Skip to main content

Table 4 Primary cognitive and behavioral outcomes in children over 24- month follow-up, according to a specific antimalarial drug 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), Na

Mean differenceb, artemisinin derivative vs. quinine (95% CI)

P value

Sig. †*

N (obs), Na

Mean differenceb, artemisinin derivative vs. quinine (95% CI)

P value

Sig. †*

Cognition outcomesc

<5 years of age

≥ 5 years of age

 Cognition

  Quinine + Artemether

1053, 351

−0.10 (−0.50, 0.30)

0.618

 

584, 248

−0.03 (−0.63, 0.58)

0.928

 

  Artemether

 

0.38 (−0.25, 1.01)

0.234

  

0.33 (−0.49, 1.15)

0.431

 

  Artesunate

 

−0.17 (−0.70, 0.36)

0.531

  

−0.36 (−1.06, 0.35)

0.319

 

 Attention

  Quinine + Artemether

1111, 352

0.09 (−0.15, 0.32)

0.463

 

590, 251

0.11 (−0.38, 0.60)

0.650

 

  Artemether

 

0.04 (−0.36, 0.44)

0.844

  

0.47 (−0.19, 1.13)

0.159

 

  Artesunate

 

0.01 (−0.31, 0.33)

0.968

  

0.10 (−0.47, 0.67)

0.727

 

 Memory

  Quinine + Artemether

1091, 350

−0.07 (−0.24, 0.10)

0.426

 

594, 251

0.14 (−0.39, 0.67)

0.602

 

  Artemether

 

0.05 (−0.22, 0.33)

0.715

  

0.11 (−0.61, 0.82)

0.766

 

  Artesunate

 

−0.22 (−0.45, 0.01)

0.060

  

0.13 (−0.48, 0.74)

0.680

 

Behavioral outcomesd

<6 years of age

≥ 6 years of age

Child Behavior Checklist

 Internalizing behavior

  Quinine + Artemether

1339, 390

−0.16 (−0.39, 0.07)

0.181

 

353, 152

−0.24 (−0.68, 0.190

0.268

 

  Artemether

 

−0.42 (−0.79, −0.05)

0.026

†

 

−0.08 (−0.62, 0.45)

0.765

 

  Artesunate

 

−0.82 (−1.13, −0.51)

<0.0001

†*

 

−0.64 (−1.11, −0.17)

0.008

†*

 Externalizing behavior

  Quinine + Artemether

1339, 390

−0.13 (−0.46, 0.10)

0.261

 

353, 152

−0.08 (−0.72, 0.56)

0.804

 

  Artemether

 

−0.51 (−0.87, −0.16)

0.005

†*

 

0.26 (−0.52, 1.05)

0.508

 

  Artesunate

 

−0.76 (−1.06, −0.46)

<0.0001

†*

 

−1.24 (−1.95, −0.54)

0.0006

†*

 Total behavior

  Quinine + Artemether

1339, 390

−0.21 (−0.46, 0.05)

0.111

 

353, 152

−0.19 (−0.79, 0.41)

0.527

 

  Artemether

 

−0.48 (−0.88, −0.07)

0.021

†

 

0.23 (−0.51, 0.97)

0.543

 

  Artesunate

 

−0.84 (−1.18, −0.50)

<0.0001

†*

 

−1.32 (−1.97, −0.66)

0.0001

†*

Behavior rating inventory

 Global executive composite

  Quinine + Artemether

735, 306

−0.49 (−0.94, −0.05)

0.031

†

247, 139

−0.21 (−0.66, 0.24)

0.361

 

  Artemether

 

−0.87 (−1.56, −0.17)

0.0144

†

 

−0.20 (−0.77, 0.36)

0.480

 

  Artesunate

 

−1.48 (−2.00, −0.95)

<0.0001

†*

 

−1.00 (−1.50, −0.50)

0.0001

†*

  1. 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
  2. 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
  3. 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
  4. dFor behavioral outcomes, a negative number is indicative of an improved outcome in children receiving artemisinin derivatives
  5. †p<0.05, *adjusted p<0.05 Benjamini-Hoch correction for false discovery rate at 0.05
Back to article page

BMC Medicine

ISSN: 1741-7015

Contact us