Several studies in Burkina Faso have indicated that people belonging to the Fulani tribe are less parasitized, have fewer clinical episodes of malaria, and higher levels of anti-malarial antibodies as compared to the sympatric ethnic groups Mossi and Rimabé, despite similar transmission intensity [17–21]. In Mali, Fulani have lower parasite density and are less affected by the disease compared to sympatric Dogon . The more susceptible Dogon population seemed to respond to infections with pronounced splenomegaly, whereas Fulani have chronically enlarged spleens already functional for protection.
The reason for malaria resistance in Fulani is still unknown, but suggested mechanisms include a functional deficiency of regulatory T cells  and different antibody- and cytokine-mediated responses [23, 24]. However, not much attention has been paid to the possible role of the different diets between Fulani and sympatric tribes. The Fulani diet is known to be mainly based on cow milk and also meat consumption is high. No detailed information on dietary habits of study subjects was available, although research on the subject is underway, so local observations and general knowledge on traditions of abundant milk consumption among Fulani in Western Africa were applied as sources of dietary data on population level. In a study in Nigeria, Fulani were described to get 28-29% of their total energy intake from milk products, which would correspond to about 700 grams of milk daily . This amount of milk would probably cause symptoms for lactase non-persistence adults. Thus it is likely that Fulani in Mali with lactase persistence genotypes consume more milk than those with non-persistence genotypes.
The hypothesis of the present study postulates that the increased ability to drink milk in individuals with lactase persistence genotypes may offer protection against malaria infection. In human evolution, lactase activity has been maintained by mutations in the enhancer region of the lactase gene in those populations which herd livestock and will thus benefit substantially from the ability to use dairy products as part of the adults' diet. Several such mutations have enriched over time in isolated livestock herding populations, although smaller than expected differences among these genetically diverse populations have been reported . In populations with European origin, C/T-13910 is the main causative mutation for lactase persistence . In Africa several polymorphisms in the enhancer region of the lactase gene have been suggested to be associated with lactase persistence (Figure 1). Among the 162 Fulani genotyped, the major Caucasian mutation C/T-13910 was by far the most common polymorphism with an allele frequency of 37%. This means that 60% of the Fulani carry the lactase persistence genotype. Possibly the above described sympatry with other ethnic groups is responsible for the lower minor allele frequency found in this study than the one described by Enattah et al . Three other SNPs in the region were found. They were found as heterozygotes in twelve, six and two subjects each. Among the 79 Dogon samples tested only one heterozygote of a lactase enhancer polymorphism, the main European mutation, was detected.
Results show that P. falciparum parasitaemia in asymptomatic Fulani is more common in individuals with lactase non-persistence genotypes. However, this finding was not statistically significant as this study did not have power to detect a difference with odds ratio smaller than 2.7. The rarity of the SNPs among Dogon and among other non-pastoralist populations in Africa further supports the hypothesis. Asymptomatic parasitaemia was used as the main phenotype, assessment of the suggested protective effects of lactase persistence on clinical malaria episodes, severe malaria or malaria mortality was not applicable. The novel T/C-13906 polymorphism detected in this study cannot be claimed to be functional without lactose tolerance test or intestinal biopsy on individuals with this variant. However, the location only 4 bp from the main mutation supports the possibility of functionality. In addition, the lack of polymorphisms in the Dogon subjects suggests that the variability in the Fulani lactase enhancer region is caused by ongoing selection for which functionality is a prerequisite.
The potential protective role of milk consumption in malaria infections has been debated for more than half a century. Studies in the 1950s indicated that a cow milk diet has a suppressive effect on malaria infections in rats, mice and monkeys . The suppression of the normal replication of the parasites was suggested to be caused mainly by the deficiency of p -aminobenzoic acid (PABA), as milk is lacking PABA in contrast to normal diets . Plasmodium species can synthesize PABA de novo, but probably not in sufficient amounts to survive without dietary intake by the host .
Infants under six months of age have a lower incidence of severe malaria than older children, which mainly has been explained by maternal antibodies acquired through breast-feeding. Deficiency of PABA might be another reason, especially for children exclusively breast fed. Additionally, there might be other still unidentified anti-malarial properties of milk, as it consists of numerous probiotics, innate immunity components (i.e. mannose binding-lectin, properdin, interferons), cytokines, chemokines and anti-inflammatory factors .
The relationship between nutrition and malaria seems to be complex. In the 1990s it was suggested that lactase non-persistence would have been selected by malaria, like beta-thalassaemia and glucose 6-phosphate dehydrogenase deficiency [31, 32]. This hypothesis was soon rejected, as it was based on the false assumption that the lactase persistence trait would be the wild-type allele [33, 34]. Reduced malaria morbidity in malnourished children and malaria outbreaks following refeeding after famines in Africa has been reported . However, Fulani with diets consisting mainly of milk, did not have increased incidences of severe malaria after refeeding .
The potential protective role against malaria infection achieved by abundant milk consumption, allowed by lactase persistence genotypes, could have many explanations. First, milk might provide a generally increased nutritional status being rich in energy, proteins and fatty acids. Secondly, milk consists of a large number of immunomodulating components. Third, a diet dominated by dairy products might lead to a relative PABA deficiency, protecting from malaria. Additionally, there might be still unrecognized factors in milk providing protection against malaria and other infections.