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Imbalanced Distribution of Plasmodium falciparum MSP-1 Genotypes Related to Sickle-Cell Trait

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Abstract

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.

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Acknowledgments

We thank the Dielmo villagers, the schoolchildren of Dienga, and their parents, who generously accepted to participate in this study. We are indebted to Gora Ndiaye, Charles Bouganali, Assane Badji, and Adrian Luty for collection of blood samples in Dielmo and Dienga, respectively. We also thank Badara Cisse and Adama Tall, Jean-Louis Sarthou, and Christian Roussilhon for expert assistance and Pierre Druilhe and Luiz Pereira da Silva for their invaluable input in the Dielmo program. We thank the Dienga school staff and Yakhya Dieye, Justice Mayomobo, Fautin Lekoulou, Paul Tshipamba, and Hélène Tiga for technical assistance. Particular thanks are due to Trinh Ngoe Minh for his help in the statistical analysis of the Dienga data and to André Spiegel for helpful advice in the statistical analysis of the Dielmo data. Part of this work was done when Francine Ntoumi was a fellow of the UNDP, World Bank, WHO Special Program for Research and Training in Tropical Diseases. The Dielmo work was funded by a grant from the Ministère de la Coopération. The work in Gabon was funded by grants from the Gabonese government, ELF Gabon, the Ministère de la Coopération, and INSERM. We thank Françoise Guinet, Peter David, Charlotte Behr, Florence Robert, and Jean-Louis Pérignon for critical reading of the manuscript.

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Author notes

  1. Christophe Rogier

    Present address: Laboratoire de Parasitologie, Institut de Médecine Tropicale du Service de Santé des Armées, Marseilles, France

Authors and Affiliations

  1. Unité d’Imunologie Moléculaire des Parasites, Institut Pasteur, 25 rue du Dr Roux, 75724, Paris, France

    Francine Ntoumi &  Odile Mercereau-Puijalon

  2. Institut Pasteur, Dakar, Senegal

    Christophe Rogier & Alioune Dieye

  3. Laboratoire de Paludologie, ORSTOM, Dakar, Senegal

    Jean-François Trape

  4. International Centre for Medical Research, Franceville, Gabon

    Francine Ntoumi & Pascal Millet

Authors
  1. Francine Ntoumi
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  6. Odile Mercereau-Puijalon
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Correspondence to Odile Mercereau-Puijalon.

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Communicated by L. Miller.

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Ntoumi, F., Rogier, C., Dieye, A. et al. Imbalanced Distribution of Plasmodium falciparum MSP-1 Genotypes Related to Sickle-Cell Trait. Mol Med 3, 581–592 (1997). https://doi.org/10.1007/BF03401815

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