was also applied in Africa, where P. falciparum malaria is hyper-endemic [4][5][6][7][8][9][10].…”