Resistance and genetic sensitivity to sleeping sickness

Human African trypanosomiasis, more commonly called sleeping sickness, is induced by a parasite, the trypanosome, transmitted to humans by the bite of an insect, the glossinid tse-tse fly. There has been a resurgence of this disease over the past 20 years in Sub-Saharan Africa. The World Health Organization (WHO) in a 1998 report estimated the number of people infected to be about 300 000. Awareness of the seriousness of the situation led to an increase in screening and treatment operations over the past five years, allowing a substantial fall in the number of subjects infected.

Sleeping sickness classically manifests itself in two forms, corresponding to two parasite subspecies. The chronic form, encountered in Central and West African countries, is caused by Trypanosoma brucei gambiense (T.b. gambiense). Its development cycle in the host vaires greatly, from a few months to several years. The acute form of the disease is brought on by Trypanosoma brucei rhodesiense (T.b. rhodesiense), in southern and eastern African countries. The infection it induces takes effect after a few weeks. More virulent than the chronic form, its development cycle is also more rapid and, consequently, clinical detection can be made earlier.

However, it is increasingly recognized that the existence of these two forms, the chronic one due to T. b. gambiense and the acute one provoked by T. b. rhodesiense, only partly reflect the real mechanisms at work. Concerning the Gambian form, the screening and treatment teams indicates the occurrence of several categories of subjects infected: some show Glossina fuscipes gorged with blood affected by classical chronic forms of the disease; others bear severe rapidly developing forms; still other people show no symptoms of human African trypanosomiasis, in spite of a long period of infection. This diversity in host clinical presentation in reaction to infection can have several sources: the host's ability to respond to infection, the degree of parasite virulence or pathogenicity and the environment.

An IRD team focused particularly on the role of host genetic diversity in response to T. b. gambiense infection (whether or not the disease develops). As human experimentation is excluded, genetic, epidemiological and statistical methods, all brought under the term genetic epidemiology, were developed in order to identify the chromosome regions and/or DNA mutations involved in the development of the disease. The researchers used association techniques in order to determine the influence of certain mutations on the DNA of genes coding for particular immune system proteins (cytokines) in manifestation of the disease. This type of study consists in comparing the frequency of a mutation in subjects with symptoms and in healthy individuals. When the frequency of a mutation is significantly higher in the sick subjects than in the healthy ones, this mutation is associated with an enhanced risk of developing the disease. Conversely, a significantly lower frequency is an expression of a protective effect conferred by the mutation.