Menu ENN Search

Developing regional weight-for-age growth references to optimise age-based dosing of anti-malarials

Summary of research1

Location: Global

What we know: Age is often used as a proxy for weight in anti-malarial drug dosing. Accurate knowledge of the weight-for-age distribution of a given at risk population could help optimise treatment regimens but country/regional specific reference data are lacking; the WHO Child Growth Standards describe optimal growth, rather than actual growth in a given place/time.

What this article adds: A recent study derived regional weight-for-age growth references to help optimise age-based dosing of anti-malarials in Africa, the Americas, South-East Asia and the Western Pacific. A model was used to combine data with varying distributions from a range of sources (largely DHS). Growth curves were modelled for adolescents and adult males for whom data were most lacking. Countries were weighted by their population at risk of malaria. The authors recommend that age-based anti-malarial dosing should shift from global to region-based regimens.    

Manufacturers of anti-malarials recommend that dosing should be based on body weight. However, in many low and middle income countries, the dose is frequently based on age, which is used as a proxy for body weight because these drugs are often sold over the counter or prescribed in settings without weighing facilities. The use of inadequate age-based dosing regimens is responsible for a considerable proportion of treatment failures. Substantial improvements could be made by optimising age-based dosing regimens but this idea has received little attention from manufacturers or policy-makers. Accurate knowledge of the weight-for-age distribution of the population at risk of malaria is vital for establishing the optimal dosing regimen. Previously, the optimal age-based dosing regimen and drug ratio of a fixed-dose combination of artesunate and amodiaquine anti-malarials, for use in sub-Saharan Africa, were predicted using weight-for-age data from 88,054 individuals in several African countries. A recent analysis of the efficacy of artesunate and amodiaquine using pooled data on 5,410 patients from 24 studies showed that administered doses of the fixed combination were significantly better with both weight-and age-based regimens than when non-fixed combinations were used.

Currently weight-for–age reference data are lacking for most middle and low income countries. Existing global growth standards are the WHO Child Growth Standards for children aged 0-59 months – based on the Multi Centre Growth Reference Study and the 2007 WHO growth reference for school-aged children and adolescents aged 5-19 years. Optimal growth can be assessed against these standards but they are inadequate for establishing optimal dosing of anti-malarials as they do not describe how children actually grow at a particular time and place. Since growth varies between regions, regional or country-specific reference data would enable dosing regimens to be tailored to the population affected.

Over the past two decades, a wealth of population-representative anthropometric data has become publicly available from low and middle income countries. A recent study has set out to derive regional weight-for-age growth references to help optimise age-based dosing of anti-malarials in Africa, the Americas, South-East Asia and the Western Pacific. This was done by compiling individual level weight-for-age population representative data sources in countries where malaria is endemic, principally in three areas: the WHO African Region; the WHO Region of the Americas; and the WHO South-East Asia and Western Pacific regions combined. Malaria endemic areas in WHO Eastern Mediterranean Region were initially considered but insufficient data were available.

The method involved constructing a weight-for-age database from pre-existing population-based anthropometric data obtained from household surveys and research groups. It contained data collected between 1995 and 2012 on 1,263,119 individuals older than 14 days and younger than 50 years in 64 malaria-endemic countries. Regional growth references were generated using a generalised additive model for location, scale and shape by combining data with varying distributions from a range of sources. Countries were weighted by their population at risk of malaria to enable references to be used in optimising the dosing of anti-malarials.

The authors of this work found that large differences in weight-for-age distributions existed between the three regions and between these regions and optimal growth curves developed by WHO, which indicates that age-based dosing should shift from global to region-based regimens. In all three regions, the models achieved good fits with the original data, which confirmed that the generalised additive model for location, scale and shape extension method is a robust way of establishing growth references using mixed-source data in situations where multicentre growth reference studies are not feasible. The relative homogeneity of countries within the regions justifies modelling pooled country data sets in each region.

The large majority of the data came from Demographic Health Surveys (DHS), which are representative of national or subnational populations and have well-established designs and quality assurance methods. Extensive data were available for most of the age range of interest which helped in modelling the age range for which fewer data were available (i.e. 5-14 years). Data for adolescents and adult males were missing for many countries, however, they were available across the full age spectrum for at least one country in each region. Since the two step modelling approach was designed to use data from adjacent countries and age groups, where these showed similar growth distributions, the researchers were able to model the growth curves for adolescents and adult males for all three regions. In order to increase the representativeness of the curves, data sets from before 1995 were not used. Even so, growth curves should be updated periodically (e.g. every 5-10 years) using the latest data from representative surveys.

The authors conclude that the growth charts generated for individual countries as part of the modelling process could serve as powerful public health tools to support decision-making at national level. The logical next step would be to further validate these charts for countries where data were limited. Country-specific growth references could be improved further by extrapolating female data to derive male growth curves.

The method provides a way of deriving regional growth references by collating weight-for-age data available for populations. Furthermore, the method facilitates the transition from generic, universal, age-based dosing practices to more data-driven optimised, regional regimens for anti-malarials. The method could also help monitor nutrition and optimise age-based dosing of other drugs. 

Read more...

Footnotes

1Hayes D et al (2015). Developing regional weight-for-age growth references for malaria-endemic countries to optimise age-based dosing of antimalarials. Bulletin of the World Health Organisation, vol 93, pp 74-83. Doi:http://dx.doi.org/10.2471/BLT.14.139113

 

More like this

FEX: WHO growth reference for children and adolescents

Summary of published research1 The need for a widely applicable growth reference for older children and adolescents has increasingly been recognised by countries attempting to...

en-net: Évaluation de la malnutrition aiguë chez les adolescents

Dear fellow nutritionists,

I have read the various previous questions regarding the question on how to assess adolescent malnutrition, including the literature (For...

FEX: A growth reference for MUAC-for-age among school age children and adolescents and validation for mortality

Summary of research1 Location: Kenya, Uganda and Zimbabwe What we know: An internationally accepted reference for mid-upper arm circumference (MUAC) does not exist for...

FEX: Combined protocol for SAM/MAM treatment: The ComPAS study

By Jeanette Bailey, Rachel Chase, Marko Kerac, André Briend, Mark Manary, Charles Opondo, Maureen Gallagher and Anna Kim Jeanette Bailey is the Project Director for...

FEX: New WHO growth standards

This New WHO Growth Standards for infants and children up to 60 months of age, highlighted in Field Exchange 27, are now available. The standards were developed using data...

FEX: Developing food supplements for moderately malnourished children: lessons learned from RUTF

Summary of research1 Location: Global What we know: RUTF is as effective as F100 in treating SAM, where weight gain is the recovery outcome. Food supplements for moderate...

FEX: Letter on WHO 2006 Growth Standards, by Marko Kerac and Andrew Seal

This new 2006 WHO Growth standards: What will they mean for emergency nutrition programmes? Dear Editor Whilst welcoming the principles which have driven the development of...

FEX: Micronutrients - The Basics

Taken from draft guideline material prepared by Fiona Watson, Institute of Child health, London. Micronutrients are essential for life and are distinct from macronutrients...

FEX: Global Trends in Malnutrition

Summary of published paper1 Child with Kwashiorkor in Kalongo, Pader. A recent study set out to estimate trends in childhood underweight by geographic regions of the world in...

FEX: Malaria Treatment in Severe Malnutrition in Angola

By Amador Gomez and Elisa Dominguez Amador Gomez is Technical Director of Acción Contra el Hambre (ACH). Previously he spent several years working on nutrition and medical...

FEX: Nutritional monitoring of pre-school children in DRC

Intrepreting weight measurements Summary of published research1 A recent published study set out to assess community volunteers' effectiveness in monitoring the growth of...

en-net: SE Asian Growth Standards

Hi, Does anyone have information on growth standards for SE Asia, specifically for Vietnam. The WHO growth standards are great reference points for assessing growth, and I know...

FEX: Effects of agricultural and nutrition education projects on child health in Malawi

Summary of published research1 Margaret Shonga, participating farmer, her husband Donald Gondwe and their baby, standing in a field of sorghum A recent study set out to...

Resource: Anthropometry at birth and at age of routine vaccination to predict mortality in the first year of life: A birth cohort study in BukinaFaso

Abstract Background The World Health Organization currently defines severe acute malnutrition (SAM) in infants aged under 6 months of age using weight-for-length Z score...

FEX: Research snapshots

Factors influencing pastoral and agropastoral household vulnerability to food insecurity in Kenya Kenya has a population of more than 38 million, 10% of whom are classified as...

FEX: WHO Growth Standards to assess Indonesian children < 2 years

Summary of published research1 A recent study set out to assess the implications of adopting the WHO Child Growth Standards to classify Indonesian children according to...

FEX: New WHO Growth Standards for 0-5 years

The WHO Multicentre Growth Reference Study (MGRS) was undertaken between 1997 and 2003 to generate new growth curves for assessing the growth and development of infants and...

FEX: Can anthropometry measure gender discrimination?

Summary of published research1 A baby girl in Bangladesh. Sex differences in life expectancy and child survival in Bangladesh have been attributed to discrimination against...

FEX: Incidence and duration of severe wasting in two African populations

Summary of review1 A child being measured during the health survey in Niakhar A recent literature review did not reveal any publication with proper estimates of incidence and...

FEX: Summary of Lancet Series on Maternal and Child Undernutrition

Below are short summaries of the recently launched Lancet series of papers on Maternal and Child Undernutrition1. This high profile series focuses on the disease burden...

Close

Reference this page

Developing regional weight-for-age growth references to optimise age-based dosing of anti-malarials. Field Exchange 50, August 2015. p29. www.ennonline.net/fex/50/regionalwfarefsmalaria

(ENN_5056)

Close

Download to a citation manager

The below files can be imported into your preferred reference management tool, most tools will allow you to manually import the RIS file. Endnote may required a specific filter file to be used.