Eosinophil blood count and anemia are associated with trypanosoma cruzi infection reactivation in chagas' heart transplant recipients
International Journal of Cardiology xxx (2009) xxx–xxx
j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / i j c a r d
Eosinophil blood count and anemia are associated with Trypanosoma cruzi infectionreactivation in Chagas' heart transplant recipients
Tatiana A.D. Theodoropoulos, Achilles Gustavo Silva, Reinaldo B. Bestetti
Division of Cardiology, Hospital de Base, São José do Rio Preto Medical School, Brazil
Trypanosoma cruzi infection reactivation is a constant threat for Chagas' heart transplant recipients. From
September 2000 to September 2007, 54 patients underwent heart transplantation at our institution. Fourteen
(70%) out of 20 Chagas' disease patients who survived the perioperative period were entered into the study.
Mean eosinophil count and mean hemoglobin plasma levels were associated to T. cruzi infection reactivation.
2009 Elsevier Ireland Ltd. All rights reserved.
Keywords:EosinophilAnemiaTrypanosoma cruzi reactivationChagas' diseaseHeart transplantation
The Kaplan–Meyer curve presented the probability of freedom from T. cruzi infectionreactivation. A p value b0.05 was considered statistically significant.
Trypanosoma cruzi (T. cruzi) infection reactivation is a constant
threat for Chagas' heart transplant recipients. The incidence of clinical
T. cruzi infection reactivation varies from 27% to 90% and manifestsby paniculitis and/or myocarditis and more rarely by intracerebral
Six (43%) out of 14 patients had documented T. cruzi infection
reactivation: 3 in the heart, and 3 in the subcutaneous tissue. Six
The histological aspect of myocardial T. cruzi infection reactivation
(43%) patients had acute myocardial inflammation consistent with
on endomyocardial biopsy usually mimics acute graft rejection. This
acute rejection graded 3A or more, which had not improved with
might lead to inadvertent treatment with steroid pulsotherapy,
steroid pulsotherapy, but improved after specific treatment for
dissemination of T. cruzi infection, or septicemia due to opportunistic
T. cruzi infection (benznidazol, 5 mg/kg, during 60 days). Such
The aim of this study, therefore, was to look for other risk factors
for T. cruzi infection reactivation in an attempt to provide the correct
diagnosis as well as the proper treatment for Chagas' heart transplant
Baseline characteristics of Chagas' heart transplant recipients cohort (n = 14).
recipients with this infection recrudescence.
From September 2000 to September 2007, about 54 patients underwent 55
orthotopic heart transplantation procedures at our institution. Twenty (37%) of them
had a positive serology for Chagas' disease.
Fourteen (70%) out of 20 Chagas' disease patients, who survived the
perioperative period, were entered the study. Baseline characteristics of Chagas'
heart transplant recipients are illustrated in
Continuous variables were compared with two-sample T test or Mann–Whitney
test, whereas categorical variables were compared by the X2 test or Fisher exact test.
⁎ Corresponding author. Division of Cardiology, Hospital de Base da FAMERP, Av. Faria
Lima, 5544, CEP: 15090-000, São José do Rio Preto, SP, Brazil. Fax: +55 17 3201 5065.
SBP = Systolic Blood Pressure; DBP = Diastolic Blood Pressure; HR = heart rate; bpm =
0167-5273/$ – see front matter 2009 Elsevier Ireland Ltd. All rights reserved. doi:
Please cite this article as: Theodoropoulos TAD, et al, Eosinophil blood count and anemia are associated with Trypanosoma cruzi infectionreactivation in Chagas' heart transplant recipients, Int J Cardiol (2009), doi:
T.A.D. Theodoropoulos et al. / International Journal of Cardiology xxx (2009) xxx–xxx
Table 2Variables associated with T. cruzi infection reactivation.
patients were considered to have T. cruzi infection reactivation. Atotal of 17 episodes of T. cruzi infection reactivation were detected: 8patients had 1 episode, 3 patients had 2 episodes, and 1 patient had3 episodes. Mean T. cruzi infection reactivation episodes per patientwas 1.21 ± 0.80. Four (23%) out 17 episodes of T. cruzi infectionreactivation occurred in the first trimester after cardiac transplanta-tion, 3 (18%) in the second trimester, 4 (23%) in the second semester,and 6 (35%) after 1 year.
Mean eosinophil count per mm3 and mean hemoglobin plasma
levels were associated to Chagas' reactivation (). Six of 12 (50%)patients had increased levels of immunosuppressant.
One (8%) patient died because of T. cruzi infection reactivation.
Fig. 1. Probability of freedom from T. cruzi infection reactivation.
Probability of freedom from T. cruzi infection reactivation was 86%at 58 days, 43% at 202 days, and 29% at 297 days after cardiac trans-plantation Mean time to the first episode of T. cruzi infection
appearance of anemia or eosinophylia in the follow up are associated
with T. cruzi recrudescence in Chagas' heart transplant recipients.
This study shows that a slight increase in eosinophil count as well
The authors of this manuscript have certified that they comply
as a marginal decrease in hemoglobin levels can be detected in
with the Principles of Ethical Publishing in the International Journal of
patients with T. cruzi infection reactivation.
A lower increase in eosinophil blood count and in bone marrow
has been detected in T. cruzi-infected rats in comparison to non-
susceptible animals . Increased eosinophil count has been ob-served in blood circulation as well as in endomyocardial biopsy
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tissue during acute rejection in non-Chagas heart transplant re-
cipients . It is noteworthy that blood eosinophil count increases
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3–4 days before the diagnosis of acute rejection. Thus, increased
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[3] Bestetti RB, Cury PM, Theodoropoulos TAD, Villafanha D. Trypanosoma cruzi
eosinophil count can be a marker of inflammation. In the context of
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Chagas' heart transplant recipient, it can be a marker of T. cruzi
heart transplant recipient. Cardiovasc Path 2004;13:323–6.
[4] Herskowitz A, Soule LM, Mellits ED, et al. Histologic predictors of acute cardiac
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Anemia was also associated with T. cruzi infection reactivation.
Experimentally, anemia can be observed in T. cruzi infected animals.
[5] Nakhle MC, de Menezes Mda C, Irulegui I. Eosinophil levels in the acute phase of
Therefore, the appearance of anemia may raise the diagnostic
experimental Chagas' disease. Rev Inst Med Trop São Paulo 1989;31:384–91.
[6] Malvezi AD, Cecchini R, de Souza F, Tadokoro CE, Rizzo LV, Pinge_Filho P.
possibility of T. cruzi infection reactivation
Involvement of nitric oxide (NO) and TNF-alpha in the oxidative stress associated
Over-immunosuppression is one of the mechanisms proposed to
with anemia in experimental Trypanosoma cruzi infection. FEMS Immunol Med
account for recrudescence of T. cruzi infection in Chagas' heart trans-
[7] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.
plant recipients. In this study, 50% of patients were found to haveincreased levels of immunosuppressant. Therefore, it is conceivablethat over-immunossuppression can account for the high frequency ofT. cruzi infection reactivation observed in this study.
In conclusion, the majority of T. cruzi infection reactivation
episodes occurs in the first year after cardiac transplantation. The
Please cite this article as: Theodoropoulos TAD, et al, Eosinophil blood count and anemia are associated with Trypanosoma cruzi infectionreactivation in Chagas' heart transplant recipients, Int J Cardiol (2009), doi:
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