Parenteral artemisinins are associated with reduced mortality and neurologic deficits and improved long-term behavioral outcomes in children with severe malaria

BMC Medicine

Allen E. Okullo¹  John M. Ssenkusu²  Robert O. Opoka³  Ruth Namazzi³  Richard Idro³  Sarah Cusick⁴  Michael K. Georgieff⁴  Paul Bangirana⁵  Andrea L. Conroy⁶  Chandy C. John⁷ 

[1] Clinical Epidemiology Unit, Makerere University College of Health Sciences, Kampala, Uganda;Department of Epidemiology and Biostatistics, Makerere University School of Public Health, Kampala, Uganda;Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda;Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA;Department of Psychiatry, Makerere University College of Health Sciences, Kampala, Uganda;Ryan White Center for Pediatric Infectious Disease and Global Health, Indiana University School of Medicine, R4 402C 1044 West Walnut St, 46202, Indianapolis, IN, USA;Ryan White Center for Pediatric Infectious Disease and Global Health, Indiana University School of Medicine, R4 402C 1044 West Walnut St, 46202, Indianapolis, IN, USA;Division of Global Pediatrics, University of Minnesota Medical School, Minneapolis, USA;

关键词: Artemisinin;    Artesunate;    Quinine;    Mortality;    Severe malaria;    Neurologic deficit;    Long-term;    Inflammation;    Behavior;    Hospital readmission;    Pediatric;    Children;    Cerebral malaria;    Severe anemia;   

DOI  :  10.1186/s12916-021-02033-1

来源: Springer

【 摘 要 】

BackgroundIn 2011, the World Health Organization recommended injectable artesunate as the first-line therapy for severe malaria (SM) due to its superiority in reducing mortality compared to quinine. There are limited data on long-term clinical and neurobehavioral outcomes after artemisinin use for treatment of SM.MethodsFrom 2008 to 2013, 502 Ugandan children with two common forms of SM, cerebral malaria and severe malarial anemia, were enrolled in a prospective observational study assessing long-term neurobehavioral and cognitive outcomes following SM. Children were evaluated a week after hospital discharge, and 6, 12, and 24 months of follow-up, and returned to hospital for any illness. In this study, we evaluated the impact of artemisinin derivatives on survival, post-discharge hospital readmission or death, and neurocognitive and behavioral outcomes over 2 years of follow-up.Results346 children received quinine and 156 received parenteral artemisinin therapy (artemether or artesunate). After adjustment for disease severity, artemisinin derivatives were associated with a 78% reduction in in-hospital mortality (adjusted odds ratio, 0.22; 95% CI, 0.07–0.67). Among cerebral malaria survivors, children treated with artemisinin derivatives also had reduced neurologic deficits at discharge (quinine, 41.7%; artemisinin derivatives, 23.7%, p=0.007). Over a 2-year follow-up, artemisinin derivatives as compared to quinine were associated with better adjusted scores (negative scores better) in internalizing behavior and executive function in children irrespective of the age at severe malaria episode. After adjusting for multiple comparisons, artemisinin derivatives were associated with better adjusted scores in behavior and executive function in children <6 years of age at severe malaria exposure following adjustment for child age, sex, socioeconomic status, enrichment in the home environment, and the incidence of hospitalizations over follow-up. Children receiving artesunate had the greatest reduction in mortality and benefit in behavioral outcomes and had reduced inflammation at 1-month follow-up compared to children treated with quinine.ConclusionsTreatment of severe malaria with artemisinin derivatives, particularly artesunate, results in reduced in-hospital mortality and neurologic deficits in children of all ages, reduced inflammation following recovery, and better long-term behavioral outcomes. These findings suggest artesunate has long-term beneficial effects in children surviving severe malaria.

【 授权许可】

CC BY