Trypanosoma cruzi (American trypanosomiasis - Chagas’ Disease)

 

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Life cycle of American trypanosomiasis:

 

TrypanosomaCruziLifeCycle

 

 

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Blood Donor Screening for Chagas Disease --- United States, 2006-2007

 

MMWR.  2007;56(7):141-143.  ©2007 Centers for Disease Control and Prevention (CDC)

Posted 03/09/2007

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Content

Chagas disease, a zoonotic disease caused by the bloodborne parasite Trypanosoma cruzi, affects an estimated 11 million persons throughout much of Latin America. In endemic areas, T. cruzi is transmitted primarily by triatomine insects (i.e., kissing bugs); infection also can occur via blood transfusion, congenital transmission, organ transplantation, laboratory incident, and ingestion of triatomine-contaminated food or drink.[1] To evaluate an investigational assay for detecting T. cruzi infection in blood donations, the American Red Cross conducted a clinical trial during August 2006-January 2007, screening 148,969 blood samples at three blood-collection centers in the United States. In January 2007, after the new assay was licensed by the Food and Drug Administration (FDA), other centers began screening donors for T. cruzi. This report describes the results of the American Red Cross study, which identified 32 donations (approximately one in 4,655) as confirmed positive for T. cruzi antibodies. As blood-donation screening for Chagas disease becomes more widespread, public health officials and health-care providers should anticipate increased numbers of questions regarding the diagnosis, evaluation, and management of Chagas disease.

Chagas disease has an acute stage, typically asymptomatic or with mild symptoms (e.g., fever, malaise, swelling at the site of innoculation and lymphadenopathy) during the first 6-8 weeks after infection. If not treated, infection is lifelong with low-level, intermittent parasitemia. The majority of infected persons remain asymptomatic in the chronic indeterminate phase (i.e., a prolonged period of clinically silent infection that follows acute primary infection). However, an estimated 30% will have onset of chronic symptomatic disease, usually decades after the initial infection, with cardiac manifestations (e.g., cardiomyopathy, arrhythmias, and sudden death) or gastrointestinal involvement (e.g., megaesophagus or megacolon).

In the United States, vector-borne transmission of Chagas disease is rare.[2] However, one study revealed an increasing Chagas seroprevalence among blood donors in Los Angeles County, California, from 1996 (one in 9,850 donors) to 1998 (one in 5,400 donors).[7] In 1991, a questionnaire was introduced to screen blood donors; those reporting a history of Chagas disease are deferred, but most persons with Chagas disease likely are unaware of their infections. Seven cases of transfusion-associated transmission have been documented in the United States and Canada during the past 20 years; all occurred in immunosuppressed recipients.[3-6] Because acute infections often are asymptomatic and the level of awareness of Chagas disease among clinicians is low, cases of transfusion-associated transmission can go undetected.

In 2005, a new commercial test for blood-donation screening for Chagas disease was developed. The test, manufactured by Ortho-Clinical Diagnostics (Raritan, New Jersey), is an enzyme-linked immunosorbent assay (ELISA) that uses epimastigote lysate antigens for detection of antibodies to T. cruzi in serum and plasma.[8] In clinical trials evaluating the test, including the American Red Cross study, blood donor specimens with initially reactive results were retested twice and considered repeat reactive if one or both of the repeat tests were reactive. Repeat reactive specimens from the clinical trials underwent further testing using a radioimmunoprecipitation assay (RIPA); those with positive RIPA results were considered confirmed positive. However, FDA has not licensed a supplemental test as a confirmatory assay in blood donation screening for T. cruzi antibodies.

After a clinical trial in 2005 with approximately 40,000 blood donors resulted in only one repeat reactive specimen (which tested negative with RIPA),[8] the American Red Cross conducted a larger study of the new screening assay in areas where Chagas was expected to be more prevalent. The study was conducted in three collection facilities of the American Red Cross, including the Southern California Region (Los Angeles, California), the Northern California Region (Oakland, California), and the Arizona Region (Tucson, Arizona). Blood donations collected during August 28, 2006-January 28, 2007, were tested with the screening assay for those blood donors willing to participate in the study. All donors were asked to participate; 78.5% agreed, and their specimens were tested.

A total of 148,969 blood-donation specimens were tested; 63 specimens from 61 donors were repeat reactive for T. cruzi antibodies (approximately one in 2,365 donations). Among the 61 donors with repeat reactive speciments, 40 (66%) were male; the age range was 17-84 years, with a mean age of 47 years and a median of 50 years. Of the 63 repeat reactive specimens, 50 (79%; one in 1,993 donations) were collected from the Los Angeles center, nine (14%; one in 3,258 donations) were collected from the Oakland center, and four (6%; one in 5,995 donations) were collected from the Tucson center. Fifty-five (90%) of the 61 donors were allogeneic donors; the remaining six included five autologous donors (two with two reactive donations each) and one directed donor. Of the 55 allogeneic donors, 18 (33%) were first-time donors, and 37 (67%) had donated blood previously. All of the 63 repeat reactive donations were tested with RIPA, of which 32 (51%) were positive and 31 (49%) were negative.

On December 13, 2006, based in part on preliminary results from the American Red Cross study, FDA licensed the Ortho T. cruzi ELISA Test System to screen blood donors in the United States. The new assay also is labeled for testing plasma and serum samples from living cell and tissue donors and from heart-beating organ donors, but is not labeled for general clinical diagnostic use.

Reported by: SL Stramer, PhD, American Red Cross, Gaithersburg; RY Dodd, PhD, DA Leiby, PhD, American Red Cross, Rockville, Maryland. RM Herron, MD, American Red Cross, Los Angeles; L Mascola, MD, Los Angeles County Dept of Public Health; LJ Rosenberg, MD, California State Health Dept. S Caglioti, Blood Systems Laboratories, Tempe; E Lawaczeck, DVM, RH Sunenshine, MD, Arizona Dept of Health Svcs. MJ Kuehnert, MD, Div of Health Care Quality Promotion, National Center for Preparedness, Detection, and Control of Infectious Diseases (proposed); S Montgomery, DVM, C Bern, MD, A Moore, MD, B Herwaldt, MD, Div of Parasitic Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases (proposed); H Kun, PhD, JR Verani, MD, EIS officers, CDC.

Editorial Note

Findings from the American Red Cross study described in this report provided evidence to support FDA approval of the first blood donor screening test for Chagas disease in the United States. Use of this test by blood centers to screen for T. cruzi antibodies is not required. However, both the American Red Cross and Blood Systems, Inc., blood-collection organizations that are responsible for approximately 65% of the U.S. blood supply, began screening all donations for T. cruzi on January 29, 2007, and providing testing services for smaller blood-collection centers and hospitals that requested testing. FDA is expected to recommend implementation of the test by all blood-collection establishments.

The AABB (formerly known as the American Association of Blood Banks) has issued recommendations to its member facilities regarding how to use the new test.* AABB recommends that all components from blood donations that are repeat reactive by the ELISA test should be quarantined and removed from distribution, and the donor should be deferred from making donations indefinitely. Recipient tracing should be conducted to identify and test recipients of blood components collected previously from donors who are confirmed positive (i.e., repeat reactive by ELISA and positive by RIPA). AABB also suggests testing at-risk family members of donors who are confirmed positive or family members with a similar history of exposure to vectors in an endemic area (e.g., the children of seropositive women). Deferred donors, at-risk family members, and potentially infected recipients should be referred to health-care providers for evaluation and management.

Screening blood donations for T. cruzi antibodies can identify persons with previously undiagnosed Chagas disease and further enhance the safety of the U.S. blood supply. However, as with any screening test, limitations exist. Although available data regarding the performance of the new assay have suggested high sensitivity and specificity,[8,9] some false-negative results have occurred with this assay[8] and with other assays used to screen for T. cruzi antibodies.[10] In addition, when a screening assay is used in a population with low disease prevalence, a greater proportion of false-positive results can be expected. Donors with reactive screening assay results require further clinical diagnostic testing to verify T. cruzi infection and to guide clinical management.

For clinical purposes, no single laboratory test is adequately sensitive and specific to diagnose Chagas disease. Diagnosis generally is made by using at least two different serologic tests (e.g., diagnostic ELISA tests, immunofluorescence assay, or indirect hemagglutination)[1] and by considering clinical findings and exposure risk. Clinical diagnostic testing for Chagas disease is available through commercial laboratories and the Division of Parasitic Diseases (DPD) at CDC. After diagnosis, health-care providers should conduct a thorough clinical evaluation to determine the stage of disease, develop an appropriate treatment plan, and provide information regarding prognosis. CDC is preparing guidance for the clinical evaluation, staging, management, and treatment of patients with Chagas disease.

Cases of Chagas disease likely will be increasingly identified as a result of screening blood donors for infection with T. cruzi. In addition, requests for diagnostic testing might become more frequent as awareness of Chagas disease increases among clinicians and the general public. Most identified cases likely will represent chronic infections that were acquired years earlier.

Chagas treatment options are limited and are most effective during the acute stage of infection. However, increasing evidence suggests that treatment of persons with chronic infections can result in seroreversion and prevent progression of cardiac morbidity.[1] Treatment of women of childbearing age with Chagas disease can decrease the risk for congenital transmission. Antitrypanosomal medication in the United States is currently available only through CDC under an investigational new drug protocol.

Questions regarding laboratory diagnosis, evaluation, and management of Chagas disease can be posed to DPD by telephone, 770-488-7775. Additional information regarding Chagas disease is available at http://www.cdc.gov/ncidod/dpd/parasites/chagasdisease/default.htm.

* Available at http://www.aabb.org/content/members_area/association_bulletins/ab06-08.htm.

References

1.    WHO Expert Committee. Control of Chagas disease. World Health Organ Tech Rep Ser 2002;905:i-vi,1-109.

2.    Herwaldt BL, Grijalva MJ, Newsome AL, et al. Use of polymerase chain reaction to diagnose the fifth reported US case of autochthonous transmission of Trypanosoma cruzi, in Tennessee, 1998. J Infect Dis 2000;181:395-9.

3.    Cimo PL, Luper WE, Scouros MA. Transfusion-associated Chagas' disease in Texas: report of a case. Tex Med 1993;89:48-50.

4.    Lane DJ, Sher G, Ward B, Ndao M, Leiby D, Hewlett B. Investigation of the second case of transfusion transmitted Chagas disease in Canada. Presented at: 42nd Annual Meeting of the American Society of Hematology, San Francisco, California; December 1-5, 2000.

5.    Leiby DA, Lenes BA, Tibbals MA, Tames-Olmedo MT. Prospective evaluation of a patient with Trypanosoma cruzi infection transmitted by transfusion. N Engl J Med 1999;341:1237-9.

6.    Saulnier Sholler GL, Kalkunte S, Greenlaw C, McCarten K, Forman E. Antitumor activity of nifurtimox observed in a patient with neuroblastoma. J Pediatr Hematol Oncol 2006;28:693-5.

7.    Leiby DA, Herron RM Jr, Read EJ, Lenes BA, Stumpf RJ. Trypanosoma cruzi in Los Angeles and Miami blood donors: impact of evolving donor demographics on seroprevalence and implications for transfusion transmission. Transfusion 2002;42:549-55.

8.    Food and Drug Administration. Product approval information licensing action. ORTHO T. cruzi ELISA Test System. Available at http://www.fda.gov/cber/products/tryorth121306.htm.

9.    Tobler LH, Contestable P, Pitina L, et al. Evaluation of a new enzyme-linked immunosorbent assay for detection of Chagas antibody in US blood donors. Transfusion 2007;47:90-6.

10. Leiby DA, Wendel S, Takaoka DT, Fachini RM, Oliveira LC, Tibbals MA. Serologic testing for Trypanosoma cruzi: comparison of radioimmunoprecipitation assay with commercially available indirect immunofluorescence assay, indirect hemagglutination assay, and enzyme-linked immunosorbent assay kits. J Clin Microbiol 2000; 38:639-42.

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Phylogeny:                              Order Kinetoplastida

 

Preferred definitive hosts:                 Humans

 

Reservoir hosts:                      Dogs, cast, opossums, armadillos, wood rat

 

Intermediate/vector hosts:                 Triatoma bugs in Uruguay, Chili, Argentina,

                                                          Rhodnius prolixus in northern South

                                                          America and Central America

 

Geographical location:            Central and South America

 

Organs affected:                      Lymph node, nervous tissue, heart muscle

 

Symptoms and clinical signs:  Swelling of lymph nodes,

                                                          progressive deterioration of

                                                          nervous tissue, resulting in loss

                                                          of strength, nervous disorders,

                                                          heart failure, megaesophagus or

                                                          megacolon

 

Treatment:                              No effective drug

 

From the November 18, 2003 issue of the New York Times:

 

Rare Infection Threatens to Spread in Blood Supply By DONALD G. McNEIL Jr.

 

A parasitic infection common in Latin America is threatening the United States blood supply, public health experts say.      They are especially concerned because there will be no test for it in donated blood until next year at the earliest.

 

The infection, Chagas disease, is still rare in this country. Only nine cases are known to have been transmitted by transfusion or transplant in the United States and Canada in the last 20 years.

 

But hundreds of blood recipients may be silently infected, experts say, and there is no effective treatment for them. After a decade or more, 10 to 30 percent of them will die when their hearts or intestines, weakened by the disease, explode.

 

Chagas is still little known in the United States, but in Mexico, Central America and South America, 18 million people are infected, and 50,000 a year die of it.

 

Experts expect it to become better known as new tests are developed.

 

"I wouldn't say that it's as rare as hen's teeth, but it's rare," said Dr. Ravi V. Durvasula, a Chagas expert at the Yale School of Public Health. "It's one of the top threats to the blood supply, but it's an emerging threat."

 

Because the disease is most common in rural areas from southern Mexico to northern Chile, the threat is greatest in American cities with many immigrants from those areas.

 

Across the United States, said Dr. David A. Leiby, a Chagas expert at the American Red Cross, the risk of getting a transfusion of infected blood is only about 1 in 25,000.

 

But in 1998 in Miami it was found to be 1 in 9,000, he said, and in Los Angeles the same year, he measured it at 1 in 5,400, up from 1 in 9,850 only two years earlier.

 

No more recent study of the blood supply has been done.

 

The only routine screening for Chagas now is in the standard set of questions asked of donors — whether they come from or have visited a country where Chagas is endemic and whether they ever slept in a thatched hut.

 

But that often isn't reliable, said Dr. Louis V. Kirchhoff, a professor at the University of Iowa's medical school who researches Chagas in Guadalajara, Mexico, where the chance of getting infected blood is 1 in 126. Potential donors "are kind of leery of those questions," he said, and may not answer honestly.

 

Since 1989, several advisory panels to the United States Food and Drug Administration have recommended that all donated blood be screened for Chagas. But no test has been approved yet.

 

Last year, the F.D.A. invited diagnostics companies to create one, and the two largest, Abbott Laboratories and Ortho-Clinical Diagnostics, are trying. But representatives of the companies said they were under little deadline pressure. Abbott's test may be ready next year.

 

Little sense of urgency exists because "there are always new things that come up," Dr. Leiby said. Hepatitis and AIDS were followed by mad cow disease, West Nile virus and bacterial contamination of platelets, so "Chagas gets pushed to the side," he said.

 

Mary Richardson, a spokeswoman for Ortho, which hopes to have a test by 2005, added: "Clinical trials take time. There's only so much speeding up you can do."

 

Nonetheless, she added, "the F.D.A. feels it's the next biggest threat."

 

An F.D.A. spokeswoman said her agency did not like to rank all the threats to the blood supply — including hepatitis, AIDS and West Nile virus — but reiterated that "we would certainly recommend a Chagas test if one is developed."

 

Prevalence rates in Latin America vary widely, from 25 percent in Bolivia to 1 percent in Mexico.

 

It is not found on Caribbean islands like Puerto Rico, the Dominican Republic or Cuba.

 

In some countries, it is a serious threat to the blood supplies; in one Bolivian city, half of the blood was infected.

 

About 30 tests are used in different countries, but none meet F.D.A. accuracy standards. Some Latin American blood banks disinfect with gentian violet, but it is unpopular because it gives recipients a purplish tinge.

 

The disease is named for Carlos Chagas, the Brazilian doctor who described it in 1909. It is caused by a protozoan, Trypanosoma cruzi, which infects humans in a particularly disgusting way. Reduviids, also called kissing or assassin bugs, drop down from the thatch, follow the trail of carbon dioxide to the mouths of sleeping humans and suck their blood. They leave behind a protozoan-laden drop of feces, which the sleeper often inadvertently rubs into the itching wound.

 

Charles Darwin may have been infected on his travels; he suffered with Chagas symptoms for many years in England.

 

There is no vaccine and no effective treatment. The first phase, which starts within weeks of infection, may include fever and swollen glands, liver or spleen, but is rarely fatal except in infants and in adults with compromised immune systems. It is often misdiagnosed.

 

The disease can then lie dormant for 10 to 30 years, then kill suddenly as weakened organs rupture.

 

The failure of the blood industry and its regulators to develop a test since it was endorsed by a Blood Products Advisory Committee in 1989 seems to be a combination of bureaucratic inertia and divided responsibility for such a decision. Blood banks cannot use a test that the F.D.A. has not approved. The agency usually defers to its advisory committees, which have many experts from blood banks as members.

 

"It's a political process that is not always fully engaged," said Dr. Stuart J. Kahn of the Infectious Disease Research Institute, a Seattle group hunting cures for tropical diseases.

 

Dr. Hira Nakhasi, director of transfusion-transmitted diseases at the F.D.A., agreed that neither the blood banks nor his agency had been very aggressive. Things tended to move when "the public and media put pressure on," he said.

 

Cost concerns made blood banks hesitant, Dr. Kirchhoff said. It may cost $50 million to $100 million a year to screen the whole United States blood supply, he estimated, and "people will reasonably say, `Why should we do this if we're not seeing a lot of sick people?' "

 

Although perhaps 120 Americans a year get infected blood, he said, between 70 and 90 percent will not become seriously ill, and few of those who do will live long enough to die of Chagas.

 

Most transfusion recipients are fairly sick, and half die of other causes within two years anyway.

 

But he pointed out that the risk was growing rapidly. Census figures show that net immigration from Mexico is about 1,000 people a day, he said. Of those, 5 to 10 are probably infected.

 

Meanwhile, blood banks increased their appeals to Hispanics in the 1990's, under extra pressure when mad cow disease eliminated donors who had made long visits to Europe and AIDS eliminated gay men and other risk groups.

 

Interest in Chagas seems to be growing, Dr. Kahn said, because breakthroughs in biogenetics make it easier to attack diseases and because the interest of the Bill and Melinda Gates Foundation in third world health "put a lot of diseases up on the radar screen."