The association of malaria morbidity with linear growth, hemoglobin, iron status, and development in young Malawian children: a prospective cohort study

Jaden Bendabenda, Noel Patson, Lotta Hallamaa, John Mbotwa, Charles Mangani, John Phuka, Elizabeth L Prado, Yin Bun Cheung, Ulla Ashorn, Kathryn G Dewey, Per Ashorn, Kenneth Maleta, Jaden Bendabenda, Noel Patson, Lotta Hallamaa, John Mbotwa, Charles Mangani, John Phuka, Elizabeth L Prado, Yin Bun Cheung, Ulla Ashorn, Kathryn G Dewey, Per Ashorn, Kenneth Maleta

Abstract

Background: Although poor complementary feeding is associated with poor child growth, nutrition interventions only have modest impact on child growth, due to high burden of infections. We aimed to assess the association of malaria with linear growth, hemoglobin, iron status, and development in children aged 6-18 months in a setting of high malaria and undernutrition prevalence.

Methods: Prospective cohort study, conducted in Mangochi district, Malawi. We enrolled six-months-old infants and collected weekly data for 'presumed' malaria, diarrhea, and acute respiratory infections (ARI) until age 18 months. Change in length-for-age z-scores (LAZ), stunting, hemoglobin, iron status, and development were assessed at age 18 months. We used ordinary least squares regression for continuous outcomes and modified Poisson regression for categorical outcomes.

Results: Of the 2723 children enrolled, 2016 (74.0%) had complete measurements. The mean (standard deviation) incidences of 'presumed' malaria, diarrhea, and ARI, respectively were: 1.4 (2.0), 4.6 (10.1), and 8.3 (5.0) episodes/child year. Prevalence of stunting increased from 27.4 to 41.5% from 6 to 18 months. 'Presumed' malaria incidence was associated with higher risk of stunting (risk ratio [RR] = 1.04, 95% confidence interval [CI] = 1.01 to 1.07, p = 0.023), anemia (RR = 1.02, 95%CI = 1.00 to 1.04, p = 0.014) and better socio-emotional scores (B = - 0.21, 95%CI = - 0.39 to - 0.03, p = 0.041), but not with change in LAZ, haemoglobin, iron status or other developmental outcomes. Diarrhea incidence was associated with change in LAZ (B = - 0.02; 95% CI = - 0.03 to - 0.01; p = 0.009), stunting (RR = 1.02; 95% CI = 1.01 to 1.03; p = 0.005), and slower motor development. ARI incidence was not associated with any outcome except for poorer socio-emotional scores.

Conclusion: In this population of young children living in a malaria-endemic setting, with active surveillance and treatment, 'presumed' malaria is not associated with change in LAZ, hemoglobin, or iron status, but could be associated with stunting and anemia. Diarrhea was more consistently associated with growth than was malaria or ARI. The findings may be different in contexts where active malaria surveillance and treatment is not provided.

Trial registration: NCT00945698 (July 24, 2009) and NCT01239693 (November 11, 2010).

Keywords: Children; Growth faltering; Infections; Longitudinal studies; Malaria; Morbidity; Stunting; iLiNS studies.

Conflict of interest statement

Ethics approval and consent to participate

The study was performed according to International Conference of Harmonization–Good Clinical Practice (ICH-GCP) guidelines and the ethical standards of the Helsinki Declaration. The protocol was reviewed and approved by the Institutional Review Boards of the University of Malawi, College of Medicine (IRB reference number P.01/09/722) and the Pirkanmaa Hospital District, Finland (IRB reference number R09130). At least one guardian signed or thumb-printed an informed consent form before enrolment of each participant. An independent data safety and monitoring board monitored the incidence of suspected SAE during the trial.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flow chart of the children enrolled and included in the final analysis. The figure shows the number of children enrolled, children lost to follow up, and children who were eventually included in the study from the iLiNS DOSE and iLiNS DYAD-M cohorts

References

    1. Dewey KG, Adu-Afarwuah S. Systematic review of the efficacy and effectiveness of complementary feeding interventions in developing countries. Maternal and Child Nutrition. 2008;4:24–85. doi: 10.1111/j.1740-8709.2007.00124.x.
    1. Iannotti LL, Jean S, Dulience L, Green J, Joseph S, Franc J, et al. Linear growth increased in young children in an urban slum of Haiti : a randomized controlled trial of a lipid-based nutrient supplement 1–3. Am J Clin Nutr. 2014;99:198–208. doi: 10.3945/ajcn.113.063883.
    1. Hadi H, Dibley MJ, West KP. Complex interactions with infection and diet may explain seasonal growth responses to vitamin a in preschool aged Indonesian children. Eur J Clin Nutr. 2004;58(7):990–999. doi: 10.1038/sj.ejcn.1601920.
    1. Hess SY, Abbeddou S, Jimenez EY, Somé JW, Vosti SA, Ouédraogo ZP, et al. Small-Quantity Lipid-Based Nutrient Supplements, Regardless of Their Zinc Content, Increase Growth and Reduce the Prevalence of Stunting and Wasting in Young Burkinabe Children: A Cluster-Randomized Trial. PLoS One. 2015;10(3):e0122242. doi: 10.1371/journal.pone.0122242.
    1. Prado EL, Abbeddou S, Yakes Jimenez E, Some JW, Ouedraogo ZP, Vosti SA, et al. Lipid-based nutrient supplements plus malaria and diarrhea treatment increase infant development scores in a cluster-randomized trial in Burkina Faso. J Nutr. 2016;146(4):814–822. doi: 10.3945/jn.115.225524.
    1. Taylor C, Sarma R, Parker R, Reinke W, Faruqee R, Kielmann A. Child and maternal health Services in Rural India: the Narangwal experiment, volume 1: integrated nutrition and health care. Vol. 2, integrated family planning and health care. Baltimore and London: The Johns Hopkins University Press; 1983.
    1. Richard SA, Black RE, Gilman RH, Guerrant RL, Kang G, Lanata CF, et al. Diarrhea in early childhood: short-term association with weight and long-term association with length. Am J Epidemiol. 2013;178(7):1129–1138. doi: 10.1093/aje/kwt094.
    1. Checkley W, Buckley G, Gilman RH, Assis AM, Guerrant RL, Morris SS et al. Multi-country analysis of the effects of diarrhoea on childhood stunting. International Journal of Epidemiology. 2008;37(4):816-830. 10.1093/ije/dyn099.
    1. Checkley W, Epstein LD, Gilman RH, Black RE, Cabrera L, Sterling CR. Effects of Cryptosporidium parvum infection in Peruvian children: growth faltering and subsequent catch-up growth. Am J Epidemiol. 1998;148(5):497–506. doi: 10.1093/oxfordjournals.aje.a009675.
    1. Alexandre MAA, Benzecry SG, Siqueira AM, Vitor-Silva S, Melo GC, Monteiro WM, et al. The association between nutritional status and malaria in children from a rural Community in the Amazonian Region: a longitudinal study. PLoS Negl Trop Dis. 2015;9(4):e0003743. doi: 10.1371/journal.pntd.0003743.
    1. Fink G, Olgiati A, Hawela M, Miller JM, Matafwali B. Association between early childhood exposure to malaria and children’s pre-school development: evidence from the Zambia early childhood development project. Malar J. 2013;12(1):1–9. doi: 10.1186/1475-2875-12-12.
    1. Lee G, Yori P, Olortegui MP, Pan W, Caulfield L, Gilman RH, et al. Comparative effects of vivax malaria, fever and diarrhoea on child growth. Int J Epidemiol. 2012;41(2):531–539. doi: 10.1093/ije/dyr190.
    1. Williams TN, Maitland K, Phelps L, Bennett S, Peto TEA, Viji J, et al. Plasmodium vivax: a cause of malnutrition in young children. QJM. 1997;90(12):751–757. doi: 10.1093/qjmed/90.12.751.
    1. Jackson BD, Black RE. A Literature Review of the Effect of Malaria on Stunting. J Nutr. 2017:jn242289 Available from: .
    1. Maleta KM, Phuka J, Alho L, Cheung YB, Dewey KG, Ashorn U, et al. Provision of 10–40 g/d lipid-based nutrient supplements from 6 to 18 months of age does not prevent linear growth faltering in Malawi. J Nutr. 2015;145(8):1909–1915. doi: 10.3945/jn.114.208181.
    1. Ashorn P, Alho L, Ashorn U, Cheung YB, Dewey KG, Gondwe A, et al. Supplementation of maternal diets during pregnancy and for 6 months postpartum and infant diets thereafter with Small-quantity lipid-based nutrient supplements does not promote child growth by 18 months of age in rural Malawi: a randomized controlled Tria. J Nutr. 2015;145(6):1345–1353. doi: 10.3945/jn.114.207225.
    1. National Statistical Office (NSO) [Malawi] and ICF . Malawi Demographic and Health Survey 2015–16. Zomba, Malawi, Rockville: NSO and ICF; 2017.
    1. National Malaria Control Programme (NMCP) [Malawi] and ICF International. Malawi Malaria Indicator Survey (MIS) 2012. Lilongwe, Malawi, and Calverton, Maryland, USA: NMCP and ICF International; 2012.
    1. Rousham EK, Northrop-Clewes CA, Lunn PG. Maternal reports of child illness and the biochemical status of the child: the use of morbidity interviews in rural Bangladesh. Br J Nutr. 1998;80(5):451–6.
    1. Kroeger A. Health interview surveys in developing countries: a review of the methods and results. Int J Epidemiol. 1983;12(4):465–481. doi: 10.1093/ije/12.4.465.
    1. WHO Multicentre Growth Reference Study Group WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl. 2006;450:76–85.
    1. Abubakar A, Holding P, van Baar A, Newton CRJC, van de Vijver FJR. Monitoring psychomotor development in a resource-limited setting: an evaluation of the Kilifi developmental inventory. Ann Trop Paediatr. 2008;28(3):217–226. doi: 10.1179/146532808X335679.
    1. Fenson L, Marchman VA, Thal DJ, Dale PS, Steven Reznick J, Bates E. The MacArthur-bates communicative development inventories User’s guide and technical manual. Baltimore: Paul H. Brookes Publishing Co; 2006.
    1. Prado EL, Phuka J, Maleta K, Ashorn P, Ashorn U, Vosti SA, et al. Provision of lipid-based nutrient supplements from age 6 to 18 months does not affect infant development scores in a randomized trial in Malawi. Matern Child Health J. 2016;20(10):2199–2208. doi: 10.1007/s10995-016-2061-6.
    1. Prado EL, Maleta K, Ashorn P, Ashorn U, Vosti SA, Sadalaki J, et al. Effects of maternal and child lipid-based nutrient supplements on infant development: a randomized trial in Malawi. Am J Clin Nutr [Internet] 2016;103(3):784–793. doi: 10.3945/ajcn.115.114579.
    1. Morris SS, Cousens SN, Kirkwood BR, Arthur P, Ross DA. Is prevalence of diarrhea a better predictor of subsequent mortality and weight gain than diarrhea incidence? Am J Epidemiol. 1996;144(6):582–588. doi: 10.1093/oxfordjournals.aje.a008968.
    1. Beard JL. Indicators of iron status of populations: free erythrocyte protoporphyrin and zinc protoporphyrin; serum and plasma iron, total iron binding capacity and transferrin receptor; and serum transferrin receptor. In: WHO, CDC, editor. Assessing the iron status of populations. Geneva: World Health Organization; 2007.
    1. Dewey KG, Domellöf M, Cohen RJ, Landa Rivera L, Hernell O, Lönnerdal B. Iron supplementation affects growth and morbidity of breast-fed infants: results of a randomized trial in Sweden and Honduras. J Nutr. 2002;132(11):3249–3255. doi: 10.1093/jn/132.11.3249.
    1. World Health Organization. Nutritional anaemias: tools for effective prevention and control. Geneva: World Health Organization; 2017.
    1. Zou G. A modified Poisson regression approach to prospective studies with binary data. Am J Epidemiol. 2004;159(7):702–706. doi: 10.1093/aje/kwh090.
    1. Coates J, Swindale A, Bilinsky P. Household Food Insecurity Access Scale (HFIAS) for Measurement of Food Access: Indicator Guide. Washington, D.C: Food and Nutrition Technical Assistance Project, Academy for Educational Development; 2007.
    1. Yelland LN, Sullivan TR, Makrides M. Accounting for multiple births in randomised trials: a systematic review. Arch Dis Child - Fetal Neonatal Ed. 2015;100(2):F116–F120. doi: 10.1136/archdischild-2014-306239.
    1. World Health Organization. Programme of Acute Respiratory Infections., World Health Organization. Malaria Control Unit . The Overlap in the clinical presentation and treatment of malaria and pneumonia in children : report of a meeting (Geneva, 8 April 1991) 1992.
    1. Luxemburger C, Nosten F, Kyle DE, Kiricharoen L, Chongsuphajaisiddhi T, White NJ. Clinical features cannot predict a diagnosis of malaria or differentiate the infecting species in children living in an area of low transmission. Trans R Soc Trop Med Hyg. 1998;92(1):45–49. doi: 10.1016/S0035-9203(98)90950-6.
    1. Bojang KA, Obaro S, Morison LA, Greenwood BM. A prospective evaluation of a clinical algorithm for the diagnosis of malaria in Gambian children. Trop Med Int Heal. 2000;5(4):231–236. doi: 10.1046/j.1365-3156.2000.00538.x.
    1. World Health Organization . Treatment of Severe Malaria. 2015. pp. 71–88.
    1. National Statistical Office (NSO) and ICF Macro. Malawi Demographic and Health Survey 2010. Zomba, Malawi, and Calverton, Maryland, USA: NSO and ICF Macro; 2011
    1. Chandramohan D, Jaffar S, Greenwood B. Use of clinical algorithms for diagnosing malaria. Trop Med Int Heal. 2002;7(1):45–52. doi: 10.1046/j.1365-3156.2002.00827.x.
    1. World Health Organization. IMCI chart booklet: WHO. World Health Organization; 2014. [cited 7 Nov 2018]. Available from:
    1. Streiner DL. Best (but oft-forgotten) practices: the multiple problems of multiplicity-whether and how to correct for many statistical tests. Am J Clin Nutr. 2015;102(4):721–728. doi: 10.3945/ajcn.115.113548.
    1. Gone T, Lemango F, Eliso E, Yohannes S, Yohannes T. The association between malaria and malnutrition among under-five children in Shashogo District, southern Ethiopia: a case-control study. Infect Dis Poverty. 2017;6(1):4–11. doi: 10.1186/s40249-016-0221-y.
    1. Hautvast JLA, Tolboom JJM, Willems JL, Mwela CM, Monnens LAH. Consequences of infections for three-month length increment in young children in rural Zambia. Acta Paediatr. 2000;89(3):296–301. doi: 10.1111/j.1651-2227.2000.tb01331.x.
    1. Olney DK, Kariger PK, Stoltzfus RJ, Khalfan SS, Ali NS, Tielsch JM, et al. Development of nutritionally at-risk young children is predicted by malaria, anemia, and stunting in Pemba, Zanzibar. J Nutr. 2009;139(4):763–772. doi: 10.3945/jn.107.086231.
    1. Kang H, Kreuels B, Adjei O, Krumkamp R, May J, Small DSDS. The causal effect of malaria on stunting: a Mendelian randomization and matching approach. Int J Epidemiol. 2013;42(5):1390–1398. doi: 10.1093/ije/dyt116.
    1. Victora CG, Barros F, Kirkwood B, Vaughan J. Pneumonia, diarrhea, and growth in the first 4 y of life: a longitudinal study of 5914 urban Brazilian children. Am J Clin Nutr. 1990;52(2):391–396. doi: 10.1093/ajcn/52.2.391.
    1. Solomons NW, Mazariegos M, Brown KH, Klasing K. The underprivileged, developing country child: environmental contamination and growth failure revisited. Nutr Rev. 1993;51(11):327–332. doi: 10.1111/j.1753-4887.1993.tb03758.x.
    1. Nyakeriga AM, Troye-Blomberg M, Chemtai AK, Marsh K, Williams TN. Malaria and nutritional status in children living on the coast of Kenya. Am J Clin Nutr. 2004;190(3):1604–1610. doi: 10.1093/ajcn/80.6.1604.
    1. Rowland MG, Cole TJ, Whitehead RG. A quantitative study into the role of infection in determining nutritional status in Gambian village children. Br J Nutr. 1977;37(3):441–450. doi: 10.1079/BJN19770047.
    1. Boivin MJ, Sikorskii A, Familiar-Lopez I, Ruiseñor-Escudero H, Muhindo M, Kapisi J, et al. Malaria illness mediated by anaemia lessens cognitive development in younger Ugandan children. Malar J. 2016;15(1):1–12. doi: 10.1186/s12936-016-1266-x.
    1. Das BS, Thurnham DI, Das DB. Influence of malaria on markers of iron status in children: implications for interpreting iron status in malaria-endemic communities. Br J Nutr. 1997;78(5):751–760. doi: 10.1079/BJN19970192.
    1. Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, Pocock SJ, et al. Strengthening the reporting of observational studies in epidemiology (STROBE): explanation studies in epidemiology (STROBE): explanation and elaboration. Int J Surg. 2014;12:1500–24. Avalable from: .
    1. Perumal N, Bassani DG, Roth DE. Use and misuse of stunting as a measure of child health. J Nutr. 2018;148(3):311–315. doi: 10.1093/jn/nxx064.
    1. Olofin I, McDonald CM, Ezzati M, Flaxman S, Black REFW. Associations of suboptimal growth with all-cause and cause-specific mortality in children under five years: a pooled analysis of ten prospective studies. PLoS one. 2013;8(5) Available from: 10.1371/journal.pone.0064636.
    1. Poskitt EME, Cole TJ, Whitehead RG. Less diarrhoea but no change in growth: 15 years’ data from three Gambian villages. Arch Dis Child. 1999;80(2):115–120. doi: 10.1136/adc.80.2.115.
    1. Moy R, CMTF D, Choto R, McNeish A, Booth I. Diarrhoea and growth faltering in rural Zimbabwe. Eur J Clin Nutr. 1994;11(48):810–821.
    1. Briend A, Hasan K, Aziz K, Hoque B. Are diarrhoea control programmes likely to reduce childhood malnutrition? Observations from rural Bangladesh. Lancet. 1989;2:319–322. doi: 10.1016/S0140-6736(89)90498-4.
    1. Dewey KG, Mayers DR. Early child growth: how do nutrition and infection interact? Matern Child Nutr. 2011;7(SUPPL. 3):129–142. doi: 10.1111/j.1740-8709.2011.00357.x.
    1. Mbuya MNN, Humphrey JH. Preventing environmental enteric dysfunction through improved water, sanitation and hygiene: an opportunity for stunting reduction in developing countries. Matern Child Nutr. 2016;12:106–120. doi: 10.1111/mcn.12220.

Source: PubMed

3
Tilaa