Developmental allometry and paediatric malaria

Abstract

WHO estimates that 80% of mortality due to malaria occurs among infants and young children. Though it has long been established that malaria disproportionately affects children under age five, our understanding of the underlying biological mechanisms for this distribution remains incomplete. Many studies use age as an indicator of exposure, but age may affect malaria burden independently of previous exposure. Not only does the severity of malaria infection change with age, but the clinical manifestation of disease does as well: younger children are more likely to suffer severe anaemia, while older children are more likely to develop cerebral malaria. Intensity of transmission and acquired immunity are important determinants of this age variation, but age differences remain consistent over varying transmission levels. Thus, age differences in clinical presentation may involve inherent agerelated factors as well as still-undiscovered facets of acquired immunity, perhaps including the rates at which relevant aspects of immunity are acquired. The concept of "allometry" -the relative growth of a part in relation to that of an entire organism or to a standard -has not previously been applied in the context of malaria infection. However, because malaria affects a number of organs and cells, including the liver, red blood cells, white blood cells, and spleen, which may intrinsically develop at rates partly independent of each other and of a child's overall size, developmental allometry may influence the course and consequences of malaria infection. Here, scattered items of evidence have been collected from a variety of disciplines, aiming to suggest possible research paths for investigating exposure-independent age differences affecting clinical outcomes of malaria infection.

The skeletal manifestation of malaria: An epidemiological approach using documented skeletal collections

“…Even in endemic areas, malaria is known to be especially dangerous for children and pregnant women (Gilles et al, 1969;Lusingu et al, 2004;World Health Organization, 2007;Billig et al, 2012). Children make up 78% of current global malaria deaths, with severe malarial anemia being more common in children up to age five, and cerebral malaria more common in children older than age four (Billig et al, 2012;World Health Organization, 2014). Lack of acquired immunity to malaria and small body size contribute to the increased severe malarial health impacts on children (Billig et al, 2012).…”

“…Children make up 78% of current global malaria deaths, with severe malarial anemia being more common in children up to age five, and cerebral malaria more common in children older than age four (Billig et al, 2012;World Health Organization, 2014). Lack of acquired immunity to malaria and small body size contribute to the increased severe malarial health impacts on children (Billig et al, 2012). In areas of high malarial transmission, falciparum malaria is the leading cause of parasitic anemia in children (Lusingu et al, 2004).…”

Foetal haemoglobin and the dynamics of paediatric malaria

“…Hence age is often considered a surrogate for cumulative exposure, and age differences in response are attributed accordingly. There may be more to the explanation, however, given that intrinsic developmental differences between children under five and older children, or adults, may affect responses to malaria infection [5,6]. Among the developmental age differences that may affect the course and outcome of a malaria infection are the age-specific abundance and properties of red blood cells (RBCs).…”

“…Foetal haemoglobin is one of a number of mechanisms, reviewed in an earlier paper [6], that could help to explain the observed neonatal protection from severe disease. Infants have immature immune systems, in which key elements are developing asynchronously [6], so any added protective factors are likely to be of particular importance. This is a difficult set of topics to study, however, given the age group and multiple confounding factors.…”

Relevance of Economic Field Microscope in Remote Rural Regions for Concurrent Observation of Malaria & Inflammation

“…Specially, the geriatric is almost in a constant state of inflammation, while the pediatric is not. Allotropy is predominant in pediatric stages [25]. Age; habit (profession); habitat based variations can all be observed and studied-in relation to therapy.…”