Background

1
Intermittent Preventive Treatment with Artesunate
plus Sulfadoxine Pyrimethamine to reduce under 5
malaria morbidity in the Sahel B Cissé1, C
Sokhna2, R Hallett1, C Sutherland1, O Gaye3, JF
Trape2, GAT Targett1, J Lines1, BM
Greenwood1. 1LSHTM, 2IRD, 3Dakar University,
Senegal

• Background
• Strong seasonality of malaria in the Sahel
• Malaria 27 of deaths among children aged 1-4
  in Senegal
• Chloroquine 31 clinical failures at day 14 in
  2001
• SP 11 clinical failures at day 14 in 2001
• Need for an efficacious, simple and affordable
  preventive strategy
• The Seasonal Intermitent Preventive Treatment
  (IPT) Concept
• Antimalarial drugs at curative doses, at specific
  timing (eg. ante natal visits,
• routine vaccination)
• with the objective of curing or preventing
  malaria for a short period of time.
• This new strategy must avoid impairment of
  natural immunity spread of
• resistance to antimalarial drugs

Bibliography Schellenberg, D., et al., Lancet
(2001) 357 1471-1477 found 60 reduction of
malaria incidence and 50 decrease of severe
anaemia after SP alone given during routine
vaccination (at 2, 3 and 9 months of age).
Massaga, J., et al., Lancet (2003) 361
1853-1860 achieved similar impressive results
with Amodiaquine in full therapeutic dose given 3
times during the first year Schellenberg, D., et
al., Lancet (2005) 365 1481-1483 found there
was no rebound in clinical attacks or anaemia
during the 2nd year of life in children who had
received IPTi as infants
Figure 1 Weekly incidence of malaria Figure
2 Kaplan Meier curves for time to first clinical
episode in the main trial (a) and during the
rebound effect assessment (b) (a) (b)
The principal objective was to determine whether
seasonal IPT can decrease malaria morbidity,
using a Randomised double-blind placebo
controlled trial In 2002 SPArt (1 dose) given
3 times to 1200 children (in September, October
November) Active passive surveillance 2
cross sectional studies before and after the
study for evaluation of infection to P falciparum
resistance to SP In 2003 Assessment of a
potential rebound effect (increase malaria in the
control arm)
MALARIA MORBIDITY REDUCED BY 86 (81.0 90.0)
222 episodes/546 control children (2250 episodes
per 1000 PYAR) versus 39 episodes/542 IPT
children (308 episodes per 1000 PYAR). Fig 1, 2a.
No adverse events recorded, no increased
malaria in the year following the trial. Fig
2b. At the end of the intervention, prevalence
of P. falciparum infection gametocyte carriages
reduced respectively by 64 and 73.
Significant Increased prevalence of triple
mutation in the pfdhfr gene mutation at codon
437 in the pfdhps in the IPT arm. However the
overall total number of children carrying
resistant alleles was fewer in children who
received the active tablets as shown in the
Table. Positive impact of the intervention on
nutritional status.
Table  Post intervention prevalence of SP
resistance markers
Proportion of
Estimated

Pa
rasitaemic

Discussion/Conclusion IPT in children is highly
effective and safe even in areas with seasonal
transmission. Implementation studies are
needed to determine the best way to scale up and
deliver drugs to children under 5 years of age.
infected children
proportion of

carrying resistant
children carrying
genotype

resistant genotype

in the population


Triple

Pfdhfr
-
Triple
Pfdhfr
-
pfdhfr

437

pfdhfr

437


Controls

37.0

75.4

43.8

27.9

16.2



IPTc

13.6

95.1

85.7

12.9

11.7