Abstract

Malaria still remains a major public health problem in Mali, although disease susceptibility varies between ethnic groups, particularly between the Fulani and Dogon. These two sympatric groups share similar socio-cultural factors and malaria transmission rates, but Fulani individuals tend to show significantly higher spleen enlargement scores, lower parasite prevalence, and seem less affected by the disease than their Dogon neighbours. We have used genetic polymorphisms from malaria-associated genes to investigate associations with various malaria metrics between the Fulanai and Dogon groups. Two cross sectional surveys (transmission season 2006, dry season 2007) were performed. Healthy volunteers from the both ethnic groups (n=939) were recruited in a rural setting. In each survey, clinical (spleen enlargement, axillary temperature, weight) and parasitological data (malaria parasite densities and species) were collected, as well as blood samples. One hundred and sixty six SNPs were genotyped and 5 immunoassays (AMA1, CSP, MSP1, MSP2, total IgE) were performed on the DNA and serum samples respectively. The data confirm the reduced malaria susceptibility in the Fulani, with a higher level of the protective O-blood group, and increased circulating antibody levels to several malaria antigens (p<10-15). We identified SNP allele frequency differences between the 2 ethnic groups in CD36, IL4, RTN3 and ADCY9. Moreover, polymorphisms in FCER1A, RAD50, TNF, SLC22A4, and IL13 genes were correlated with antibody production (p-value<0.003). Further work is required to understand the mechanisms underpinning these genetic factors.

Highlights

  • Malaria remains the major public health problem in more than 90 countries inhabited by more than 40% of the world’s population, with at least one million deaths every year

  • The classical genetic markers involved in malaria resistance, such as haemoglobin C (HbC) and S (HbS), glucose-6-phosphate dehydrogenase (G6PD) and blood group polymorphisms [9], are not sufficient to explain the differences between Fulani and Dogon

  • The higher total IgE and antigenic (AMA1, CSP, MSP1 and MSP2) responses and the lower parasite rate displayed among the Fulani ethnic group, suggests a higher protection against P. falciparum in Fulani compared with the Dogon, and potentially other sympatric ethnic groups

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Summary

Introduction

Malaria remains the major public health problem in more than 90 countries inhabited by more than 40% of the world’s population, with at least one million deaths every year. In Mali, there are over 800,000 recorded cases of malaria among the 14 million people affected worldwide every year, and it accounts for 17 percent of child deaths overall [2]. It is a major burden for the public health system, where prevention, treatment and control measures are administered by the Ministry of Health. There are differences in malaria infection and susceptibility between ethnic groups. There are inter-ethnic differences in susceptibility to malaria between the two sympatric groups from Manterou in Mali, namely the Fulani ( known as Peulh) and Dogon [8]. The classical genetic markers involved in malaria resistance, such as haemoglobin C (HbC) and S (HbS) (in the HBB gene), glucose-6-phosphate dehydrogenase (G6PD) and blood group polymorphisms [9], are not sufficient to explain the differences between Fulani and Dogon

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