Chronically Infected Patients with Trypanosoma cruzi Parasitemia: Further Support for Screening

Abstract & Commentary

By Brian Blackburn, MD

Clinical Assistant Professor of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine

This article originally appeared in the October 2008 issue of Infectious Disease Alert. It was edited by Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center. It was peer reviewed by Connie Price, MD, Assistant Professor, University of Colorado School of Medicine.

Dr. Blackburn reports no financial relationships relevant to this field of study. Dr. Deresinski serves on the speaker's bureau of Merck, Pharmacia, GlaxoSmithKline, Pfizer, Bayer, and Wyeth, and does research for Merck. Dr. Price reports no financial relationships relevant to this field of study.

Synopsis: A cohort of patients seropositive for Chagas disease were tested by PCR and hemoculture for patent Trypanosoma cruzi infection. Sixty-three percent had parasitemia, confirming the transmission potential in such persons.

Source: Leiby DA, et al. Trypanosoma cruzi parasitemia in US blood donors with serologic evidence of infection. J Infect Dis. 2008;198:609-613.

Chagas disease (American trypanosomiasis) is caused by infection with the protozoan parasite Trypanosoma cruzi, and is spread primarily by triatomine insect vectors ("kissing bugs"). Although vector-borne transmission is primarily confined to rural Latin America, other routes of transmission (eg, blood transfusion) are also possible. Untreated infection seems to persist indefinitely, and the estimated lifetime risk of developing cardiac or other sequelae is about 20%-30%.1 When combined with increasing migration from Latin America, this long-term infection persistence means there is an increasing risk of blood transfusion-associated T. cruzi transmission in non-endemic areas such as the United States; estimates of the number of infected US immigrants range from tens of thousands to more than 100,000.2 Furthermore, some data indicate that the estimated T. cruzi-seropositivity rate among blood donors in Los Angeles rose between 1996 and 1998.3

In the United States, the largest contributor to the blood supply (the American Red Cross) began screening blood products for T. cruzi in 2007 with an ELISA-based test that had been FDA approved just months earlier.4 Recent data suggest one in 4,655 donations to be positive by both ELISA and a confirmatory, second immunologic assay (data were derived from donors in California and Arizona) for T. cruzi.4 Although hundreds of potentially infective blood products are transfused annually, only five US transfusion-associated cases have been documented to date.5 This discordance raises the question of whether seropositive persons have patent infection and, thus, the potential to transmit T. cruzi to others through blood transfusion, or simply evidence of prior infection.

Leiby et al undertook a study that attempted to confirm that T. cruzi-seropositive donors do have persistent, patent infection by identifying 147 persons who had previously been identified as seropositive for T. cruzi. Fifty-two (35%) of these 147 persons consented to enrollment, and they were asked to provide both epidemiologic data and blood for analysis by T. cruzi-polymerase chain reaction (PCR) and hemoculture testing. Although three samples (drawn six months apart) were requested from all participants, only 17 (33%) of the 52 patients in the study submitted more than a single sample for analysis.

Overall, 33 (63%) of the 52 participants had T. cruzi detectable in their blood by PCR; three of the PCR-positive samples were also positive by hemoculture. Of the 11 PCR-positive persons who provided more than one blood sample for testing, eight (73%) were positive on multiple occasions, although most only intermittently (ie, not on every sample tested). Epidemiologic data indicated that 80% were from either Mexico or El Salvador, and the median time since immigration to the United States was 18 years. Eighty-six percent of the cohort reported living in substandard housing during their time in Latin America, and 64% reported seeing triatomine insects at some point in their lives.

Commentary

This study supports the notion that untreated patients who are infected with T. cruzi probably remain so indefinitely (the patients in the study had immigrated to the United States approximately two decades, on average, before testing), and are at least intermittently parasitemic.

Primarily through the use of PCR technology, Leiby et al confirmed that seropositive patients likely do pose some risk of T. cruzi transmission through blood transfusion.

Almost two-thirds of the patients in the study were parasitemic, and it is also possible that the observed parasitemia prevalence was an underestimate, as suboptimal sensitivity could have occurred (depending on true vs. false-negative PCR, and given the difficulties in properly performing hemoculture). Furthermore, most participants provided only one blood specimen (instead of the three requested). Given the intermittent parasitemia that was observed in the PCR-positive patients, the prevalence may have been higher if all patients had provided three samples; during the chronic phase of T. cruzi infection, fluctuating, low-level parasitemia is characteristic.

The data in this paper serve to strengthen the scientific basis for the development of screening programs to prevent transmission of Chagas disease in countries like the United States. With the FDA approval of the ELISA screening test in 2006, and subsequent initiation of the American Red Cross screening program in 2007, such programs are now beginning to appear. While the majority of the blood supply is now tested for T. cruzi, universal screening in the United States is not yet a reality. Donor testing also has the potential to lead to prevention of morbidity and mortality in persons who remain undiagnosed and untreated for T. cruzi. These findings are also applicable to the solid organ and bone marrow transplant communities, as transmission risk from T. cruzi-seropositive donors exists with these procedures as well.

References:

  1. Bern C, et al. Evaluation and treatment of Chagas disease in the United States: a systematic review. JAMA. 2007;298:2171-2181.
  2. Wendel S. Transfusion-transmitted American and African trypanosomiasis (Chagas disease and sleeping sickness): neglected or reality? ISBT Science Series. 2006;1:140-151.
  3. Leiby DA, et al. Trypanosoma cruzi in Los Angeles and Miami blood donors: impact of evolving donor demographics on seroprevalence and implications for transfusion transmission. Transfusion. 2002;42:549-555.
  4. CDC. Blood donor screening for Chagas disease — United States, 2006-2007. MMWR Morb Mortal Wkly Rep. 2007;56:141-143.
  5. Young C, et al. Transfusion-acquired Trypanosoma cruzi infection. Transfusion. 2007;47:540-544.