Haemoglobin C (HbC; beta6Glu --> Lys) is common in malarious areas of West Africa, especially in Burkina Faso. Conclusive evidence exists on the protective role against severe malaria of haemoglobin S (HbS; beta6Glu --> Val) heterozygosity, whereas conflicting results for the HbC trait have been reported and no epidemiological data exist on the possible role of the HbCC genotype. In vitro studies suggested that HbCC erythrocytes fail to support the growth of P. falciparum but HbC homozygotes with high P. falciparum parasitaemias have been observed. Here we show, in a large case-control study performed in Burkina Faso on 4,348 Mossi subjects, that HbC is associated with a 29% reduction in risk of clinical malaria in HbAC heterozygotes (P = 0.0008) and of 93% in HbCC homozygotes (P = 0.0011). These findings, together with the limited pathology of HbAC and HbCC compared to the severely disadvantaged HbSS and HbSC genotypes and the low betaS gene frequency in the geographic epicentre of betaC, support the hypothesis that, in the long term and in the absence of malaria control, HbC would replace HbS in central West Africa.

The Fulani are less clinically susceptible and more immunologically responsive to malaria than neighbouring ethnic groups. Here we report that anti-malarial antibody levels show a wide distribution amongst the Fulani themselves, raising the possibility that quantitative analysis within the Fulani may be an efficient way of screening for important genetic factors. The Th2 cytokine interleukin-4 is an obvious candidate: in Fulani, the IL4-524 T allele is at high frequency and is associated with elevated antibody levels against malaria antigens. These data highlight the possibility of combining inter- and intra-ethnic comparisons to characterize critical determinants of malarial immunity in a natural setting.

The gene frequencies in 1993-94 for haemoglobin S, haemoglobin C, alpha-3.7 deletional thalassaemia, G6PDA-, HLAB*5301 were estimated in Fulani, Mossi and Rimaibé ethnic groups of Burkina Faso, West Africa. The aim of the study was to verify whether the previously reported Fulani lower susceptibility to Plasmodium falciparum malaria was associated with any of these malaria-resistance genes. Similar frequencies for haemoglobin S were recorded in the 3 ethnic groups (0.024 +/- 0.008, 0.030 +/- 0.011, 0.022 +/- 0.013; in Mossi, Rimaibé and Fulani, respectively). The Mossi and Rimaibé showed higher frequencies when compared to Fulani for haemoglobin C (0.117 +/- 0.018, 0.127 +/- 0.020, 0.059 +/- 0.020), alpha-3.7 deletional thalassaemia (0.227 +/- 0.040, 0.134 +/- 0.032, 0.103 +/- 0.028), G6PDA- (0.196 +/- 0.025, 0.187 +/- 0.044, 0.069 +/- 0.025) and HLA B*5301 (0.189 +/- 0.038, 0.202 +/- 0.041, 0.061 +/- 0.024). Among Fulani the proportion of individuals not having any of these protective alleles was more than 3-fold greater than in the Mossi-Rimaibé group (56.8% vs 16.7%; P < 0.001). These findings exclude the involvement of these genetic factors of resistance to P. falciparum in the lower susceptibility to malaria of Fulani. This evidence, in association with the previously reported higher immune reactivity to malaria of Fulani, further supports the existence in this ethnic group of unknown genetic factor(s) of resistance to malaria probably involved in the regulation of humoral immune responses.

The humoral immune response against synthetic peptides of two Plasmodium falciparum blood-stage antigens, Pf155/ring-infected erythrocyte surface antigen (RESA) (EENV) 6 and Pf332 (SVTEEIAEEDK) 2 , in individuals belonging to three sympatric ethnic groups (Mossi, Rimaibe, and Fulani) living in the same conditions of hyperendemic transmission in a Sudan savanna area northeast of Ouagadougou, Burkina Faso were examined. The Mossi and Rimaibe are Sudanese Negroid populations with a long tradition of sedentary farming, while the Fulani are nomadic pastoralists partly settled and characterized by non-Negroid features of possible Caucasoid origin. A total of 764 subjects (311 Mossi, 273 Rimaibe, and 180 Fulani) were tested. A lower P. falciparum prevalence was observed in the Fulani of all age groups. The serologic results clearly indicate the existence of interethnic differences in the capacity to respond to these two P. falciparum antigens. The Mossi and Rimaibe showed similar responses, whereas the Fulani displayed consistently higher prevalences and levels of antibodies against both epitopes tested. The anti-(EENV) 6 and anti-(SVTEEIAEEDK) 2 seroprevalences were 29.9% and 38.9% in Mossi, 29.7% and 39.2% in Rimaibe, 86.1% and 76.1% in Fulani (all P values of Fulani-Mossi and Fulani-Rimaibe comparisons K 0.001). Anti-RESA and anti-Pf332 antibody levels were approximately 65% (P K 0.001) and 45% (P K 0.001), respectively, higher in seropositive Fulani than in seropositive Mossi and Rimaibe, who showed very similar values. The observed differences cannot be explained in terms of interethnic heterogeneity of malaria exposure since these communities have lived in the same area for more than 30 years and the P. falciparum inoculation rate, measured during two consecutive years, was substantially uniform for the three ethnic groups. The possibility of remarkable heterogeneities in the capacity to mount immune responses against P. falciparum antigens among populations with different genetic backgrounds must be taken into account in the development of anti-malaria vaccines.