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

Conroy, Andrea L.; Opoka, Robert O.; Bangirana, Paul; Namazzi, Ruth; Okullo, Allen E.; Georgieff, Michael K.; Cusick, Sarah; Idro, Richard; Ssenkusu, John M.; John, Chandy C.

doi:10.1186/s12916-021-02033-1

Table 3 Primary cognitive and behavioral outcomes in children over 24-month follow-up, according to antimalarial treatment

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

	Preschool age at testing				School age at testing
	N (obs), N ^a	Mean difference^b, artemisinin derivatives vs. quinine (95% CI)	P value	Sig.†*	N (obs), N ^a	Mean difference^b, artemisinin derivatives vs. quinine (95% CI)	P value	Sig.†*
Cognition outcomes ^c	<5 years of age				≥ 5 years of age
Cognition	1053, 351	-0.04 (-0.37, 0.29)	0.83		584, 248	-0.05 (-0.51, 0.41)	0.84
Attention	1111, 352	0.06 (-0.14, 0.26)	0.55		590, 251	0.19 (-0.18, 0.56)	0.31
Memory	1091, 350	-0.09 (-0.23, 0.06)	0.23		594, 251	0.13 (-0.27, 0.53)	0.53
Behavioral outcomes ^d	<6 years of age				≥ 6 years of age
Child Behavior Checklist
Internalizing behavior	1339, 390	-0.38 (-0.57, -0.18)	0.0002	†*	353, 152	-0.33 (-0.64, -0.02)	0.039	†
Externalizing behavior	1339, 390	-0.37 (-0.56, -0.27)	0.0002	†*	353, 152	-0.36 (-0.84, 0.12)	0.145
Total behavior	1339, 390	-0.42 (-0.64, -0.21)	0.0001	†*	353, 152	-0.44 (-0.89, 0.02)	0.060
Behavior rating inventory
Global Executive Composite	735, 306	-0.87 (-1.24, -0.51)	<0.0001	†*	247, 139	-0.45 (-0.80, -0.10)	0.012	†

^aN (obs) refers to the number of observations of cognitive or behavioral measures included in the model and N refers to the number of study participants
^bMean difference and 95% confidence interval (CI) are derived from a linear mixed effects model, with the beta coefficient representing the mean difference. Models included a subject-specific random intercept and random caretaker effect, time as a categorical variable (to allow for non-linearity between study visits), and adjusted for age, sex, height-for-age and weight-for-age z score, socioeconomic status and home environment z score, disease severity during the acute illness (number of seizures, coma, acute kidney injury), child schooling, enrollment in the iron study (not enrolled, enrolled in the immediate iron arm, enrolled in the delayed iron arm), and the number of hospital admissions over 24 months follow-up
^cFor cognitive outcomes a positive number is indicative of an improved outcome in children receiving artemisinin derivatives. In preschool-aged children (<5 years of age), cognition was assessed using the Mullen Scales of Early Learning, attention was assessed using the early childhood vigilance test, and memory was assessed using the color object association test. In school aged children (≥5 years of age), cognition was assessed using the Kauffman Assessment Battery for Children (K-ABC) second edition using the mental processing index, attention was assessed using the Test of Variables of Attention using the D-prime measure, and memory was assessed using the sequential processing score from the K-ABC
^dFor behavioral outcomes, a negative number is indicative of an improved outcome in children receiving artemisinin derivatives
†p<0.05, *adjusted p<0.05 Benjamini-Hoch correction for false discovery rate at 0.05 adjusting for 7 comparisons within each age strata

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