By Melissa R. Mac

imageChagas disease, which afflicts more than 18 million people in the tropical regions of the Americas, is caused by the parasite, Trypansoma cruzi, which enters the body through mucous membranes, passes through the circulatory system and invades individual cells.

According to the Centers for Disease Control, Chagas has a geographic distribution from the southern United States to southern Argentina, affecting mostly those from poor, rural areas of Central and South America. Chronic Chagas disease is a major health problem in many Latin American countries. With increased population movements, the possibility of transmission has become fairly substantial in the United States.

Clinical features of Chagas disease include a local lesion at the site of inoculation. The acute phase is usually asymptomatic but can be characterized by fever, anorexia, lymphadenopathy, mild hepatosplenomegaly and myocarditis. Most acute cases resolve over two to three months into an asymptomatic chronic stage. The symptomatic chronic stage may not occur for years or decades after infection. Its manifestations include cardiomyopathy (the most serious manifestation), pathologies of the digestive tract such as megaesophagus and megacolon; weight loss and pulmonary infection. Chronic Chagas disease and its complications can be fatal.

About 25 percent of the Latin American population, approximately 100 million people, are at risk for Chagas disease. The risk of infection today is directly related to poverty, just as it was in 1909 when Carlos Chagas first described the disease. The triatomine bug that transmits the parasite lives in crevices in the walls and roofs of poorly constructed houses in rural and outlying slum areas. However, recent urban migration in Latin America has changed the epidemiological pattern of Chagas, making it a more metropolitan infection, — one that can be transmitted via blood transfusion. The figures on blood bank infection in selected cities vary between 3.0 and 53.0 percent, which would make the prevalence of T. cruzi infected blood higher than that of HIV and Hepatitis B and C, according to the World Health Organization.

imageNorth America has seen an increased incidence of Chagas in recent years, especially in border states such as Texas and California, the target destinations of millions of immigrants. U.S. blood bank guardians offer differing opinions about how serious a threat Chagas is to the American blood supply and whether the U.S. blood centers should mandate donor screening for the disease.

Celso Bianco, MD, executive vice president of business and medical affairs at America’s Blood Centers, was trained in Brazil, an endemic country for Chagas. While there, Bianco worked with both Chagas patients and related blood donor issues. He does not downplay the relevance of controlling and screening for Chagas, but said North American prevalence is low, with only six cases in the last 20 years. Bianco recommends a watchful eye on Chagas disease, but no mandatory screening yet.

In the developed countries of Latin America, where Chagas transmission via blood is a major concern, they are screening, not once but twice. In Brazil, Bianco said, centers are required to screen every blood donation for Chagas with two test formats. One test used is Hemagen’s ELISA assay, which has helped to drastically cut the number of Chagas blood transmissions. Testing combinations for Chagas include an ELISA and an immunofluorescence, or an ELISA and hemagglutination, the most popular combination. (See sidebar.)

“This [screening] has practically eliminated the transmission of Chagas by transfusion,” Bianco said. “The problem with the tests is their specificity is not ideal, but considering the risks, there is no choice.”

After much research, the U.S. Food and Drug Administration’s Blood Products Advisory Committee (BPAC) on Chagas disease decided against mandatory screening for the disease, although it is on the watch list. That’s because in regions where the immigration rate from Chagas endemic countries is rising, reports of the disease may be on the rise as well.

Morven S. Edwards, MD, a professor of pediatrics at Baylor College of Medicine in Houston, Texas completed a Chagas study in 1997 with specimens collected from 1993-1996. The study was published in 1999 (Di Pentima et al: Prevalence of antibody to Trypanosoma cruzi in pregnant Hispanic women in Houston. Clin Infect Dis 1999;28: 1281-5).

The symptoms and diagnostics of Chagas disease

American trypanosomiasis (Chagas’ disease) is a protozoan infection caused by the flagellate Trypanosoma cruzi. In both the acute and chronic phases of this disease, patients may demonstrate severe myocardial, hepatic, and gastric anomalies. In the acute phase, which may be acquired by blood transfusion or organ transplant, parasites are found in nearly all tissues and organs. In the chronic phase, parasites are rare; the heart and digestive tract are the major targets. Inflammation and degeneration may be found, together with areas of focal fibrosis causing myocardial destruction. Alterations may be observed in any part of the digestive tract, but predominantly the esophagus and large bowel are involved.

Chagas’ disease was previously limited to Latin America with transmission primarily by hematophagous insects and blood transfusion. With the increasing numbers of emigrants to developed countries, this situation has the potential to be a worldwide problem.

Infected donors can be divided into 3 groups:

  1. Serological Chagas’ disease — donors who have only serological evidence but do not present any visceral symptoms (about 70%)
  2. Latent chronic phase — this population shows some abnormalities evidenced by diagnostic tests but are still asymptomatic
  3. Symptomatic — this small group exhibits symptoms which are persistent and specific

The current transmission by blood transfusion is difficult to access since screening tests are not mandatory in most North American countries. In the United States, estimates show about 2 million immigrants from Latin America, which may mean at least 50,000 infected with T. cruzi.

Among the existing serological tests for Chagas’ are:

  • Complement fixation test — developed in 1913 as a practical alternative for xenodiagnosis; not used today due to poor sensitivity and specificity.
  • Direct agglutination test — developed in 1944 using a suspension of T. cruzi epimastigotes as antigen. This was replaced by enzyme-treated, formalin-fixed antigen. It is a very sensitive test for IgM antibodies.
  • Latex agglutination — developed in 1970; used widely, but a wide variability of results with poor reproducibility seen.
  • Hemagglutination (IHA) — developed in 1970; uses tanned human red cells coated with aqueous extract of T. cruzi. Used largely in Latin America for screening blood donors. Commercial kits are available with possibilities for automation. Available in the US for research use only.
  • Flocculation — developed in 1975 using freeze-dried T. cruzi fragments. The test showed a high degree of sensitivity and specificity, but was not reliable for large-scale applications.
  • Indirect immunofluorescence — developed in 1959; used formalin-treated epimastigotes of T. cruzi; showed a high degree of sensitivity and specificity. Still used in some labs and blood banks as a confirmatory test when a discrepancy is observed with routine tests.
  • Enzyme-linked immunosorbent assay (ELISA) — developed in 1975; a reliable test for screening blood donors or to confirm a clinical diagnosis. In Brazil where 2 assays are required to screen blood donors, the ELISA and IHA are used. The ELISA is available in the US for in vitro diagnostic use; it is not yet licensed to screen blood donors.

by Ricardo M. de Oliveira, M.D., Physician in Chief, Hospital do Cancer, Sao Paulo, Brazil, and Senior Vice President for R&D at Hemagen

Edwards’ study provides evidence that screening the blood supply for these parasites might be important in places like southern California and southern Texas. As a pediatrician, she was interested in determining if Hispanic women, who may have recently emigrated from endemic countries, might benefit from Chagas screening as part of their perinatal care. Edwards collaborated with a physician who had thousands of maternal and cord blood samples obtained as part of an epidemiological study examining Hepatitis C. She and her team selected almost 4,000 samples, 2,000 from women with Hispanic surnames and 1,700 from non-Hispanic women.

Using the Hemagen ELISA for screening and the Hemagen agglutination assay for confirmation, they found Chagas seroconversion in .4 percent of the women with Hispanic surnames. Edwards noted that the rate is higher than for other routine STD screens for delivering mothers. “It was a first set of data saying we have a potentially preventable infection that it would be really easy to screen for in an at-risk population,” Edwards said.

Her goal is to continue with prospective studies, in part because 85 percent of her county hospital’s 5,200 annual deliveries are to Hispanic women.

Edwards found Hemagen’s Chagas screening products user friendly, even for a research lab that is not fully automated. Using the ELISA, Edwards’ semi-automated lab ran through hundreds of samples at a time. “I can see how easy it would be if it were shown cost-effective and beneficial to screen in high-risk areas,” Edwards said.

As for an increased incidence of Chagas showing up in the U.S. blood supply, Edwards believes clinicians can expect an increase in infection that’s proportional with population shifts.

Chagas is a disease that needs to be seriously monitored, Edwards said, even though it may only show up on the U.S. infectious disease radar sporadically. Because of the continuing influx of people into the U.S. from endemic countries, and its lengthy latency period, Chagas has the potential to become the disease that no one was prepared for. “Usually those are ones that lay low for a while, and then all of the sudden everybody says ‘Chagas disease? Why haven’t we been doing something about this?’ ”

For more information on the Hemagen Chagas test Select No. 260 on the reader service card, call 800-436-2436 or go to www.hemagen.com.