The fear behind the Chagas disease

https://www.youtube.com/watch?v=2Buhct1P0HY

This video show the fear behind the Chagas disease where it is a silent but deadly killer. In this video, researchers, doctors and patients speak about Chagas disease. There are real patients who is experiencing Chagas disease and they shared how they are affected by it. The video highlight the urgent need to treat the patients today but also the importance of finding better treatments for the future. Hence it show the challenge that we are facing now in the healthcare sector, the limitation to treatment.

Also known as The Chagas Disease

This video give a real quick overview of the Chagas disease. We hope you will take a look at this short 9 minutes video to have a quick understanding of Chagas disease before reading the other posts to find out more details and information of Chagas Disease.

Recently I have read an article, titled: "More Than Ebola, Other Tropical Diseases Pose Growing Threat to U.S." by Katherine Hobson for National Geographic (1). The article reminds us that although ebola has recently become a hot topic, there are actually a handful of other tropical diseases that pose a greater threat should we allow them to gain a foothold in local insect populations and one of these diseases is the Chagas Disease.

The Chagas Disease or scientifically: American Trypanosomiasis, is a parasitic disease that can be commonly transmitted through an insect vector, or directly from an infected beings’ blood. The disease is named after the Brazilian Carlos Chagas who discovered the disease in 1909, and is a disease that used to be only found in the Americas.(2) However with technological advancements and improved population mobility, it can now be found in many European and Western Pacific countries(3)

Insect vectors such as kissing bugs* help to transmit the disease in a disgusting manner: They bite people’s faces at night (usually around the mouth) and leave poop behind. The parasite known as Trypanosoma cruzi, in the bug’s faeces and enters the victim’s body through the bites or via the eyes or mouth.(1) That being said, the parasite can also go from mother to child and through contaminated blood and organ donations. That being said, blood supply has been screened for T.cruzi since 2007. (1)

*Kissing bugs are bloodsucking North American assassin bugs that are members of the Triatomina, a subfamily of reduviidae. They usually give a painful bite to the face of the victim. (1)

The kissing bug (Triatoma dimidiata) spreads Chagas disease by biting people's faces while they sleep and leave infected feces behind. (1) 

PHOTOGRAPH BY JOHN CANCALOSI


(The Life Cycle of the parasite)

This video will better explain and show the process of the cycle of the parasite where it show how the kissing bug transmits the Trypanosoma cruzi parasite to human and cause Chagas disease.

References:

(1) http://news.nationalgeographic.com/news/2014/11/141119-ebola-dengue-chagas-chikungunya-tropical-diseases-health/ (Picture and Article)

(2) http://www.cdc.gov/parasites/chagas/

(Obtained information of how it was named at first)

(3) http://www.who.int/mediacentre/factsheets/fs340/en/

(4)http://www.cdc.gov/parasites/chagas/biology.html (Diagram)

Biochemistry of Chagas disease

Biochemistry of the parasite 

Trypanosomes contain a variety of enzymes such as proteases, gelatinases, and collagenases that are capable of degrading native type I collagen, heat-denatured type I collagen (gelatin), and native type IV collagen (42, 78, 98). Proteolytic activities against laminin and fibronectin were also detected. These enzymes are most likely responsible for the degradation of the ECM and the subsequent tissues to aid in the parasite's invasion into the bloodstream.

The degradation of the collagen matrix, evident in acute murine Chagas' disease, may result in chronic pathologic changes such as apical thinning (77, 182). Finally, supernatants obtained from cultures of infected fibroblasts, vascular smooth muscle cells, and myocardial cells were found to stimulate fibroblast DNA and protein synthesis as well as proliferation, whereas supernatants from uninfected cells did not. This suggests that there is a mechanism by which fibrosis may occur in chronic chagasic cardiomyopathy (284).

The relationship between this enzyme and T. cruzi transsialidase has recently been investigated (230).It was found out that T. cruzi neuraminidase is inhibited by anti-neuraminidase antibodies and high-density lipoprotein, which is associated with enhanced infectivity of cells in vitro (202, 203). The significance of these observations in the pathogenesis of Chagas' disease is unclear. However, it is noteworthy that mice with higher levels of high-density lipoprotein are more susceptible to T. cruzi infection (202). The relationship between the synthesis of these parasite enzymes and the pathogenesis of the disease remains to be elucidated.

Note that most of the above results and conclusions are obtained directly from the research paper, and none of which are results obtained on my own. Please click on the link at the bottom of this update for the full paper.

Biochemistry of invasion

Trypomastigotes are refractory to complement-mediated lysis, whereas epimastigotes activate the alternate complement pathway. The mechanism of the resistance of trypomastigotes to complement is unclear, and several different mechanisms have been proposed (104, 114, 115, 235). Amastigotes activate complement but are not lysed. Trypomastigotes bind small amounts of C3 but can also infect cells that do not have C3 fragment receptors. Other host cell surface molecules may be important in the process of entry into the cell. In this regard, it has been suggested that fibronectin increases the internalization of trypomastigotes in both phagocytic and nonphagocytic cells (53) and may act as a bridge to facilitate the attachment of the parasite to the target host cell (104).The parasite undergoes a complex process involving a variety of different factors to gain host cell entry and (216). Schenkman et al. (229) shows that trypomastigotes enter cells in a polarized manner preferably along the basolateral membrane, where there is a concentrated amount of fibronectin and host cell receptors. Thus the invasion is an active process associated with factors such ashost cell protein synthesis and parasite energy(232). Parasite phospholipase A2 has also been implicated in this process (49). A T. cruzi trans-sialidase has been shown to have facilitated the generation of a trypomastigote-specific epitope, Ssp-3,which is required for invasion (231). The entry of trypomastigotes into the host cells has not been reported to be associated with a respiratory burst, suggesting that non-oxidative intracellular mechanisms may be important in limiting intracellular infection (151). Parasites may be killed by cytocidal mechanisms such as production of hydrogen peroxide within the parasitophorous vacuole. This process may be associated with lysosomal fusion (247, 256).

Note that most of the above results and conclusions are obtained directly from the research paper, and none of which are results obtained on my own. Please click on the link at the bottom of this update for the full paper.

Biochemistry of Differentiation In the complex

Three morphogenetic forms of the parasite can be recognized in the life cycle of T. cruzi

From the life cycle, these parasites multiply as epimastigotes in the midgut of the insect vector. After transformation into metacyclic trypomastigotes, the organisms are deposited with the faeces of the vector and infect mammalian cells in mucosal surfaces, conjunctiva, or breaks in the skin. Once it has successfully invaded the host cells, the parasites transform into amastigotes and, after several cycles of multiplication, revert back into bloodstream amastigotes, which are morphologically similar to the trypomastigotes present in insect faeces. The host cell then ruptures, releasing these parasites into the adjacent tissues and blood circulation. The cycle is completed when the circulating trypomastigotes are ingested in a blood meal taken by another insect vector and transforms in to epimastigotes in its midgut.

Ref:
http://cmr.asm.org/content/5/4/400.full.pdf

Symptoms, cures and prevention ~

Signs & symptoms

There are two phases to the disease: the acute phase which occurs shortly after the parasite enters the body and the chronic phase which happens if it is left untreated and allowed to develop past the acute phase.

The acute phase will last from weeks to months and is usually unnoticeable because there are no obvious signs. It can exhibit mild symptoms like fever, fatigue, body aches, rashes, headaches, diarrhea and vomiting whereby none are unique to the Chagas disease. Hence, it is hard to identify whether you have been infected with the Chagas disease.The most recognizable sign is the Romaña's sign. It appears as a swelling of the eyelid on the side of the face near the bite wound or where the bug faeces were deposited or rubbed into the eye. 

Although it is rare for someone to die during the acute phase, it can be severe in people with a weak immune system. With treatment, these symptoms can be resolved, but the infection may yet persist and enter the chronic phase. 

In the chronic phase, the Chagas disease can be categorized into two types: determinate chronic Chagas disease and indeterminate chronic Chagas disease. Individuals that suffer from determinate chronic Chagas disease will develop life-threatening and digestive disorders during their remaining lifespan while Individuals that suffer from indeterminate chronic Chagas disease will not develop any symptoms. Statistics show that 60 to 80% of individuals that pass into the chronic phase will have indeterminate chronic Chagas disease, while the remaining 20% to 40% will suffer from determinate chronic Chagas disease. 
Among those suffering from determinate chronic Chagas disease, two-thirds of them will develop cardiac alterations and cardiac damage (incl. dilated cardiomyopathy) which may result in a sudden death. The rest of these individuals may go on to accumulate damage in the neurological, digestive systems or develop mixed alterations which will require treatment. The damage to the digestive system may result in the dilation of the digestive tract (megacolon and megaesophagus) and severe weight loss. This may then lead to malnutrition. 

Treatment

To cure the Chagas disease, the parasite must be killed. The parasite is treated with benznidazole and nifurtimox. This treatment must be done in the early stages because it is only then, that these medicines have an almost 100 % chance of curing the Chagas diseas. As the parasite continues to grow and develop, these medicines becomes less and less effective. Thus it is very important to go for a check up immediately  if you are suspected to have, show signs (Romaña's sign) or have been to places infested with 'kissing bugs' (triatomine bugs). Additionally, benzidazole and nifurtimox should not be taken by pregnant women or individuals with kidney or liver failure. Infected adults with no obvious symptoms will be treated with antiparasitic treatment to prevent and curb disease progression.

Control and prevention

There is no vaccine against the Chagas disease. Hence the most effective measure is to avoid triatomine bugs and it's vector infestations.  Some precautions that can be taken to reduce the spread of the disease, is to (a) do blood screening tests to prevent the spread of infection through transfusion and organ transplantation. (b) spray the surrounding areas and houses with residual insecticides. (c) the screening of newborns and children of infected mothers to provide early diagnosis and treatment. Last but not least, (d) to have good hygiene practices in food preparations, transportation, storage and consumptions should be taken.

Ref:

http://www.who.int/mediacentre/factsheets/fs340/en/

https://en.wikipedia.org/wiki/Chagas_disease
http://www.webmd.com/a-to-z-guides/chagas-disease-overview?page=2
http://www.who.int/mediacentre/factsheets/fs340/en/