Asymptomatic Plasmodium infection and cognition among primary schoolchildren in a high malaria transmission setting in Uganda

Joaniter Nankabirwa, Bonnie Wandera, Noah Kiwanuka, Sarah G Staedke, Moses R Kamya, Simon J Brooker, Joaniter Nankabirwa, Bonnie Wandera, Noah Kiwanuka, Sarah G Staedke, Moses R Kamya, Simon J Brooker

Abstract

Asymptomatic parasitemia is common among schoolchildren living in areas of high malaria transmission, yet little is known about its effect on cognitive function in these settings. To investigate associations between asymptomatic parasitemia, anemia, and cognition among primary schoolchildren living in a high malaria transmission setting, we studied 740 children enrolled in a clinical trial in Tororo, Uganda. Parasitemia, measured by thick blood smears, was present in 30% of the children. Infected children had lower test scores for abstract reasoning (adjusted mean difference [AMD] -0.6, 95% confidence interval [CI] -1.01 to -0.21) and sustained attention (AMD -1.6 95% CI -2.40 to -0.81) compared with uninfected children. There was also evidence for a dose-response relationship between parasite density and scores for sustained attention. No associations were observed between anemia and either test of cognition. Schoolchildren in high transmission settings may experience cognitive benefits, from interventions aimed at reducing the prevalence of asymptomatic parasitemia.

References

    1. Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature. 2005;434:214–217.
    1. Nankabirwa J, Cundill B, Clarke S, Kabatereine N, Rosenthal PJ, Dorsey G, Brooker S, Staedke SG. Efficacy, safety, and tolerability of three regimens for prevention of malaria: a randomized, placebo-controlled trial in Ugandan schoolchildren. PLoS ONE. 2010;5:e13438.
    1. Pullan RL, Bukirwa H, Staedke SG, Snow RW, Brooker S. Plasmodium infection and its risk factors in eastern Uganda. Malar J. 2010;9:2.
    1. Kabatereine NB, Standley CJ, Sousa-Figueiredo JC, Fleming FM, Stothard JR, Talisuna A, Fenwick A. Integrated prevalence mapping of schistosomiasis, soil-transmitted helminthiasis and malaria in lakeside and island communities in Lake Victoria, Uganda. Parasit Vectors. 2011;4:232.
    1. Brooker S, Clarke S, Njagi JK, Polack S, Mugo B, Estambale B, Magnusen P, Cox J. Spatial clustering of malaria and associated risk factors during an epidemic in a highland area of western Kenya. Trop Med Int Health. 2004;9:757–766.
    1. Lalloo DG, Olukoya P, Olliaro P. Malaria in adolescence: burden of disease, consequences, and opportunities for intervention. Lancet Infect Dis. 2006;6:780–793.
    1. Clarke SE, Jukes MC, Njagi JK, Khasakhala L, Cundill B, Otido J, Crudder C, Estambale BA, Brooker S. Effect of intermittent preventive treatment of malaria on health and education in schoolchildren: a cluster-randomized, double-blind, placebo-controlled trial. Lancet. 2008;372:127–138.
    1. Holding PA, Snow RW. Impact of Plasmodium falciparum malaria on performance and learning: review of the evidence. Am J Trop Med Hyg 64 (1–2 Suppl) 2001:68–75.
    1. Kihara M, Carter JA, Newton CR. The effect of Plasmodium falciparum on cognition: a systematic review. Trop Med Int Health. 2006;11:386–397.
    1. Al Serouri AW, Grantham-McGregor SM, Greenwood B, Costello A. Impact of asymptomatic malaria parasitemia on cognitive function and school achievement of schoolchildren in the Yemen Republic. Parasitology. 2000;121:337–345.
    1. Thuilliez J. Fever, malaria and primary repetition rates amongst school children in Mali: combining demographic and health surveys (DHS) with spatial malariological measures. Soc Sci Med. 2010;71:314–323.
    1. Thuilliez J, Sissoko MS, Toure OB, Kamate P, Berthelemy JC, Doumbo OK. Malaria and primary education in Mali: a longitudinal study in the village of Doneguebougou. Soc Sci Med. 2010;71:324–334.
    1. Fernando SD, Fau-Rodrigo C, Rodrigo C, Fau-Rajapakse S, Rajapakse S. The ‘hidden’ burden of malaria: cognitive impairment following infection. Malar J. 2010;9:366.
    1. Hay SI, Guerra CA, Gething PW, Patil AP, Tatem AJ, Noor AM, Kabaria CW, Manh BH, Elyazar IR, Brooker S, Smith DL, Moyeed RA, Snow RW. A world malaria map: Plasmodium falciparum endemicity in 2007. PLoS Med. 2009;6e1000048
    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. Halliday EK, Karanja P, Turner LE, Okello G, Njagi K, Dubeck MM, Allen E, Jukes CHM, Brooker JS. Plasmodium falciparum, anaemia and cognitive and educational performance among school children in an area of moderate malaria transmission: baseline results of a cluster randomized trial on the coast of Kenya. Trop Med Int Health. 2012;17:532–549.
    1. Manly T, Robertson IH, Anderson V, Nimmo-Smith I. Test of Everyday Attention for Children: TEA-Ch. Bury St. Edmunds, UK: Thames Valley Test Company; 1999.
    1. Raven JC, Styles I, Raven MA. Raven's Progressive Matrices. Oxford, UK: Oxford Psychologists Press; 1998.
    1. WHO . Iron Deficiency Anaemia: Assessment, Prevention and Control. A guide for programme managers. Geneva: World Health Organization; 2001.
    1. WHO . Worldwide prevalence of anaemia 1993–2005. In: de Benoist B, McLean E, Egli I, Cogswell M, editors. WHO Global Database on Anaemia. Geneva: World Health Organization; 2008. p. 7.
    1. Vidmar Suzanna, Carlin John, Kylie H, Tim C. Standardizing anthropometric measures in children and adolescents with new functions for egen. Stata J. 2004;4:50–55.
    1. Filmer D, Fau-Pritchett LH, Pritchett LH. Estimating wealth effects without expenditure data–or tears: an application to educational enrollments in states of India. Demography. 2001;38:115–132.
    1. Gitonga CW, Edwards T, Karanja PN, Noor AM, Snow RW, Brooker SJ. Plasmodium infection, anaemia and mosquito net use among school children across different settings in Kenya. Trop Med Int Health. 2012;17:858–870.
    1. Nokes C, Grantham-McGregor SM, Sawyer AW, Cooper ES, Robinson BA, Bundy DA. Moderate to heavy infections of Trichuris trichiura affect cognitive function in Jamaican school children. Parasitology. 1992;104:539–547.
    1. Falkingham M, Abdelhamid A, Curtis P, Fairweather-Tait S, Dye L, Hooper L. The effects of oral iron supplementation on cognition in older children and adults: a systematic review and meta-analysis. Nutr J. 2010;9:4.
    1. Fernando D, Wickremasinghe R, Mendis KN, Wickremasinghe AR. Cognitive performance at school entry of children living in malaria-endemic areas of Sri Lanka. Trans R Soc Trop Med Hyg. 2003;97:161–165.
    1. Fernando SD, Gunawardena DM, Bandara MR, De Silva D, Carter R, Mendis KN, Wickremasinghe AR. The impact of repeated malaria attacks on the school performance of children. Am J Trop Med Hyg. 2003;69:582–588.
    1. Kurtzhals JA, Addae MM, Akanmori BD, Dunyo S, Koram KA, Appawu MA. Anaemia caused by asymptomatic Plasmodium falciparum infection in semi-immune African schoolchildren. Trans R Soc Trop Med Hyg. 1999;93:623–627.
    1. Halterman JS, Kaczorowski JM, Aligne CA, Auinger P, Szilagyi PG. Iron deficiency and cognitive achievement among school-aged children and adolescents in the United States. Pediatrics. 2001;107:1381–1386.
    1. Grantham-McGregor S, Ani C. A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr. 2001;131:649S–666S. discussion 66S–68S.
    1. Agaoglu L, Torun O, Unuvar E, Sefil Y, Demir D. Effects of iron deficiency anemia on cognitive function in children. Arzneimittelforschung. 2007;57:426–430.
    1. John CC, Panoskaltsis-Mortari A, Opoka RO, Park GS, Orchard PJ, Jurek AM, Idro R, Byarugaba J, Boivin MJ. Cerebrospinal fluid cytokine levels and cognitive impairment in cerebral malaria. Am J Trop Med Hyg. 2008;78:198–205.
    1. Jukes MC, Pinder M, Grigorenko EL, Smith HB, Walraven G, Bariau EM, Sternberg RJ, Drake LJ, Milligan P, Cheung YB, Greenwood BM, Bundy DA. Long-term impact of malaria chemoprophylaxis on cognitive abilities and educational attainment: follow-up of a controlled trial. PLoS Clin Trials. 2006;1:e19.
    1. Carter JA, Mung'ala-Odera V, Neville BG, Murira G, Mturi N, Musumba C, Newton CR. Persistent neurocognitive impairments associated with severe falciparum malaria in Kenyan children. J Neurol Neurosurg Psychiatry. 2005;76:476–481.
    1. John CC, Bangirana P, Byarugaba J, Opoka RO, Idro R, Jurek AM, Wu B, Boivin MJ. Cerebral malaria in children is associated with long-term cognitive impairment. Pediatrics. 2008;122:e92–e99.
    1. Vitor-Silva S, Reyes-Lecca RC, Pinheiro TR, Lacerda MV. Malaria is associated with poor school performance in an endemic area of the Brazilian Amazon. Malar J. 2009;8:230.
    1. Bangirana P, Musisi S, Boivin MJ, Ehnvall A, John CC, Bergemann TL, Allebeck P. Malaria with neurological involvement in Ugandan children: effect on cognitive ability, academic achievement and behavior. Malar J. 2011;10:334.
    1. International RTI . Early Grade Reading Kenya: Baseline Assessment: Analyses and Implications for Teaching Interventions. Research Triangle Park, NC: RTI International; 2008. Final Report.
    1. Sakti H, Nokes C, Hertanto WS, Hall A, Bundy DA, Satoto Evidence for an association between hookworm infection and cognitive function in Indonesian school children. Trop Med Int Health. 1999;4:322–334.
    1. Nokes C, McGarvey ST, Shiue L, Wu G, Wu H, Bundy DA, Olds GR. Evidence for an improvement in cognitive function following treatment of Schistosoma japonicum infection in Chinese primary schoolchildren. Am J Trop Med Hyg. 1999;60:556–565.
    1. Jukes MC, Nokes CA, Alcock KJ, Lambo JK, Kihamia C, Ngorosho N, Mbise A, Lorri W, Yona E, Mwanri L, Baddeley AD, Hall A, Bundy DA. Heavy schistosomiasis associated with poor short-term memory and slower reaction times in Tanzanian schoolchildren. Trop Med Int Health. 2002;7:104–117.
    1. Ezeamama AE, Friedman JF, Acosta LP, Bellinger DC, Langdon GC, Manalo DL, Olveda RM, Kurtis JD, McGarvey ST. Helminth infection and cognitive impairment among Filipino children. Am J Trop Med Hyg. 2005;72:540–548.
    1. Stoltzfus RJ, Albonico M, Tielsch JM, Chwaya HM, Savioli L. School-based deworming program yields small improvement in growth of Zanzibari school children after one year. J Nutr. 1997;127:2187–2193.
    1. Bellisle F. Effects of diet on behavior and cognition in children. Br J Nutr. 2004;92((Suppl 2)):S227–S232.

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