Why do some African children develop severe malaria?

Greenwood, Brian; Marsh, Kevin; Snow, Robert W.

doi:10.1016/0169-4758(91)90096-7

Cited by 311 publications

(213 citation statements)

References 31 publications

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“…In Africa, malaria is a major cause of morbidity and mortality especially in younger children (Greenwood et al 1991;Marsh 1992). Since in areas of high endemicity infants 4-12 months of age are the most affected by malaria morbidity and parasite density (Binka et al 1994;Kitua et al 1996;Smith et al 1999), questions concerning the impact of the outcome and susceptibility of malaria infection should address this age group.…”

Section: Introductionmentioning

confidence: 99%

Malaria infection and morbidity in infants in relation to genetic polymorphisms in Tanzania

Stirnadel

Stöckle

Felger

et al. 1999

Tropical Med Int Health

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SummaryTo investigate the effects of host polymorphisms on malaria morbidity and infection, the frequency distributions of TNF ␣ promotor gene and sickle cell trait were studied in infants in an area highly endemic for Plasmodium falciparum transmission in Tanzania. Differences in parasite prevalence, density, febrile episodes with and without parasitaemia, PCV levels and the frequencies of different MSP-2 parasite infections were assessed by genotype. The frequency of the TNF ␣ promotor allele 2 was 0.09, and the trait was in Hardy-Weinberg equilibrium. There were no differences in malariametric indices between infants with the normal TNF ␣ promoter gene and those who were heterozygous for this trait. Infants heterozygous for the TNF ␣ promotor gene appeared to have fewer febrile episodes when they were free of parasites. The two infants homozygous for the TNF ␣ promoter allele 2 had both a much higher incidence of fever, independently of parasitaemia, than the average for the other genotypes. The frequency of the sickle cell allele S was 0.06 and the trait was also in Hardy-Weinberg equilibrium. Infants heterozygous for the sickle cell trait had significantly lower parasite densities, but similar prevalence, and MSP-2 infections compared to infants with normal haemoglobin. PCV levels, and the incidence of febrile episodes both with and without parasitaemia were also similar. In contrast to the sickle cell trait, the TNF ␣ promotor polymorphism appeared not to have any protective effect on malaria in this study, and its importance in other unspecified fever-causing diseases in this population needs further investigation.keywords Plasmodium falciparum malaria, tumour necrosis factor-␣ promotor polymorphism, sickle-cell trait, infants correspondence Heide A. Stirnadel,

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Section: Introductionmentioning

confidence: 99%

Malaria infection and morbidity in infants in relation to genetic polymorphisms in Tanzania

Stirnadel

Stöckle

Felger

et al. 1999

Tropical Med Int Health

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“…By contrast, in malaria-endemic areas the majority of individuals are parasitized at any given time, but only a minority of episodes is associated with disease, and an even smaller proportion with severe life-threatening disease (Marsh 1992). Although many factors combine to act on the risk of developing disease (Greenwood et al 1991), acquired immunity has a dominant e¡ect and its most obvious manifestation is the virtual absence of life-threatening disease in older children and adults. Immunity to malaria not only modi¢es the age-speci¢c prevalence of disease but also has major e¡ects on the clinical spectrum of resulting pathology.…”

Section: Introductionmentioning

confidence: 99%

Host—parasite interaction and morbidity in malaria endemic areas

Marsh

Snow

1997

Phil. Trans. R. Soc. Lond. B

121

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Severe morbidity due to Plasmodium falciparum is a major health problem in African children. The patterns of morbidity in endemic areas are modi¢ed by the immune response, and vary markedly with transmission intensity. Severe disease falls into three overlapping syndromes: coma, respiratory distress, and severe anaemia. Recently, it has become clear that metabolic acidosis plays a major role in the pathogenesis of severe disease and is particularly important in the overlap between the di¡erent clinical syndromes. We propose that the di¡erent manifestations of severe malarial morbidity arise from the interaction of a limited number of pathogenic processes: red cell destruction, toxin-mediated activation of cytokine cascades, and infected cell sequestration in tissue microvascular beds. The pattern of severe morbidity varies with age within any one endemic area, with severe anaemia predominating in the youngest children and coma having its highest incidence in older children. Between endemic areas there is a marked variation in mean age of children with severe malaria, and therefore in the importance of di¡erent clinical syndromes. The shift in mean age is due to a combination of increased challenge and more rapid development of immunity at higher levels of transmission. Recent comparative studies indicate that at higher levels of transmission the net e¡ect of these shifts may be a paradoxical reduction in total severe malarial morbidity.

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“…Much of this variation can be attributed to prior exposure and acquired immunity, but clearly other factors operate too. These include parasite species (most mortality is due to infection with Plasmodium falciparum), age, nutrition, inoculum size, socioeconomic factors, host genetics and parasite genetics (reviewed in Greenwood et al 1991;Marsh 1992;Baird 1998;Phillips 2001;Miller et al 2002). The relative importance of these different factors has not been well quantified.…”

Section: Introductionmentioning

confidence: 99%

Virulence in malaria: an evolutionary viewpoint

Mackinnon

Read

2004

Phil. Trans. R. Soc. Lond. B

227

205

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Malaria parasites cause much morbidity and mortality to their human hosts. From our evolutionary perspective, this is because virulence is positively associated with parasite transmission rate. Natural selection therefore drives virulence upwards, but only to the point where the cost to transmission caused by host death begins to outweigh the transmission benefits. In this review, we summarize data from the laboratory rodent malaria model, Plasmodium chabaudi, and field data on the human malaria parasite, P. falciparum, in relation to this virulence trade-off hypothesis. The data from both species show strong positive correlations between asexual multiplication, transmission rate, infection length, morbidity and mortality, and therefore support the underlying assumptions of the hypothesis. Moreover, the P. falciparum data show that expected total lifetime transmission of the parasite is maximized in young children in whom the fitness cost of host mortality balances the fitness benefits of higher transmission rates and slower clearance rates, thus exhibiting the hypothesized virulence trade-off. This evolutionary explanation of virulence appears to accord well with the clinical and molecular explanations of pathogenesis that involve cytoadherence, red cell invasion and immune evasion, although direct evidence of the fitness advantages of these mechanisms is scarce. One implication of this evolutionary view of virulence is that parasite populations are expected to evolve new levels of virulence in response to medical interventions such as vaccines and drugs.

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Why do some African children develop severe malaria?

Cited by 311 publications

References 31 publications

Malaria infection and morbidity in infants in relation to genetic polymorphisms in Tanzania

Malaria infection and morbidity in infants in relation to genetic polymorphisms in Tanzania

Host—parasite interaction and morbidity in malaria endemic areas

Virulence in malaria: an evolutionary viewpoint

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