Infectious disease complications of transplant tourism

Introduction

The dramatic deficiency of organs throughout the world results in a significant number of transplant candidates who seek organs through alternative routes, including ‘transplant tourism,’ which denotes travel of either the organ donor or recipient for purposes of organ transplantation. This involves an estimated tenth of organ transplants worldwide. Transplant tourism is more likely to occur in commercial or for-profit settings, and may convey significant ethical and infectious disease risks. The reasons for this are many, including lack of local transplant programs (or lack of living donors), denial by the local programs, lack of knowledge, or a desire to expedite transplant. Some programs, such as bone marrow transplant for multiple sclerosis, are only available in certain centers. An analysis of transplant tourism studies from 2000 to 2015 reported that 6002 individuals were involved in travel for transplant, and 20.6% reported paying for transplant [1].

Some transplant tourism is proper and is likely to be lower risk, such as when the living donor or recipient reside in different jurisdictions, or when there is an official, regulated, deceased donor organ sharing program. This review focuses on the less legal, more commercial aspects of transplant tourism, sometimes associated with organ trafficking. Numerous international transplant organizations, including The World Health Organization, The Transplantation Society, The International Society of Nephrology (through the Declaration of Istanbul), and The Council of Europe Convention Against Organ Trafficking, have made major efforts to decrease the purchase and sale of organs on ethical grounds. Outcomes from the studies and case reports of transplantation overseas show reduced graft and patient survival, higher infectious complications, and higher rates of rejection [2]. Reports of transplant tourism in PubMed peaked in 2008–2010, when there were 17–19/year with ‘transplant tourism’ in the title or abstract. In the past decade, there have been fewer published reports of donor-derived infections from transplant tourism compared with earlier times, now down to almost half of the prior reports, suggesting that recognition of the issues and changes in policy may be helping [3].

Understanding the extent of transplant tourism and associated incidence of infection is challenging, given their commercial and sometimes illegal nature, such that many of these organ transplants are not recorded in databases. Reports that immigrants are more likely to access transplant tourism in their countries of origin suggest that this may be more common in wealthy and educated groups but also vulnerable and disenfranchised populations, and reflect inequities in global healthcare [4]. A review of US national waiting-list data identified 373 foreign transplants, predominantly kidney (89.3%); male sex, Asian race, resident and nonresident alien status, and college education were significantly and independently associated with foreign transplant in 35 countries, led by China, the Philippines, and India [4]. In a series of 93 foreign transplant recipients from British Columbia, Canada, 90% were ethnic minorities who often returned to their country of origin; China (42%), the Philippines (17%), India (15%), Pakistan (12%), and Iran (5%) [5]. Twenty-seven had a preemptive transplant. Of those also on a Canadian waiting list, they pursued tourism after waiting a median of 2 years.

The pre-transplant evaluation of the donor and recipient may be insufficient and unsafe. Recipients may not have had standard vaccines in preparation [2]. Documentation from the transplant center and infection prophylaxis may be incomplete or nonexistent [6]. Infectious disease testing upon return to their home country may enhance safety (Table 1), along with initiation of infection prophylaxis (depending on time after transplant and local protocols). For those recipients who are ill upon return, consultation with infectious diseases specialists with familiarity in both geographic medicine and immunocompromised hosts would be essential. Ensuring these recipients are accepted back to the transplant centers where they live is crucial for optimal outcomes [6].

Table 1. Post-transplant tourism screening upon return to usual location of residence

Screening tests that should be performed upon return of the recipient to their home country

Serology for hepatitis B and C

Hepatitis B surface antigen or nucleic acid testing

Hepatitis C nucleic acid testing

HIV-1/2 antibody or 4th generation HIV antigen/antibody assay

Cytomegalovirus IgG and viral load

Syphilis serology screening

Toxoplasma IgG (especially with heart transplant)

Blood, urine, and sputum cultures as clinically indicated

Tuberculosis screening (purified protein derivative or interferon-γ release assay)

Examples of testing to consider if ill, based on geographic location of transplant and/or symptoms (this is not an exhaustive list; refer also to reference works [7])

Blood, urine, and sputum cultures as clinically indicated

Diagnostic testing for malaria

Strongyloides antibody or stool examination

Trypanosoma cruzi antibody and molecular diagnostic testing

Toxoplasma nucleic acid testing (PCR)

Histoplasma antibody and antigen testing

Coccidioides immitis antibody and antigen testing

Hepatitis E antibody and nucleic acid testing

Brucella antibody

Cryptococcus antigen

All types of infections can occur. Transplant tourism recipients are at risk both for acquisition of new indigenous infections (both community or nosocomial) and reactivation of latent infections; knowledge of the specific infections existing in those regions can direct further evaluation [7]. Surgical site infections are more commonly reported in the literature, and associated surgical issues can be problematic to correct by a new surgical team. Some infections, such as dengue virus and other arboviruses, malaria and T. cruzi, could be transmitted by blood products as well as organs [8].

Viral infections are among the most commonly reported, and include HIV, hepatitis B, hepatitis C, and cytomegalovirus. Other more unusual endemic infections of concern for potential exposure include hepatitis E, Zika, Chikungunya, and rabies. One review found transplant-related infections of HIV at rates of 4–6% and hepatitis B at rates of 2–12% in those who had undergone commercial transplants in foreign countries [9]. A study comparing 540 patients who had undergone commercial renal transplants in India between 1978 and 1993 with 75 recipients of emotionally related (i.e. friend, family) renal transplants performed at two institutions in the Middle East found that graft survival rates were similar, but a higher incidence of human immune deficiency virus (HIV) infection (5% vs. 0%), and hepatitis B virus infection rate (8% vs. 1%) in those who had commercial transplants [10]. A case report from England discussed de novo hepatitis B infection in a patient who underwent renal transplant in India, with subsequent hepatitis B infection of four patients in England due to breaks in infection control practices, including another renal transplant recipient and his spouse [11].

Bacterial infections can include highly resistant organisms. A recent case of a kidney transplant in Pakistan resulted in necrotizing kidney allograft infection and subsequent external iliac artery rupture due to New Delhi metallo-beta-lactamase-1-producing Enterobacter cloacae and Rhizopus oryzae [12]. Given that a third of the world has latent tuberculosis, which could be readily transmitted via an organ especially kidney or lung, tuberculosis infections may occur in transplant recipients with ‘no risk factors’ and may also be more likely to be antibiotic resistant. Clinicians should be prepared for such unexpected and sometimes drug-resistant pathogens.

Parasitic infections that have been transmitted by donor organs, all with potentially devastating outcomes, include malaria, Strongyloides, Trypanosoma cruzi (Chagas disease), and Microsporidia [13]. While standard travel medicine guidance might recommend preventative measures such as malaria prophylaxis for travel to such regions, this is often overlooked in cases of transplant tourism.

Invasive fungal infection frequently originating at the graft site have been reported in multiple series, including at a rate of 8% from a single center in Oman, of whom 77% underwent nephrectomy [14,15]. Fungal surgical-site infections suggest poor infection control in the operating room. Endemic fungal infections (histoplasmosis, coccidioidomycosis) may be harder to recognize, diagnose, and treat in non-endemic regions.

The global pandemic of COVID-19 highlights the impact of globalization on the spread of international pathogens and the possible impact on transplant recipients and programs. Although there are many larger forces that could result in migration of pathogens, transplant tourism could certainly be an additional vector, especially for more opportunistic pathogens that might not otherwise travel as easily.

Moving forward, we must focus on methods to deter the need for unethical transplant tourism, and to enhance more accurate knowledge. Efforts to decrease transplant tourism should be made at multiple phases of the transplant evaluation [5]. Those who continue to pursue transplant tourism should be educated and encouraged to consider about the higher rates of infectious complications as well as morbidity and mortality. We have found that open discussions with patients and families from higher risk backgrounds to be useful; many are familiar with the concept, and some are reluctant to discuss it with their doctors, given the commercial and sometimes illegal nature. Developing a reporting code for transplant professionals to report organ trafficking networks may be a potential strategy to collect and quantify cases [1]. Upon return to care, having a plan to collect transplant data, initiate routine prophylaxis (along with consideration of tuberculosis chemoprophylaxis), and screen for organ-borne and other pathogens (Table 1) can enhance post-transplant safety and outcomes. Understanding the substantial risks of transplant tourism, organ trafficking, and the associated infections can hopefully help all of us in the medical community support better policies and education of both clinicians and patients to help eradicate this pernicious problem.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.