Trypanosoma cruzi: pathogenesis, epidemiology, and recent developments in the potential treatment of Chagas' disease

From MicrobeWiki, the student-edited microbiology resource

Background and Significance

Emigration routes of individuals with Chagas disease. Numbers indicate total infected individuals in various regions. Nature.

By [Sriya Chadalavada]


Trypanosoma cruzi is a protozoan parasite that is most frequently transmitted through triatomine bugs. The genome of T. cruzi was fully sequenced in 2005. [8] Triatomine bugs belong to the Rediviidae family and are colloquially known as “kissing bugs” due to sucking blood near the victim’s face when feeding. [4] The infection of T. cruzi results in a lifelong condition known as American trypanosomiasis or Chagas disease. Although only a few species are known to cause Chagas disease, over 130 Triatomine bugs species have been identified. [6] At least eleven species of triatomine bugs are confirmed to be capable of transmitting the T. cruzi parasite. [2] Of these Triatoma infestans, Rhodnius prolixus, and Triatoma dimidiate result in the highest number of infections. Triatonimes themselves appear to be unaffected by T. cruzi infections. [6]


There is less research and international concern for T. cruzi and Chagas disease than what many scientists believe is required. The World Health Organization (WHO) has categorized Chagas Disease as “one of the world’s 13 most neglected tropical diseases.” [6] Although the disease and parasite were discovered over a century ago, there remains to be a lack in scientific efforts for better treatment and cures. The human infection of Chagas disease is endemic to Latin America. [11] Although Chagas disease was once centered in Latin America, it has gradually spread across the world.[6] Chagas, a Brazillian physician initially identified the disease in 1909. Later, it was discovered that Chagas disease had afflicted humans at least as early as 9000 years ago when T. cruzi DNA was isolated from human mummies. Some historians believe that Charles Darwin may have suffered from Chagas Disease according to his recorded accounts of coming in contact with triatomine in South America and symptoms later in life. [6] Since the turn of the century, the incidence rates of Chagas disease has greatly decreased. [11]


Humans are typically bitten when asleep. As the face is often left uncovered, most bites occur in this area. Prior to feeding, kissing bugs extend mouthparts from underneath their body. It is then used to feed on blood. [12] Feeding can continue for up to a few minutes. If interrupted when feeding, kissing bugs may leave a cluster of bites. Defecating during feeding is common. [4] Chagas disease spreads to humans when the fecal matter of T. cruzi enters the bloodstream through a break in the skin. Very rarely, it can also be transmitted if consumed with food or drink. [2][6]


T. cruzi is a hemoflagellate, meaning it can live in the bloodstream and has flagella. T. cruzi has a life cycle with three stages: epimastigotes, trypomastigotes, and amastigotes. Replication occurs at the epimastigotic stage, typically in the midgut of kissing bugs. They then become trypomastigotes. This process differentiates the stage from when T. cruzi is nonpathogenic to becoming pathogenic. They are non-replicative. When the insect defecates, the parasite is also released and has the ability to enter the bloodstream and infect a mammalian host. Once inside cells, the T. cruzi begin transforming to amastigotes, the principal form of the parasite in vertebrate hosts. [4] T. cruzi replicate through binary fission. [13]While other mammalian tryposomes divide in the bloodstream, T. cruzi can only replicate in cells. [21] Following replication for multiple generations, they then become trypomastigotes before leaving infected cells for new cells. They then alternate between these last two stages as they enter and leave cells. [14]


There has been research on additional physiological, biochemical, and pathological variations between these forms. As epimastigotes transform to trypomastigotes, there are notable changes to multiple organelles, primarily within the mitochondria and glycosomes. During this stage of differentiation, the parasite was also found to accumulate significantly more lipids to use as its primary energy reserve. [17] Epimastigotes exhibit lower negative surface charges than trypomastigotes. This was found to be due to the presence of increased sialic acid on the surface of the trypomastigotic form. [19]The epimastigotic form of T. cruzi fixes CO2 as facultative anaerobe and produces succinate during glucose metabolism. It is believed that either PEP carboxykinase or malic enzyme is responsible for CO2 fixation. [23]













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Epidemiology

Reduviidae can be found across the world, but Tritominae are specific to the Americas. [12] They prefer to live in grassy or wooded regions. [10] Triatomines have a strong preference for warm climates. [12] June is the month when the most bites are reported. [4] Factors such as deforestation and habitat loss may contribute to the spread and growing prevalence of triatomines, particularly in rural regions of Latin America. 11] The North American population of Triatome bugs is continuously expanding. Although additional research is necessary to make this claim, some believe that global warming is contributing the spread of these bugs northwards. [4]

In some regions studied, half of the triatomine bugs contained the parasite. [2] In one survey, 25% of the bugs collected in the Tuscan, Arizona area contained T. cruzi and this ratio was almost 50% in San Diego, California. They obtain T. cruzi when feeding on mammalian hosts of this parasite. The following animals have been found particularly vulnerable to the parasite: rodents, possums, raccoons, armadillos, skunks, and dogs, cats, chickens. [2] [3] In the United States, there are approximately 300,000 people living with Chagas disease, most of which are Latin American immigrants. [2] [4] Only six cases of direct bug to human transmission have been reported in the United States. Concurrently, in Latin America there are around 8 million people living with Chagas disease. The disparity in infections between these regions is notable.

It is thought to be in part due to the unsuitability of Triatonite bug colonization in homes in the United States. [4]. This is a socioeconomic factor of infestation. In homes built of mud, sticks, and tiles, there is a greater chance of kissing bug infestation. Such homes are more common in Latin America. In homes built of cement and brick, a housing style customary in the United States, there was a greatly lowered chance of infestation. Another reason could be the absence of certain foliage in proximity to homes in the United States. One study found that kissing bugs were more prevalent in Latin American homes with certain fruit-bearing trees such as avocado or coffee. This was thought to be due to the specific leaf litter from the trees enabling an ideal breeding location. [3] Other factors could include the bugs preferring other mammalian hosts over humans and delayed defecation after biting [4].

Another method of control is the use of synthetic parathyroid insecticides. Depending on the surface used, the insecticide may be effective from 2 months up to a year. Resistance among kissing bugs is very low since they have long lifespans and low tendencies of genetic variability. [5] In South and Central America, the main form of transmission to humans is from insects. Chagas disease is more prevalent in the poor and rural areas of this region. In the 1980’s there was an expansive survey that suggested around 25% of Latin America was at risk of contracting Chaga’s disease. This would be 100 million individuals. [6]

Approximately 12,000 people die from Chagas disease every year. [2] The United States is the country with the highest number of Chagas disease infected migrants. The country with the second highest number is Spain with an estimated 67,000 affected immigrants. [6] Due to the rising number of affected individuals in the United States, extra precautions have been implemented. For example, donated blood has been tested for Chagas disease since 2007. [4] The primary precautionary effort has been through screening blood donations. This practice has been legally implemented and enforced in almost all endemic countries such as Uruguay, Chile, and Brazil. Another preventative method is the use of insecticides. The incidence statistics indicate that the number of people newly infected every year has decreased drastically. This number went from around 700,000 in the year 1990 to just 41, 200 in 2006. The number of fatalities every year from Chagas disease has also decreased from 50,000 to 12,500 within the aforementioned years. [6]

Pathogenesis

Treatment

References


1. de Andrade, Ana Lucia S. Sgambatti, et al. "Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection." The Lancet 348.9039 (1996): 1407-1413.

2. Montgomery, Susan P., et al. "Neglected parasitic infections in the United States: Chagas disease." The American journal of tropical medicine and hygiene 90.5 (2014): 814-818.

3. Bustamante, Dulce M., et al. "Ecological, social and biological risk factors for continued Trypanosoma cruzi transmission by Triatoma dimidiata in Guatemala." PLoS One 9.8 (2014): e104599.

4. Klotz, John H., et al. "“Kissing bugs”: potential disease vectors and cause of anaphylaxis." Clinical Infectious Diseases 50.12 (2010): 1629-1634.

5. History of insecticide resistance of Triatominae vectors, 48, Revista da Sociedade Brasileira de Medicina Tropical, 2015

6. Rassi, Anis, and José Antonio Marin-Neto. "Chagas disease." The Lancet 375.9723 (2010): 1388-1402.

7. Cardoso, Mariana S., João Luís Reis-Cunha, and Daniella C. Bartholomeu. "Evasion of the immune response by Trypanosoma cruzi during acute infection." Frontiers in immunology 6 (2016): 659.

8. El-Sayed, Najib M., et al. "The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease." Science 309.5733 (2005): 409-415.

9. Trischmann, Thomas, et al. "Trypanosoma cruzi: role of the immune response in the natural resistance of inbred strains of mice." Experimental parasitology 45.2 (1978): 160- 168.

10. Ibarra-Cerdeña, Carlos N., et al. "Ecology of north american triatominae." Actatropica 110.2 (2009): 178-186.

11. Abad-Franch, Fernando, et al. "Ecology, evolution, and the long-term surveillance of vector-borne Chagas disease: a multi-scale appraisal of the tribe Rhodniini (Triatominae)." Acta tropica 110.2 (2009): 159-177.

12. Schofield, C. J., and Cleber Galvão. "Classification, evolution, and species groups within the Triatominae." Acta tropica 110.2 (2009): 88-100.

13. Combs, Terry P., et al. "The adipocyte as an important target cell for Trypanosoma cruzi infection." Journal of Biological Chemistry 280.25 (2005): 24085-24094.

14. Bonaldo, Myrna Cristina, et al. "Cell-substrate adhesion during Trypanosoma cruzi differentiation." The Journal of cell biology 106.4 (1988): 1349-1358.

15. Cunha-Neto, Edécio, et al. "Autoimmunity in Chagas' disease. Identification of cardiac myosin-B13 Trypanosoma cruzi protein crossreactive T cell clones in heart lesions of a chronic Chagas' cardiomyopathy patient." Journal of Clinical Investigation 98.8 (1996): 1709.

16. Cantey, Paul T., et al. "The United States Trypanosoma cruzi Infection Study: evidence for vector‐borne transmission of the parasite that causes Chagas disease among United States blood donors." Transfusion 52.9 (2012): 1922-1930.

17. Soares, M. J., et al. "A stereological study of the differentiation process inTrypanosoma cruzi." Parasitology research 75.7 (1989): 522-527.

18. De Souza, E. M., et al. "Antiparasitic activity of aromatic diamidines is related to apoptosis-like death in Trypanosoma cruzi." Parasitology 133.01 (2006): 75-79.

19. Souto-Padron, T., et al. "Further studies on the cell surface charge of Trypanosoma cruzi." Acta tropica 41.3 (1984): 215-225.

20. Piñeyro, María Dolores, et al. "Peroxiredoxins from Trypanosoma cruzi: virulence factors and drug targets for treatment of Chagas disease?." Gene 408.1 (2008): 45-50.

21. Culbertson, James T., and Maxwell H. Kolodny. "Acquired immunity in rats against Trypanosoma cruzi." The Journal of Parasitology 24.1 (1938): 83-90.

22. Hauschka, Theodore S. "Sex of host as a factor in Chagas' disease." The Journal of parasitology 33.5 (1947): 399-404.

23. de Flombaum, María A. Cataldi, et al. "CO2-fixing enzymes in Trypanosoma cruzi." Comparative Biochemistry and Physiology Part B: Comparative Biochemistry 58.1 (1977): 67-69.

24. Fragata Filho, Abílio Augusto, Marco Aurélio Dias da Silva, and Elias Boainain. "Ethiological treatment of acute and chronic Chagas' heart disease." Sao Paulo Medical Journal 113.2 (1995): 867-872.




Authored for BIOL 238 Microbiology, taught by Joan Slonczewski, 2017, Kenyon College.