Reflections on the population dynamics of Trypanosoma cruzi: heterogeneity versus plasticity.

Abstract

Trypanosoma cruzi, the etiological agent ofChagas disease, exists in nature as a complex ofheterogeneous populations. There is a wide spec-trum of human disease manifestations (Z Brener1987 Mem Inst Oswaldo Cruz 82: 205-212) andthe crucial problem in the study of Chagas diseaseis a lack of understanding of the factors involvedin its pathology. The imposition of natural and ar-tificial pressures can result in the selection of asubset of the population. The marked heterogene-ity of T. cruzi leads to a search for a relationshipbetween functional parameters of parasites isolatedfrom patients or specific geographical areas andthe manifestation of the disease itself. Anothercrucial, and someway, unsolved question is theinfluence of this heterogeneity on the stability ofthe parasite population (JA Dvorak 1984 J CellBiochem 24: 357-371, RW Finley & JA Dvorak1987 J Protozool 34: 409-415).In essence, the fundamental problems associ-ated with the attempts to understanding Chagasdisease were reported by Carlos Chagas in 1909(Mem Int Oswaldo Cruz 1: 159-218) and most ofthe phenomena currently under study were identi-fied by himself. As the disease can be manifestedin different clinical forms from symptomless to anacute fulminate infection or to severe or even in-apparent chronic infection, FL Lambrecht (1965Rev Inst Med Trop Sao Paulo 7: 346-352) advancedthe premise that T. cruzi may be composed of agenetically heterogeneous population of parasitesand that such heterogeneity may be one of the fac-tors that modulate the disease process. In fact, dif-ferences in isolates or strains from wide geographi-cal and host ranges have already been well docu-mented (Z Brener 1965 Ann Trop Med Parasitol59: 19-26, SG Andrade et al. 1970 Gaz Med Ba-hia 1: 32-42, Z Brener 1980 Advances Parasitol18: 247-292, WE Gutteridge 1981 Trans R SocTrop Med Hyg 75: 484-492).With the argument of population heterogene-ity in mind, some years ago, researchers from Bra-zil and outside begun to develop new biologicaland biochemical approaches to investigate this in-triguing parasite. Restriction analyses of kDNA(CM Morel et al 1980 Proc Natl Acad Sci USA 77:6810-6814) have shown a considerable degree ofheterogeneity in natural T. cruzi populations andimportant findings such as the occurrence of mixedinfection in human, reinfection and selection ofsubpopulations have been reported (CM Morel1984 TDR Series 5 : 333-375, MP Deane et al. 1984J Protozool 31: 276-280, CM Morel et al. 1986Parasitol Today 2: 97-101). Isoenzymatic analy-ses also confirmed the heterogeneity although ini-tial studies revealed discrete variability showingthree or four principal zymodemes (MA Miles etal. 1977 Trans R Soc Trop Med Hyg 71: 217-225,1980 Trans R Soc Trop Med Hyg 74: 221-237, AJRomanha 1979 Comp Biochem Physiol 62: 139-142). In recent times, new concepts, models andmethods have been introduced to elucidate the com-plexity of the population dynamics of T. cruzi. In1986, Tibayrenc and co-workers ( Proc Natl AcadSci USA 83: 115-119) have proposed that naturalpopulations of T. cruzi have a complex multiclonalstructure. Although T. cruzi is diploid (Tibayrencloc. cit , WC Gibson & MA Miles 1986 EMBO J 5:1299-1305) its reproduction is primarily clonal andsexual recombination is rare or even absent. Anextensive zymodeme diversity among distinctclones was discovered indicating that they couldhardly be clustered in a few groups (M Tibayrenc& FJ Ayala 1988 Evolution 42 : 277-292). The termclonet (M Tibayrenc 1990 Proc Natl Acad Sci USA87: 2414-2418) was introduced to explain the in-tragroup or infraspecific variation. On that ac-count, how many relevant phylogenetic subdivi-sion are there? (M Tibayrenc 1995 Adv Parasitol36: 47-115, RP Souto et al. 1996 Mol BiochemParasitol 83: 141-152). It seems that there is an