Chagasic Cardiac Arrest: The Silent Latin Killer

by MR

Imagine a disease that can remain largely asymptomatic for decades, and then one day drop you dead seemingly out of the blue. Well, just such a disease happens to have been prowling the South American continent for thousands of years, and is advancing into the United States as you read this very article.

This silent killer is known as Chagas disease and is caused by the protozoan parasite Trypanosoma cruzi. T. cruz, is progressively becoming better understood as the prevalence of the disease within scientific literature continues to expand. The Brazilian physician Carlos Chagas first characterized the organism and disease in 1909, but recent paleoparasitological studies have revealed the presence of T. cruzi in Chilean mummies dating from nearly 4000 BC (1). T. cruzi is protozoan parasite with a single flagellum and a single, specialized organelle known as a kinetoplast. The kinetoplast is a mitochondrial DNA rich area of the protozoan associated with the basal body, and thus is capable of independent replication (2). Despite the presence of this mitochondria-like structural component, T. cruzi remains an obligate intracellular protozoan parasite.

Figure 1: T. cruzi  takes several forms throughout its

lifecycle. An infectious trypomastigote form can be found

in the human bloodstream, while an intracellular amastigote

form inhabits the hosts tissues. Additionally, a reproductive

epimastigote form can mainly be found within the insect

gut prior to infection of the host (4).

The protozoan is primarily transmitted by members of the reduviidee family, commonly titled “Kissing Bugs”, where the T. cruzi multiply in the bug’s midgut. “Kissing Bugs”, similar to cockroaches, are nocturnal insects that hide in cracks and crevases in bright environments. When a room becomes dark the insects preferentially crawl to softer tissues on the human face, including the eyelids and lips. When obtaining a blood meal from a human host these insects initially puncture the skin with their mouthparts and often proceed to defecate near the puncture site. T. cruzi largely inhabit the gastrointestinal tract of the Kissing bugs, and are thus excreted directly near the open wound site. Often, the human host will rub the area surrounding the puncture site, thereby introducing T. cruzi directly into the bloodstream (3). In the process of this transfer from the Kissing Bug vector to the human host, T. cruzi takes several distinct forms to optimize its infective capabilities in producing Chagas disease (Figure 1).

Chagas disease can have a variety of symptoms that are largely condensed into two distinct phases: acute and chronic. The early acute phase typically lasts for the first several weeks or months following infection and shows a high level of T. cruzi parasitemia. Symptoms are generally mild and indiscriminate at this point, and may include: infection site swelling, fever, headache, and nausea (5). Often these symptoms will disappear after this initial period, and the infected person will resume normal life activities. Unfortunately, the cessation of these symptoms is not the end of the infection, but merely the beginning of an intricate immunodepression mechanism used by T. cruzi to avoid triggering the immune response (6,7). The mild nature and short span of these acute symptoms rarely leads the infected person to seek medical care, allowing for the disease to progress into a chronic intermediate phase. At this point the infecting T. cruzi enter a lifelong infection characterized by a low level of sequestered cells in the host tissue that remains largely asymptomatic. Roughly 20-40% of these cases eventually enter a severe chronic phase that can include irregular heartbeat, cardiomyopathy, congestive heart failure, and sudden cardiac arrest (5,8). Onset of these symptoms can vary greatly in length, but often prove fatal under conditions of immediate occurrence. The mechanisms behind these sudden symptoms can include: severe bradarrhythmia, ventricular fibrillation or tachycardia, severe embolic complications, and spontaneous ventricular rupture (9). What is most fantastical about these instances of sudden death is that the individuals often are asymptomatic leading up to the event. It is in this manifestation of abrupt mortality that Chagas disease has gained increased interest within the medical and public health fields today. 

Chagas disease, once largely limited to Latin America, has begun to move northward into the United States as immigration from endemic areas has steadily increased. In addition to immigration concerns, recent studies have indicated that the risk for T. cruzi infection may be higher in the southern United States than previously thought (10). Consequently, the CDC currently recognizes Chagas disease as one of five neglected parasitic infections that is targeted for public health action (11). With an estimated 8-11 million infected persons in Latin America and over 300,000 infected persons in the United States, Chagas disease is undoubtedly a growing public health concern today (12).

In a world of ever expanding globalization it is becoming essential for previously isolated diseases to be better characterized and researched. Chagas’ disease is a prime example of this need, presenting an expanding real life possibility of superstitious instant death. It is only through increased exposure that such a fantastical silent killer might someday be fully unveiled.

References:

1) Aufderheide AC, Salo W, Madden M et al. 2004. A 9,000-year record of Chagas’ disease. Proc Natl Acad Sci USA, 101:2034-2039.

2) Shapiro TA and PT Engulund. 1995. The structure and replication of kinetoplast DNA. Annu Rev Microbiol, 49:117-43.

3) Stevens L, Dorn PL, Schmidt JO, Klotz JH, Lucero D, and SA Klotz. 2011. Kissing bugs. The vectors of Chagas. Adv Parasitol, 75:169-92.

4) Carvalho MF, de Franco MF, and VA Soares. 1997. Amastigotes forms of Trypanosoma cruzi detected in a renal allograft. Rev Inst Med Trop Sao Paulo, 39(4):223-6.

5) “Chagas Disease: Symptoms.” Mayo Clinic, 2012.

6) Ouaissi A, Da Silva AC, Guevara AG, Borges M, and E Guilvard. 2001. Trypanosoma cruzi-induced host immune system dysfunction: a rationale for parasite immunosuppressive factor(s) encoding gene targeting. J Biomed Biotechnol, 1(1):11-17.

7) Leon JS, Godsel LM, Wang K, and DM Engman. September 2001. Cardiac myosin autoimmunity in acute Chagas' heart disease. Infect Immun, 69(9):5643-5649.

8) Hagar JM and SH Rahimtoola. 1991. Chagas’ heart disease in the United States. N Engl J Med, 325:763-768.

9) Mendoza I, Moleiro F, and J Marques. 1992. Morte subita na doenca de Chagas. Arq Bras Cardiol, 59:3-4.

10) Reisenman CE, Lawrence G, Guerenstein PG, Gregory T, Dotson E, and JG Hildebrand. March 2010. Infection of kissing bugs with Trypanosoma cruzi, Tucson, Arizona, USA. Emerg Infect Dis, 16(3):400-405.

11) “Neglected Parasitic Infections in the United States.” Centers for Disease Control and Prevention, 2012.

12) “Chagas Disease in the Americas.” Centers for Disease Control and Prevention, 2011.