Skip to main content
Top
Published in: BMC Pediatrics 1/2017

Open Access 01-12-2017 | Research article

Anaemia in hospitalised preschool children from a rural area in Mozambique: a case control study in search for aetiological agents

Authors: Cinta Moraleda, Ruth Aguilar, Llorenç Quintó, Tacilta Nhampossa, Montserrat Renom, Augusto Nhabomba, Sozinho Acácio, John J. Aponte, Delino Nhalungo, Ariel H. Achtman, Louis Schofield, Helder Martins, Eusebio Macete, Pedro L. Alonso, Clara Menéndez

Published in: BMC Pediatrics | Issue 1/2017

Login to get access

Abstract

Background

Young children bear the world’s highest prevalence of anaemia, the majority of which is of multifactorial aetiology, which in turn hampers its successful prevention. Even moderate degrees of anaemia are associated with increased mortality and morbidity. Despite this evidence, there is a lack of effective preventive programs and absence of consensus in the safety of iron supplementation in malaria areas, which reflects the poor understanding of the contribution of different aetiologies to anaemia. In order to reduce the anaemia burden in the most vulnerable population, a study to determine the aetiology of anaemia among pre-school Mozambican children was performed.

Methods

We undertook a case–control study of 443 preschool hospitalized children with anaemia (haemoglobin concentration <11 g/dl) and 289 community controls without anaemia. Inclusion criteria were: age 1–59 months, no blood transfusion in the previous month, residence in the study area and signed informed consent. Both univariable and multivariable logistic regression analyses were performed to identify factors associated with anaemia and adjusted attributable fractions (AAF) were estimated when appropriate.

Results

Malaria (adjusted odds ratio (AOR) = 8.39, p < 0.0001; AAF = 37%), underweight (AOR = 8.10, p < 0.0001; AAF = 43%), prealbumin deficiency (AOR = 7.11, p < 0.0001; AAF = 77%), albumin deficiency (AOR = 4.29, p = 0.0012; AAF = 30%), HIV (AOR = 5.73, p = 0.0060; AAF = 18%), and iron deficiency (AOR = 4.05, p < 0.0001; AAF = 53%) were associated with anaemia. Vitamin A deficiency and α-thalassaemia were frequent (69% and 64%, respectively in cases) but not independently related to anaemia. Bacteraemia (odds ratio (OR) = 8.49, p = 0.004), Parvovirus-B19 (OR = 6.05, p = 0.017) and Epstein-Barr virus (OR = 2.10, p = 0.0015) infections were related to anaemia only in the unadjusted analysis. Neither vitamin B12 deficiency nor intestinal parasites were associated with anaemia. Folate deficiency was not observed.

Conclusions

Undernutrition, iron deficiency, malaria, and HIV are main factors related to anaemia in hospitalised Mozambican preschool children. Effective programs and strategies for the prevention and management of these conditions need to be reinforced. Specifically, prevention of iron deficiency that accounted in this study for more than half of anaemia cases would have a high impact in reducing the burden of anaemia in children living under similar conditions. However this deficiency, a common preventable and treatable condition, remains neglected by the international public health community.
Literature
1.
go back to reference Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, Amann M, Anderson HR, Andrews KG, Aryee M, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2224–60. doi:10.1016/S0140-6736(12)61766-61768.CrossRefPubMedPubMedCentral Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, Amann M, Anderson HR, Andrews KG, Aryee M, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2224–60. doi:10.​1016/​S0140-6736(12)61766-61768.CrossRefPubMedPubMedCentral
3.
go back to reference WHO. Worldwide prevalence of anaemia 1993–2005: WHO global database on anaemia. 2008. WHO. Worldwide prevalence of anaemia 1993–2005: WHO global database on anaemia. 2008.
4.
go back to reference Brabin BJ, Premji Z, Verhoeff F. An analysis of anemia and child mortality. J Nutr. 2001;131(2S-2):636S–45S. discussion 646S-648S.PubMed Brabin BJ, Premji Z, Verhoeff F. An analysis of anemia and child mortality. J Nutr. 2001;131(2S-2):636S–45S. discussion 646S-648S.PubMed
6.
go back to reference Martins H. Proposta de componente estratégica dum plano de desenvolvimento nutricional em Moçambique. In. Nutrição Rd, editor. Maputo: MISAU; 2004 Martins H. Proposta de componente estratégica dum plano de desenvolvimento nutricional em Moçambique. In. Nutrição Rd, editor. Maputo: MISAU; 2004
7.
go back to reference Omar C, Martins H. Indicadores a utilizar no processo de produção do plano de desenvolvimento sanitario 2000–2005, vol. CNCS/XXIV/98/PA-7. Maputo: Ministery of Health of Mozambique; 1998. Omar C, Martins H. Indicadores a utilizar no processo de produção do plano de desenvolvimento sanitario 2000–2005, vol. CNCS/XXIV/98/PA-7. Maputo: Ministery of Health of Mozambique; 1998.
8.
go back to reference WHO, UNICEF. Joint statement by the World Health Organization and the United Nations Children’s Fund. Focusing on anaemia. 2004. WHO, UNICEF. Joint statement by the World Health Organization and the United Nations Children’s Fund. Focusing on anaemia. 2004.
9.
go back to reference Aguilar R, Moraleda C, Quinto L, Renom M, Mussacate L, Macete E, Aguilar JL, Alonso PL, Menendez C. Challenges in the diagnosis of iron deficiency in children exposed to high prevalence of infections. PLoS One. 2012;7(11):e50584.CrossRefPubMedPubMedCentral Aguilar R, Moraleda C, Quinto L, Renom M, Mussacate L, Macete E, Aguilar JL, Alonso PL, Menendez C. Challenges in the diagnosis of iron deficiency in children exposed to high prevalence of infections. PLoS One. 2012;7(11):e50584.CrossRefPubMedPubMedCentral
10.
go back to reference Sacoor C, Nhacolo A, Nhalungo D, Aponte JJ, Bassat Q, Augusto O, Mandomando I, Sacarlal J, Lauchande N, Sigauque B, et al. Profile: Manhica Health Research Centre (Manhica HDSS). Int J Epidemiol. 2013;42(5):1309–18.CrossRefPubMed Sacoor C, Nhacolo A, Nhalungo D, Aponte JJ, Bassat Q, Augusto O, Mandomando I, Sacarlal J, Lauchande N, Sigauque B, et al. Profile: Manhica Health Research Centre (Manhica HDSS). Int J Epidemiol. 2013;42(5):1309–18.CrossRefPubMed
12.
go back to reference Guinovart C, Bassat Q, Sigauque B, Aide P, Sacarlal J, Nhampossa T, Bardaji A, Nhacolo A, Macete E, Mandomando I, et al. Malaria in rural Mozambique. Part I: children attending the outpatient clinic. Malar J. 2008;7:36.CrossRefPubMedPubMedCentral Guinovart C, Bassat Q, Sigauque B, Aide P, Sacarlal J, Nhampossa T, Bardaji A, Nhacolo A, Macete E, Mandomando I, et al. Malaria in rural Mozambique. Part I: children attending the outpatient clinic. Malar J. 2008;7:36.CrossRefPubMedPubMedCentral
13.
go back to reference Gonzalez R, Munguambe K, Aponte J, Bavo C, Nhalungo D, Macete E, Alonso P, Menendez C, Naniche D. High HIV prevalence in a southern semi-rural area of Mozambique: a community-based survey. HIV Med. 2012;13(10):581–8.CrossRefPubMed Gonzalez R, Munguambe K, Aponte J, Bavo C, Nhalungo D, Macete E, Alonso P, Menendez C, Naniche D. High HIV prevalence in a southern semi-rural area of Mozambique: a community-based survey. HIV Med. 2012;13(10):581–8.CrossRefPubMed
14.
go back to reference MISAU, INS. Inquérito Nacional de Prevalecia, Riscos Comportamentais e Informaçao sobre o HIV e SIDA em Moçambique. INSIDA 2009. Relatorio Preliminar sobre Prevâlencia da Infecçao por HIV. Maputo: Ministerio de Saúde Mozambique & Instituto Nacional de Saúde; 2010. MISAU, INS. Inquérito Nacional de Prevalecia, Riscos Comportamentais e Informaçao sobre o HIV e SIDA em Moçambique. INSIDA 2009. Relatorio Preliminar sobre Prevâlencia da Infecçao por HIV. Maputo: Ministerio de Saúde Mozambique & Instituto Nacional de Saúde; 2010.
15.
go back to reference Moraleda C, de Deus N, Serna-Bolea C, Renom M, Quinto L, Macete E, Menendez C, Naniche D. Impact of HIV exposure on health outcomes in HIV-negative infants born to HIV-positive mothers in Sub-Saharan Africa. J Acquir Immune Defic Syndr. 2014;65(2):182–9. doi:10.1097/QAI.0000000000000019.CrossRefPubMed Moraleda C, de Deus N, Serna-Bolea C, Renom M, Quinto L, Macete E, Menendez C, Naniche D. Impact of HIV exposure on health outcomes in HIV-negative infants born to HIV-positive mothers in Sub-Saharan Africa. J Acquir Immune Defic Syndr. 2014;65(2):182–9. doi:10.​1097/​QAI.​0000000000000019​.CrossRefPubMed
16.
go back to reference Nhampossa T, Sigauque B, Machevo S, Macete E, Alonso P, Bassat Q, Menendez C, Fumado V. Severe malnutrition among children under the age of 5 years admitted to a rural district hospital in southern Mozambique. Public Health Nutr. 2013;16(9):1565–74. doi:10.1017/S1368980013001080.CrossRefPubMed Nhampossa T, Sigauque B, Machevo S, Macete E, Alonso P, Bassat Q, Menendez C, Fumado V. Severe malnutrition among children under the age of 5 years admitted to a rural district hospital in southern Mozambique. Public Health Nutr. 2013;16(9):1565–74. doi:10.​1017/​S136898001300108​0.CrossRefPubMed
17.
go back to reference Pastor MC, Codoceo R, Deulofeu R, Dolade M, Farré V, Fernandez P, Masia F, Matallana MC, Navarro E, Ortiz de Apodaca A, et al. Procedimiento recomendado para la determinacion de retinol en suero o plasma. Quimica Clínica. 1998;17:38–41. Pastor MC, Codoceo R, Deulofeu R, Dolade M, Farré V, Fernandez P, Masia F, Matallana MC, Navarro E, Ortiz de Apodaca A, et al. Procedimiento recomendado para la determinacion de retinol en suero o plasma. Quimica Clínica. 1998;17:38–41.
18.
go back to reference WHO. Sedimentation Method. In: In Basic Laboratory Methods in Medical Parasitology. Geneva: World Health Organization; 1991. p. 33–5. WHO. Sedimentation Method. In: In Basic Laboratory Methods in Medical Parasitology. Geneva: World Health Organization; 1991. p. 33–5.
19.
go back to reference Sapero JJ, Lawless DK. The MIF stain-preservation technic for the identification of intestinal protozoa. AmJTrop Med Hyg. 1953;2(4):613–9. Sapero JJ, Lawless DK. The MIF stain-preservation technic for the identification of intestinal protozoa. AmJTrop Med Hyg. 1953;2(4):613–9.
20.
go back to reference Dode C, Krishnamoorthy R, Lamb J, Rochette J. Rapid analysis of -alpha 3.7 thalassaemia and alpha alpha alpha anti 3.7 triplication by enzymatic amplification analysis. Br J Haematol. 1993;83(1):105–11.CrossRefPubMed Dode C, Krishnamoorthy R, Lamb J, Rochette J. Rapid analysis of -alpha 3.7 thalassaemia and alpha alpha alpha anti 3.7 triplication by enzymatic amplification analysis. Br J Haematol. 1993;83(1):105–11.CrossRefPubMed
21.
go back to reference Beutler E, Blume KG, Kaplan JC, Lohr GW, Ramot B, Valentine WN. International Committee for Standardization in Haematology: recommended screening test for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Br J Haematol. 1979;43(3):465–7.CrossRefPubMed Beutler E, Blume KG, Kaplan JC, Lohr GW, Ramot B, Valentine WN. International Committee for Standardization in Haematology: recommended screening test for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Br J Haematol. 1979;43(3):465–7.CrossRefPubMed
22.
go back to reference CDC. Centers for Disease Control and Prevention Clinical Growth Charts. Available at: http://wwwcdcgov/growthcharts/clinical_chartshtm. CDC. Centers for Disease Control and Prevention Clinical Growth Charts. Available at: http://​wwwcdcgov/​growthcharts/​clinical_​chartshtm.​
23.
go back to reference Nicholson JF, Pesce MA. Pruebas de laboratorio: Valores de referencia. In: Nelson Textbook of Pediatrics, vol. I. 17th ed. Madrid: Elsevier España; 2004. p. 2396–426. Nicholson JF, Pesce MA. Pruebas de laboratorio: Valores de referencia. In: Nelson Textbook of Pediatrics, vol. I. 17th ed. Madrid: Elsevier España; 2004. p. 2396–426.
25.
go back to reference Selhub J, Jacques PF, Dallal G, Choumenkovitch S, Rogers G. The use of blood concentrations of vitamins and their respective functional indicators to define folate and vitamin B12 status. Food Nutr Bull. 2008;29(2 Suppl):S67–73.CrossRefPubMed Selhub J, Jacques PF, Dallal G, Choumenkovitch S, Rogers G. The use of blood concentrations of vitamins and their respective functional indicators to define folate and vitamin B12 status. Food Nutr Bull. 2008;29(2 Suppl):S67–73.CrossRefPubMed
26.
go back to reference Ouma C, Keller CC, Davenport GC, Were T, Konah S, Otieno MF, Hittner JB, Vulule JM, Martinson J, Ong’echa JM, et al. A novel functional variant in the stem cell growth factor promoter protects against severe malarial anemia. Infect Immun. 2010;78(1):453–60.CrossRefPubMed Ouma C, Keller CC, Davenport GC, Were T, Konah S, Otieno MF, Hittner JB, Vulule JM, Martinson J, Ong’echa JM, et al. A novel functional variant in the stem cell growth factor promoter protects against severe malarial anemia. Infect Immun. 2010;78(1):453–60.CrossRefPubMed
27.
go back to reference Bruzzi P, Green SB, Byar DP, Brinton LA, Schairer C. Estimating the population attributable risk for multiple risk factors using case–control data. Am J Epidemiol. 1985;122(5):904–14.CrossRefPubMed Bruzzi P, Green SB, Byar DP, Brinton LA, Schairer C. Estimating the population attributable risk for multiple risk factors using case–control data. Am J Epidemiol. 1985;122(5):904–14.CrossRefPubMed
28.
go back to reference Oehlert GW. A note on the delta method. Am Stat. 1992;46:27–9. Oehlert GW. A note on the delta method. Am Stat. 1992;46:27–9.
30.
go back to reference Fleck A. Clinical and nutritional aspects of changes in acute-phase proteins during inflammation. Proc Nutr Soc. 1989;48(3):347–54.CrossRefPubMed Fleck A. Clinical and nutritional aspects of changes in acute-phase proteins during inflammation. Proc Nutr Soc. 1989;48(3):347–54.CrossRefPubMed
31.
go back to reference Rosales FJ, Topping JD, Smith JE, Shankar AH, Ross AC. Relation of serum retinol to acute phase proteins and malarial morbidity in Papua New Guinea children. Am J Clin Nutr. 2000;71(6):1582–8.PubMed Rosales FJ, Topping JD, Smith JE, Shankar AH, Ross AC. Relation of serum retinol to acute phase proteins and malarial morbidity in Papua New Guinea children. Am J Clin Nutr. 2000;71(6):1582–8.PubMed
32.
go back to reference Wieringa FT, Dijkhuizen MA, West CE, Northrop-Clewes CA, Muhilal. Estimation of the effect of the acute phase response on indicators of micronutrient status in Indonesian infants. J Nutr. 2002;132(10):3061–6.PubMed Wieringa FT, Dijkhuizen MA, West CE, Northrop-Clewes CA, Muhilal. Estimation of the effect of the acute phase response on indicators of micronutrient status in Indonesian infants. J Nutr. 2002;132(10):3061–6.PubMed
33.
go back to reference Calis JC, Phiri KS, Faragher EB, Brabin BJ, Bates I, Cuevas LE, de Haan RJ, Phiri AI, Malange P, Khoka M, et al. Severe anemia in Malawian children. N Engl J Med. 2008;358(9):888–99.CrossRefPubMed Calis JC, Phiri KS, Faragher EB, Brabin BJ, Bates I, Cuevas LE, de Haan RJ, Phiri AI, Malange P, Khoka M, et al. Severe anemia in Malawian children. N Engl J Med. 2008;358(9):888–99.CrossRefPubMed
34.
go back to reference Metz J. A high prevalence of biochemical evidence of vitamin B12 or folate deficiency does not translate into a comparable prevalence of anemia. Food Nutr Bull. 2008;29(2 Suppl):S74–85.CrossRefPubMed Metz J. A high prevalence of biochemical evidence of vitamin B12 or folate deficiency does not translate into a comparable prevalence of anemia. Food Nutr Bull. 2008;29(2 Suppl):S74–85.CrossRefPubMed
35.
go back to reference Klee GG. Cobalamin and folate evaluation: measurement of methylmalonic acid and homocysteine vs vitamin B(12) and folate. Clin Chem. 2000;46(8 Pt 2):1277–83.PubMed Klee GG. Cobalamin and folate evaluation: measurement of methylmalonic acid and homocysteine vs vitamin B(12) and folate. Clin Chem. 2000;46(8 Pt 2):1277–83.PubMed
36.
go back to reference Bradley-Moore AM, Greenwood BM, Bradley AK, Akintunde A, Attai ED, Fleming AF, Flynn FV, Kirkwood BR, Gilles HM. Malaria chemoprophylaxis with chloroquine in young Nigerian children. IV. Its effect on haematological measurements. Ann Trop Med Parasitol. 1985;79(6):585–95.CrossRefPubMed Bradley-Moore AM, Greenwood BM, Bradley AK, Akintunde A, Attai ED, Fleming AF, Flynn FV, Kirkwood BR, Gilles HM. Malaria chemoprophylaxis with chloroquine in young Nigerian children. IV. Its effect on haematological measurements. Ann Trop Med Parasitol. 1985;79(6):585–95.CrossRefPubMed
37.
go back to reference Ellaurie M, Burns ER, Rubinstein A. Hematologic manifestations in pediatric HIV infection: severe anemia as a prognostic factor. Am J Pediatr Hematol Oncol. 1990;12(4):449–53.CrossRefPubMed Ellaurie M, Burns ER, Rubinstein A. Hematologic manifestations in pediatric HIV infection: severe anemia as a prognostic factor. Am J Pediatr Hematol Oncol. 1990;12(4):449–53.CrossRefPubMed
39.
go back to reference Koduri PR. Parvovirus B19-related anemia in HIV-infected patients. AIDS Patient Care STDs. 2000;14(1):7–11.CrossRefPubMed Koduri PR. Parvovirus B19-related anemia in HIV-infected patients. AIDS Patient Care STDs. 2000;14(1):7–11.CrossRefPubMed
40.
go back to reference Moormann AM, Chelimo K, Sumba OP, Lutzke ML, Ploutz-Snyder R, Newton D, Kazura J, Rochford R. Exposure to holoendemic malaria results in elevated Epstein-Barr virus loads in children. J Infect Dis. 2005;191(8):1233–8. Epub 2005 Mar 1239.CrossRefPubMed Moormann AM, Chelimo K, Sumba OP, Lutzke ML, Ploutz-Snyder R, Newton D, Kazura J, Rochford R. Exposure to holoendemic malaria results in elevated Epstein-Barr virus loads in children. J Infect Dis. 2005;191(8):1233–8. Epub 2005 Mar 1239.CrossRefPubMed
41.
go back to reference Kung’u JK, Goodman D, Haji HJ, Ramsan M, Wright VJ, Bickle QD, Tielsch JM, Raynes JG, Stoltzfus RJ. Early helminth infections are inversely related to anemia, malnutrition, and malaria and are not associated with inflammation in 6- to 23-month-old Zanzibari children. Am J Trop Med Hyg. 2009;81(6):1062–70. doi:10.4269/ajtmh.2009.1009-0091.CrossRefPubMed Kung’u JK, Goodman D, Haji HJ, Ramsan M, Wright VJ, Bickle QD, Tielsch JM, Raynes JG, Stoltzfus RJ. Early helminth infections are inversely related to anemia, malnutrition, and malaria and are not associated with inflammation in 6- to 23-month-old Zanzibari children. Am J Trop Med Hyg. 2009;81(6):1062–70. doi:10.​4269/​ajtmh.​2009.​1009-0091.CrossRefPubMed
42.
go back to reference Kahigwa E, Schellenberg D, Sanz S, Aponte JJ, Wigayi J, Mshinda H, Alonso P, Menendez C. Risk factors for presentation to hospital with severe anaemia in Tanzanian children: a case–control study. Trop Med Int Health. 2002;7(10):823–30.CrossRefPubMed Kahigwa E, Schellenberg D, Sanz S, Aponte JJ, Wigayi J, Mshinda H, Alonso P, Menendez C. Risk factors for presentation to hospital with severe anaemia in Tanzanian children: a case–control study. Trop Med Int Health. 2002;7(10):823–30.CrossRefPubMed
44.
46.
go back to reference WHO. Conclusions and recommendations of the WHO Consultation on prevention and control of iron deficiency in infants and young children in malaria-endemic areas. Food Nutr Bull. 2007;28(4 Suppl):S621–7. WHO. Conclusions and recommendations of the WHO Consultation on prevention and control of iron deficiency in infants and young children in malaria-endemic areas. Food Nutr Bull. 2007;28(4 Suppl):S621–7.
Metadata
Title
Anaemia in hospitalised preschool children from a rural area in Mozambique: a case control study in search for aetiological agents
Authors
Cinta Moraleda
Ruth Aguilar
Llorenç Quintó
Tacilta Nhampossa
Montserrat Renom
Augusto Nhabomba
Sozinho Acácio
John J. Aponte
Delino Nhalungo
Ariel H. Achtman
Louis Schofield
Helder Martins
Eusebio Macete
Pedro L. Alonso
Clara Menéndez
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2017
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-017-0816-x

Other articles of this Issue 1/2017

BMC Pediatrics 1/2017 Go to the issue