Elsevier

The Lancet

Volume 349, Issue 9066, 7 June 1997, Pages 1650-1654
The Lancet

Articles
Relation between severe malaria morbidity in children and level of Plasmodium falciparum transmission in Africa

https://doi.org/10.1016/S0140-6736(97)02038-2Get rights and content

Summary

Background

Malaria remains a major cause of mortality and morbidity in Africa. Many approaches to malaria control involve reducing the chances of infection but little is known of the relations between parasite exposure and the development of effective clinical immunity so the long-term effect of such approaches to control on the pattern and frequency of malaria cannot be predicted.

Methods

We have prospectively recorded paediatric admissions with severe malaria over three to five years from five discrete communities in The Gambia and Kenya. Demographic analysis of the communities exposed to disease risk allowed the estimation of age-specific rates for severe malaria. Within each community the exposure to Plasmodium falciparum infection was determined through repeated parasitological and serological surveys among children and infants. We used acute respiratory-tract infections (ARI) as a comparison.

Findings

3556 malaria admissions were recorded for the five sites. Marked differences were observed in age, clinical spectrum and rates of severe malaria between the five sites. Paradoxically, the risks of severe disease in childhood were lowest among populations with the highest transmission intensities, and the highest disease risks were observed among populations exposed to low-to-moderate intensities of transmission. For severe malaria, for example, admission rates (per 1000 per year) for children up to their 10th birthday were estimated as 3·9, 25·8, 25·9, 16·7, and 18·0 in the five communities; the forces of infection estimated for those communities (new infections per infant per month) were 0·001, 0·034, 0·050, 0·093, and 0·176, respectively. Similar trends were noted for cerebral malaria and for severe malaria anaemia but not for ARI. Mean age of disease decreased with increasing transmission intensity.

Interpretation

We propose that a critical determinant of life-time disease risk is the ability to develop clinical immunity early in life during a period when other protective mechanisms may operate. In highly endemic areas measures which reduce parasite transmission, and thus immunity, may lead to a change in both the clinical spectrum of severe disease and the overall burden of severe malaria morbidity.

Introduction

Plasmodium falciparum is probably the single most important pathogen encountered by children growing up in sub-Saharan Africa. About 1 million African children die of malaria every year and millions more suffer both the mild and severe clinical consequences of infection. Everyone living in an endemic area becomes infected with P falciparum during childhood yet only a small proportion experience life-threatening complications.1, 2

Despite our increasing knowledge of the genetic and molecular basis of this parasite we do not know what determines the outcome of individual infections or how outcome varies with exposure at a population level. A clearer understanding of the relation between the frequency of exposure and the development of immune mechanisms which prevent death is essential to rationalise malaria interventions aimed at reducing host-parasite encounters.3 We document, for the first time, the epidemiological features of severe, potentially life-threatening malaria morbidity across a range of malaria ecologies typical of sub-Saharan Africa.

Section snippets

Study populations

Five communities in Kenya and The Gambia were selected on the basis of their proximity to hospitals with clinical research teams providing detailed surveillance of all paediatric admissions. The geographical limits of these communities were predefined using local administrative boundaries and represented by either surveyed populations or discrete villages with stable populations. The five were: the area immediately surrounding Siaya District Hospital in western Kenya, communities north and

Transmission intensity

The five childhood communities differed greatly in their-risks of P falciparum infection (table 1). At Bakau the prevalence of infection among children aged 1–9 years was 2%,4 less than one-tenth that for Sukuta village only 8 km away. Similarly, dramatic differences were observed between the two communities separated by only a few kilometres north and south of Kilifi District Hospital. The highest rates of infection were observed in children in Siaya. The estimated force of infection (h)

Discussion

There is much debate over the long-term effects of control measures which reduce malaria transmission (eg, insecticide-treated bednets or transmission-blocking vaccines) upon the development of immunity to malaria.3, 17 Similar discussions were held over 50 years ago18, 19, 20 but until now the debate has been hampered by a lack of reliable data on relations between intensity of parasite transmission and disease outcome. The most important consequence of malaria infection is death. However, the

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