Small malnourished child in Darfur

ACT Malaria and Malnutrition Study Group

Assessing the effect of various nutritional indicators in treatment outcome in children aged 6-59 months treated with artemisinin based combination therapies for uncomplicated P. falciparum malaria.

Update and overview

This study group has now closed to new data contributions. A detailed Statistical Analysis Plan is available to Study Group members, with statistical analysis ongoing. Results and draft publication are expected by 2018.

Rationale

Malaria and malnutrition are major causes of morbidity and mortality in low and middle income countries. Annually, approximately 3.1 million under-five mortality is attributed to malnutrition 1. In children, the severity and extent of malnutrition is measured by various anthropometric indicators estimated from standardised growth reference curves. These metrics include wasting (low weight-for-height, a measure of acute malnutrition and the Mid-Upper Arm Circumference (MUAC) used as proxy of nutritional status in children under five years of age), stunting (low height-for-age, a measure of linear growth), and underweight (low weight-for-age, a composite of linear growth and stunting). In 2011, stunting and wasting affected at least 165 and 52 million children respectively worldwide 1. The relationship between malnutrition and malaria is still not clearly understood. Some studies have reported that malnutrition was associated with a higher risk of malaria 2,3, others have suggested a protective effect 4–6, while other studies have shown no association at all 6,7. Similarly, the relationship between nutritional indicators and antimalarial drug efficacy has not be clearly understood with results often contrasting 8–10. The non-generalizability of these results could be due to the heterogeneity in study population, the diversity in transmission intensity, use of different growth metrics and references and different definitions 9, but also small sample sizes of the studies. Hence, there is a knowledge gap in association between malnutrition and antimalarial drug efficacy which needs to be addressed.

Objectives

  • Assess the impact of acute global malnutrition (based on anthropometric indicators) on the efficacy of treatment of uncomplicated P. falciparum malaria with an ACTs in children under 5 years of age. The ACTs considered are artemether-lumefantrine (AL), artesunate-amodiaquine (AS-AQ), dihydroartemisinin-piperaquine (DP) and artesunate-mefloquine (AS-MQ)
  • Investigate the impact of malnutrition on early parasitological response in the first three days post treatment by an ACT
  • Investigate the impact of malnutrition on late parasitological response post treatment by an ACT

Essential inclusion criteria for data sets

  • Clinical trials including artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine and artesunate-mefloquine in children aged 6-59 months
  • Data available on patients age, weight, gender and height
  • Minimum follow-up duration of 28 days 

Desirable criteria (not required for inclusion)

  • Data available on patients mid upper arm circumference (MUAC)
  • PCR genotyping results
  • Dosage (mg/kg)
  • Haemoglobin level
  • Daily parasite counts

Data standardisation

The data shared with WWARN will be standardised according to the WWARN Clinical Data Management and Statistical Analysis Plan and pool into a single database of quality-assured individual patient data. 

Anthropometric indicators

Nutritional status would be assessed by using standardised age, weight, height and gender specific growth reference according to the WHO 2006 recommendations using igrowup stata package11. Anthropometric indicators include weight-for-age (WAZ), height-for-age (HAZ), and weight-for-height (WHZ).

Study Group governance

The Study Group comprises participating investigators who contribute relevant data sets to the pooled analysis. Data sets remain the property of the investigator. The Study Group collectively makes decisions with respect to including additional studies, data analysis and plans for publication, in line with the WWARN publication policy. The Study Group will identify one or two people to coordinate activities including data analysis, and drafting of publications and reports for group review. 

For further information, or to learn about joining the study group, contact Prof. Philippe Guerin (philippe [dot] guerin [at] wwarn [dot] org).

References

1.        Black, R. E. et al. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet 382, 427–451 (2013).

2.        Nyakeriga, A. M., Troye-Blomberg, M., Chemtai, A. K., Marsh, K. & Williams, T. N. Malaria and nutritional status in children living on the coast of Kenya. Am. J. Clin. Nutr. 80, 1604–1610 (2004).

3.        Ehrhardt, S. et al. Malaria, anemia, and malnutrition in african children--defining intervention priorities. J. Infect. Dis. 194, 108–114 (2006).

4.        Genton, B., Al-Yaman, F., Ginny, M., Taraika, J. & Alpers, M. P. Relation of anthropometry to malaria morbidity and immunity in Papua New Guinean children. Am. J. Clin. Nutr. 68, 734–741 (1998).

5.        Murray, M. J., Murray, A. B., Murray, N. J. & Murray, M. B. Diet and cerebral malaria: The effect of famine and refeeding. Am. J. Clin. Nutr. 31, 57–61 (1978).

6.        Snow, R. W., Byass, P., Shenton, F. C. & Greenwood, B. M. The relationship between anthropometric measurements and measurements of iron status and susceptibility to malaria in Gambian children. Trans. R. Soc. Trop. Med. Hyg. 85, 584–589 (1991).

7.        Müller, O., Garenne, M., Kouyaté, B. & Becher, H. The association between protein-energy malnutrition, malaria morbidity and all-cause mortality in West African children. Trop. Med. Int. Heal. 8, 507–511 (2003).

8.        P. Mitangala Ndeba, U. D’Alessandro, P. Hennart, P. Donnen, D. Porignon, G. Bisimwa Balaluka, A. Bisimwa Nkemba, N. C. M. and M. D. W. Efficacy of Artesunate Plus Amodiaquine for Treatment of Uncomplicated Clinical Falciparum Malaria in Severely Malnourished Children Aged 6–59 Months, Democratic Republic of Congo. Clin. Exp. Pathol. (2012). doi:10.4172/2161-0681.S3-005

9.        Verret, W. J. et al. Effect of nutritional status on response to treatment with artemisinin-based combination therapy in young Ugandan children with malaria. Antimicrob. Agents Chemother. 55, 2629–2635 (2011).

10.      Hess, F. I. et al. Anti-malarial drug resistance, malnutrition and socio-economic status. Trop. Med. Int. Health 2, 721–728 (1997).

11.      WHO. WHO child growth standards: length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: methods and development. (2006).