Several factors influence the severity of Plasmodium falciparum; here, we investigate the impact of alpha+-thalassaemia genotype on P. falciparum parasitemia and prevalence of severe anaemia amongst microcytic children from Kumasi, Ghana.

Methods

Seven hundred and thirty-two children (≤10 years) with P. falciparum were categorised into normocytic and microcytic (mean cell volume ≤76 fL). Microcytic individuals were genotyped for the −α^3.7deletional thalassaemia mutation and parasite densities determined.

Results

Amongst microcytic patients both parasite densities and prevalence of severe malaria parasitemia (≥100 000/μL) were significantly lower (P < 0.001) in the presence of an alpha+-thalassaemia genotype compared with non-alpha+-thalassaemia genotype. There was no evidence that alpha+-thalassaemia protected against severe anaemia. The protection conferred by alpha-thalassaemia genotype against severe P. falciparum parasitemia did not change with increasing age.

Conclusion

The severity of P. falciparum parasitemia was significantly lower in both the homozygous and heterozygous alpha+-thalassaemia groups compared with microcytic individuals with non-alpha+-thalassaemia genotype. The protective effect, from severe malaria, of the alpha+-thalassaemia allele does not alter with age.

References

1 World Malaria Report 2012, WHO. 2012; Available at:http://www.who.int/malaria/publications/world_malaria_report_2012/report/en/index.html.
Google Scholar
2Klinkenberg E, McCall PJ, Wilson MD, Akoto AO, Amerasinghe FP, Bates I, Bates I, Verhoeff FH, Barnish G, Donnelly MJ Urban malaria and anaemia in children: a cross-sectional survey in two cities of Ghana. Trop Med Int Health 2006; 11: 578–88.
10.1111/j.1365-3156.2006.01609.x
CAS PubMed Web of Science® Google Scholar
3 Ministry of Health. National Guidelines for Laboratory Diagnosis of Malaria. Ghana: Ministry of Health; 2010.
Google Scholar
4Weatherall DJ. Genetic variation and susceptibility to infection: the red cell and malaria. Br J Haematol 2008; 141: 276–86.
10.1111/j.1365-2141.2008.07085.x
CAS PubMed Web of Science® Google Scholar
5Kattamis AC, Camaschella C, Sivera P, Surrey S, Fortina P. Human alpha-thalassemia syndromes: detection of molecular defects. Am J Hematol 1996; 53: 81–91.
10.1002/(SICI)1096-8652(199610)53:2<81::AID-AJH5>3.0.CO;2-#
CAS PubMed Web of Science® Google Scholar
6Mockenhaupt FP, Ehrhardt S, Gellert S, Otchwemah RN, Dietz E, Anemana SD, Bienzle U Alpha(+)-thalassemia protects African children from severe malaria. Blood 2004; 104: 2003–6.
10.1182/blood-2003-11-4090
CAS PubMed Web of Science® Google Scholar
7Fowkes FJ, Allen SJ, Allen A, Alpers MP, Weatherall DJ, Day KP. Increased microerythrocyte count in homozygous alpha(+)-thalassaemia contributes to protection against severe malarial anaemia. PLoS Med 2008; 5: e56.
10.1371/journal.pmed.0050056
CAS PubMed Web of Science® Google Scholar
8May J, Evans JA, Timmann C, Ehmen C, Busch W, Thye T, Agbenyega T, Horstmann RD. Hemoglobin variants and disease manifestations in severe falciparum malaria. JAMA 2007; 297: 2220–6.
10.1001/jama.297.20.2220
CAS PubMed Web of Science® Google Scholar
9Wambua S, Mwangi TW, Kortok M, Uyoga SM, Macharia AW, Mwacharo JK, Weatherall DJ, Snow RW, Marsh K, Williams TN. The effect of alpha+-thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya. PLoS Med 2006; 3: e158.
10.1371/journal.pmed.0030158
PubMed Web of Science® Google Scholar
10Allen SJ, O'Donnell A, Alexander ND, Alpers MP, Peto TE, Clegg JB, Weatherall DJ. alpha+-Thalassemia protects children against disease caused by other infections as well as malaria. Proc Natl Acad Sci USA 1997; 94: 14736–41.
10.1073/pnas.94.26.14736
CAS PubMed Web of Science® Google Scholar
11Williams TN, Wambua S, Uyoga S, Macharia A, Mwacharo JK, Newton CR, Maitland K. Both heterozygous and homozygous alpha+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya. Blood 2005b; 106: 368–71.
10.1182/blood-2005-01-0313
CAS PubMed Web of Science® Google Scholar
12Mockenhaupt FP, Bienzle U, May J, Falusi AG, Ademowo OG, Olumese PE, Meyer CG. Plasmodium falciparum infection: influence on hemoglobin levels in alpha-thalassemia and microcytosis. J Infect Dis 1999a; 180: 925–8.
10.1086/314959
CAS PubMed Web of Science® Google Scholar
13Mockenhaupt FP, Falusi AG, May J, Ademowo OG, Olumese PE, Meyer CG, Bienzle U. The contribution of alpha+-thalassaemia to anaemia in a Nigerian population exposed to intense malaria transmission. Trop Med Int Health 1999b; 4: 302–7.
10.1046/j.1365-3156.1999.00386.x
CAS PubMed Web of Science® Google Scholar
14Enevold A, Lusingu JP, Mmbando B, Alifrangis M, Lemnge MM, Bygbjerg IC, Theander TGVestergaard LS. Reduced risk of uncomplicated malaria episodes in children with alpha+-thalassemia in northeastern Tanzania. Am J Trop Med Hyg 2008; 78: 714–20.
PubMed Web of Science® Google Scholar
15Williams TN, Maitland K, Bennett S, Ganczakowski M, Peto TE, Newbold CI, Bowden DK,Weatherall DJ,Clegg JB, High incidence of malaria in alpha-thalassaemic children. Nature 1996; 383: 522–5.
10.1038/383522a0
CAS PubMed Web of Science® Google Scholar
16 WHO. Malaria Microscopy Quality Assurance Manual - version 1. 2009; Available from: http://www.who.int/malaria/publications/atoz/mmicroscopy_qam/en/ (3 May 2013).
Google Scholar
17Kohn J. Separation of haemoglobins on cellulose acetate. J Clin Pathol 1969; 22: 109–11.
10.1136/jcp.22.1.109
CAS PubMed Web of Science® Google Scholar
18Brewer GJ, Tarlov AR, Alving AS. The methemoglobin reduction test for primaquine-type sensitivity of erythrocytes. A simplified procedure for detecting a specific hypersusceptibility to drug hemolysis. JAMA 1962; 180: 386–8.
10.1001/jama.1962.03050180032008
CAS PubMed Web of Science® Google Scholar
19Wonke B, Modell M, Marlow T, Khan M, Modell B. Microcytosis, iron deficiency and thalassaemia in a multi-ethnic community: a pilot study. Scand J Clin Lab Invest 2007; 67: 87–95.
10.1080/00365510601046474
CAS PubMed Web of Science® Google Scholar
20Chong SS, Boehm CD, Higgs DR, Cutting GR. Single-tube multiplex-PCR screen for common deletional determinants of alpha-thalassemia. Blood 2000; 95: 360–2.
10.1182/blood.V95.1.360
CAS PubMed Web of Science® Google Scholar
21Donnelly MJ, McCall PJ, Lengeler C, Bates I, D'Alessandro U, Barnish G, Konradsen F, Klinkenberg E, Townson H, Trape JF, Hastings IM, Mutero C. Malaria and urbanization in sub-Saharan Africa. Malar J 2005; 4: 12.
10.1186/1475-2875-4-12
PubMed Web of Science® Google Scholar
22Asante FA, Asenso-Okyere K. Economic Burden of Malaria in Ghana. 2003. WHO Report 2003: 6–7
Google Scholar
23Ronald LA, Kenny SL, Klinkenberg E, Akoto AO, Boakye I, Barnish G, Donnelly MJ. Malaria and anaemia among children in two communities of Kumasi, Ghana: a cross-sectional survey. Malar J 2006; 5: 105.
10.1186/1475-2875-5-105
PubMed Web of Science® Google Scholar
24Borges E, Wenning MR, Kimura EM, Gervasio SA, Costa FF, Sonati MF. High prevalence of alpha-thalassemia among individuals with microcytosis and hypochromia without anemia. Braz J Med Biol Res 2001; 34: 759–62.
10.1590/S0100-879X2001000600009
CAS PubMed Web of Science® Google Scholar
25Mockenhaupt FP, Rong B, Till H, Thompson WN, Bienzle U. Short report: increased susceptibility to Plasmodium malariae in pregnant alpha(+)-thalassemic women. Am J Trop Med Hyg 2001; 64: 6–8.
10.4269/ajtmh.2001.64.6
CAS PubMed Google Scholar
26Rahim F. Genotyping of thalassemia in microcytic hypochromic anemia patients from SouthWest Region of Iran. Pakistan J Med Sci 2008; 24: 23–8.
Web of Science® Google Scholar
27Williams TN, Mwangi TW, Wambua S, Peto TE, Weatherall DJ, Gupta S, Recker M, Penman BS, Uyoga S, Macharia A, Mwacharo JK, Snow RW, Marsh K. Negative epistasis between the malaria-protective effects of alpha+-thalassemia and the sickle cell trait. Nat Genet 2005a; 37: 1253–7.
10.1038/ng1660
CAS PubMed Web of Science® Google Scholar
28Kreuels B, Kreuzberg C, Kobbe R, Ayim-Akonor M, Apiah-Thompson P, Thompson B, Ehmen C, Adjei S, Langefeld I, Adjei O, May J. Differing effects of HbS and HbC traits on uncomplicated falciparum malaria, anemia, and child growth. Blood 2010; 115: 4551–8.
10.1182/blood-2009-09-241844
CAS PubMed Web of Science® Google Scholar
29 WHO. 59th World Health Assembly Guidelines for the Treatment of Malaria A59/9. WHO; 2006: 8–9. Available at: https://apps.who.int/gb/ebwha/pdf_files/WHA59/A59_9-en.pdf
Google Scholar
30Nyakeriga AM, Troye-Blomberg M, Mwacharo JK, Wambua S, Williams TN. Nutritional iron status in children with alpha+ thalassemia and the sickle cell trait in a malaria endemic area on the coast of Kenya. Haematologica 2005; 90: 552–4.
CAS PubMed Web of Science® Google Scholar
31Pattanapanyasat K, Yongvanitchit K, Tongtawe P, Tachavanich K, Wanachiwanawin W, Fucharoen S, Walsh DS. Impairment of Plasmodium falciparum growth in thalassemic red blood cells: further evidence by using biotin labeling and flow cytometry. Blood 1999; 93: 3116–9.
10.1182/blood.V93.9.3116
CAS PubMed Web of Science® Google Scholar

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Volume36, Issue1

February 2014

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An investigation of the protective effect of alpha+-thalassaemia against severe Plasmodium falciparum amongst children in Kumasi, Ghana

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An investigation of the protective effect of alpha+-thalassaemia against severe Plasmodium falciparum amongst children in Kumasi, Ghana

Summary

Introduction

Methods

Results

Conclusion

References

Citing Literature

References

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