The neurological assessment in young children treated with artesunate monotherapy or artesunate-mefloquine combination therapy for uncomplicated Plasmodium falciparum malaria.
BACKGROUND
Mefloquine and artesunate combination therapy is the recommended first-line treatment for uncomplicated malaria throughout much of south-east Asia. Concerns have been raised about the potential central nervous system (CNS) effects of both drug components and there are no detailed reports in very young children.


METHODS
Children, aged between three months and five years, with acute uncomplicated Plasmodium falciparum malaria were randomized to either 7 days of artesunate monotherapy or the same schedule of artesunate plus mefloquine on day 7 and 8. Neurological testing targeting coordination and behaviour was carried out at day 0, 7, 9, 10, 14 and 28. Non-febrile healthy control children from the same population were tested on days 0, 7, 14 and 28.


RESULTS
From December 1994 to July 1997, 91 children with uncomplicated P. falciparum, 45 treated with artesunate monotherapy, 46 treated with mefloquine and artesunate combination therapy and 36 non-febrile controls, underwent neurological testing. Malaria and fever had a significant negative impact on testing performance. By contrast, the anti-malarial treatments were not associated with worsening performances in the various components of the test. Artesunate and mefloquine do not appear to have a significant influence on coordination and behaviour. Children treated with mefloquine were significantly less likely to suffer recurrent malaria infection during follow-up compared to those treated with artesunate alone (P = 0.033).


CONCLUSIONS
In keeping with the results of randomized controlled trials in adults, mefloquine was not associated with a decrease in specific items of neurological performance. Likewise, children treated with artesunate did not perform significantly differently to control children. This study does not exclude subtle or rare treatment CNS effects of artesunate or mefloquine. Treatment of acute uncomplicated malaria results in a significant improvement on items of neurological performance.
Ambler
Michael T
MT
Shoklo Malaria Research Unit, PO Box 46, Mae Sot, Tak, Thailand. m.ambler@ucl.ac.uk
Dubowitz
Lilly M
LM
Arunjerdja
Ratree
R
Hla
Eh Paw
EP
Thwai
Kyaw Lay
KL
Viladpainguen
Jacher
J
Singhasivanon
Pratap
P
Luxemburger
Christine
C
Nosten
François
F
McGready
Rose
R
D000818:Animals; D000962:Antimalarials / Q000009:adverse effects* / Q000627:therapeutic use; D037621:Artemisinins / Q000009:adverse effects* / Q000627:therapeutic use; D000077332:Artesunate; D001208:Asia; D001210:Asia, Southeastern; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D015767:Mefloquine / Q000009:adverse effects* / Q000627:therapeutic use; D009422:Nervous System Diseases / Q000139:chemically induced*; D009460:Neurologic Examination
D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; D015767:Mefloquine