Fast track — ArticlesIntermittent treatment for malaria and anaemia control at time of routine vaccinations in Tanzanian infants: a randomised, placebo-controlled trial
Introduction
An estimated 1000 000 malaria deaths per year underline the need for improved malaria control. National malaria control programmes continue to rely on effective case management while attempting the large-scale deployment of insecticide-treated nets and waiting for an effective and affordable vaccine. The dearth of new developments in malaria control makes the optimisation of currently available interventions a priority.
Efficient malaria control depends on targeting measures at the groups at highest risk of disease and death. These groups are defined by the level and pattern of malaria endemicity, since the intensity of Plasmodium falciparum transmission and the age pattern of clinical malaria are inversely related. In areas of high falciparum transmission, such as the Kilombero Valley in southern Tanzania, about half of all malaria hospital admissions and deaths are in children younger than 1 year.1 The clinical manifestations of falciparum infection can also be dependent on the age and intensity of transmission, since younger children tend to present with more severe anaemia than older ones. Because the signs and symptoms of anaemia are non-specific, this disorder commonly goes unrecognised and untreated. Hence a preventive, rather than curative, approach is appealing and would reduce the impact of poor access to curative services. The well-established Expanded Program on Immunisation (EPI) routinely delivers vaccinations to infants and, in the absence of adverse interactions with the vaccines, could be used to deliver antimalarial interventions to the target group in certain settings.
Antimalarial chemoprophylaxis in endemic areas has been shown to reduce malaria morbidity, school absenteeism, and all-cause mortality.2, 3, 4, 5 Chemoprophylaxis has been used in some African schoolchildren,6, 7 but was abandoned due to the threat of resistance.7 Chemoprophylaxis can also result in the loss of acquired immunity8 or delay its acquisition,9, 11 leading to a period of increased clinical malaria on cessation of the intervention. There is no evidence of an associated increase in mortality,10 and the relevance of this rebound still needs to be established. A trial in Tanzania, in which infants aged 2–12 months received weekly Deltaprim (3·125 mg pyrimethamine and 25 mg dapsone), showed the potential positive and negative effects of chemoprophylaxis in this age group.9 The rate of clinical malaria and severe anaemia was reduced by 61% and 60%, respectively, but discontinuation of chemoprophylaxis was followed by a period of increased clinical malaria and severe anaemia. The rebound effect, fears over the spread of resistance, costs, and logistical difficulties have made chemoprophylaxis an unattractive option for widespread malaria control.
With the aim of maximising the protective effects of chemoprophylaxis without compromising the development of malaria immunity, we explored the use of intermittent malaria treatment in the first year of life. This approach consists of the provision of doses of antimalarials irrespective of the presence of parasites or symptoms. To what extent intermittent treatment might prevent malaria and anaemia in infancy, and whether it would be followed by the rebound phenomenon is unknown. We did a randomised, placebo-controlled, double-blind study in Tanzanian infants of intermittent doses of sulphadoxine-pyrimethamine, delivered alongside routine EPI vaccinations at the ages of 2, 3, and 9 months.
Section snippets
Study area and patients
The study was based in Ifakara, a semi rural area situated in the floodplains of the Kilombero river, southern Tanzania, and described in detail elsewhere.9, 12 The population is estimated to be about 55 000. Most villagers are subsistence farmers growing rice and maize, athough there are an increasing number of small traders. Houses are typically made of thatched roofs and mud walls. Infants account for 44% of all paediatric malaria admissions, and 54% of all paediatric inpatient malaria
Results
Figure 1 shows that 661 (94%) of the 701 recruited children completed the first year of follow-up. The groups were similar in terms of baseline characteristics and age at the time of each treatment (table 1), and in completeness of follow-up, and number and type of withdrawals (figure 1). Compliance with iron supplementation was also similar in the two groups (table 1). One child randomised to receive placebo received a dose of sulphadoxine-pyrimethamine at the time of dose 3, but was included
Discussion
Intermittent treatment doses of sulphadoxine-pyrimethamine given to Tanzanian infants were safe, well tolerated, reduced the rate of clinical malaria by 59%, the rate of severe anaemia by 50%, the number of hospital admissions by 30%, and the rate of all febrile episodes by 13%. The assessments of the protective effect were robust, with similar estimates irrespective of case definition or scope of analysis. The reduction in anaemia occurred despite all children receiving prophylactic ferrous
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