Chagas Disease An Unfolding Tragedy In North America

An Open Access editorial in the PLOS Neglected Tropical Diseases Journal (PLoS Negl Trop Dis 7(10): e2300. doi:10.1371/journal.pntd.0002300) reports that Chagas disease, which many Americans have likely never heard of, is now a leading cause of heart disease among people living in extreme poverty in the Western Hemisphere, especially in Latin America, where it is a major parasitic killer.

According to the Centers For disease Control, Chagas disease is caused by the parasite Trypanosoma cruzi, which is transmitted to animals and people by insect vectors (Trypanosoma cruzi) that are found only in the Americas, mainly, in rural areas of Latin America where poverty is widespread). Chagas (T. cruzi infection) is also referred to as American trypanosomiasis. In North America, Chagas disease was first reported in Mexico in 1940, and in the United States in Texas in 1955. However, ancient mummified remains discovered in the Rio Grande Valley, indicate that human T. cruzi infection has been present in North America since prehistoric times.

The CDC estimates that as many as 8 million people in Mexico, Central America, and South America have Chagas disease, most of them not knowing they are infected. Left untreated, infection is lifelong and can be life threatening. The PLOS NTD editorial co-authors note that while confirmatory data are scarce, Mexico ranks number three, and the United States number seven, in numbers of infected individuals with Chagas disease in the Western Hemisphere, where 99% of cases occur, and that in Mexico, an national seroprevalence survey reported a rate of 1.6 percent. However, they say other reports provide alternative estimates ranging between 1.0 percent and 5.9 percent (i.e., between one to six million cases nationwide), and that in the U.S., approximately 300,000 cases are believed to be present, although one alternative estimate reports more than 250,000 cases in Texas alone, with up to one million or more cases nationwide. Including several thousand cases in Canada, there are between 1.5 million (lower estimate) and 7 million (highest estimate) cases of Chagas disease among the 500 million people living in North America, including estimates that 40,000 pregnant North American women may be infected with T. cruzi at any given time, resulting in 2,000 congenital cases through mother-to-child transmission, and that according to the Pan American Health Organization, congenital transmission may currently account for more than one-quarter of the world’s new Chagas disease cases.

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The CDC observes that much of the clinical information about Chagas disease derives from experience with people who became infected as children through vectorborne transmission. The severity and course of infection may be different in people infected at other times of life, in other ways, or with different strains of the T. cruzi parasite.

There are two Chagas disease phases: acute and chronic, both of which can range from being symptom-free to being life threatening. The CDC notes that the acute phase lasts for the first few weeks or months of infection, usually occurring unidentified because it is symptom-free or manifests only mild symptoms and signs not unique to Chagas disease. Symptoms experienced by the patient can include fever, fatigue, body aches, headache, rash, loss of appetite, diarrhea, and vomiting. Signs of Chagas upon physical examination may include mild enlargement of the liver or spleen, swollen glands, and local swelling (a chagoma) where the parasite entered the body. The most recognized marker of acute Chagas disease is called Romaña’s sign, which includes swelling of the eyelids on the side of the face near the bite wound or where the bug feces were deposited or accidentally rubbed into the eye.

Even if symptoms develop during the acute phase, they usually fade away on their own, within a few weeks or months, but even though the symptoms resolve, if untreated the infection persists. Rarely, young children (<5%) die from severe inflammation/infection of the heart muscle (myocarditis) or brain (meningoencephalitis). The acute phase also can be severe in people with weakened immune systems, and a when untreated in the acute stage, the disease becomes chronic, with up to 30% or more of infected individuals progressing to Chagasic cardiomyopathy or megavisceral disease associated with debilitating morbidity or death. Today, Chagas disease is a leading cause of heart disease among people living in extreme poverty in the Western Hemisphere, especially in Latin America, where it is a major parasitic killer.

During the chronic phase of Chagas disease the infection may remain silent for decades or even for life. However, some people develop cardiac complications, which can include an enlarged heart (cardiomyopathy); heart failure; altered heart rate or rhythm; and cardiac arrest (causing sudden death). Intestinal complications may be present, including enlarged esophagus (megaesophagus) or colon (megacolon) and can lead to difficulties with eating or with passing stool.

People can become infected in several ways. In regions where Chagas disease is endemic, the most common channel is through vectorborne transmission. The T. cruzi vectors are blood-sucking insects that become infected themselves by biting an infected animal or person. Once infected they pass T. cruzi parasites in their feces.

dr peter hotezThe PLOS NTG editorial’s co-authors are Peter J. Hotez (corresponding author), and Maria Elena Bottazzi of the National School of Tropical Medicine at Baylor College of Medicine and the Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development at Houston, Texas (Dr. Hotez is also affiliated with the James A. Baker III Institute for Public Policy at Rice University, Houston); Eric Dumonteil of the Autonomous University of Yucatan (UADY) at Merida, Mexico; Miguel Betancourt Cravioto, and Roberto Tapia-Conyer of the Carlos Slim Health Institute in Mexico; Sheba Meymandi of the Olive View-UCLA Medical Center at Los Angeles; Unni Karunakar of Medecins Sans Frontieres/Doctors Without Borders (MSF), Geneva, Switzerland; and Isabela Ribeiro, Rachel M. Cohen, and Bernard Pecoul of Drugs for Neglected Diseases initiative (DNDi) Geneva and New York, NY.

They note that the established link between poverty and Chagas disease transmission derives largely from poor-quality housing that facilitates triatomine bug invasion, together with lack of access to adequate health care and antenatal care. Triatomine bugs are typically found in houses made from materials such as mud, adobe, straw, and palm thatch. During the day, they hide in crevices in the walls and roofs, but at night, when the inhabitants are sleeping, they emerge, and because they tend to feed on people’s faces, they are colloquially known as “kissing bugs. ” After they bite and ingest blood, they leave a parting contribution by defecating on the person, who then may become infected if T. cruzi parasites in the bug feces enter the body through mucous membranes or breaks in the skin. The unsuspecting, sleeping person may accidentally scratch or rub the feces into the bite wound, eyes, or mouth.

People can also become infected through congenital transmission (from a pregnant woman to her baby); blood transfusion; organ transplantation; consumption of uncooked food contaminated with feces from infected bugs; and accidental laboratory exposure.

Additional factors related to poverty also include lack of health education and environmental management leading to vector invasion and colonization, and despite enormous strides made in Chagas vector control, through housing improvements and aggressive insecticide spraying, and case reduction or even elimination in parts of Latin America, important areas of high endemicity persist, including in North America.

Dr. Hotez et al. note despite North America appearing to have a high disease burden resulting from T. cruzi infection, remarkably little is actually known about the Chagas disease epidemiology, since no systematic effort has been undertaken to ascertain the true extent of Chagas in Mexico where some isolated communities are withering because 30 percent to 50 percent of their populations are infected with T. cruzi, and according to one estimate, overall economic losses from Chagas disease in Mexico may exceed $3 billion annually.

Nor in the U.S. has an effort to conduct widespread surveillance testing has ever been organized in states considered at highest risk of T. cruzi infection. Most human cases are presumed to have been introduced through immigration, but the researchers say it’s also known that triatomine vectors infected with T. cruzi are present throughout southern Texas and elsewhere in the U.S., and the editorial notes that there is pervasive ignorance among physicians and other health-care providers on how to recognize and diagnose Chagas disease and how it is transmitted.

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Exacerbating these gaps in surveillance is a dearth of health-care facilities offering diagnosis and treatment of Chagas disease in the U.S. The co-authors observe that until recently, treatment of Chagas with benznidazole (one of two drugs for the antiparasitic chemotherapy of Chagas disease) was thought to be safe and effective only for newborns and infants, but that the experience of Doctors Without Borders/Médecins Sans Frontières in Latin American countries has demonstrated that treatment with benznidazole is both possible and safe for children and adults alike, provided regular medical checks are performed, and advocate that investing in research for new diagnostics, drugs, and vaccines to combat Chagas is imperative. They note that the waiting list for benznidazole can be excessively long and that a program to accelerate access to this essential medicine needs to be implemented. Moreover, pregnant women in Chagas-endemic regions of Mexico should be tested for T. cruzi infection and offered treatment after delivery and/or after completing breastfeeding, and obviously infants with congenital Chagas disease need to be treated with a new pediatric dosage form of benznidazole developed by the Drugs for Neglected Diseases initiative (DNDi) made more widely available.

Another PLOS NTG recommendation is that increased support for U.S. federal, state, and local public health agencies is needed to facilitate implementing programs of surveillance, disease burden assessment, and treatment programs in Texas and other southern states, and for some urban communities with large populations of immigrants from Chagas disease-endemic areas. Regulatory issues surrounding use of benznidazole in the U.S. need address in order to provide expanded treatment options, along with expanded training for doctors and other healthcare personnel on how to recognize signs and symptoms of Chagas disease, identify at-risk individuals, obtain clinical testing, and begin appropriate care for patients, especially for obstetricians who may be caring for T. cruzi-infected expectant mothers.

Additionally, health research in Mexico needs prioritization commensurate on disease burden estimates, and research capacity for Chagas disease across North America expanded to develop or improve current treatments, and there is a desperate need to develop improved drugs, since the two currently available to treat Chagas are of limited efficacy in some clinical situations, have undesirable adverse events, and are contraindicated in pregnancy. There is currently nothing to offer pregnant women at risk of passing their T. cruzi infection onto their unborn fetuses. They note that DNDi is currently developing a new azole drug candidate that may have a better safety profile, with clinical testing in progress, and that concurrently a therapeutic Chagas vaccine is under development by a consortium of Mexican (including the Carlos Slim Health Institute) and Texan scientific institutions. More sensitive diagnostics that can be used at point-of-care, and biomarkers to assess therapeutic response and progression of cardiac disease in the setting of T. cruzi infection are also called for, since without new tools, disease control will not be possible for Chagas disease, and the U.S. and other governments have a major role to play in ensuring innovation is funded and carried out, and that ultimately, scientific breakthroughs for new technologies to fight Chagas will be key to bringing this disease under control.

PLOS is a non-profit organization of scientists and physicians committed to making the world’s scientific and medical literature a freely available public resource. For more information about PLOS, visit:
http://www.plos.org

PLOS Neglected Tropical Diseases (eISSN 1935-2735) is the first open-access journal devoted to the world’s most neglected tropical diseases (NTDs), such as elephantiasis, river blindness, leprosy, hookworm, schistosomiasis, and African sleeping sickness. The journal publishes high-quality, peer-reviewed research on all scientific, medical, and public-health aspects of these forgotten diseases affecting the world’s forgotten people. The journal’s start-up phase is supported by a grant from the Bill and Melinda Gates Foundation.

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