begins near the center of the parasite between the nucleus and kinetoplast, extends along the anterior undulating membrane, and protrudes from the prow (Schmidt and Roberts 1989:57). In trypomastigotes, the kinetoplast and kinetosome are found in the posterior tip, from where the flagellum begins, flows along the membrane of the parasite, and extends from the prow. The epimastigotes in the midgut of the insect are small, 10 to 20 microns, multiply profusely by binary fission, provide a reservoir of parasites, and thus maintain the infection in the bug (Molyneux and Ashford 1983:168).
Longer epimastigotes (35 to 40 microns) travel from the midgut to the rectum of vinchucas, where they adhere to the epithelium of the rectal glands with their flagella. Epimastigotes develop into metacyclic trypomastigotes, which swim freely in the rectal lumen. Metacyclics are 17 to 22 microns long. They no longer divide and are very active. This life cycle takes anywhere from six to fifteen days, depending on the stage of the bug which ingests the parasite and the temperature at which the bug lives (Molyneux and Ashford 1983:168). This reproductive and infective cycle of T. cruzi continues throughout the life of the bug and apparently does no harm to it.
In observation, T. cruzi have no stages outside the gut of insects and the blood and cells of vertebrates. Drugs aside, once host and vector are infected, they generally remain so throughout their lives. This is because T. cruzi can reproduce asexually by binary fission in both the vector and the definitive host.
After metacyclic trypomastigotes enter a mammal’s cells, they reproduce by binary fissions into amastigotes. Amastigotes cluster into cyststiny, entangled snakelike bundles of evolving forms that burst cells, exploding amastigotes into the bloodstream, once again to repeat the process in another cell with such speed that industrial mass production looks slow in comparison. Meanwhile, they also produce stumpy trypomastigotes that circulate in the blood in order that they can be absorbed by blood-ingesting vinchucas. This reproductive cycle is constant, so that infected humans have trypomastigotes permanently circulating within their blood and amastigotes reproducing in their cells.
Amastigotes frequently develop into short and stumpy trypomastigotes, which are found in chronic phases of the disease. Stumpy trypomastigotes are thought to be the most infective stage to triatomine bugs (Molyneux and Ashford 1983:167). As with African trypanosomes, the morphological form of the trypomastigotes that the insect ingests with blood influences the level of infection: “stout” forms seem to be more infective than are “slender” forms (WHO 1991:22). During the acute phase, triatomines are less likely to ingest trypomastigotes in the blood of the host because the host’s immune system is attacking these forms and driving them into the sanctuary offered by host cells. In the chronic phase, the slower, short, stumpy trypomastigotes can leisurely wait for ingestion by “kissing bugs,” because immunosuppression has reduced the risks of attack in the circulation system of the host. Although the numbers of trypomastigotes seldom reach the levels seen in the blood during the acute phase of Chagas’ disease or during African trypanosomiasis, the trypomastigotes of T. cruzi are able to increase their numbers in the peripheral circulation system of the chronic patient.
The advantage of circulating in the blood is that T. cruzi can then readily transmit its progeny to insects, who provide another environment for development and transportation to other hosts. This strategy assures that even though T. cruzi ultimately destroy the host in which they presently reside, their offspring will carry on in another host. Their migration between cells within the same host ensures a ready supply of new nurseries for their offspring, while transmission via insects promotes their movement from one host to another, whether sylvatic or domestic animals or humans. The disadvantages of circulating in the blood are that T. cruzi are under attack by the humoral immune system, and one strategy the organism has developed is to spend as little time in the blood as possible.
Trypanosome cruzi employ an important adaptive strategy seen with many parasites in that they try to maintain their own population levels within the carrying capacity of the host organism. It is not to their advantage to destroy their hosts too quickly, or, as George Stewart says, “They don’t want to burn down their home before they have acquired a replacement.”[77] With sound practicality, then, Chagas’ disease has a relatively low incidence of parasitemia in its acute phase.
After the vinchuca bug has ingested trypomastigotes, another reproductive process takes place within the insect’s gut. Insects do not get sick or suffer from T. cruzi— except for the loss of nutrients (WHO 1991:22). In contrast, however, a closely related parasite, Trypanosoma rangeli, which is harmless to humans, has a pathogenic effect on insects. After trypomastigotes have traveled to the anterior intestine, they take on epimastigote forms, then travel to the midgut and change into amastigotes and proliferate. Amastigotes next give birth to metacyclic trypomastigotes in the rear of the intestines and from there are transported through the feces the next time the insect takes a blood meal. Delay time between ingestion of a blood meal and defecation is a large factor in infection rates of triatomine vectors; Triatoma infestans, vinchucas, have a rapid time period.
Within the insect, T. cruzi go through their reproductive cycle in eight to ten days and produce as many as 100 protozoa. The number produced is affected by the blood-meal size, the number of parasites ingested, the stage and age of the insect vector, the ability of the parasite to establish rectal gland infections in the vector, and the kinetics of parasite transformation in the insect’s digestive tract (WHO 1991:22).
The susceptibility of triatomine vectors to infection with T. cruzi varies greatly among different vector species and with their interaction with strains of T. cruzi (WHO 1991:22). The presence of three main isoenzymic strains (zymodemes) within T. cruzi was discovered in Brazil (Miles et al. 1977; Ready and Miles 1980) and more have been found in Bolivia (Tibayrenc et al. 1984) and Chile (Gonzalez et al. 1995). The geographic frequency of occurrence of the principal isoenzymic strains has been described in these countries and is important to pathogenicity (Breniere et al. 1989, Miles, Provoa, Prata, et al. 1981) and genetic variability of T. cruzi (see Appendix 2).
APPENDIX 2
Strains of T. cruzi
T. cruzi strains are classified into schizodemes and zymodemes: schizodeme classification is based on electrophoretic mobility of kinetoplast DNA (see Gonzalez et al. 1995 for description of methodology). Electrophoresis indicates characteristic mobility in an electric field by the DNA of various strains. Zymodeme classification is based upon enzymatic profiles of parasite strains (see Miles et al. 1977, Ready and Miles 1980). Metacyclic trypomastigotes are examined in vitro for genetic variation indicated by isoenzyme analysis (Breniere et al. 1991).
Zymodeme (schizodeme) classification is useful for identifying strains of differing pathogenic potential and for distinguishing between organisms which cause human diseases and those that cause animal diseases (Breniere 1989). Genetic interpretation of zymograms of T. cruzi from various hosts over a broad geographical range (from Argentina to the United States) has revealed great genetic variability (WHO 1991:13). Supposedly, these characteristics are fairly stable in a strain, but this is not always the case.
Schizodemes or zymodemes are important classifications to determine in infected patients because different strains show affinity for different tissues and cause varied pathologies. The fact that patients in Sucre, Bolivia, have a high incidence of colonopathy may be explained by zymodemes distinct from those found in La Paz, which favor cardiopathy (Breniere et al. 1989). In highly endemic areas of Santa Cruz, patients are often infected with more than one strain. These strains may cause differing pathologies in the same individual. This implies that humans may be challenged by different strains even after developing so-called partial immunity to one strain.
In the Amazonian basin of Brazil, zymodemes Z1 and Z3 have been isolated from sylvatic sources, principally with armadillos (Dasypus) and opossums (Didelphis) as hosts and reduviids (Panstronglyus megistus) as vectors that are associated with these mammals (Miles, Provoa, Prata, et al. 1981 and Miles, Provoa, de Sovza, et al. 1981). Z1 is also found in some domestic environments of Venezuela, where megasyndromes infrequently occur. These sylvatic zymodemes are more frequently associated with acute Chagas’ disease than are Z2 zymodemes. Zymodeme Z2
