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Relationship between weight status and anti-malarial drug efficacy and safety in children in Mali
Moussa Djimde1,2, Hanen Samouda3, Julien Jacobs3
1Malaria Research and Training Center (MRTC), University of Sciences of Techniques and Technologies of Bamako (USTTB), Bamako, Mali.
Insights
Weight status does not impact anti-malarial drug efficacy. However, overweight children treated with artesunate plus amodiaquine (AS+AQ) showed an increased risk of new malaria infections, warranting further study.
Area of Science:
- Malariology
- Clinical Pharmacology
- Pediatric Infectious Diseases
Background:
- Anti-malarial drug efficacy is crucial for disease control programs.
- Standard dosing relies on age-based weight estimations, potentially leading to under- or over-dosing.
- Investigating the impact of weight status on malaria treatment outcomes is essential.
Purpose of the Study:
- To evaluate the relationship between children's weight status and the efficacy of anti-malarial drugs.
- To determine if weight variations affect the clearance of Plasmodium falciparum infection and reinfection rates.
- To assess the influence of weight status on treatment outcomes with different anti-malarial drug combinations.
Main Methods:
- A clinical trial involving 749 children in Mali (2002-2004) treated with artesunate + amodiaquine (AS+AQ), artesunate + sulfadoxine-pyrimethamine (AS+SP), or artesunate (AS).
- Weight status was determined using the World Health Organization (WHO) z-score.
- Statistical analyses, including Chi-square tests and logistic regression, were used to assess drug efficacy and the impact of baseline parameters.
Main Results:
- Without molecular correction, underweight children in the AS+AQ arm had a higher adequate clinical and parasitological response (ACPR) rate (94.74%) compared to normal (91.24%) and overweight (80.43%) children.
- After PCR correction, treatment efficacy exceeded 98% across all weight groups, indicating no significant impact of weight on recrudescence.
- Overweight children in the AS+AQ arm showed no increased risk of recrudescence but had a significantly higher risk of new infections (OR=0.21, p=0.03).
Conclusions:
- Weight deficiency does not appear to negatively affect the efficacy of anti-malarial drugs.
- The increased rate of reinfection observed in overweight children treated with AS+AQ requires further investigation in larger studies.
- Current anti-malarial dosing strategies may need re-evaluation to account for weight variations, particularly in overweight children.
Background:
Anti-malarial treatments effectiveness remains a critical challenge for control programmes. However, when drug efficacy is established, the dose is calculated based on a predefined weight according to the patient age. Based on the hypothesis that the standard assumption of weight according to the age when administering the drug could lead to a therapeutic failure potentially due to under-dosing (in the case of overweight) or over-dosing (in case of underweight). In this study, the relationship between weight status and malaria drug efficacy in clearing current Plasmodium falciparum infection and preventing reinfection after treatment was investigated.
Methods:
Data were drown from a clinical trial conducted previously to investigate malaria drug efficacy in 749 children from Mali (2002-2004). Participants were treated either with artesunate + amodiaquine (AS + AQ, n1 = 250), artesunate + sulfadoxine-pyrimethamine (AS + SP, n2 = 248) or artesunate (AS, n3 = 251) and followed for 28 days after treatment. The World Health Organization (WHO) z-score was used to define weight status. A Chi square test was used to compare outcomes according to drugs, weight status and the dynamic of ALAT, ASAT, creatinine and haemoglobin level. Logistic regression models were developed to determine the effect of baseline parameters (weight status, aspartate transaminase, alanine aminotransferase, creatinine and haemoglobin level) on drug efficacy as per WHO criteria.
Results:
Without molecular correction, in AS + AQ arm, the rate of adequate clinical and parasitological response (ACPR) was higher in the group of underweight children 94.74% compared to children with normal and overweight (91.24% and 80.43% respectively, p = 0.03). After PCR correction, treatment efficacy was similar in the three groups of patients and was above 98% (p = 0.4). Overweight was observed to have no impact on recrudescence. However, it was associated with an increased risk of new infections in the (AS + AQ) arm (OR = 0.21, 95% CI [0.06; 0.86], p = 0.03).
Conclusions:
The findings suggest that weight deficiency has no deleterious effect on anti-malarial drug efficacy. An increase in the rate of reinfection in overweight children treated by AS + AQ should be further explored in larger studies.
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