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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 2010  |  Volume : 21  |  Issue : 1  |  Page : 105-108
Visceral leishmaniasis in a renal transplant recipient treated with allopurinol


1 Unity of Organ Transplantation, Military Hospital, Tunis, Tunisia
2 Department of Parasitology, Military Hospital, Tunis, Tunisia
3 Department of Urology, Military Hospital, Tunis, Tunisia
4 Coordinator of the Transplantation Program, Military Hospital, Tunis, Tunisia
5 Unity of Hemodialysis, Department of Internal Medicine , Military Hospital, Tunis, Tunisia

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Date of Web Publication8-Jan-2010
 

   Abstract 

Leishmaniasis is an infection caused by a protozoan parasite belonging to the genus Leishmania and transmitted by the Phlebotomus sandfly. We report a case of visceral leishmaniasis in a 49-year-old male renal transplant recipient, a resident of the western part of Tunisia, which is an endemic zone for the disease. Just before and after the transplantation, the patient resided in Tunis, which is non-endemic for leishmaniasis. Visceral leishmaniasis occurred eight years after renal transplantation, and the clinical picture was characterized by fever and pancytopenia. Leish­maniae were detected by bone marrow aspiration. Pentavalent antimonal was used for 28 days and was substituted by allopurinol (20 mg/kg per day). One year after the infection, the patient remains totally asymptomatic. Our report suggests that visceral leishmaniasis may complicate the clinical course of organ transplantation and can be fatal, particularly when untreated. Relapses may occur after completion of the apparently effective treatment. Allopurinol could be a solution to avoid these relapses.

How to cite this article:
Harzallah K, Belhadj R, Jemli B, Haloues M, Berraies N, Gargouri S, Hmida J, Battikh R, Manaa J. Visceral leishmaniasis in a renal transplant recipient treated with allopurinol. Saudi J Kidney Dis Transpl 2010;21:105-8

How to cite this URL:
Harzallah K, Belhadj R, Jemli B, Haloues M, Berraies N, Gargouri S, Hmida J, Battikh R, Manaa J. Visceral leishmaniasis in a renal transplant recipient treated with allopurinol. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2020 May 26];21:105-8. Available from: http://www.sjkdt.org/text.asp?2010/21/1/105/58782

   Introduction Top


Leishmaniasis is a zoonotic infection that has a high prevalence in endemic areas such as India, China, East Africa, Southern Europe, Mediter­ranean basin and South America. The causative agent is a protozoan of the genus Leishmania, which is transmitted by the bile of insect vectors, the phlebotomus sandfly. [1]

Cell-mediated immune deficiency is known to increase a patient's susceptibility to this infec­tion, and cases of visceral leishmaniasis have been reported in transplant patients; [2] about 61 such cases have been described in the litera­ture. [3]

Pentavalent antimonal drugs have been classi­cally considered the ideal treatment, [4] but the high degree of serious adverse events and the increasing incidence of primary parasitic resis­tance and relapses have enhanced the need for alternative treatments like allopurinol. [5] We he­rein report on a patient with visceral leishmaniasis who was treated with allopurinol.


   Case Report Top


Mm, a 49-year-old Caucasian man with end­stage renal disease (ESRD) secondary to ne­phroangiosclerosis, received a kidney allograft in October 1999, from a 37-year-old male de­ceased donor. Immunosuppression was induced with thymoglobulin, methylprednisolone and aza­thioprine. Cyclosprorin was introduced on day­four after transplantation and evolution was fa­vorable with serum creatinine stabilizing at 100μmol/L at day seven. The patient originally came from the west of Tunisia (Sebitla). Before and after transplantation, the patient has always lived in urban area (Tunis).

He was hospitalized in May 2007, eight years after transplantation, with complaints of high fever at 40°C, fatigue, and weakness. He denied having night sweats, cough, dyspnea, or diarrhea. Physical examination did not reveal any evi­dence of infection and he did not have spleno­megaly. He was receiving 150 mg/day of cy­closporine, 100 mg/day of azathioprine and 7.5 mg/day of prednisone, at presentation.

Laboratory tests revealed the following: hemo­globin (Hb) of 10 g/dL; white blood cell (WBC) count of 2400/mm 3 (lymphocytes 600/mm 3 ), platelet count of 127000/mm 3 , normal coagu­lation parameters, normal liver function tests, serum creatinine of 124 μmol/L, blood urea ni­trogen (BUN) of 6 mmol/L, cyclosporin trough level of 110 ng/ml, serum total proteins of 67 g/L, albumin of 37 g/L and gamma globulin of 12 g/L. The C-reactive protein was elevated at 114 mg/L. Blood culture grew methicillin-sen­sitive coagulase-negative staphylococcus as well as positive cytomegalovirus (CMV) viral cul­ture. Culture for  Mycobacterium tuberculosis Scientific Name Search i>on Lowestein-Jensen medium was negative. Urine culture was negative.

Evolution was characterized by persistent fe­ver and marked pancytopenia despite intrave­nous ganciclovir and antibiotics. Culture and Giesma staining of a bone marrow aspirate re­vealed massive intracellular amastigotes, con­firming the diagnosis of visceral lesihmaniasis (VL) [Figure 1]. Therapy with meglutamine anti­moniate (glucantim® ) was immediately started at the dose of 20 mg/kg/day. On day three after the beginning of treatment, the patient became afebrile. The WBC count rose up to normal va­lues after ten days of treatment [Figure 2]. Se­ven days later, the patient developed features of pancreatitis with elevated amylase, and hepatic cytolysis. The treatment was discontinued for two days and then restarted progressively at a quarter dose, which was gradually increased. The treatment lasted 28 days [Figure 2]. Allopu­rinol monotherapy was then initiated (20 mg/ kg/day in four divided doses) and continued for one year. At the introduction of allopurinol, aza­thioprine was switched over to mycophenolate mofetil (2 grams/day). Ganciclovir was continued for a total of 21 days [Figure 2].

After one year of follow-up, the patient is in good health, free of symptoms, with normal re­nal function (serum creatinine 105 μmol/L) and there is no evidence of relapse.


   Discussion Top


Species of leishmania can be separated by geo­graphic distribution and the usual clinical mani­festations of infection. In Tunisia, VL has in­creased in incidence, and its area of transmi­ssion has noticeably extended, during the last few years, towards the center and south of the country. [6]

Leishmania exists in two forms: within the sandfly (phlebotomus) vector or in culture, they develop from amastigotes into single-celled, fla­gellated extracellular promastigotes. The promas­tigotes migrate to the pharynx of the sandfly in a non-diving or stationary phase within the cells of vertebrate hosts, where the organisms be­come small, rounded amastigotes. [5]

In recent years, the increasing frequency of organ transplantations and improvement of the associated immunosuppressive treatments have led to the recognition of several cases of VL complicating organ transplantation. In immuno­competent patients, the disease may occur as late as 30 years after the initial infection. [5] In transplanted patients, the use of pulse steroids, antilymphocyte antibodies, and intensified im­munosuppression to treat graft rejection may accelerate disease. [7],[8] Generally, infection occurs early after the transplantation and the average time is about eight months. [4] Our patient had a gap of eight years between transplantation and the occurrence of infection; a similar occu­rrence has been reported in one other renal allo­graft recipient who had exposure to the infec­tion in the pre-transplant period, but developed clinical disease almost seven years after trans­plantation. [9]

Generally, it is recognized that infection occurs in transplanted patients who are either living in, or who travel frequently to endemic areas. [1] Our patient is from an endemic zone but he has always lived in an urban area (Tunis) before and after transplantation. The simultaneous oc­currence of leishmaniasis and high CMV vire­mia may have been a coincidence. It is also possible that the clinical presentation of the pa­rasitic infection was triggered by the CMV di­sease.

Without adequate treatment, VL in transplant recipients is fatal. [7],[8] Usually, leishmaniasis is treated with pentavalent antimonals. Treatment with these drugs poses therapeutic problems with heart, liver, pancreas, and kidney toxicity, which might result in discontinuation of treat­ment. [10]

Close follow-up and meticulous surveillance are mandatory in leishmaniasis, because relapse is reported in 28.5% of cases, [6],[7],[8] occurring bet­ween one month and five years after completion of treatment. [4] Sabbatini et al, [4] successfully used Glucantim; in conjunction with allopurinol in a case of relapse observed one month after dis­continuation of therapy. Hueso et al used a com­bination of ketoconazole and allopurinol for a full course of 30 days in a patient who deve­loped abdominal pain, nausea and vomiting due to Glucantim®. [10] Llorente et al have reported a case of VL treated with glucantim who deve­loped acute pancreatitis; subsequent treatment with the combination of ketoconazole and allopurinol for 21 days was effective to eradicate the infection.[11]

According to the recommendations of the Ame­rican society of transplantation, allopurinol (20 mg/kg/d in four divided doses) may have addi­tive efficacy with pentavalent antimonials in patients with unresponsive disease.[5] Allopurinol monotherapy may be less toxic, less costly and more effective than the antimony compounds. In our case, no relapse was observed after one year of treatment with allopurinol.

In conclusion, visceral leishmaniasis may com­plicate the clinical course of organ transplan­tation and can be fatal, particularly when un­treated. Relapses may occur after the comple­tion of the apparently effective treatment. Allo­purinol could be a solution to avoid the re­lapses.

 
   References Top

1.Basset D, Faraut F, Marty P, et al. Visceral leishmaniasis in organ transplant recipients: 11 new cases and a review of the literature. Microbes Infect 2005;7(13):1370.  Back to cited text no. 1      
2.Berenguer J, GOmez-Campdera F, Padilla B, et al. Visceral leishmaniasis (Kala-Azar) in transplant recipients: case report and review. Transplantation 1998;65(10):1401.  Back to cited text no. 2      
3.Antinori S, Cascio A, Parravicini C, Bianchi R, Corbellino M. Leishmaniasis among organ trans­plant recipients. Lancet Infect Dis 2008;8:191.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Sabbatini M, Pisani A, Ragosta A, Gallo R, Borrelli F, Cianciaruso B. Visceral Leishmania­sis in renal transplant recipients: is it still a challenge to the nephrologist? Transplantation 2002;73(2):299.  Back to cited text no. 4      
5.Parasitic infections. Am J Transplant 2004;4 (s10):142.  Back to cited text no. 5      
6.Belhadj S, Pratlong F, Toumi NH, et al. Visceral leishmaniasis in Tunisia: result of the isoenzy­matic characterization of 65 Leishmania infantum strains. Trans R Soc Trop Med Hyg 2002;96 (6):627.  Back to cited text no. 6      
7.Broeckaert-van Orshoven A, Michielsen P, Vandepitte J. Fatal leishmaniasis in renal trans­plant patient. Lancet 1979;6;2(8145):740.  Back to cited text no. 7      
8.Aguado JM, Bonet F, Plaza JJ, Escudero A. Visceral leishmaniasis in a renal transplant pa­tient: a diagnostic and therapeutic challenge. Clin Transplant 1986;135.  Back to cited text no. 8      
9.Ma DD, Concannon AJ, Hayes J. Fatal leishma­niasis in renal-transport patient. Lancet 1979;11; 2(8137):311.  Back to cited text no. 9      
10.Hueso M, Bover J, Seron D, et al. The renal transplant patient with visceral leishmaniasis who could not tolerate meglumine antimonia­tecure with ketoconazole and allopurinol. Nephrol Dial Transplant 1999;14:2941.  Back to cited text no. 10      
11.Llorente S, Gimeno L, Navarro MJ, Moreno S, Rodriguez-Girones M. Therapy of visceral leish­maniasis in renal transplant recipients intolerant to pentavalent antimonials. Transplantation 2000; 70(5):800.  Back to cited text no. 11      

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Correspondence Address:
Kais Harzallah
Unity of Organ Transplantation, Military Hospital, Tunis
Tunisia
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