INFLUENCE OF SICKLE CELL GENE ON THE ALLELIC DIVERSITY AT THE MSP-1 LOCUS OF PLASMODIUM FALCIPARUM IN ADULT PATIENTS WITH SEVERE MALARIA
Main Article Content
Keywords
Sickle Gene, Malaria, msp-1, Plasmodium falciparum, Severe, Adult
Abstract
Although several studies have supported that sickle cell trait (HbAS) protects against falciparum malaria, the exact mechanism by which sickle gene confers protection is unclear. Further, there is no information on the influence of sickle gene on parasitic diversity of P. falciparum population in severe symptomatic malaria. This study was undertaken to assess the effect of the sickle gene on the parasite densities and diversities in hospitalized adult patients with severe falciparum malaria. The study was carried out in 166 adult hospitalized subjects with severe falciparum malaria at Sickle Cell Clinic and Molecular Biology Laboratory, Veer Surendra Sai Institute of Medical Sciences and Research, Burla, Odisha, India . They were divided into three groups on the basis of hemoglobin variants HbAA (n=104), HbAS (n=30) and HbSS (n=32). The msp-1 loci was genotyped using a PCR based methodology. The parasite densities were significantly high in HbAA compared to HbAS and HbSS. The multiplicity of infection (MOI) and multiclonicity for msp-1 were significantly low in HbSS and HbAS compared to HbAA. The prevalence of K1 (p<0 .0001) and MAD20 (p=0.0003) alleles were significantly high in HbAA. The RO33 allele was detected at a higher frequency in HbSS and HbAS, compared to K1 and MAD20. Sickle gene was found to reduce both the parasite densities and diversity of P. falciparum in adults with severe malaria.
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References
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26. Stirnadel, H.A., Stockle, M., Felger, I., et al., Malaria infection and morbidity in infants in relation to genetic polymorphisms in Tanzania. Trop Med Int Health. 1999;4(3):187-193.
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29. Williams, T.N., Mwangi, T.W., Wambua, S., et al., Sickle Cell Trait and the Risk of Plasmodium falciparum Malaria and Other Childhood Diseases. The Journal of Infectious Diseases. 2005;192:178-86.
30. Achidi, E.A., Salimonu, L.S., Asuzu, M.C., Berzins, K., Walker, O. Studies on Plasmodium falciparum parasitemia and development of anemia in Nigerian infants during their first year of life. Am J Trop Med Hyg. 1996 Aug;55(2):138-43.
31. Ntoumi, F., Rogier, C., Dieye, A., et al., Imbalanced distribution of Plasmodium falciparum MSP-1 genotypes related to sickle-cell trait. Mol Med. 1997;3:581-592.
32. Ntoumi, F., Mercereau-Puijalon, O., Ossari, S., et al., Plasmodium falciparum: sickle-cell trait is associated with higher prevalence of multiple infections in Gabonese children with asymptomatic infections. Exp Parasitol.1997; 87:39-46.
33. Amodu, O.K., Olaniyan, S.A., Adeyemo, A.A., et al., Association of the sickle cell trait and the ABO blood group with clinical severity of malaria in southwest Nigeria. Acta Tropica. 2012; 123:72- 77.
34. Aidoo, M., Terlouw, D.J., Kolczak, M.S., et al., Protective effects of the sickle cell gene against malaria morbidity and mortality. Lancet. 2002;359(9314):1311-2.
35. Komba, A.N., Makani, J., Sadarangani, M., et al., Malaria as a cause of morbidity and mortality in children with homozygous sickle cell disease on the coast of Kenya. Clin Infect Dis. 2009;49(2):216- 222.
36. Mockenhaupt, F.P., Ehrhardt, S., Otchwemah, R., et al., Limited influence of haemoglobin variants on Plasmodium falciparum msp1 and msp2 alleles in symptomatic malaria. Trans R Soc Trop Med Hyg. 2004;98:302-310.
37. Mayor, A., Serra-Casas, E., Rovira-Vallbona, E., et al., Immunoglobulins against the surface of Plasmodium falciparum-infected erythrocytes increase one month after delivery. Malar J. 2012;11:130.
38. Greenwood, B., Marsh, K., Snow, R. Why Do Some African Children Develop Severe Malaria? Parasitology Today. 1991;7(10):277-281.
39. Amodu, O.K., Adeyemo, A.A., Ayoola, O.O., et al., Genetic diversity of the msp-1 locus and symptomatic malaria in south-west Nigeria. Acta Trop. 2005 Sep;95(3):226-32.
40. de Roode, J.C., Helinski, M.E., Anwar, M.A., Read, A.F. Virulence and competitive ability in genetically diverse malaria infections. Proc Natl Acad Sci U S A. 2005; 102(21):7624-7628.
41. Balmer, O., Tanner, M. Prevalence and implications of multiple-strain infections. Lancet Infect Dis. 2011;11: 868-78.
42. Robert, F., Ntoumi, F., Angel, G., et al., Extensive genetic diversity of Plasmodium falciparum isolates collected from patients with severe malaria in Dakar, Senegal. Trans R Soc Trop Med Hyg. 1996 Nov-Dec;90(6):704-11.
43. Ranjit, M.R., Das, A., Das, B.P., et al., Distribution of Plasmodium falciparum genotypes in clinically mild and severe malaria cases in Orissa, India. Trans R Soc Trop Med Hyg. 2005; 99(5): 389-95.
44. Konate, L., Zwetyenga, J., Rogier, C., et al., Variation of Plasmodium falciparum msp1 block 2 and msp2 allele prevalence and of infection complexity in two neighbouring Senegalese villages with different transmission conditions. Trans R Soc Trop Med Hyg. 1999; 93(Suppl 1):21-28.
45. Vafa, M., Troye-Blomberg, M., Ancgang, J., et al., Multiplicity of Plasmodium falciparum in asymptomatic children in Senegal: relation to transmission, age and erythrocyte variants. Malaria J. 2008;7:17.
46. Koussounda, F.K., Malonga, V., Mayengue, P.I., et al., Genetic polymorphism of merozoit surface protein 2 and prevalence of K76T pfcrt mutation in Plasmodium falciparum field isolates from Congolese children with asymptomatic infections. Malaria J. 2012;11:105.
47. Kwiatkowski, D. Cytokines and anti-disease immunity to malaria. Res Immunol. 1991;142(8): 707-712.
48. Felger, I., Irion, A., Steiger, S., Beck, H.P. Genotypes of merozoite surface protein 2 of Plasmodium falciparum in Tanzania. Trans R Soc Trop Med Hyg. 1999;93 Suppl 1:3-9.
49. Kiwuwa, M.S., Ribacke, U., Moll, K., et al., Genetic diversity of Plasmodium falciparum infections in mild and severe malaria of children from Kampala, Uganda. Parasitol Res. 2013;112:1691-1700.
2. Murray, C.J.L., Rosenfeld, L.C., Lim, S.S., et al., Global malaria mortality between 1980 and 2010: a systematic analysis. Lancet .2012; 379: 413–31.
3. Pierce, S.K., Miller, L.H. World Malaria Day 2009. What malaria knows about the immune system that immunologists still do not? The Journal of Immunolog. 2009;182: 5171-5177.
4. Holder, A.A., Patino, J.A.G., Uthaipibull, C., et al., Merozoite surface protein 1, immune evasion, and vaccines against asexual blood stage malaria. Parassitologia. 1999; 41: 409-414.
5. Kiwanuka, G.N. Genetic diversity in Plasmodium falciparum merozoite surface protein 1 and 2 coding genes and its implications in malaria epidemiology: a review of published studies from 1997-2007. J Vector Borne Dis. 2009; 46:1-12.
6. Olasehinde, G.I., Yah, C.S., Singh, R., et al., Genetic diversity of Plasmodium falciparum field isolates from south western Nigeria. African Health Sciences. 2012; 12(3): 355-361.
7. Evans, A.G., Wellems, T.E. Co-evolutionary genetics of Plasmodium malaria parasites and their human hosts. Integ and Comp Biol. 2002; 42:401-407.
8. Williams, T.N., Mwangi, T.W., Wambua, S., et al., Negative epistasis between the malaria protective effects of ?-thalassemia and the sickle cell trait. Nat Genet. 2005;37:1253-1257.
9. May, J., Evans, J.A., Timmann, C., et al., Hemoglobin variants and disease manifestations in severe falciparum malaria. JAMA. 2007;297(20):2020-26.
10. Weatherall, D.J., Clegg, J.B. Inherited haemoglobin disorders: an increasing global health problem. Bulletin of the World Health Organization. 2001;79: 704-712.
11. Piel, F.B., Hay, S.I., Gupta, S., Weatherall, D.J., Williams, T.N. Global Burden of Sickle Cell Anaemia in Children under Five, 2010–2050: Modelling based on demographics, excess mortality, and interventions. PLoS Med. 2013; 10(7): e1001484.
12. Purohit, P., Mashon, R.S., Patel, S., et al., Clinical and molecular characterization of Hb Hofu in eastern India. Int Jnl Lab Hem. 2014;36:71-76.
13. Patel, D.K. Clinical aspects of sickle cell disease in India. 5th Brazilian Symposium for Sickle cell disease and other hemoglobinopathies. Belo Horizonte, Brazil; 2009. http://www.cehmob.org.br/simposio/html/english/download.html
14. Kwiatkowski, D.P. How malaria has affected the human genome and what human genetics can teach us about malaria. Am J Hum Genet. 2005;77:171-192.
15. Purohit, P., Dehury, S., Patel, S., Patel, D.K., Prevalence of Deletional Alpha Thalassemia and Sickle Gene in a Tribal Dominated Malaria Endemic Area of Eastern India. ISRN Hematology. 2014 (2014), ID 745245.
16. Epidemiological Report up to the month of September 2012-2013”, Directorate of National Vector Borne Disease Control Programme (NVBDCP), India. http://nvbdcp.gov.in/Doc/mal-MES-Sept13.pdf.
17. Pradhan, M.M. Malaria: Bringing down the burden in Odisha. MMV Stakeholders’ Meeting, Delhi (India), 8th November 2012. http://www.mmv.org/sites/default/files/uploads/docs/events/2012/Stakeholder_meeting_presentations/Pradhan_Odisha.pdf
18. World Health Organization, 2000. Severe falciparum malaria. Trans R Soc Trop Med Hyg. 94(Suppl 1,S1-90).
19. Panda, A.K., Panda, S.K., Sahu, A.N., et al., Association of ABO blood group with severe falciparum malaria in adults: case control study and meta-analysis. Malar J. 2011;10: 309.
20. Old, J.M., Varawalla, N.Y., Weatherall, D.J. The rapid detection and prenatal diagnosis of b thalassaemia in the Asian Indian and Cypriot populations in the UK. Lancet. 1990;336:834.
21. Patsoula, E., Spanakos, G., Sofianatou, D., et al., A single-step, PCR-based method for the detection and differentiation of Plasmodium vivax and P. falciparum. Ann Trop Med Parasitol. 2003;97:15-21.
22. Zwetyenga, J., Rogier, C., Tall, A., et al., No influence of age in infection complexity and allelic distribution in Plasmodium falciparum infections in Ndiop, a Senegalese village with seasonal, mesoendemic malaria. Am J Trop Med Hyg. 1998;59:726-735.
23. Joshi, H., Valecha, N., Verma, A., et al., Genetic structure of Plasmodium falciparum field isolates in eastern and northeastern India. Malaria J. 2007;6:60.
24. Ariey, F., Hommel, D., Scanf, C.L., et al., Association of Severe Malaria with a Specific Plasmodium falciparum Genotype in French Guiana. The Journal of Infectious Diseases. 2001;184:237-41.
25. Kun, J.F., Schmidt-Ott, R.J., Lehman, L.G., et al,. Merozoite surface antigen 1 and 2 genotypes and rosetting of Plasmodium falciparum in severe and mild malaria in Lambarene, Gabon. Trans R Soc Trop Med Hyg. 1998 Jan-Feb;92(1):110-4.
26. Stirnadel, H.A., Stockle, M., Felger, I., et al., Malaria infection and morbidity in infants in relation to genetic polymorphisms in Tanzania. Trop Med Int Health. 1999;4(3):187-193.
27. Branch, O.H., Takala, S., Kariuki, S., et al., Plasmodium falciparum Genotypes, Low Complexity of Infection, and Resistance to Subsequent Malaria in Participants in the Asembo Bay Cohort Project. Infection and Immunity. 2001;69(12):7783-7792.
28. Kiwanuka, G.N., Joshi, H., Isharaza, W.K., Eschrich, K. Dynamics of Plasmodium falciparum alleles in children with normal haemoglobin and with sickle cell trait in western Uganda. Trans R Soc Trop Med Hyg. 2009;103:87-94.
29. Williams, T.N., Mwangi, T.W., Wambua, S., et al., Sickle Cell Trait and the Risk of Plasmodium falciparum Malaria and Other Childhood Diseases. The Journal of Infectious Diseases. 2005;192:178-86.
30. Achidi, E.A., Salimonu, L.S., Asuzu, M.C., Berzins, K., Walker, O. Studies on Plasmodium falciparum parasitemia and development of anemia in Nigerian infants during their first year of life. Am J Trop Med Hyg. 1996 Aug;55(2):138-43.
31. Ntoumi, F., Rogier, C., Dieye, A., et al., Imbalanced distribution of Plasmodium falciparum MSP-1 genotypes related to sickle-cell trait. Mol Med. 1997;3:581-592.
32. Ntoumi, F., Mercereau-Puijalon, O., Ossari, S., et al., Plasmodium falciparum: sickle-cell trait is associated with higher prevalence of multiple infections in Gabonese children with asymptomatic infections. Exp Parasitol.1997; 87:39-46.
33. Amodu, O.K., Olaniyan, S.A., Adeyemo, A.A., et al., Association of the sickle cell trait and the ABO blood group with clinical severity of malaria in southwest Nigeria. Acta Tropica. 2012; 123:72- 77.
34. Aidoo, M., Terlouw, D.J., Kolczak, M.S., et al., Protective effects of the sickle cell gene against malaria morbidity and mortality. Lancet. 2002;359(9314):1311-2.
35. Komba, A.N., Makani, J., Sadarangani, M., et al., Malaria as a cause of morbidity and mortality in children with homozygous sickle cell disease on the coast of Kenya. Clin Infect Dis. 2009;49(2):216- 222.
36. Mockenhaupt, F.P., Ehrhardt, S., Otchwemah, R., et al., Limited influence of haemoglobin variants on Plasmodium falciparum msp1 and msp2 alleles in symptomatic malaria. Trans R Soc Trop Med Hyg. 2004;98:302-310.
37. Mayor, A., Serra-Casas, E., Rovira-Vallbona, E., et al., Immunoglobulins against the surface of Plasmodium falciparum-infected erythrocytes increase one month after delivery. Malar J. 2012;11:130.
38. Greenwood, B., Marsh, K., Snow, R. Why Do Some African Children Develop Severe Malaria? Parasitology Today. 1991;7(10):277-281.
39. Amodu, O.K., Adeyemo, A.A., Ayoola, O.O., et al., Genetic diversity of the msp-1 locus and symptomatic malaria in south-west Nigeria. Acta Trop. 2005 Sep;95(3):226-32.
40. de Roode, J.C., Helinski, M.E., Anwar, M.A., Read, A.F. Virulence and competitive ability in genetically diverse malaria infections. Proc Natl Acad Sci U S A. 2005; 102(21):7624-7628.
41. Balmer, O., Tanner, M. Prevalence and implications of multiple-strain infections. Lancet Infect Dis. 2011;11: 868-78.
42. Robert, F., Ntoumi, F., Angel, G., et al., Extensive genetic diversity of Plasmodium falciparum isolates collected from patients with severe malaria in Dakar, Senegal. Trans R Soc Trop Med Hyg. 1996 Nov-Dec;90(6):704-11.
43. Ranjit, M.R., Das, A., Das, B.P., et al., Distribution of Plasmodium falciparum genotypes in clinically mild and severe malaria cases in Orissa, India. Trans R Soc Trop Med Hyg. 2005; 99(5): 389-95.
44. Konate, L., Zwetyenga, J., Rogier, C., et al., Variation of Plasmodium falciparum msp1 block 2 and msp2 allele prevalence and of infection complexity in two neighbouring Senegalese villages with different transmission conditions. Trans R Soc Trop Med Hyg. 1999; 93(Suppl 1):21-28.
45. Vafa, M., Troye-Blomberg, M., Ancgang, J., et al., Multiplicity of Plasmodium falciparum in asymptomatic children in Senegal: relation to transmission, age and erythrocyte variants. Malaria J. 2008;7:17.
46. Koussounda, F.K., Malonga, V., Mayengue, P.I., et al., Genetic polymorphism of merozoit surface protein 2 and prevalence of K76T pfcrt mutation in Plasmodium falciparum field isolates from Congolese children with asymptomatic infections. Malaria J. 2012;11:105.
47. Kwiatkowski, D. Cytokines and anti-disease immunity to malaria. Res Immunol. 1991;142(8): 707-712.
48. Felger, I., Irion, A., Steiger, S., Beck, H.P. Genotypes of merozoite surface protein 2 of Plasmodium falciparum in Tanzania. Trans R Soc Trop Med Hyg. 1999;93 Suppl 1:3-9.
49. Kiwuwa, M.S., Ribacke, U., Moll, K., et al., Genetic diversity of Plasmodium falciparum infections in mild and severe malaria of children from Kampala, Uganda. Parasitol Res. 2013;112:1691-1700.