Chagas disease is a parasitic infection caused by the protozoan Trypanosoma cruzi. It is most often transmitted by nocturnal, blood-sucking insects called kissing bugs. When the kissing bug feeds, it defecates, and the sleeping victim unconsciously scratches the bite scene and introduces the infected feces into their blood stream. The disease affects not only humans, but several species of mammals, including dogs, raccoons, bats, and opossums. Chagas disease can also spread through blood transfusion or organ transplant, from mother to child in the womb, and via consumption of contaminated food. Chagas disease is on the World Health Organization’s list of neglected diseases because it predominantly affects poor people in rural areas of Latin America, and because it has received little attention from pharmaceutical research and development. Annually, some 300,000 new cases of Chagas disease are diagnosed worldwide, and it claims about 15,000 lives per year. Today, it is considered one of the most serious so-called neglected diseases, due to its current geographical reach. Over 6 million people worldwide have Chagas disease, the majority in Latin America. Estimates suggest over 300,000 Latin American immigrants in the U.S. have Chagas disease.
However, it is important to note that kissing bugs also inhabit the entire southern half of the country and Chagas disease has existed in the U.S. for centuries. While Chagas is often considered a foreign, exotic disease of the tropics, this characterization is inaccurate. Since screening of the blood supply began in 2007, many infected individuals have been identified who never lived or traveled in Latin America. The extent of the disease in the U.S.-born population is unknown because there is no routine screening outside of blood donations. Individuals from certain areas of Latin America are at higher risk, though, because rural housing construction and insect behavior there cause higher rates of transmission. A person who is newly infected may experience an acute stage with flu-like symptoms which is seldom recognized as Chagas disease. Afterwards, T. cruzi hides in organ tissue, especially within the heart and digestive system, and the infection is asymptomatic. However, in 30-40% of infected individuals, chronic complications will develop, usually 20-30 years after transmission. Most often, Chagas disease causes cardiac damage and can lead to heart failure and death. Studies in Argentina demonstrated that treatment with antiparasitic medications could halt or significantly delay the complications of advanced chronic Chagas disease.
Unfortunately, the results of a major clinical trial, BENEFIT, show that once such complications have developed, treatment may no longer be as effective. This makes it essential to identify patients early, while they are still in the indeterminate stage. Yet, this is challenging because people in the indeterminate phase feel perfectly healthy and do not perceive a need to get screened or treated for a life-threatening disease. Furthermore, Chagas disease has been severely neglected by public health systems in Latin America and the United States. There is an absence of health education campaigns about Chagas disease in the U.S., and we have found that the vast majority of people at risk of the disease have never heard of it. This is compounded by low awareness of Chagas disease among medical professionals. Most U.S. physicians do not consider it in their differential diagnosis, even if patients are from highly endemic areas. Even if patients have been diagnosed, U.S. physicians are rarely up to date with treatment guidelines and may operate under the assumption that there is no treatment for the disease. Patients who are diagnosed after giving blood often go from specialist to specialist in a vain effort to obtain treatment, losing months or years which could mean the difference between life and death.
The Center of Excellence for Chagas Disease at the Olive View-UCLA Medical Center in Los Angeles was founded in 2007. The recommended first-line treatment can cause side effects, particularly in older patients. People older than 60 are usually not treated, partly because of the severity of the side effects and partly because they may no longer need antiparasitic treatment if they have not yet developed complications. There is a simple protocol in place for managing the side effects which involves lowering doses and/or using supportive medications. Most side effects are mild. Latest research shows that there is an unknown number of US-born cases who are infected locally by vectors. Early detection and treatment of these individuals can halt or significantly delay cardiomyopathy and other life-threatening complications associated with Chagas disease, preventing a substantial burden of morbidity and mortality. Moreover, a recent study in Europe shows screening for Chagas disease in primary care facilities is highly cost effective. Efforts need to be made to raise awareness of Chagas disease, both in the general public and the medical community, so that the neglect of this disease in the U.S. and elsewhere can finally be converted into an active intervention of both prevention and care.
An about the mechanisms of invasion, a team of scientists from the University of Granada has successfully identified how the exosomes (extracellular nanovesicles) released by the parasite responsible for the disease attack heart cells, thereby causing one of its most frequent complications, cardiac illness. Exosomes are nanovesicles released by cells that play an important role in transmitting biological components, both physiologically and pathologically. This finding could make an invaluable contribution to designing new therapies to combat the disease. The study, led by Professor Antonio Osuna, Director of the UGR’s Biotechnology Institute, has demonstrated how these vesicles are able to affect healthy cells, alter their mobility, and help the parasite to enter the body. Doctor Osuna explained that these exosomes are also capable of affecting the permeability of membranes and the cytoskeleton, which facilitates the entry of molecules that would not normally have access. Among the cell types investigated, the team tested the parasitic exosomes on cultured HL-1 heart cells for the cardiac implications of the disease, detecting a dramatic change in intracellular calcium concentrations and rearrangement of actin cytoskeleton after exosome exposure.
The team’s findings have thus contributing to identifying the mechanism that could explain the clinical manifestations of Chagas disease, as well as possible therapeutic targets.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific references
Retana Moreira L et al. PLoS Negl Trop Dis. 2019; 13(2):e0007163.
de Pablos Torró LM et al., Osuna A. Front Microbiol. 2018; 9:1190.
Scarim CB et al. Eur J Med Chem. 2018 Jul 15; 155:824-838.
