Early transmission of sensitive strain slows down emergence of drug resistance in Plasmodium vivax

Abstract

The spread of drug resistance of Plasmodium falciparum and Plasmodium vivax parasites is a challenge towards malaria elimination.P. falciparum has shown an early and severe drug resistance in comparison to P. vivax in various countries. In fact, these Plasmodium species differ in their life cycle and treatment in various factors: development and duration of sexual parasite forms differ, symptoms severity are unequal, relapses present only in P. vivax cases, and the Artemisinin-based combination therapy (ACT) is only mandatory in all P. falciparum cases. We compared the spread of drug resistance for both species through two compartmental models using ordinary differential equations. The model structure describes how sensitive and resistant parasite strains infect a human population treated with antimalarials. We found that the early transmission before treatment and the low effectiveness of drug coverage support the prevalence of sensitive parasites delaying the emergence of resistant P. vivax. These results imply that earlier attention of symptomatic and reservoirs of P. vivax accelerates the spread of drug resistance as P. falciparum. Spread of drug resistance ofPlasmodium falciparum and Plasmodium vivax parasites challenges malaria programmes 2 towards elimination, as previous studies have confirmed the spread of drug resistance to the first-line drugs: chloroquine 3 (CQ) and artemisinin-based combination therapies (ACTs) [1-6]. Nevertheless, resistant parasites have emerged in 4 different geographical and temporal patterns around the endemic regions on the world [5]. Thus, efficient malaria 5 programs require considering the variations in treatment regimens and environmental conditions.6Apart from external conditions, P. falciparum and P. vivax parasites differ in their life cycle and treatment exhibiting 7 distinct patterns in drug resistance. P. falciparum has shown an early and severe drug resistance in comparison to P. 8 vivax. Currently, chloroquine (CQ) remains as the first-line treatment against P. vivax and ACTs to P. falciparum due to 9 the reports of CQ resistance in P. falciparum dating from 1950 [2,3,7]. On the other hand, these Plasmodium species 10 differ in various factors: relapses only in P. vivax cases, development and duration of sexual parasite forms, symptoms 11 severity and host immunity response [6,8,9]. Therefore, these species diverge and require specific studies in order to 12 understand and compare determinants in their particular evolution of drug resistance. 13Although most previous studies focused on P. falciparum resistance, a few works have compared the evolution of drug 14 resistance between both species [5,8,10]. Most of previous studies evaluated P. falciparum-resistance factors such as 15 cost-resistance, selection after treatment, transmission of resistant parasites, epidemiological factors, asymptomatic 16 infections and treatment regimens [11][12][13][14][15][16][17][18][19][20][21][22]. Even though P. vivax caused the 74% of malaria cases in the Americas and 17 the 37% o...