More than a century ago, Carlos Chagas discovered American trypanosomiasis , now known as Chagas disease (CD) and named in his honor. He detailed the clinical characteristics of the disease, as well as the aetiological agent: Trypanosoma cruzi , a parasite, and the insect vector. At first it was thought that Chagas disease was a hidden and little obvious disease that only occurred in Latin America . Recently, it has become a global neglected disease, with a high morbidity rate and serious social effects, which is a serious public health problem.
Trypanosoma cruzi infects around 6-8 million people worldwide and kills around 14,000 people each year. Although discovered more than a century ago, this disease remains one of the most serious public health problems in most Latin American countries. Due to the continuous migration of people from endemic places, Chagas disease has in recent decades become a concern for non-endemic places, such as Canada, the United States, Europe, Australia and Japan.
What is Chagas disease?
Chagas disease is caused by a parasite known as Trypanosoma cruzi . It is known as a vector- borne disease , which means that the parasite needs to live on insects or bugs, using them as a source of nutrition and function. These insects become vectors, and through them the parasites that cause the disease are transmitted.
In Chagas disease, Triatominae (or Triatomine) bugs transmit T. cruzi in South and Central America, in Mexico, and very rarely in the United States. The other reservoirs for T. cruzi are domestic dogs, opossums, armadillos, rats, raccoons, and a wide variety of other animals.
Pathophysiology of Trypanosoma cruzi
The most typical way of spreading Chagas disease is when a triatomine attacks an infected human or animal, and then attacks another person. Carrier bugs, when they bite , not only ingest blood, but also leave excrement carrying T. cruzi on the skin , in the form of metacyclic trypomastigotes (the first morphological stage of T. cruzi ). These infective forms enter the body through bite wounds or through mucous membranes, such as the conjunctiva or nasal mucosa.
Once inside the host, they invade cells close to the inoculation cycle, where they transform into amastigotes (the second morphological stage of T. cruzi), which have the capacity to multiply. Once multiplied, they can transform into blood trypomastigote (or promastigotes) (the third morphological stage of T. cruzi ) and spread throughout the body through the bloodstream.
At this point, the protomastigote can either end up in a new cell, which when it infects it, transforms back into an amastigote, or in a new bedbug when they bite and ingest the infected blood.
When the triatomine “sucks” the carrier’s blood, it is ingesting trypomastigotes, which, once in the midgut of the bug, will transform into epimastigote (the fourth morphological stage of T. cruzi), where they will multiply. When these epimastigotes reach the hindgut, they will evolve into metacyclic trypomastigotes again, paving the way for infecting a new being.
It should be noted that the most commonly affected cells are those of the reticuloendothelial system, the myocardial region, the muscles, and the nervous system.
Signs and symptoms
Chagas disease can be divided into three different stages : the acute stage, the indeterminate chronic stage, and the chronic stage.
In endemic settings, acute T. cruzi infection frequently occurs in childhood and may be silent and asymptomatic. Symptoms appear 1 to 2 weeks after exposure, if they occur at all. At the site of entry of the parasite, a chagoma (wrinkled and inflamed skin lesion) forms. Acute Chagas disease kills a very limited percentage of people; mortality is caused by rapid myocarditis with cardiac arrest or meningoencephalitis. The rest of the time, the symptoms go away on their own. In immunosuppressed individuals, such as those with AIDS, primary acute Chagas disease may be more severe than usual, with skin lesions and, in rare cases, ring-shaped brain lesions.
On the other hand are people with chronic indeterminate infection . These people have parasitological and/or antibody evidence of T. cruzi infection, but no symptoms, clinical signs, or evidence of cardiac or gastrointestinal involvement in tests that determine Chagas disease. When they donate blood, many contaminated patients are recognized through screening techniques.
After the previous phase, which can last years or decades, chronic Chagas disease can develop. It usually occurs in only 20-30% of people with an undetermined chronic infection. Parasites may be present in chronic diseases, and an immune response may also play a role in organ damage. The most common problems caused by this disease are the enormous dilatation and muscular hypertrophy of the affected organs , especially the cardiac ones (causing ventricular enlargement, cardiomyopathy, heart blocks, arrhythmias,…) and gastrointestinal ones (causing dysphagia, pulmonary infections due to aspiration, malnutrition , constipation,…).
It should also be noted that there are congenital infections , which are acquired because the mother was infected during pregnancy. They are mostly asymptomatic, but nonspecific manifestations appear in 10 to 40% of cases (prematurity, low birth weight, anemia, fever, thrombocytopenia, or liver and spleen enlargement). Signs of acute infection resolve even without treatment in most congenital infections.
Causes and transmission
As we have already mentioned, T. cruzi parasites are transmitted mainly through contact with the feces/urine of infected triatomine bugs . Bed bugs that carry the parasite live in cracks in the walls or roofs of houses and peri-domiciliary structures in rural and suburban regions, such as chicken coops, farmyards, and warehouses. They usually hide during the day and come out at night to feed on the blood of animals, which includes human blood. They bite an exposed part of the skin, and defecate or urinate along with the bite. A person becomes infected when they introduce the fecal matter or urine of the bug into the bite, or into any other wound or mucosa (eyes, mouth, nose,…), and the parasites enter the body.
It can also be transmitted by blood transfusions from infected donors , although it is quite unusual because extensive tests are usually done on donated blood before administering it. Other forms of transmission are from mother to child during pregnancy or childbirth, through organ transplants from infected donors, and, rarely, from bedbug-infected food.
Diagnosis and treatment
Chagas disease can be diagnosed by examining blood or affected tissue under a microscope . To confirm that it is this disease, a second confirmation test is required, in which an antigen test against T. cruci or a PCR is performed. Occasionally, the antigens and the PCR can give false positives, since there are other diseases that react in the same way as Chagas disease, as is the case with leishmaniasis.
Both microscopic testing and PCR are completely dependent on parasites being present at the time of testing, but when we are in a chronic phase, we hardly have any parasites to assess, and they can give false negatives. Therefore, the best way to confirm Chagas disease is through an antigen test against T. cruci and a thorough examination of the lymph nodes and the gastrointestinal and cardiac systems .
Chagas disease can only be treated with antiparasitics in its acute, congenital (in those under 18 years of age) or reactivated phase. It should be noted that the younger the patient, and the sooner treatment is started, the greater the chances of cure. However, the effectiveness of treatment decreases the longer the infection lasts. The only antiparasitic drugs that have been shown to work are Bezonidazole and Nifurtimox .
References:
Chagas disease (also known as American trypanosomiasis ) (2022). World Health Organization. https://www.who.int/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis)
Lidani, K. C. F., Andrade, F. A., Bavia, L., Damasceno, F. S., Beltrame, M. H., Messias-Reason, I. J., y Sandri, T. L. (2019). Chagas Disease: From Discovery to a Worldwide Health Problem. Frontiers in Public Health, 7, 166. https://doi.org/10.3389/fpubh.2019.00166
Pch.vector(s.f.). Fat patient visiting doctor. woman suffering from overweight, obesity, heart disease, having diabetes risk [Free Vector]. Freepik. https://www.freepik.com/pch.vector
Pearson, R.D. (2020). Chagas disease . MSD Manuals. https://www.msdmanuals.com/es-es/hogar/infecciones/parasitic-infections-extraintestinal-protozoa/chagas-disease
Kirchhoff, L.V. (2019). Which organ systems are affected by Chagas disease (American trypanosomiasis)? Medscape. https://www.medscape.com/answers/214581-112024/which-organ-systems-are-affected-by-chagas-disease-american-trypanosomiasis
