Recommendations for management of Chagas disease in organ and hematopoietic tissue transplantation programs in nonendemic areas

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Abstract

The substantial immigration into Spain from endemic areas of Chagas disease such as Latin America has increased the number of potential donors of organs and tissues. In addition, an increasing number of patients with advanced Chagas heart disease may eventually be eligible to receive a heart transplant, a universally accepted therapeutic strategy for the advanced stages of this disease. Therefore, it is necessary to establish protocols for disease management. This document is intended to establish the guidelines to be followed when a potential donor or a tissue or organ recipient is potentially affected by Chagas disease and summarizes the action criteria against the possibility of Chagas disease transmission through the donation of organs, tissues, or hematopoietic stem cells and aims to help professionals working in this field. A single registry of transplants in Trypanosoma cruzi infected donors and/or recipients will provide and disseminate experience in this area, which has shown a low recorded incidence to date.

Introduction

American trypanosomiasis or Chagas disease is a major public health problem in Latin American countries. It currently affects 8–10 million people, and it has been estimated that 40 million are at risk of contracting the infection [1], [2].

Trypanosoma cruzi (T. cruzi) can be transmitted through triatomine vectors, vertical transmission, blood products, infected tissues or organs, and orally. Vertical transmission and transmission through blood products, infected organs and tissues are possible in non-endemic areas. In fact, in Europe, there have been several cases of vertical transmission of T. cruzi [3], [4], and of transmission through infected tissue or blood products [5], [6], [7]. The need for organs and the increase in the number of potential donors from countries where the disease is endemic made us reconsider the evaluation and acceptance of patients infected by T. cruzi as both potential organ donors and recipients.

Acceptance or rejection of a donor with positive serology for T. cruzi is a controversial issue because of the possibility of transmitting the disease to an immunosuppressed recipient whose treatment can have side effects. On the other hand, rejecting organs or tissues that are useful or vital to people in need may be considered as unethical and jeopardize the patient's life, especially if there are no alternatives and if tools are available for evaluating and monitoring the potential impact of T. cruzi in the recipient.

Drug-induced immunosuppression during the transplantation process increases the risk of reactivation of the disease in patients previously infected with T. cruzi, which has been reported to occur in between 10% and 75% of cases [8], [9], [10]. Patients infected with T. cruzi are at risk for short-term infection reactivation, and—although it has not been described—in the long term, the progression of the infection could end in a symptomatic chronic disease with heart, digestive, or other damage [11], [12]. The potential risks for the seronegative T. cruzi recipient receiving an organ or blood stem cells from a seropositive T. cruzi donor are the transmission of the parasite, an acute infection with T. cruzi, and possibly a chronic T. cruzi infection.

Reactivations have been mainly reported in cases of transplantation of hematopoietic progenitor transplantation (HPT), especially allogeneic and cord blood transplantations (40% of relapses) [13]. Less commonly, reactivation has been reported in solid organ transplantation (SOT), especially of the heart and kidney [13], [14]. According to a number of transplants performed in Argentina, transmission through a positive transplant was 18.7% in negative kidney recipients [13].

In addition, as Chagas is a usually asymptomatic chronic disease with a long latency period, patients awaiting an organ or tissue (and the doctors in charge of them) are often unaware of its existence, so it is necessary to implement active screening strategies for potential recipients.

In recent years, the substantial immigration into Spain from endemic areas of Chagas disease such as Latin America has increased the number of potential donors of blood and blood products [15] and also of organs and tissues. Foreign citizens represent approximately 12% of the current Spanish population. Upon arrival in Spain, this population has access to health care, so donation is considered as a possibility for them. Thus, the number of foreign organ donors has been steadily increasing in Spain over the last decade, representing 8.4% of all donations in 2007 (Fig. 1). Organ donors from Latin America represent one third of all non-national donors and the donation rate of Latin Americans is similar to that of the Spanish population.

In addition, an increasing number of patients with advanced Chagas heart disease are being diagnosed and treated in Spanish hospitals [16] and may eventually be eligible to receive a heart transplant, a universally accepted therapeutic strategy for the advanced stages of this disease [8]. Finally, an undetermined percentage of people with chronic Chagas disease (symptomatic or asymptomatic, diagnosed or undiagnosed) living in Spain may also have other pathologies treatable by organ or tissue transplantation. All these premises make it necessary to create a protocol for the evaluation and acceptance of patients infected by T. cruzi as potential donors or transplant recipients.

Chagas is an emerging disease in Europe and Spain and is often unknown to health professionals. Therefore, it is necessary to establish protocols for disease management. So far, the Spanish Society of Tropical Medicine and International Health has developed and published 3 consensus documents: one related to diagnosis [17] and the other 2 related to the management of cardiac and gastrointestinal involvement of the disease [18], [19].

This document is intended to establish the guidelines to be followed when a potential donor or a tissue or organ recipient is potentially affected by Chagas disease.

Section snippets

Epidemiology

Migration from Latin America has caused substantial changes in the epidemiology of Chagas disease. Initially, it was a disease linked to poverty and rural areas of Latin America. However, today, it has also become an urban disease due, first, to migration from rural areas to the cities within Latin America and, second, to migration to nonendemic areas such as Europe and North America. Table 1 shows the estimated prevalence of Chagas Disease in endemic countries [1].

Spain currently has more than

Attitude towards potential donor assessment in non-endemic areas

Because of the limited availability of organs for transplantation, we need to consider as potential donors those patients who have an epidemiological history indicating infection with T. cruzi and/or positive serological tests. If we have a potential donor or a transplant recipient with unknown serology for Chagas disease, we need to perform an individualized screening based on the presence or absence of epidemiological risk factors for T. cruzi infection (Table 3) through the patient's medical

Exclusion criteria for transplantation

A kidney transplantation study shows that the percentage of transmission from T. cruzi –infected donors to uninfected recipients was 18.7% [36]. According to 2007 data from the Instituto Nacional Central Único Coordinador de Ablación e Implante de Argentina, the prevalence of T. cruzi –infected donors was 4.82%. In transplant candidates, the percentage of infection with T. cruzi was between 2% (for kidney recipients) and 8.9% (for heart recipients). When the donor is infected with T. cruzi,

Evaluation criteria for transplant candidates

According to current legislation, every patient on the waiting list having risk factors for Chagas disease should be submitted to a serology test (see Section 2.3). If, for whatever reason, the patient is immunocompromised and serological tests are negative, parasitological tests need to be done (see Section 2.3). Because of the low efficiency of current antiparasitic treatment to eradicate T. cruzi [43], serological and parasitological tests must be carried out even in those patients who have

Post-transplant monitoring of patients receiving an organ from an infected donor or those previously infected with T. cruzi

A Brazilian study shows that the survival rate of heart transplant patients with Chagas disease is higher than that of patients transplanted due to other etiologies (such as ischemic heart disease and idiopathic dilated myocardiopathy), despite the higher risk of neoplasia that was detected in some previous studies [38], [39]. This increase in neoplasia has not yet been confirmed by other authors [40]. The same authors also found a lower incidence of graft vascular disease and low mortality due

Living donors

For patients infected with T. cruzi a pretreatment with benznidazole is recommended, if possible, for at least 30 days and ideally for 60 days. This treatment aims to reduce the parasitemia of the donor before donation. Due to benznidazole-related adverse events, a careful and strict monitoring of the patients is necessary.

Pretransplant treatment (on the waiting list) of the potential recipient infected with T. cruzi/Chagas disease

Despite the low therapeutic efficacy of current treatments (defined as the eradication of the parasite), some studies indicate that treatment with trypanocidal drugs modifies

Management of immunosuppression

The adjustment of immunosuppression and the reduction in the dose of cyclosporine resulted in lower rates of Chagas disease reactivation and neoplasias [8]. The introduction of mycophenolate mofetil (MMF) instead of azathioprine as an immunosuppressive agent increased the reactivation of Chagas disease [69]. A study published by Bacal et al [8] shows that the probability of reactivation was six times higher in the group of patients who received MMF in the immunosuppression protocol than in the

Conclusions and recommendations

Considering the increase in the population infected with T. cruzi in Spain and other non-endemic countries, there is a higher likelihood of obtaining organs for transplantation from these potential donors and of recipients having the infection. This document summarizes the action criteria against the possibility of Chagas disease transmission through the donation of organs, tissues or hematopoietic stem cells and aims to help professionals working in this field. The working group proposes the

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      It has been estimated that it affects 6 million people in Latin America, where other 70 million people are at risk of acquiring the disease [1]. Because international immigration, it is believed that 700,000 people with Chagas disease live in non-endemic countries, mainly in United States and Europe [2]. This results in an impressive burden to world economy, as about 7 billion euros have been spent in the treatment of the disease annually [3].

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