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Guidelines for the treatment of malaria – 2 edition

to 2 years (elimination half-life for metabolized drugs in infants aged 6 months to 2 years
is 0.6 times that in adults).

Renal clearance

Glomerular filtration rate only reaches surface-area-adjusted adult levels at around 6
months of age. Thus for drugs that rely on renal elimination, elimination half-lives in
very young infants may be up to 2–3 times longer than in adults. After 2 months, half-
lives are shorter (0.35–0.5 times adult values) until about 2 years of age.

A3.15.2 Malnutrition and antimalarials

Malaria and malnutrition frequently coexist. The relationship between malaria and
nutritional status is complex and has been the subject of debate for many years (81).
Given that a significant proportion of the world’s malnourished children live in malaria
endemic countries (82) it is important to understand how antimalarial drug disposition
may be affected when malnutrition is severe. This section outlines the physiological
changes that occur in malnourished patients and discusses how these may influence the
pharmacokinetic properties of antimalarials, drawing on the few studies of antimalarial
drug disposition in malnutrition that are available
Note: In reviewing the literature it was apparent that many studies were conducted in
populations and settings where some degree of malnutrition would have been expected.
However, this was only rarely mentioned as a possible confounder for drug efficacy,
although there was an occasional comment that obviously malnourished patients appeared
to respond differently to treatment than did other patients (83). Several ongoing studies
are planning to look specifically at treatment outcomes in this group of patients.

Definitions
There are different ways of classifying malnutrition. Earlier studies employ the Wellcome
classification: where body weight is given as a percentage of standard weight (50th
percentile of the Harvard value): underweight 80–60%; marasmus 60%; kwashiorkor
80–60% + oedema; marasmic kwashiorkor 60% + oedema. Other studies refer to low
weight-for-height (wasting); low weight-for-age (underweight); or low height-for-age
(stunting) and use anthropometric indicators and reference standards. Protein-energy
malnutrition is defined as a range of pathological conditions arising from coincident lack,
in varying proportions, of protein and calories, occurring most frequently in infants and
young children and commonly associated with infections (84).

Pharmacokinetics

• Absorption
Anorexia, diarrhoea and vomiting are common. Anorexia will affect the absorption of drugs
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