Chagas Disease Is Going Global

"Parasites are very smart."

So says physician-scientist Dr. Herbert Tanowitz, professor of pathology and of medicine (infectious diseases), and director of the Global Infectious Disease Training Program at Einstein, who has been involved in research on the pathogenesis of parasitic disease for more than 35 years.

Herbert Tanowitz, M.D.Among the wide range of organisms he has diagnosed, studied and treated over the span of his career, Dr. Tanowitz specializes in Trypanosoma cruzi (T. cruzi), the cause of Chagas disease. In a recent article in Cellular Microbiology, Dr. Tanowitz and his co-authors referred to Chagas as one of "the most important neglected tropical diseases of mankind."

"It's a persistent infection that has a lot of clinical implications," said the Einstein alumnus (class of 1967).

This vector-borne disease is an important cause of heart disease and gastrointestinal dysfunction in widespread regions throughout Latin America, where triatome insects, otherwise known as Kissing Bugs, transmit T. cruzi. The World Health Organization estimates that Chagas affects approximately 10 million people in nations including Mexico, Guatemala, Bolivia, El Salvador and Brazil.

In what Dr. Tanowitz calls a "double whammy," the insects defecate on their host and the parasite-laden feces enter through mucous membranes or bite wounds.

"What is striking about infection with T. cruzi," he said, "is the development of chronic infection with disease symptoms manifesting decades after the acute infection." Because current therapeutic agents for T. cruzi are highly toxic, and there is no effective treatment for chronic Chagas, new drug targets must be discovered. In addition, research on T. cruzi has been limited by difficulties in genetic manipulation.

The kissing bug delivers the parasite that causes Chagas diseaseIn recent years, the disease has gone global with a rise in cases of Chagas disease in the United States - including in the Bronx.  According to the Centers for Disease Control and Prevention (CDC), some 300,000 people throughout the nation may have Chagas disease, although many remain undiagnosed.

"They have no way of knowing if they have the disease until symptoms appear," said Dr. Tanowitz.

At Jacobi Medical Center, where Dr. Tanowitz serves as the director of the Diagnostic Parasitology Laboratory and associate director of the Parasitology Clinic, he is currently following 30 people with Chagas disease who were diagnosed in the metropolitan area.

Among them are two Long Island sisters who contracted the disease from their Bolivian-born mother, who was unaware of having the disease. Like 70 percent of individuals with Chagas disease, their mother remains asymptomatic, even though she has had lifelong low-level measurements of parasites in her blood.

An estimated 30 percent of infected individuals will have the onset of chronic symptomatic disease, usually decades after the initial infection, most often presenting as cardiac issues that can include cardiomyopathy, arrhythmias, and sudden death, or as gastroenterology (GI) problems such as achalasia, constipation and megacolon.

The diagnosis of the two Long Island sisters came in the wake of news that a Virginia boy was diagnosed as the first congenital case reported in the U.S., and the CDC has noted that more cases likely exist.

While most cases of Chagas disease are transmitted through blood transfusion and organ transplantation, these recent cases demonstrate that congenital transmission from mother to child is on the rise.

Despite the growing health risk, prevention and control outside Latin America is only beginning to be addressed. It wasn't until 2007 that the Food and Drug Administration approved a screening test that was implemented by the blood banking industry. About 1,300 cases have since been diagnosed in donated blood.

Huan Huang, M.D.At Jacobi's parasitology clinic, the focus is to identify people who are positive, to test for heart or GI diseases, and to determine if they should be treated. "Though very effective the drugs are unfortunately highly toxic, especially in chronic Chagas disease" said Dr. Tanowitz.

When he's not tending to his clinical work at Jacobi, Weiler Hospital and Montefiore Medical Center, Dr. Tanowitz can be found in his Forchheimer laboratory, investigating the pathogenesis of chagasic heart disease and the consequences of this infection on the pathophysiology of the host.

Dr. Tanowitz also is well known to Einstein students as a frequent lecturer for the Parasitology, General Pathology, and Microbial Pathogenesis courses. In addition, as director and principal investigator of a Fogarty International Training Grant aimed at training students and postdoctoral fellows from Brazil in research methods in infectious diseases and geographic medicine.

He also serves as senior associate editor of the American Journal of Pathology; managing editor of Frontier Bioscience; and co-editor-in-chief of the Journal of Neuroparasitology. He recently co-authored a two-volume book on Chagas disease in Advances in Parasitology with colleague Dr. Louis Weiss.

Joining Dr. Tanowitz in the overarching goal to understand the factors that lead to Chagas heart disease, and to determine the contributions of host and parasite, are Drs. Huan Huang and Fnu Nagajyothi.

Dr. Nagajyothi, assistant professor of pathology, focuses her studies on the interaction of T. cruzi and adipose tissue, a haven for the parasite, and adipocytes and the influence of diabetes and obesity.

Dr. Huang, associate professor of pathology, has explored aspects of T. cruzi for more than 20 years, including molecular biology, cell signaling pathways and the development of new and improved genetic techniques for working with this organism. He also has advanced molecular genetics in T. cruzi by designing a modified pTREX vector that allows for rapid and reversible protein expression and efficient functional analysis of proteins in different T. cruzi life cycle stages.

These researchers are part of a larger team of infectious disease scientists, rounded out by Dr. Weiss, professor of pathology and of medicine (infectious diseases) and co-director of the Einstein Global Health Center, whose lab studies Toxoplasma gondii and microsporidiosis; and by Dr. Mahalia Desruisseaux, assistant professor of pathology and of medicine (infectious diseases), whose lab focuses on cerebral malaria.

Editor's Note: This feature originally was published in longer form on the pathology website.