Chagas' Disease Highlights

Pre-Meeting Course of the ASTMH -2008

Michele Barry, MD, FACP

Professor of Medicine, Co-Director Tropical Medicine and International Travelers' Clinic, Yale University School of Medicine.

Dr. Barry is a consultant for the Ford Foundation and receives funds from Johnson & Johnson.

A clinical pre-meeting course at the 56th annual meeting at ASTMH was conducted and entitled, Chagas' Disease: (American Trypanosomiasis): No Longer an Exotic Disease. Experts from CDC, Brazil, Argentina, in addition to leading researchers in the United States presented a review of diagnosis, treatment and the currently changing epidemiology of the disease. The focus and purpose of the course was to raise consciousness about the rise of imported Chagas' disease into the United States. As the frequency of Chagas' disease decreases in Latin America, with between 8-11 million people infected, the prevalence of infection within the United States is increasing due to immigration; 2003 census demonstrated that 17.9 million people in the U.S. were born in Latin America, many in endemic areas of Chagas' disease. Most recent data on the donated blood supply reveals that blood donors in certain geographic areas of the United States are as likely to be seropositive for Chagas' disease as they are to be seropositive for HIV infection.

Chagas' disease, a zoonotic disease caused by a blood borne parasite is transmitted primarily by triatome insects (i.e. kissing bugs). Infection can also occur via blood transfusion, congenital transmission, organ transplantation, laboratory accident and ingestion of triatome-contaminated food or drink. In the United States, vector-borne transmission of Chagas' disease is rare, although there have been six autochthonous cases reported, half in Texas, where indigenous triatome insects are found.

Chagas' has been identified as a disease infecting humans as long as 9,000 years ago. In a group of 283 mummies from northern Chile and southern Peru, 40.6% were infected with T. cruzi when tested with DNA probes for kinetoplast DNA. Of the more than 100 recognized triatomine species, only 10 are widespread colonizers of human dwellings. Examples of these dead insects were actually passed through the class meetingfor examination.

Chagas' disease has an acute stage, typically symptomatic or with mild symptoms; fever, malaise, swelling at the site of inoculation and lymphadenopathy during the first 6 - 8 weeks after infection. If not treated the infection becomes lifelong with low-level intermittent parasitemia. The majority of infected persons remain asymptomatic in a chronic indeterminate phase. However, an estimated 30% will have onset of chronic symptomatic disease, usually decades after the initial infection with cardiac manifestations in particular: dilated cardiomyopathy, apical fibrosis and aneurysms, right bundle branch block, frequent brady- and tachy-arrythmias) or gastrointestinal manifestations such as megaesophagus or megacolon. Typical features described for a U.S. immigrant presenting with Chagas' heart disease were a male between 30 to 50 years of age with childhood residency in Latin America and symptoms of palpitations, a right bundle branch block or right-sided heart failure.

During the ASTMH course four different aspects of the disease were updated: 1) The changing epidemiology in the U.S., 2) changing concepts of clinical manifestations and current treatment, 3) new diagnostic methods and 4) the challenges of the CDC and Red Cross in attempting to prevent transmission of disease through donated blood supply.

Highlights:

1. The changing epidemiology in the U.S. of Chagas Disease

  • 1916 - the first report of T. cruzi in triatomes found within the U.S.
  • 1983 - first transfusion associated case of Chagas' Disease
  • 2001 - first case in a transplant recipient
  • 2006 - U.S. blood banks begin screening for infection with T.cruzi
  • 2007 - an estimated 150,000 infected people in the U.S. (approximately 1 in 25 - 30,000 blood donations) seropositive by screening in 2007.

2. Changing Concepts of Clinical Manifestations and Treatment

The concept of parasite persistence in chronic Chagas' disease was reviewed and two competing, but not mutually exclusive, concepts were discussed: disease as the result of over-reactive immune/autoimmune reactivity and disease as a result of persistent parasitic infection. Although acute disease has always been treated, controversy continued as to whether to treat chronic Chagas disease until a recent landmark study by Viotti et al. which demonstrated that treatment of chronic cardiac Chagas' disease with benznidazole slowed rate of disease progression.1 Dr. Rassi, from Brazil, discussed the pathogenesis of chronic Chagas' cardiomyopathy and argued for treatment of all patients with either nifurtimox (available in United States) or benznida zole, the preferential treatment in Latin America due to less adverse side effects. A definitive, prospective and randomized study of treatment for chronic cardiomyopathy is underway. Dr. Maguire reviewed gastrointestinal disease due to destruction of myenteric Auerbach's plexus. He noted the rarity of gastrointestinal disease in countries north of the equator, with Chile and Argentina reporting the most prevalence of gastrointestinal disease.

3. Diagnostic methods for diagnosing chronic disease

Assay for anti-T. cruzi IgG is the recommended approach to diagnosing chronic infections and titers are not related to clinical status or infectivity.

Diagnosis was discussed by Drs. Sosa Estani, Kirchhoff and Tarleton. Examples of serologic test types currently available are ELISA, indirect immunofluorescence (IFA), hemagglutination, complement fixation and radioimmune precipitation assays (RIPA). The procedure for diagnosing chronic Chagas' disease in the United States as of 2007 includes positive serologic reaction on two of three tests. Confirmatory parasitological tests (PCR, blood culture for the causative organism or xenodiagnosis) are rarely performed for chronic disease.

4. New Screening of Blood Donors

For blood donations only, the Ortho T. cruzi Elisa test is approved by FDA with RIPA use for confirmatory testing of positive donor samples. Use of donor screening in the United States is not required; however, both the American Red Cross and Blood Systems Inc., organizations, responsible for 65% of the U.S. blood supply, began screening for all donations for T. cruzi on Jan. 29, 2007. Unfortunately, undocumented legal status of many positive donors contributes to lack of free treatment of such donors by CDC after being informed of their seropositivity.

References:

  1. Viotti R., et al. Ann Int Med 2006. May 16;144:724-34.