As of January 1 st 2022, there were 5,417,883 foreigners resident in Spain; the figure has tripled in the last 20 years. Morocco is the leading country of origin and Latin America is the leading region of origin, with more than one million of immigrants.1,2

The risk of kidney disease is higher among some minority populations due to a higher prevalence of cardiovascular risk factors and more limited access to health resources.3 According to data from the Registre de Malalts Renals de Catalunya (RMRC), 11.7% of patients who started renal replacement therapy in 2021 were born outside Spain. During the first 9 months of 2022, 19% of the people on the waiting list for kidney transplants (KT) in Catalonia came from other countries. Morocco was, in both cases, the most frequent country of origin the RMRC reports. Adequate care for this population, including the endemic infectious pathology of their countries of origin, is essential for the correct assessment of the KT candidate and post-transplant outcomes.

Within the framework of the Sustainable Development Goals, the World Health Organisation (WHO) has developed a structured plan to address neglected tropical diseases (NTDs).4 These are 20 diseases prevalent in tropical areas that affect more than one billion people in impoverished socio-economic circumstances.4 The causative agents are different pathogens including viruses, bacteria, parasites, fungi and toxins and have devastating social, economic, sanitary and health consequences for the population.5,6 The processes of climate change, globalization and migration have been linked to an increase in the spread of these diseases in previously non-endemic territories, such as Spain.7–9

The international KDIGO guidelines10 (Kidney Disease: Improving Global Outcomes on KT candidate evaluation and management recommends postponing the procedure in all those with active bacterial, fungal, viral and parasitic processes, as these should be treated and resolved prior to KT. In addition, people at risk of having been in contact with NTD, due to being born in or living in an endemic area, should be screened for potentially treatable chronic infections.10

NTDs in the renal transplant population have been reported to be more prevalent in areas including Brazil, Argentina, Mexico, India, China and thoughout Africa, due to their geographical location, the endemic presence of NTDs and particularities of health, surveillance and disease notification systems.11 However, current migratory flows and globalization make it necessary to screen for NTDs in foreign-born KT candidates.7,12 The importance of this screening is directly related to the reduction of infectious complications and mortality after TR.11–13 However, health training in international health is limited,14 which may lead to under-diagnosis of these diseases in non-endemic settings.15,16 Although there are specialists in tropical diseases in many health centers, not all of them have a specific service that can adapt screening of foreign-born patients according to their country of origin.

The main objective of this study is to present the screening method implemented at the KT center and used in this context, as well as to describe the courses of the most prevalent tropical and imported infections in migrant KT candidates in our setting.

This study describes the implementation of a screening program for tropical and imported infections in our KT center and the frequency of such infections in a cohort of migrant KT candidates. We found a high prevalence of strongyloidiasis and LTI. The prevalence of all other infections in the study population was very low, however, since the screening was performed using indirect techniques, there was probably a loss of sensitivity in detecting some latent infections.25,26

Given the expected increase in the incidence of tropical and imported infections in non-endemic areas11,16,27,28 and the potential consequences of their under-diagnosis in the transplant candidate population,10–12 specific screening and treatment prior to transplantation is essential. Infections are the leading cause of death in transplant recipients in tropical and subtropical countries and, in so-called "developed settings", they are the second or third leading cause of death in these patients.11,29,30 Furthermore, infectious processes represent 21% of the causes of hospitalization in the population with chronic kidney disease, behind only cardiovascular causes.31 The complications that may arise from the failure to detect and treat these diseases can be fatal for the person having access to KT, the same consequences as a de novo post-TR infection.10–12

Regarding the general infectious screening in foreign-born KT candidates, we found a high percentage with LTI (34.3%). It is also noteworthy that almost half of the patients were no vaccinated against hepatitis B (44.8%), and most of those were non-responders to the vaccine, although we found six patients who had not received vaccination despite its specific indication in the population with advanced CKD. According to the RMRC, of the patients who started renal replacement therapy in Catalonia in 2020, only 60.6% were vaccinated against hepatitis B.

Regarding the specific study of tropical and imported diseases, more than one third of the cohort had eosinophilia at the time of the study, a finding that may be related to an active or latent parasitic form. In one case an active parasitic form was confirmed via stool screening and six patients received empirical treatment with antiparasitic drugs. Eosinophilia in the CKD population may be related to other diagnoses or syndromes32 and therefore its value as a screening for tropical diseases is limited.33 In the cohort studied, most of these eosinophilias corresponded to the finding of a positive Strongyloides serology. It has been reported that only 50% of Strongyloides patients have eosinophilia, although its predictive value in this disease and other helminthiases is high.21

Strongyloides stercoralis is a helminth that affects 10–60% of the population in tropical and subtropical areas.28 In Spain, it is uncertain whether it is already an endemic disease,34 and a prevalence of around 10% has been reported at hospital level in populations from Africa and Latin America.35 In the case of KT candidates who are going to undergo immunosuppression, infection by this parasite can have fatal consequences, as it can become highly replicating and develop the so-called "hyperinfestation syndrome" or spread to other vital organs, causing high mortality via bacteremias caused by gram-negative bacilli, Loeffler's syndrome, secondary bacterial meningitis or severe colitis, among others. This especially affects patients receiving immunosuppressants, including corticosteroids.36 In addition, the parasite's life cycle allows for auto-infection cycles, so infection could have occurred more than 30 years ago.34 Screening and appropriate pre-KT treatment of the population at risk is essential to minimise the negative impact of immunosuppressive treatment.

Conversely, in our cohort, we did not find other parasitic forms such as Plasmodium, Entamoeba or Trypanosoma cruzi. However, Plasmodium is the most prevalent parasitic infection worldwide, affecting more than 228 million people and causing the death of 405,000 people annually in 108 countries around the world.21,37 Cases were probably not detected because malaria was ruled out only with antigen and peripheral blood smear (PBS) which are low-sensitivity tests in patients with subacute/chronic infection, the ideal test for these patients being Plasmodium sp. PCR.26Entamoeba is the second leading cause of death due to protozoan infection worldwide,28 and Chagas disease has a prevalence of 8–10 million people in 21 Latin American countries,38,39 although we also found no cases in the cohort analyzed. We did detect one case of schistosomiasis in a patient from Senegal. The prevalence of this parasite is moderate/high in sub-Saharan Africa, reaching more than 50% of the population in countries such as Sierra Leone, Ghana, Tanzania, Mozambique and Madagascar.28

Although the screening for fungus causing histoplasmosis is not recommended for pre-KT screening due to its low incidence after KT, we identified 2 IgG-positive patients in this study.

It should be kept in mind that the sensitivity of serological techniques in patients with CKD may be compromised by a state of baseline immunosuppression associated with the disease itself. It is therefore essential: (1) to perform early screening in this group of patients (in the advanced CKD phase), before the state of pharmacological immunosuppression further compromises the validity of the available techniques, and (2) to use more sensitive techniques such as PCR or direct stool analysis.26

Patients receiving KT can develop a tropical or imported infection through different pathways: (1) through reactivation of a latent infection acquired prior to KT, (2) through transmission of the infection from the donor carrying the pathogen, or (3) through the development of a de novo infection acquired after KT in an endemic area.27 Before KT, both the recipient and the donor should undergo preventive screening for the described infections. After transplantation, health education for the recipient and prophylaxis to prevent de novo infections will be important.12,27 Some 25–30% of transplant recipients may travel to tropical and subtropical areas without prior knowledge of the healthcare team, and 5–10% may develop a complication derived from an NTD.12,39,40 Correct follow-up, pre- and post-transplant health education on possible risks, and individualization of immunosuppressive treatment are necessary to avoid this type of action due to lack of knowledge.41,42

In this study, an interdisciplinary pre-KT screening program was followed with the main objective of adequately evaluating infectious risks and ensuring suitability for KT. The screening program is initiated at the KT access consultation and, depending on the findings, the candidate is referred or not to the infectious diseases department. Almost two thirds of the patients required this referral and/or consultation. The initiation and coordination of the study by the nephrology department has advantages. In addition, it avoids unnecessary visits for the patient (which in many cases will go to another referral center) and avoids prolonging the screening time for KT. In addition, first-hand knowledge of the patient's risks promotes a state of alertness for early detection of the problem.

Within the framework of the UN Sustainable Development Goals, by 2030 this group of NTDs should be under control and this requires increased recognition of the current situation in order to be able to act accordingly and apply the relevant preventive or curative measures at the appropriate time.4,5 Screening for NTDs in both the general population and in the CKD population awaiting KT is now a real need in all those who may have been in direct contact in endemic areas. Immunosuppressive treatment can cause asymptomatic or unmanifested infections to be exacerbated or reactivated.37–39 Thus, to guarantee the safety of the people treated and the quality of the care provided, it is essential to promote the recognition of these diseases, which are becoming increasingly prevalent in our environment.

The present study is a single-center study with a small sample size that has limitations. The main limitation is that screening for tropical diseases was mainly performed by indirect serological diagnosis and stool concentration (not fresh samples), which in this type of patient could have led to false negatives. Furthermore, the protocol does not cover 100% of the NTDs considered by the WHO, focusing instead on those with the highest prevalence in our setting. Due to the characteristics of the sample and the long time since migration, the prevalence of acute/subacute tropical diseases could not be explored either. However, it is known that chronic tropical diseases can also cause morbidity and mortality in immunocompromised patients.43 Despite these limitations, the reported findings are significant, in line with the reference literature, and set out a clear strategy for action to tailor the proposed interventions to the specific needs of the target population. It will be necessary to increase the prospective sample size and conduct multicenter studies to achieve more relevant evidence.

The prevalence of strongyloidiasis and LTI in screening for tropical and imported diseases in asymptomatic migrants who were KT candidates was high. Their detection and treatment are essential to avoid serious complications in post-KT. To this end, the implementation of an interdisciplinary screening program, led by the nephrology department, is a feasible healthcare practice, with the potential advantage of streamlining screening and shortening the waiting times involved in inter-specialty consultations.

The authors declare that they have not received any funding for this work.

GPR, ABP and MJPS conceived of and designed the study and conducted data acquisition, analysis and interpretation.

SCN, EP, CAC, DRP, FS, JPH, JP and MC participated in the critical revision of the final manuscript, contributing important intellectual content to the outcome.

All authors have read and approve the final manuscript.

GPR, JVG and MJPS take responsibility for the published document.

The authors declare that they have no conflicts of interest.