Genetically Diverse Plasmodium Falciparum Infections, Within-host Competition and Symptomatic Malaria in Humans

Overview

Journal Sci Rep

Specialty Science

Date 2019 Jan 16

PMID 30644435

Citations 29

Authors

Paul Sondo

Karim Derra

Thierry Lefevre

Seydou Diallo-Nakanabo

Zekiba Tarnagda

Odile Zampa

Adama Kazienga

Innocent Valea

Hermann Sorgho

Jean-Bosco Ouedraogo

Tinga Robert Guiguemde

Halidou Tinto

Affiliations

Soon will be listed here.

Abstract

There is a large genetic diversity of Plasmodium falciparum strains that infect people causing diverse malaria symptoms. This study was carried out to explore the effect of mixed-strain infections and the extent to which some specific P. falciparum variants are associated with particular malaria symptoms. P. falciparum isolates collected during pharmacovigilance study in Nanoro, Burkina Faso were used to determine allelic variation in two polymorphic antigens of the merozoite surface (msp1 and msp2). Overall, parasite density did not increase with additional strains, suggesting the existence of within-host competition. Parasite density was influenced by msp1 allelic families with highest parasitaemia observed in MAD20 allelic family. However, when in mixed infections with allelic family K1, MAD20 could not grow to the same levels as it would alone, suggesting competitive suppression in these mixed infections. Host age was associated with parasite density. Overall, older patients exhibited lower parasite densities than younger patients, but this effect varied with the genetic composition of the isolates for the msp1 gene. There was no effect of msp1 and msp2 allelic family variation on body temperature. Haemoglobin level was influenced by msp2 family with patients harboring the FC27 allele showing lower haemoglobin level than mono-infected individuals by the 3D7 allele. This study provides evidence that P. falciparum genetic diversity influenced the severity of particular malaria symptoms and supports the existence of within-host competition in genetically diverse P. falciparum.

Citing Articles

Assessing fitness costs in malaria parasites: a comprehensive review and implications for drug resistance management.

Segovia X, Srivastava B, Serrato-Arroyo S, Guerrero A, Huijben S Malar J. 2025; 24(1):65.

PMID: 40025552 PMC: 11871665. DOI: 10.1186/s12936-025-05286-w.

Plasmodium falciparum merozoite surface protein 2 genetic polymorphism and multiplicity of infection in selected malarious areas of Northwest Ethiopia.

Ashagre A, Deressa J, Mekonnen D, Abdu M, Eshetu T, Keffale M BMC Infect Dis. 2025; 25(1):282.

PMID: 40011796 PMC: 11866721. DOI: 10.1186/s12879-025-10676-1.

Malaria: Factors affecting disease severity, immune evasion mechanisms, and reversal of immune inhibition to enhance vaccine efficacy.

Su X, Xu F, Stadler R, Teklemichael A, Wu J PLoS Pathog. 2025; 21(1):e1012853.

PMID: 39847577 PMC: 11756774. DOI: 10.1371/journal.ppat.1012853.

Plasmodium falciparum genetic diversity and multiplicity of infection among asymptomatic and symptomatic malaria-infected individuals in Uganda.

Mwesigwa A, Ocan M, Cummings B, Musinguzi B, Kiyaga S, Kiwuwa S Trop Med Health. 2024; 52(1):86.

PMID: 39543779 PMC: 11562702. DOI: 10.1186/s41182-024-00656-7.

Genomic malaria surveillance of antenatal care users detects reduced transmission following elimination interventions in Mozambique.

Brokhattingen N, Matambisso G, Da Silva C, Vickers E, Pujol A, Mbeve H Nat Commun. 2024; 15(1):2402.

PMID: 38493162 PMC: 10944499. DOI: 10.1038/s41467-024-46535-x.

References

Mackinnon M, Read A . Selection for high and low virulence in the malaria parasite Plasmodium chabaudi. Proc Biol Sci. 1999; 266(1420):741-8. PMC: 1689830. DOI: 10.1098/rspb.1999.0699. View

Lord C, Barnard B, Day K, Hargrove J, McNamara J, Paul R . Aggregation and distribution of strains in microparasites. Philos Trans R Soc Lond B Biol Sci. 1999; 354(1384):799-807. PMC: 1692560. DOI: 10.1098/rstb.1999.0432. View

Smith T, Felger I, Tanner M, Beck H . Premunition in Plasmodium falciparum infection: insights from the epidemiology of multiple infections. Trans R Soc Trop Med Hyg. 1999; 93 Suppl 1:59-64. DOI: 10.1016/s0035-9203(99)90329-2. View

Tanabe K, Sakihama N, Kaneko O, Saito-Ito A, Kimura M . A PCR method for molecular epidemiology of Plasmodium falciparum Msp-1. Tokai J Exp Clin Med. 2000; 23(6):375-81. View

Bruce M, Donnelly C, Alpers M, Galinski M, Barnwell J, Walliker D . Cross-species interactions between malaria parasites in humans. Science. 2000; 287(5454):845-8. DOI: 10.1126/science.287.5454.845. View

Read A, Taylor L . The ecology of genetically diverse infections. Science. 2001; 292(5519):1099-102. DOI: 10.1126/science.1059410. View

Ariey F, Hommel D, Le Scanf C, Duchemin J, Peneau C, Hulin A . Association of severe malaria with a specific Plasmodium falciparum genotype in French Guiana. J Infect Dis. 2001; 184(2):237-41. DOI: 10.1086/322012. View

Mackinnon M, Sowa M, Koram K, Nkrumah F, Osei Y, Hill W . Novel Plasmodium falciparum clones and rising clone multiplicities are associated with the increase in malaria morbidity in Ghanaian children during the transition into the high transmission season. Parasitology. 2001; 123(Pt 2):113-23. DOI: 10.1017/s0031182001008162. View

Peyerl-Hoffmann G, Jelinek T, Kilian A, Kabagambe G, Metzger W, von Sonnenburg F . Genetic diversity of Plasmodium falciparum and its relationship to parasite density in an area with different malaria endemicities in West Uganda. Trop Med Int Health. 2001; 6(8):607-13. DOI: 10.1046/j.1365-3156.2001.00761.x. View

10.

Chattopadhyay R, Sharma A, Srivastava V, Pati S, Sharma S, Das B . Plasmodium falciparum infection elicits both variant-specific and cross-reactive antibodies against variant surface antigens. Infect Immun. 2003; 71(2):597-604. PMC: 145347. DOI: 10.1128/IAI.71.2.597-604.2003. View

11.

Kanunfre K, Leoratti F, Hoffmann E, Durlacher R, Ferreira A, Moraes-Avila S . Differential recognition of Plasmodium falciparum merozoite surface protein 2 variants by antibodies from malaria patients in Brazil. Clin Diagn Lab Immunol. 2003; 10(5):973-6. PMC: 193907. DOI: 10.1128/cdli.10.5.973-976.2003. View

12.

Mockenhaupt F, Ehrhardt S, Eggelte T, Markert M, Anemana S, Otchwemah R . Plasmodium falciparum multiplicity correlates with anaemia in symptomatic malaria. Trop Med Int Health. 2003; 8(10):857-9. DOI: 10.1046/j.1365-3156.2003.01117.x. View

13.

de Roode J, Read A, Chan B, Mackinnon M . Rodent malaria parasites suffer from the presence of conspecific clones in three-clone Plasmodium chabaudi infections. Parasitology. 2003; 127(Pt 5):411-8. DOI: 10.1017/s0031182003004001. View

14.

de Roode J, Culleton R, Bell A, Read A . Competitive release of drug resistance following drug treatment of mixed Plasmodium chabaudi infections. Malar J. 2004; 3:33. PMC: 517944. DOI: 10.1186/1475-2875-3-33. View

15.

Greenwood B, Marsh K, Snow R . Why do some African children develop severe malaria?. Parasitol Today. 1991; 7(10):277-81. DOI: 10.1016/0169-4758(91)90096-7. View

16.

Gaur D, Mayer D, Miller L . Parasite ligand-host receptor interactions during invasion of erythrocytes by Plasmodium merozoites. Int J Parasitol. 2004; 34(13-14):1413-29. DOI: 10.1016/j.ijpara.2004.10.010. View

17.

Karunaweera N, Grau G, Gamage P, Carter R, Mendis K . Dynamics of fever and serum levels of tumor necrosis factor are closely associated during clinical paroxysms in Plasmodium vivax malaria. Proc Natl Acad Sci U S A. 1992; 89(8):3200-3. PMC: 48833. DOI: 10.1073/pnas.89.8.3200. View

18.

Ranjit M, Das A, Das B, Das B, Dash B, Chhotray G . 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. DOI: 10.1016/j.trstmh.2004.09.010. View

19.

de Roode J, Pansini R, Cheesman S, Helinski M, Huijben S, Wargo A . Virulence and competitive ability in genetically diverse malaria infections. Proc Natl Acad Sci U S A. 2005; 102(21):7624-8. PMC: 1140419. DOI: 10.1073/pnas.0500078102. View

20.

Talisuna A, Erhart A, Samarasinghe S, Van Overmeir C, Speybroeck N, DAlessandro U . Malaria transmission intensity and the rate of spread of chloroquine resistant Plasmodium falciparum: Why have theoretical models generated conflicting results?. Infect Genet Evol. 2005; 6(3):241-8. DOI: 10.1016/j.meegid.2005.06.003. View