Slow clearance of Plasmodium vivax with chloroquine amongst children younger than six months of age in the Brazilian Amazon

Abstract

Plasmodium vivax is the most widespread parasite causing malaria, being especially prevalent in the Americas and Southeast Asia. Children are one of the most affected populations, especially in highly endemic areas. However, there are few studies evaluating the therapeutic response of infants with vivax malaria. This study retrospectively evaluated the parasitaemia clearance in children diagnosed with vivax malaria during the first five days of exclusive treatment with chloroquine (CQ). Infants aged less than six months old had a significantly slower parasitaemia clearance time compared to the group of infants and children between six months and 12 years old (Kaplan-Meier survival analysis; Wilcoxon test; p = 0.004). The impaired clearance of parasitaemia in younger children with vivax malaria is shown for the first time in Latin America. It is speculated that CQ pharmacokinetics in young children with vivax malaria is distinct, but this specific population may also allow the detection of CQ-resistant parasites during follow-up, due to the lack of previous immunity.

Doses of chloroquine in the treatment of malaria by Plasmodium vivax in patients between 2 and 14 years of age from the Brazilian Amazon basin

“…In fact, when the aged-based total dose of chloroquine was transformed to milligrams of drug per kilogram of body weight (mg/kg), there was a normal distribution of the data demonstrating a high variation in chloroquine doses. Moreover, there was an elevated proportion of patients receiving a suboptimal dose of the drug (< 25 mg/kg), which ranges from 27.5 to 60.5% in the age groups investigated, with the highest proportion in children aged 2–3 years old, which corroborates reports of the high risk of under dosing in young children [7–10].…”

“…Accurate dosing contributes to the therapeutic efficacy of anti-malarial drugs, and children constitute a group at risk for suboptimal dosing, since organ maturation, body composition, and the ontogeny of drug elimination pathway affect the disposition of these drugs [24, 25]. Moreover, vomiting, diarrhoea, malnutrition and other comorbidities, pharmaceutical formulation and ethnicity can modify drug exposure, increasing the risk of suboptimal dosing of anti-malarial drugs [7, 26, 27].…”

“…In children and adolescents, a probable cause is suboptimal treatment with the drug, which can delay the clearance of parasites and result in recurrent parasitaemia thus contributing to resistance. Moreover, sub dosing can increase the risk of developing severe signs and symptoms of vivax malaria estimated at 4.7/10.000 of cases in this endemic setting [2, 7–11]. Therefore, the doses of anti-malarial drugs should be carefully estimated in children and adolescents.…”

Fixed-Dose Artesunate–Amodiaquine Combination vs Chloroquine for Treatment of Uncomplicated Blood Stage P. vivax Infection in the Brazilian Amazon: An Open-Label Randomized, Controlled Trial

“…This population is at higher risk of treatment failure [53, 54], for which age-stratified sampling would be important. There was a higher loss to follow-up in the ASAQ arm, which had an impact on the efficacy assessment in the ITT population.…”

Evaluation of the paediatric dose of chloroquine in the treatment of Plasmodium vivax malaria

“…On the other hand, the lack of acquired immunity in children affects the spread of resistance to anti-malarial drugs [ 29 ], although this seems to be more related to infants [ 30 ]. In this respect recent reports have shown that paediatric doses of anti-malarial drugs should be re-evaluated [ 31 , 32 ].…”