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Chemoprophylaxis and intermittent treatment for preventing malaria in children

25 Jul 2008

Maria Victoria Valero

Source: Cochrane Database of Systematic Reviews (see original article)

Citation: Meremikwu MM, Donegan S, Esu E. Chemoprophylaxis and intermittent treatment for preventing malaria in children. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD003756.

Most children living in areas where malaria is endemic have acquired some degree of immunity to serious malaria by time they have reached the age of seven, but for children under five the disease can be serious. A million under-fives die from the disease every year, most of them in Africa.

While visitors to regions where malaria is endemic are recommended to take prophylactic antimalarial drugs throughout their stay, it is not feasible for people who live there to take such drugs constantly. There is increasing use of intermittent preventive treatment (IPT) – i.e., the administration of a full therapeutic course of an anti-malarial to at risk subjects at specified times regardless of whether they are infected or not. IPT is therefore distinct from chemoprophylaxis, because the drugs are not taken for a prolonged period.

Sulfadoxine-pyrimethamine (SP) is the drug that is most widely used for IPT. Childhood and pregnancy are the periods where it is considered that IPT could be most useful. It is thought that IPT is likely to cause fewer adverse effects than prophylaxis, because it is taken less often, and that is easier to deliver through clinics or schools, reducing poor adherence with self-administration. While some experts maintain that intermittent treatment is of benefit through a mechanism that is different from that of prophylaxis, others believe mechanisms to be the same (1).

In a Cochrane systematic review, Meremikwu et al. set out to evaluate the benefits and harms of giving drugs at regular intervals to prevent malaria in preschool children living in areas where malaria is endemic. They searched for data from studies meeting their pre-defined inclusion criteria: ‘individually randomized and cluster-randomized controlled trials comparing antimalarial drugs given at regular intervals (prophylaxis or intermittent treatment) with placebo or no drug in children aged one month to six years or less living in a malaria-endemic area.’ (They included both chemoprophylaxis and IPT data in their review in order to explore whether the different types of administration explain differences in effects between trials.)

The reviewers found 21 trials with over 19,000 participants. Children who received either regular antimalarial prophylaxis or intermittent treatment were less likely to develop malaria, severe anaemia, or be admitted to hospital, although there was no change in the overall death rate.

The reviewers stress that much more needs to be known. Further information on adverse effects is required and there remains the worry that the administration of antimalarials during childhood might delay the acquisition of immunity, leading to increased morbidity and mortality later.

The conclusion of the reviewers is that IPT, given at the same time as routine childhood immunization, is a potentially beneficial public health intervention, but they caution that, ‘...decisions to promote its use on a wide scale should await the result of long-term follow-up studies to resolve uncertainties about long-term safety.’

The control of malaria will require a combination of preventive interventions, as well as improved treatment. National programmes may, for example, introduce IPT for children and in pregnancy, alongside the promotion of insecticide-treated mosquito nets (ITNs), on which Cochrane reviews have already been published (2,3). Evidence for the effectiveness of such combined interventions in different settings is now needed.

Reference

1. White NJ (2005). Intermittent presumptive treatment for malaria. PLoS Medicine; 2(1):e3. Available from: http://dx.doi.org/10.1371/journal.pmed.0020003

2. Lengeler C (2004). Insecticide-treated bed nets and curtains for preventing malaria. Cochrane Database of Systematic Reviews 2004, Issue 2.Art. No.: CD000363. Available from: http://dx.doi.org/10.1002/14651858.CD000363.pub2

3. Gamble C, Ekwaru JP, ter Kuile FO (2006). Insecticide-treated nets for preventing malaria in pregnancy. Cochrane Database of Systematic Reviews 2006, Issue 2.Art. No.: CD003755. Available from: http://dx.doi.org/10.1002/14651858.CD003755.pub2

Note: This article is published in the Cochrane Database of Systematic Reviews which is not freely available in all countries. It may not be possible to see the full article from your country without taking out a subscription. In some developing countries, readers who are based in institutions may be able to access it through the HINARI programme.

2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Source

Title:
Chemoprophylaxis and intermittent treatment for preventing malaria in children.

Authors:
Meremikwu MM, Donegan S, Esu E

References:
Cochrane Database Syst Rev 2008: pp. CD003756

Abstract:
BACKGROUND: Malaria causes repeated illness in children living in endemic areas. Policies of giving antimalarial drugs at regular intervals (prophylaxis or intermittent treatment) are being considered for preschool children. OBJECTIVES: To evaluate prophylaxis and intermittent treatment with antimalarial drugs to prevent malaria in young children living in malaria-endemic areas. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (August 2007), CENTRAL (The Cochrane Library 2007, Issue 3), MEDLINE (1966 to August 2007), EMBASE (1974 to August 2007), LILACS (1982 to August 2007), mRCT (February 2007), and reference lists of identified trials. We also contacted researchers. SELECTION CRITERIA: Individually randomized and cluster-randomized controlled trials comparing antimalarial drugs given at regular intervals (prophylaxis or intermittent treatment) with placebo or no drug in children aged one month to six years or less living in a malaria-endemic area. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed methodological quality. We used relative risk (RR) or weighted mean difference with 95% confidence intervals (CI) for meta-analyses. Where we detected heterogeneity and considered it appropriate to combine the trials, we used the random-effects model (REM). MAIN RESULTS: Twenty-one trials (19,394 participants), including six cluster-randomized trials, met the inclusion criteria. Prophylaxis or intermittent treatment with antimalarial drugs resulted in fewer clinical malaria episodes (RR 0.53, 95% CI 0.38 to 0.74, REM; 7037 participants, 10 trials), less severe anaemia (RR 0.70, 95% CI 0.52 to 0.94, REM; 5445 participants, 9 trials), and fewer hospital admissions for any cause (RR 0.64, 95% CI 0.49 to 0.82; 3722 participants, 5 trials). We did not detect a difference in the number of deaths from any cause (RR 0.90, 95% CI 0.65 to 1.23; 7369 participants, 10 trials), but the CI do not exclude a potentially important difference. One trial reported three serious adverse events with no statistically significant difference between study groups (1070 participants). Eight trials measured morbidity and mortality six months to two years after stopping regular antimalarial drugs; overall, there was no statistically significant difference, but participant numbers were small. AUTHORS' CONCLUSIONS: Prophylaxis and intermittent treatment with antimalarial drugs reduce clinical malaria and severe anaemia in preschool children.

PMID: 18425893
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