In malaria endemic areas, pre-school children are at high risk of
severe and repeated malaria illness. One possible public health
strategy, known as Intermittent Preventive Treatment in children (IPTc),
is to treat all children for malaria at regular intervals during the
transmission season, regardless of whether they are infected or not.
To evaluate the effects of IPTc to prevent malaria in preschool
children living in endemic areas with seasonal malaria transmission.
We searched the Cochrane Infectious Diseases Group Specialized Register
(July 2011), CENTRAL (The Cochrane Library 2011, Issue 6), MEDLINE (1966
to July 2011), EMBASE (1974 to July 2011), LILACS (1982 to July 2011),
mRCT (July 2011), and reference lists of identified trials. We also
contacted researchers working in the field for unpublished and ongoing
Individually randomized and cluster-randomized controlled trials of
full therapeutic dose of antimalarial or antimalarial drug combinations
given at regular intervals compared with placebo or no preventive
treatment in children aged six years or less living in an area with
seasonal malaria transmission.
Data collection and analysis
Two authors independently assessed eligibility, extracted data and
assessed the risk of bias in the trials. Data were meta-analysed and
measures of effects (ie rate ratio, risk ratio and mean difference) are
presented with 95% confidence intervals (CIs). The quality of evidence
was assessed using the GRADE methods.
Seven trials (12,589 participants), including one cluster-randomized
trial, met the inclusion criteria. All were conducted in West Africa,
and six of seven trials were restricted to children aged less than 5
IPTc prevents approximately three quarters of all clinical malaria
episodes (rate ratio 0.26; 95% CI 0.17 to 0.38; 9321 participants, six
trials, high quality evidence), and a similar proportion of severe
malaria episodes (rate ratio 0.27, 95% CI 0.10 to 0.76; 5964
participants, two trials, high quality evidence). These effects remain
present even where insecticide treated net (ITN) usage is high (two
trials, 5964 participants, high quality evidence).
IPTc probably produces a small reduction in all-cause mortality
consistent with the effect on severe malaria, but the trials were
underpowered to reach statistical significance (risk ratio 0.66, 95% CI
0.31 to 1.39, moderate quality evidence).
The effect on anaemia varied between studies, but the risk of moderately
severe anaemia is probably lower with IPTc (risk ratio 0.71, 95% CI 0.52
to 0.98; 8805 participants, five trials, moderate quality evidence).
Serious drug-related adverse events, if they occur, are probably rare,
with none reported in the six trials (9533 participants, six trials,
moderate quality evidence). Amodiaquine plus sulphadoxine-pyrimethamine
is the most studied drug combination for seasonal chemoprevention.
Although effective, it causes increased vomiting in this age-group (risk
ratio 2.78, 95% CI 2.31 to 3.35; two trials, 3544 participants, high
When antimalarial IPTc was stopped, no rebound increase in malaria was
observed in the three trials which continued follow-up for one season
In areas with seasonal malaria transmission, giving antimalarial drugs
to preschool children (age
Plain Language Summary: Administering antimalarial drugs to prevent
malaria in children during the malaria transmission season.
In areas where malaria is common, younger children have repeated
episodes of malarial illness, which can sometimes be severe and
life-threatening. In areas where malaria is seasonal, a practical policy
option is to give drugs to prevent malaria at regular intervals during
the transmission season, regardless of wether the child has malaria
symptoms or not. This is known as Intermittent Preventive Treatment
The authors identified seven trials (12,589 participants); all were
conducted in West Africa, and six of seven trials were restricted to
children aged less than 5 years. The results show IPTc prevents three
quarters of all malaria episodes, including severe episodes, and
probably prevents some deaths.
Several antimalarial drugs or combinations have been tried, and shown to
be effective. The most studied is amodiaquine plus
sulphadoxine-pyrimethamine (AQ+SP). This combination probably doesn't
have serious side effects but does cause vomiting in some children.
Meremikwu, M.M.; Donegan, S.; Sinclair, D.; Esu, E.; Oringanje, C. Intermittent preventive treatment for malaria in children living in areas with seasonal transmission. Cochrane Database of Systematic Reviews (2012) (Issue 2) Art. No.: CD003756. [DOI: 10.1002/14651858.CD003756.pub4]
Intermittent preventive treatment for malaria in children living in areas with seasonal transmission