Search tips
Search criteria 


Logo of molmedLink to Publisher's site
Mol Med. 1997 September; 3(9): 581–592.
PMCID: PMC2230086

Imbalanced distribution of Plasmodium falciparum MSP-1 genotypes related to sickle-cell trait.


BACKGROUND: The sickle-cell trait protects against severe Plasmodium falciparum malaria and reduces susceptibility to mild malaria but does not prevent infection. The exact mechanism of this protection remains unclear. We have hypothesized that AS individuals are protected by virtue of being less susceptible to a subset of parasite strains; thus we compared some genetic characteristics of parasites infecting AS and AA subjects. MATERIALS AND METHODS: Blood was collected from asymptomatic individuals living in two different regions of Africa. The polymorphic MSP-1 and MSP-2 loci were genotyped using a PCR-based methodology. Individual alleles were identified by size polymorphism, amplification using family-specific primers, and hybridization using family-specific probes. Multivariate logistic regression was used to analyze allele distribution. RESULTS: In Senegalese carriers, age and hemoglobin type influenced differently the distribution of the three MSP-1 families and had an impact on distinct individual alleles, whereas the distribution of MSP-2 alleles was marginally affected. There was no influence of other genetic traits, including the HLA Bw53 genotype, or factors such as place of residence within the village. In a cohort of Gabonese schoolchildren in which the influence of age was abrogated, a similar imbalance in the MSP-1 allelic distribution but not of MSP-2 allelic distribution by hemoglobin type was observed. CONCLUSIONS: The influence of the host's hemoglobin type on P. falciparum genotypes suggests that parasite fitness for a specific host is strain-dependent, which is consistent with our hypothesis that innate resistance might result from reduced fitness of some parasite strains for individuals with sickle-cell traits.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.9M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • ALLISON AC. The distribution of the sickle-cell trait in East Africa and elsewhere, and its apparent relationship to the incidence of subtertian malaria. Trans R Soc Trop Med Hyg. 1954 Jul;48(4):312–318. [PubMed]
  • Miller LH. Impact of malaria on genetic polymorphism and genetic diseases in Africans and African Americans. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2415–2419. [PubMed]
  • Fleming AF, Storey J, Molineaux L, Iroko EA, Attai ED. Abnormal haemoglobins in the Sudan savanna of Nigeria. I. Prevalence of haemoglobins and relationships between sickle cell trait, malaria and survival. Ann Trop Med Parasitol. 1979 Apr;73(2):161–172. [PubMed]
  • Hill AV, Allsopp CE, Kwiatkowski D, Anstey NM, Twumasi P, Rowe PA, Bennett S, Brewster D, McMichael AJ, Greenwood BM. Common west African HLA antigens are associated with protection from severe malaria. Nature. 1991 Aug 15;352(6336):595–600. [PubMed]
  • Chippaux JP, Massougbodji A, Boulard JC, Akogbeto M. Etude de la morbidité palustre et de la gravité des accès pernicieux chez les porteurs du trait drépanocytaire. Rev Epidemiol Sante Publique. 1992;40(4):240–245. [PubMed]
  • Chippaux JP, Massougbodji A, Castel J, Akogbeto M, Zohoun I, Zohoun T. Parasitémies à Plasmodium falciparum ou P. malariae chez les porteurs du trait drépanocytaire dans différents biotopes du Bénin. Rev Epidemiol Sante Publique. 1992;40(4):246–251. [PubMed]
  • Bayoumi RA, Abu-Zeid YA, Abdulhadi NH, Saeed BO, Theander TG, Hviid L, Ghalib HW, Nugud AH, Jepsen S, Jensen JB. Cell-mediated immune responses to Plasmodium falciparum purified soluble antigens in sickle-cell trait subjects. Immunol Lett. 1990 Aug;25(1-3):243–249. [PubMed]
  • Abu-Zeid YA, Abdulhadi NH, Hviid L, Theander TG, Saeed BO, Jepsen S, Jensen JB, Bayoumi RA. Lymphoproliferative responses to Plasmodium falciparum antigens in children with and without the sickle cell trait. Scand J Immunol. 1991 Aug;34(2):237–242. [PubMed]
  • Friedman MJ. Erythrocytic mechanism of sickle cell resistance to malaria. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1994–1997. [PubMed]
  • Pasvol G, Weatherall DJ, Wilson RJ. Cellular mechanism for the protective effect of haemoglobin S against P. falciparum malaria. Nature. 1978 Aug 17;274(5672):701–703. [PubMed]
  • Roth EF, Jr, Friedman M, Ueda Y, Tellez I, Trager W, Nagel RL. Sickling rates of human AS red cells infected in vitro with Plasmodium falciparum malaria. Science. 1978 Nov 10;202(4368):650–652. [PubMed]
  • Mozzarelli A, Hofrichter J, Eaton WA. Delay time of hemoglobin S polymerization prevents most cells from sickling in vivo. Science. 1987 Jul 31;237(4814):500–506. [PubMed]
  • Rogier C, Commenges D, Trape JF. Evidence for an age-dependent pyrogenic threshold of Plasmodium falciparum parasitemia in highly endemic populations. Am J Trop Med Hyg. 1996 Jun;54(6):613–619. [PubMed]
  • Marsh K, Otoo L, Hayes RJ, Carson DC, Greenwood BM. Antibodies to blood stage antigens of Plasmodium falciparum in rural Gambians and their relation to protection against infection. Trans R Soc Trop Med Hyg. 1989 May-Jun;83(3):293–303. [PubMed]
  • ALLISON AC. Protection afforded by sickle-cell trait against subtertian malareal infection. Br Med J. 1954 Feb 6;1(4857):290–294. [PMC free article] [PubMed]
  • Fandeur T, Mercereau-Puijalon O, Bonnemains B. Plasmodium falciparum: genetic diversity of several strains infectious for the squirrel monkey (Saimiri sciureus). Exp Parasitol. 1996 Oct;84(1):1–15. [PubMed]
  • Cooper JA. Merozoite surface antigen-I of plasmodium. Parasitol Today. 1993 Feb;9(2):50–54. [PubMed]
  • Fenton B, Clark JT, Khan CM, Robinson JV, Walliker D, Ridley R, Scaife JG, McBride JS. Structural and antigenic polymorphism of the 35- to 48-kilodalton merozoite surface antigen (MSA-2) of the malaria parasite Plasmodium falciparum. Mol Cell Biol. 1991 Feb;11(2):963–971. [PMC free article] [PubMed]
  • Miller LH, Roberts T, Shahabuddin M, McCutchan TF. Analysis of sequence diversity in the Plasmodium falciparum merozoite surface protein-1 (MSP-1). Mol Biochem Parasitol. 1993 May;59(1):1–14. [PubMed]
  • Snewin VA, Herrera M, Sanchez G, Scherf A, Langsley G, Herrera S. Polymorphism of the alleles of the merozoite surface antigens MSA1 and MSA2 in Plasmodium falciparum wild isolates from Colombia. Mol Biochem Parasitol. 1991 Dec;49(2):265–275. [PubMed]
  • Prescott N, Stowers AW, Cheng Q, Bobogare A, Rzepczyk CM, Saul A. Plasmodium falciparum genetic diversity can be characterised using the polymorphic merozoite surface antigen 2 (MSA-2) gene as a single locus marker. Mol Biochem Parasitol. 1994 Feb;63(2):203–212. [PubMed]
  • Viriyakosol S, Siripoon N, Petcharapirat C, Petcharapirat P, Jarra W, Thaithong S, Brown KN, Snounou G. Genotyping of Plasmodium falciparum isolates by the polymerase chain reaction and potential uses in epidemiological studies. Bull World Health Organ. 1995;73(1):85–95. [PubMed]
  • Contamin H, Fandeur T, Bonnefoy S, Skouri F, Ntoumi F, Mercereau-Puijalon O. PCR typing of field isolates of Plasmodium falciparum. J Clin Microbiol. 1995 Apr;33(4):944–951. [PMC free article] [PubMed]
  • Ntoumi F, Contamin H, Rogier C, Bonnefoy S, Trape JF, Mercereau-Puijalon O. Age-dependent carriage of multiple Plasmodium falciparum merozoite surface antigen-2 alleles in asymptomatic malaria infections. Am J Trop Med Hyg. 1995 Jan;52(1):81–88. [PubMed]
  • Robert F, Ntoumi F, Angel G, Candito D, Rogier C, Fandeur T, Sarthou JL, Mercereau-Puijalon O. 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):704–711. [PubMed]
  • Luty AJ, Mayombo J, Lekoulou F, Mshana R. Immunologic responses to soluble exoantigens of Plasmodium falciparum in Gabonese children exposed to continuous intense infection. Am J Trop Med Hyg. 1994 Dec;51(6):720–729. [PubMed]
  • Dieye A, Diaw ML, Rogier C, Trape JF, Sarthou JL. HLA-A, -B, -C, -DR, -DQ typing in a population group of Senegal: distribution of HLA antigens and HLA-DRB1*13 and DRB1*11 subtyping by PCR using sequence-specific primers (PCR-SSP). Tissue Antigens. 1996 Mar;47(3):194–199. [PubMed]
  • Stiratelli R, Laird N, Ware JH. Random-effects models for serial observations with binary response. Biometrics. 1984 Dec;40(4):961–971. [PubMed]
  • Trape JF, Rogier C. Combating malaria morbidity and mortality by reducing transmission. Parasitol Today. 1996 Jun;12(6):236–240. [PubMed]
  • Creasey A, Fenton B, Walker A, Thaithong S, Oliveira S, Mutambu S, Walliker D. Genetic diversity of Plasmodium falciparum shows geographical variation. Am J Trop Med Hyg. 1990 May;42(5):403–413. [PubMed]
  • Luzzatto L. Genetics of red cells and susceptibility to malaria. Blood. 1979 Nov;54(5):961–976. [PubMed]
  • Robert V, Tchuinkam T, Mulder B, Bodo JM, Verhave JP, Carnevale P, Nagel RL. Effect of the sickle cell trait status of gametocyte carriers of Plasmodium falciparum on infectivity to anophelines. Am J Trop Med Hyg. 1996 Feb;54(2):111–113. [PubMed]

Articles from Molecular Medicine are provided here courtesy of The Feinstein Institute for Medical Research at North Shore LIJ