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A possible ancient origin for tuberculoses in Casablanca

23.11.2004

Each year tuberculosis kills about three million people in the world. In particular it is responsible for the death of more than one-third of HIV- infected people, who prove particularly susceptible owing to a decline in immune defences. The agent responsible is a bacterium of the species Mycobacterium tuberculosis, also termed Koch’s bacillus, after the scientist who discovered it in 1882.

Molecular epidemiology has proved valuable for understanding the transmission and control of tuberculosis, thanks to the development of different methods of characterization of the M. tuberculosis genome. However, little genetic data is currently available in the countries of the South, where this disease is often a major public health problem. In Morocco, tuberculosis incidence is still high, with about 30 000 new cases are recorded each year, in spite of a level of HIV infection that remains of quite low concern and the application since 1991 of a WHO strategy called DOTS (2). Researchers from the IRD and their scientific partners (1) studied the genetic diversity and structure of a Moroccan population consisting of 150 strains of the species M. tuberculosis. These strains come from 150 pulmonary tuberculosis infected subjects living in Casablanca, the country’s economic capital, which on its own accounts for one-fifth of all tuberculosis cases declared in Morocco.

Two independent and complementary molecular genotyping techniques were applied to the specimens collected. The first used generalist genetic markers which allow analysis of the genetic diversity of the population considered, but also comparison of the genetic diversity of the pathogenic species M. tuberculosis with that of other microorganisms. The second, which is the most recent technique used for characterizing the M. tuberculosis genome, calls on specific markers of this mycobacterium, adapted to the identification of the different strains isolated.

The statistical analyses performed on the basis of data obtained concerning the population studied shows that it has a clonal structure: its constituent strains behave and evolve overall like natural clones that are stable with time.

Moreover, analysis of the genetic profiles of the different strains revealed a large genetic diversity in the population (3). This result was unexpected, because the populations of M. tuberculosis coming from high-incidence countries, as in Morocco, generally show a low degree of polymorphism. The polymorphism that did occur was seen between the strains of one and the same district of the city of Casablanca, between strains collected the same year and often between those resulting from the same infected family. The population studied consequently consisted of many circulating clones.

The results taken overall suggest that there is an ancient origin of tuberculosis in Casablanca. No one genetic profile was numerically dominant. Therefore transmission of the disease would be effected by reactivation of pre-existing, latent, strains rather than by recent transmissions of novel strains. The fact that several genetically different strains can affect the members of a single family shows that contamination, in this context of high incidence, can also be exogenous, the disease being contracted outside the family home. Important pieces of information on the biological, clinical and epidemiological behaviour of this mycobacterium, especially in terms of identification and treatment of different sources of contamination, have thus been contributed.

No genetic study had previously been conducted in Morocco on M. tuberculosis populations. The work performed on the sample collected at Casablanca therefore provided the first indices for understanding tuberculosis transmission in this area. Such molecular epidemiology investigations, conducted in other towns and villages of Morocco, and in other countries where the disease is endemic, favour an overall approach to the transmission dynamics of tuberculosis. This is vital if effective control measures of this disease are to be deployed.

Marie Guillaume – DIC

(1) The joint CNRS-IRD research unit Génétique et Evolution des Maladies Infectieuses (Genetics and Evolution of Infectious Diseases) has worked in tandem with the INSERM Laboratory of Molecular Mechanisms of Bacterial Pathogenesis at the Lille Pasteur Institute. Sample collection and the epidemiological survey were conducted in conjunction with the Mycobacteria Department of the Morocco Pasteur Institute at Casablanca.

(2) DOTS: Directly observed Treatment Short-course. This strategy for tuberculosis control was implemented in Morocco in 1991, with the following main objectives: application of the standard short chemotherapy course (6 months) for all new microscopically positive cases of pulmonary tuberculosis; treatment of all the other forms of tuberculosis once the diagnosis established; maintenance of vaccination cover using BCG at over 90 % in newborns. These different objectives involve the permanent commitment of government authorities in tuberculosis control and the necessity for regular, consistent supply of high-quality medicines.

(3) Moreover, this diversity appears highly significant when compared with that of other species of microorganism (bacteria, yeasts, protozoans) that evolve on the same clonal model. M. tuberculosis has a greater genetic diversity than the 4 species of Leishmania tested (average values are 0.48 as against 0.14; 0.07; 0.19 and 0.14). The value obtained for M. tuberculosis (0.48) is close to that of Saccharomyces cerevisiae (0.42) and Candida albicans (0.51).