The association between malnutrition and the incidence of malaria among young HIV-infected and -uninfected Ugandan children: a prospective study

Emmanuel Arinaitwe, Anne Gasasira, Wendy Verret, Jaco Homsy, Humphrey Wanzira, Abel Kakuru, Taylor G Sandison, Sera Young, Jordan W Tappero, Moses R Kamya, Grant Dorsey, Emmanuel Arinaitwe, Anne Gasasira, Wendy Verret, Jaco Homsy, Humphrey Wanzira, Abel Kakuru, Taylor G Sandison, Sera Young, Jordan W Tappero, Moses R Kamya, Grant Dorsey

Abstract

Background: In sub-Saharan Africa, malnutrition and malaria remain major causes of morbidity and mortality in young children. There are conflicting data as to whether malnutrition is associated with an increased or decreased risk of malaria. In addition, data are limited on the potential interaction between HIV infection and the association between malnutrition and the risk of malaria.

Methods: A cohort of 100 HIV-unexposed, 203 HIV-exposed (HIV negative children born to HIV-infected mothers) and 48 HIV-infected children aged 6 weeks to 1 year were recruited from an area of high malaria transmission intensity in rural Uganda and followed until the age of 2.5 years. All children were provided with insecticide-treated bed nets at enrolment and daily trimethoprim-sulphamethoxazole prophylaxis (TS) was prescribed for HIV-exposed breastfeeding and HIV-infected children. Monthly routine assessments, including measurement of height and weight, were conducted at the study clinic. Nutritional outcomes including stunting (low height-for-age) and underweight (low weight-for-age), classified as mild (mean z-scores between -1 and -2 during follow-up) and moderate-severe (mean z-scores < -2 during follow-up) were considered. Malaria was diagnosed when a child presented with fever and a positive blood smear. The incidence of malaria was compared using negative binomial regression controlling for potential confounders with measures of association expressed as an incidence rate ratio (IRR).

Results: The overall incidence of malaria was 3.64 cases per person year. Mild stunting (IRR = 1.24, 95% CI 1.06-1.46, p = 0.008) and moderate-severe stunting (IRR = 1.24, 95% CI 1.03-1.48, p = 0.02) were associated with a similarly increased incidence of malaria compared to non-stunted children. Being mildly underweight (IRR = 1.09, 95% CI 0.95-1.25, p = 0.24) and moderate-severe underweight (IRR = 1.12, 95% CI 0.86-1.46, p = 0.39) were not associated with a significant difference in the incidence of malaria compared to children who were not underweight. There were no significant interactions between HIV-infected, HIV-exposed children taking TS and the associations between malnutrition and the incidence of malaria.

Conclusions: Stunting, indicative of chronic malnutrition, was associated with an increased incidence of malaria among a cohort of HIV-infected and -uninfected young children living in an area of high malaria transmission intensity. However, caution should be made when making causal inferences given the observational study design and inability to disentangle the temporal relationship between malnutrition and the incidence of malaria.

Trial registration: ClinicalTrials.gov: NCT00527800.

Figures

Figure 1
Figure 1
Study profile.
Figure 2
Figure 2
Relationship between mean height-for-age Z scores (HAZ) and weight-for-age Z scores (WAZ) across age stratified by HIV status (using lowess smoothing).

References

    1. Rosen JB, Breman JG. Malaria intermittent preventive treatment in infants, chemoprophylaxis, and childhood vaccinations. Lancet. 2004;363:1386–1388. doi: 10.1016/S0140-6736(04)16052-2.
    1. World Health Organization (WHO) World Malaria Report 2009. Geneva, Switzerland: World Health Organization; 2009.
    1. Progress for Children. A World Fit for Children: Statistical Review. New York: United Nations; 2007. pp. 19–24.
    1. Caulfield LE, Richard SA, Black RE. Undernutrition as an underlying cause of malaria morbidity and mortality in children less than five years old. Am J Trop Med Hyg. 2004;71:55–63.
    1. Katona P, Katona-Apte J. The interaction between nutrition and infection. Clin Infect Dis. 2008;46:1582–1588. doi: 10.1086/587658.
    1. Pelletier DL, Frongillo EA, Schroeder DG, Habicht JP. The effects of malnutrition on child mortality in developing countries. Bull World Health Organ. 1995;73:443–448.
    1. Fillol F, Cournil A, Boulanger D, Cisse B, Sokhna C, Targett G, Trape JF, Simondon F, Greenwood B, Simondon KB. Influence of wasting and stunting at the onset of the rainy season on subsequent malaria morbidity among rural preschool children in Senegal. Am J Trop Med Hyg. 2009;80:202–208.
    1. Genton B, Al-Yaman F, Ginny M, Taraika J, Alpers MP. Relation of anthropometry to malaria morbidity and immunity in Papua New Guinean children. Am J Clin Nutr. 1998;68:734–741.
    1. Murray MJ, Murray AB, Murray MB, Murray CJ. Somali food shelters in the Ogaden famine and their impact on health. Lancet. 1976;1:1283–1285.
    1. Carswell F, Hughes AO, Palmer RI, Higginson J, Harland PS, Meakins RH. Nutritional status, globulin titers, and parasitic infections of two populations of Tanzanian school children. Am J Clin Nutr. 1981;34:1292–1299.
    1. Snow RW, Byass P, Shenton FC, Greenwood BM. The relationship between anthropometric measurements and measurements of iron status and susceptibility to malaria in Gambian children. Trans R Soc Trop Med Hyg. 1991;85:584–589. doi: 10.1016/0035-9203(91)90351-X.
    1. Deribew A, Alemseged F, Tessema F, Sena L, Birhanu Z, Zeynudin A, Sudhakar M, Abdo N, Deribe K, Biadgilign S. Malaria and under-nutrition: a community based study among under-five children at risk of malaria, south-west Ethiopia. PLoS One. 2010;5:e10775. doi: 10.1371/journal.pone.0010775.
    1. Deen JL, Walraven GE, von Seidlein L. Increased risk for malaria in chronically malnourished children under 5 years of age in rural Gambia. J Trop Pediatr. 2002;48:78–83. doi: 10.1093/tropej/48.2.78.
    1. Ehrhardt S, Burchard GD, Mantel C, Cramer JP, Kaiser S, Kubo M, Otchwemah RN, Bienzle U, Mockenhaupt FP. Malaria, anemia, and malnutrition in african children-defining intervention priorities. J Infect Dis. 2006;194:108–114. doi: 10.1086/504688.
    1. Suttmann U, Ockenga J, Selberg O, Hoogestraat L, Deicher H, Muller MJ. Incidence and prognostic value of malnutrition and wasting in human immunodeficiency virus-infected outpatients. J Acquir Immune Defic Syndr Hum Retrovirol. 1995;8:239–246. doi: 10.1097/00042560-199503010-00004.
    1. Padmapriyadarsini C, Pooranagangadevi N, Chandrasekaran K, Subramanyan S, Thiruvalluvan C, Bhavani PK, Swaminathan S. Prevalence of underweight, stunting, and wasting among children infected with human immunodeficiency virus in South India. Int J Pediatr. 2009;200(9):837627..
    1. Whitworth J, Morgan D, Quigley M, Smith A, Mayanja B, Eotu H, Omoding N, Okongo M, Malamba S, Ojwiya A. Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study. Lancet. 2000;356:1051–1056. doi: 10.1016/S0140-6736(00)02727-6.
    1. French N, Nakiyingi J, Lugada E, Watera C, Whitworth JA, Gilks CF. Increasing rates of malarial fever with deteriorating immune status in HIV-1-infected Ugandan adults. AIDS. 2001;15:899–906. doi: 10.1097/00002030-200105040-00010.
    1. Kamya MR, Gasasira AF, Yeka A, Bakyaita N, Nsobya SL, Francis D, Rosenthal PJ, Dorsey G, Havlir D. Effect of HIV-1 infection on antimalarial treatment outcomes in Uganda: a population-based study. J Infect Dis. 2006;193:9–15. doi: 10.1086/498577.
    1. Patnaik P, Jere CS, Miller WC, Hoffman IF, Wirima J, Pendame R, Meshnick SR, Taylor TE, Molyneux ME, Kublin JG. Effects of HIV-1 serostatus, HIV-1 RNA concentration, and CD4 cell count on the incidence of malaria infection in a cohort of adults in rural Malawi. J Infect Dis. 2005;192:984–991. doi: 10.1086/432730.
    1. Mermin J, Ekwaru JP, Liechty CA, Were W, Downing R, Ransom R, Weidle P, Lule J, Coutinho A, Solberg P. Effect of co-trimoxazole prophylaxis, antiretroviral therapy, and insecticide-treated bednets on the frequency of malaria in HIV-1-infected adults in Uganda: a prospective cohort study. Lancet. 2006;367:1256–1261. doi: 10.1016/S0140-6736(06)68541-3.
    1. Kamya MR, Gasasira AF, Achan J, Mebrahtu T, Ruel T, Kekitiinwa A, Charlebois ED, Rosenthal PJ, Havlir D, Dorsey G. Effects of trimethoprim-sulfamethoxazole and insecticide-treated bednets on malaria among HIV-infected Ugandan children. AIDS. 2007;21:2059–2066. doi: 10.1097/QAD.0b013e3282ef6da1.
    1. Okello PE, Van Bortel W, Byaruhanga AM, Correwyn A, Roelants P, Talisuna A, D'Alessandro U, Coosemans M. Variation in malaria transmission intensity in seven sites throughout Uganda. Am J Trop Med Hyg. 2006;75:219–225.
    1. Arinaitwe E, Sandison TG, Wanzira H, Kakuru A, Homsy J, Kalamya J, Kamya MR, Vora N, Greenhouse B, Rosenthal PJ, Tappero J, Dorsey G. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for falciparum malaria: a longitudinal, randomized trial in young Ugandan children. Clin Infect Dis. 2009;49:1629–1637. doi: 10.1086/647946.
    1. Sandison TG, Homsy J, Arinaitwe E, Wanzira H, Kakuru A, Bigira V, Kalamya J, Vora N, Kublin J, Kamya MR, Dorsey G, Tappero JW. Protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children in rural Uganda: a randomised clinical trial. BMJ. 2011;342:d1617. doi: 10.1136/bmj.d1617.
    1. Bates B. Bate's Guide to Physical Examination and History Taking. 7. Philadelphia: Lippincott; 1999.
    1. Cogill B. Anthropometric Indicators Measurement Guide. Food and Nutrition Technical Assistant. 2003.
    1. World Health Organization (WHO) Multicentre Growth Reference Study Group. WHO Child Growth Standards: Methods and Development. Geneva, Switzerland: World Health Organization; 2006.
    1. Mangili A, Murman DH, Zampini AM, Wanke CA. Nutrition and HIV infection: review of weight loss and wasting in the era of highly active antiretroviral therapy from the nutrition for healthy living cohort. Clin Infect Dis. 2006;42:836–842. doi: 10.1086/500398.
    1. Tang AM, Forrester J, Spiegelman D, Knox TA, Tchetgen E, Gorbach SL. Weight loss and survival in HIV-positive patients in the era of highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2002;31:230–236. doi: 10.1097/00126334-200210010-00014.
    1. Arpadi S, Fawzy A, Aldrovandi GM, Kankasa C, Sinkala M, Mwiya M, Thea DM, Kuhn L. Growth faltering due to breastfeeding cessation in uninfected children born to HIV-infected mothers in Zambia. Am J Clin Nutr. 2009;90:344–353. doi: 10.3945/ajcn.2009.27745.
    1. Mane NB, Simondon KB, Diallo A, Marra AM, Simondon F. Early breastfeeding cessation in rural Senegal: causes, modes, and consequences. Am J Public Health. 2006;96:139–144. doi: 10.2105/AJPH.2004.048553.
    1. World Health Organization. Effect of breastfeeding on infant and child mortality due to infectious diseases in less developed countries: a pooled analysis. Lancet. 2000;355:451–455.
    1. Castetbon K, Anglaret X, Toure S, Chene G, Ouassa T, Attia A, N'Dri-Yoman T, Malvy D, Salamon R, Dabis F. Prognostic value of cross-sectional anthropometric indices on short-term risk of mortality in human immunodeficiency virus-infected adults in Abidjan, Cote d'Ivoire. Am J Epidemiol. 2001;154:75–84. doi: 10.1093/aje/154.1.75.
    1. Hendrickse RG, Hasan AH, Olumide LO, Akinkunmi A. Malaria in early childhood. An investigation of five hundred seriously ill children in whom a "clinical" diagnosis of malaria was made on admission to the children's emergency room at University College Hospital, Ibadan. Ann Trop Med Parasitol. 1971;65:1–20.
    1. Murray MJ, Murray NJ, Murray AB, Murray MB. Refeeding-malaria and hyperferraemia. Lancet. 1975;1:653–654.
    1. Cunningham-Rundles SD, McNeeley F, Moon A. Mechanisms of nutrient modulation of the immune response. J Allergy Clin Immunol. 2005;115:1119–1128. doi: 10.1016/j.jaci.2005.04.036.
    1. Field CJ, Johnson IR, Schley PD. Nutrients and their role in host resistance to infection. J Leukoc Biol. 2002;71:16–32.
    1. Semba RD. The role of vitamin A and related retinoids in immune function. Nutr Rev. 1998;56:S38–S48.
    1. Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998;68:447S–463S.
    1. Bradley-Moore AM, Greenwood BM, Bradley AK, Kirkwood BR, Gilles HM. Malaria chemoprophylaxis with chloroquine in young Nigerian children. III. Its effect on nutrition. Ann Trop Med Parasitol. 1985;79:575–584.
    1. Snow RW, Molyneux CS, Njeru EK, Omumbo J, Nevill CG, Muniu E, Marsh K. The effects of malaria control on nutritional status in infancy. Acta Trop. 1997;65:1–10. doi: 10.1016/S0001-706X(96)00601-8.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel