Medical and Scientific Updates

Number 99-1
Present Status of Studies on Trypanosoma cruzi in U.S. Blood Donors

David A. Leiby, Ph.D.
Holland Laboratory, American Red Cross

Introduction

Effective October 1, 1998 the American Red Cross (ARC) ceased to collect and test selected blood donations in the Southern California Region for antibodies to Trypanosoma cruzi, the etiologic agent of Chagas’ disease. With the termination of the study in the Southern California Region, there are no active studies on the prevalence of T. cruzi antibodies among U.S. blood donors. Through a cooperative agreement with the Centers for Disease Control and Prevention, we maintain an ongoing study characterizing seropositive donors in Los Angeles that were previously identified and deferred from future donations. Thus, in light of a shift from active multi-center studies to discussions concerning the potential need to implement strategies designed to prevent donation or transmission by T. cruzi-infected donors we provide the following summary and implications of results to date.

Results to Date

The ARC has completed seroprevalence studies in three regions: Southern California (Los Angeles), South Florida (Miami), and Southwest (Tulsa). Studies in Los Angeles and Miami, which focused on donors stratified by birth or long-term sojourn in T. cruzi-endemic countries, demonstrated overall minimum seroprevalence rates of 1 in 7,600 and 1 in 9,500 donors, respectively (Table 1). These rate estimates should be interpreted as conservative because only a subset of donors was tested. In contrast, the frequency of seropositivity in Tulsa was 1 in 33,000 overall donors, however, all 3 seropositive donors were from Waco, resulting in a local rate of 1 in 7,700 donors. Of note, 2 of the donors from Waco were U.S. born and had no apparent risk factors for infection. Similar observations regarding seropositive donors without risk factors have been made in Los Angeles and in both instances suggest a possible role for vertical transmission of the parasite. Further, case-control studies completed by the ARC suggested that questioning strategies would be neither sensitive nor specific for identification of infected donors. The results of a nationwide postcard survey conducted by the ARC estimated that the overall seroprevalence rate among U.S. blood donors is 1 in 35,000. 

Table 1.
Seroprevalence of Trypanosoma cruzi in Three ARC Regions

Attempts have been made to define the infectivity of seropositive donors. In lookback studies, 20 recipients of prior donations from antibody-positive donors were seronegative (even though the prior donations were almost certainly positive). An additional 16 lookbacks have been performed by the REDS group, also with negative results. However, a seropositive platelet unit from Miami was accidentally released and transfused and the recipient became infected, as demonstrated by the evolution of an antibody response and by detection of the parasite by PCR and hemoculture. The donor was also PCR and hemoculture positive. The patient died presumably of her underlying disease without any overt symptoms of T. cruzi-infection, however, an autopsy was not performed to determine cause of death. 

Further studies of seropositive donors from Los Angeles are ongoing. In cooperation with the CDC, seropositive donors are tested by hemoculture and PCR for active parasitemia, and interviewed regarding medical, health, and travel histories. As indicated in Table 2, at least 71% of seropositive donors demonstrate evidence of active parasitemia. Hemoculture, which is less sensitive and for which results lag by up to 16 weeks, was positive in 2 of 20 (10%). Comparisons of PCR positive and negative donors did not reveal any significant differences with regard to risk factors for acquiring infection, or more importantly, length of time (years) since emigration to the U.S.

Table 2.
Results for PCR and Hemoculture Testing of Seropositive Blood Donors

*Samples also PCR positive.

Finally, patient samples from the FACT study, representing 11,532 cardiac surgery patients receiving 120,312 units of blood collectively are presented in Table 3. Six patients were confirmed to be positive for T. cruzi antibodies, but four of these were also positive prior to surgery. Pre-operative samples were unavailable for 2 of the confirmed positive samples, but these 2 patients had undergone heart transplants. Tissues from excised hearts were obtained, tested by PCR for T. cruzi, and in both instances found to be negative suggesting the possibility of acquiring infection from one of multiple blood transfusions prior to surgery.

Table 3.
Seroprevalence of T. cruzi Antibodies in Multiply Transfused Cardiac Surgery Patients.

Conclusions

Significant numbers of blood donors seropositive for antibodies to T. cruzi are present in the U.S. The number of seropositive donors varies by location and is directly related to the proportion of donors from countries where T. cruzi is endemic. A large majority of donors identified as seropositive also have evidence of parasitemia, and thus, are likely to donate units of blood containing parasites. In contrast, lookback investigations have not demonstrated transmission, suggesting that the frequency of transmission may be low. However, other factors including type of component transfused, parasite strain differences, or lack of suitable tests for detecting transmission may have contributed to these negative findings. Indeed, transmission of T. cruzi by blood transfusion is reported throughout Latin American, and in the U.S. as evidenced by the recent case and Miami and possible cases related to cardiac surgery patients. 

References

Kirchhoff LV. American trypanosomiasis (Chagas’ disease) - a tropical disease now in the United States. N Engl J Med 1993;329:639-644.

Leiby DA, Read EJ, Lenes BA, et al. Seroepidemiology of Trypanosoma cruzi, etiologic agent of Chagas’ disease in US blood donors. J Infect Dis 1997;176:1047-52.

Leiby DA, Fucci MH, Stumpf RJ. Trypanosoma cruzi in a low to moderate risk blood donor population: seroprevalence and possible congenital transmission. Transfusion 1999;39: 310-315.

Schmunis GA. Trypanosoma cruzi, the etiologic agent of Chagas’ disease: status in the blood supply in endemic and nonendemic countries. Transfusion 1991;31:547-57.

Addendum: Clinical Implications of T. Cruzi Infection

There does not seem to be any comprehensive treatment of the clinical outcomes of transfusion-transmitted T. cruzi infection. In large part, published accounts which are substantially based on the Latin American experience suggest that the course and frequency of different outcomes replicates that seen in insect-borne transmission. It must be recognized that the strain of trypanosome and enviromental factors may influence pathogenesis and clinical behavior and that therefore the Latin American experience may not be directly transferable to the United States. CDC characterizes Chagas disease as a "serious illness."

In general, T. cruzi (Chagas) disease may be considered in three phases: acute, indeterminate and chronic.

• Acute phase. For transfusion recipients, the acute phase is similar to that seen in natural infection, with the exception that the characteristic swelling (chagoma) at the site of inoculation is absent. The incubation period is 20 to 40 days, although periods of up to 120 days have been described. Fever is the most common symptom and may be the only one. Lymphadenopathy and hepatosplenomagaly may be present. Cardiac disturbances may occur: these can include disturbance of atrioventricular conduction, ECG changes or reduction of ejection fraction, sometimes leading to pericardial effusion and cardiac failure or cardiac arrest. There may be CNS disturbances with somnolence, fatigue and tremors most common, and myoclonus, seizures and meningitis or meningoencephalitis in the worst cases. Death is uncommon, but may occur in the most severe cases, particularly if the patient is immunocompromised. Treatment may reverse the symptoms; figures of 30% to 70% success rate are quoted. In natural infection, children are more susceptible to acute disease, and in this group, mortality may be as high as 5%. One study in Bolivia noted that, of 21 seronegative individuals transfused with seropositive blood, 10 were infected. Of these 10, 6 had acute clinical symptoms. However, up to 20% of cases are completely asymptomatic and most acute disease resolves spontaneously over a period of 6-8 weeks, although it can take up to 4 months. Further stages of transfusion-transmitted disease are said to parallel those for natural infections
• Indeterminate phase. The majority of infected individuals (no matter what route of infection) enter the so-called indeterminate phase, representing long-term, asymptomatic infection, which may last for decades.
• Chronic Disease: In 30-40% of those infected, chronic symptoms develop 10-20 years after infection; overt, symptomatic cardiac disease will be seen in 10-20% of those infected. Patients who develop chronic disease, according to CDC will, on average, have life expectancy reduced by 9 years.  

One Brazilian study (Wendel & Dias reference below) followed 360 (presumably naturally-infected) patients for some 30 years following the acute phase. As shown in the table below, the incidence of cardiac and gastrointestinal problems was high, and increased with time.

Table 4.
Incidence of Cardiac and GI Problems after Acute Chagas Infection.

For those with  heart disease, most patients (68%) continued to have minimal disease and only 16% progressed to more significant disease after 12-17 years. Beginning at about 10 years after infection, conversion to overt chronic disease in this study and others appears to occur at a rate of about 1% year.

Cardiac manifestations include ventricular wall thinning, cardiomegaly and disturbances of atrioventricular conduction. There may be apical aneurysm of the left ventricle with attached thrombi. Arrythmias may occur and sudden cardiac death is a possibility. Less frequent chronic outcomes include megaesophagus and or megacolon, both of which can have serious outcomes. They are probably attributable to loss of autonomic nervous function.

References

Dias, JCP. Historia Natural. In Cardiopatia Chagasica – J.R. Cancado & M Chuster (eds), Fundacão Carlos Chagas, Belo Horizonte, 1985.

Dias JCP. The indeterminate form of human chronic Chagas’ disease a clinical epidemological review. Revista da Sociedade Brasileira de Medicina Tropical 22(3): 147-157, Jul-Sep, 1989.

Hagar JM and Rahimtoola SH. Chagas Heart Disease. Curr Probl Cardiol, 20(12): 826-924, 1995.

Mady C and Nacruth R. Natural history of chronic Chagas’ heart disease: prognosis factors. São Paulo Medical Journal/RPM 113(2) Mar/Apr 1995.

Rossi M and Bestetti RB. The Challenge of Chagasic Cardiomyopathy. Cardiology 86:1-7, 1995.

Wendel S and Dias JCP. Transfusion transmitted Chagas disease. In: Wendel S, Brener Z, Camargo ME, Rassi A, eds. Chagas Disease (American trypanosomiasis): its impact on tranfusion and clinical medicine. ISBT Brazil ’92 – SBHH, Sao Paulo, Brazil 1992-103-133.

Zuna H, La Fuente C, Valdez E, Recacoechea M, Franco JL, et al. Estudio prospectivo de la transmission del Trypanosoma cruzi por vía sanguínea, en Bolivia. Ann Soc Belge Med Trop 65: Suppl 1: 107-113, 1985.

Fact Sheet on Chagas Disease (for the general public) - from Centers for Disease Control

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