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Saudi Journal of Kidney Diseases and Transplantation
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RENAL DATA FROM THE ARAB WORLD  
Year : 2012  |  Volume : 23  |  Issue : 5  |  Page : 1099-1103
Malaria incidence among kidney-transplanted recipients in an endemic malaria area, Sudan


1 Department of Nephrology, Gezira Hospital for Renal Diseases, Khartoum, Sudan
2 Ministry of Health, Khartoum, Sudan

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Date of Web Publication13-Sep-2012
 

   Abstract 

Malaria is endemic all over Sudan. The population are at risk of malaria infection to variable degrees. Kidney-transplanted patients on maintenance immunosuppressive therapy are known to be prone to infection, but there is not enough data in the medical literature as to whether they are more susceptible to malaria infection in endemic areas. This study was conducted in the Gezira Hospital for Renal Diseases and Surgery to assess the effect of maintenance immunosuppressive therapy in renal transplantation on malaria incidence. A total of 110 individuals were enrolled: 55 were renal-transplanted patients with end-stage renal disease who received kidney transplantation at least one year earlier and were on maintenance immunosuppressive medi­cations. The other 55 individuals were the compatible healthy group. Thorough follow-up was exercised for both groups for one year (January-December 2009). Following the World Health Organization criteria for malaria diagnosis, a total of 51 malarial attacks were reported in both the groups, 25 in the transplanted group and 26 in the controls. The incidence difference between both groups was statistically insignificant [0.76 (΁1.170) and 1.09 (΁1.917) P = 0.282 among transplanted group and control group, respectively]. Providing routine malaria prophylaxis is not required for renal transplant recipients on maintenance immunosuppressive.

How to cite this article:
Elsharif ME, Malik EM, Imam ME, Omran MO, Elsharif EG. Malaria incidence among kidney-transplanted recipients in an endemic malaria area, Sudan. Saudi J Kidney Dis Transpl 2012;23:1099-103

How to cite this URL:
Elsharif ME, Malik EM, Imam ME, Omran MO, Elsharif EG. Malaria incidence among kidney-transplanted recipients in an endemic malaria area, Sudan. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2020 Oct 31];23:1099-103. Available from: https://www.sjkdt.org/text.asp?2012/23/5/1099/100970

   Introduction Top


Malaria in Sudan is a major public health problem heading the list of outpatients' atten­dance, hospital admission and reported deaths. [1],[2],[3] The disease is endemic all over the country with variable degrees of transmission. [1],[2],[3],[4] Therefore, malaria is a disease that should be kept in mind whenever a patient complains of fever. This is of particular importance in immunocompromised patients including kidney-trans­planted patients.

Immunity to malaria is extremely complex: the replicative cycle of the parasite goes through intra- and extracellular phases in which a pre­valent cell-mediated or a predominant humoral immunity is necessary to contain the infection. Cell-mediated immunity is more implicated in this, in particular CD8+ T lymphocytes. [5]

Malaria infection induces solid T lymphocyte effector functions; additionally, the persistence of malaria-specific memory T cells in infected individuals is comparable to what is observed in bacterial and viral infections. [6]

In recent years, the incidence of end-stage renal failure has shown an increasing trend. Many dialysis centers were established through­out Sudan and many patients have been transplanted. [7] Kidney transplantation is the treat­ment of choice for patients with end-stage re­nal disease (ESRD). [8] Transplanting an immunologically non-identical kidney into a pa­tient without administering immunosuppressive agents invariably results in allograft re­jection and loss. The optimal maintenance immunosuppressive therapy in renal transplanta­tion is not established yet. The major immunosuppressive agents that are currently being used in various combination regimens are corticosteroids, azathioprine, mycophenolate mofetil (MMF), cyclosporine, tacrolimus, everolimus and rapamycin. [9],[10],[11] In Sudan, everolimus and rapamycin are rarely used.

The predominant action of cyclosporine is di­rected against CD4+ T (T helper) lymphocytes. [12],[13],[14],[15],[16],[17],[18] This effect on the CD4+ T cell pre­vents the production of lymphokines, especially IL-2, [19],[20],[21] which inhibits the further prolifera­tion of CD4+ T cells and the generation of cytotoxic T cells from the cytotoxic T cell precursor.

Tacrolimus inhibits T lymphocyte activation by binding to FK BP-12, an intracellular pro­tein. A complex is then formed of tacrolimus- FK BP-12, calcium, calmodulin and calcineurin, which inhibits the phosphatase activity of calcineurin. This complex prevents the dephosphorylation and subsequent translocation of the nuclear factor of activated T cells (NF-AT), a nuclear component that initiates gene trans­cription for the formation of interleukin-2. As a result, T lymphocyte activation is inhibited. [22] Tacrolimus is 10- to 100-times more potent than cyclosporine in its immunosuppressive effects. [23]

Azathioprine inhibits DNA and RNA synthe­sis by preventing interconversion among the precursors of purine synthesis and suppressing de novo purine synthesis. Azathioprine and mercaptopurine block lymphocyte proliferation in vitro and the production of interleukin-2, which is probably an important aspect of its antiproliferative activity. [24] The mechanism of action of corticosteroids is extremely complex and is still not understood fully. [25],[26],[27]

There is not enough data in the medical lite­rature on whether kidney-transplanted patients on maintenance immunosuppressive therapy have higher malaria infection rates in endemic areas of malaria such as Gezira state in Sudan. [1] The aim of this study is to assess the effect of maintenance immunosuppressive therapy in renal transplantation in the number of malaria infections per year in endemic areas.


   Patients and Methods Top


This case-control study was conducted in Gezira Hospital for Renal Diseases and Sur­gery (Wad Madani-Sudan) from January to De­cember 2009. A total of 110 individuals were enrolled in this study. Half of them (55 indivividuals) were renal-transplanted patients, which included patients of ESRD who had received kidney transplantation at least one year before and were on regular immunosuppressive medi­cations. The control group included randomly selected individuals (from co-patients) not known to suffer from chronic kidney diseases. Exclusion criteria included individuals with sickle cell triad, individuals who are not resi­dent at Gezira state, individuals who were re­ceiving prophylaxis for malaria and individuals known to have acquired or inherited immuno­deficiency disorders. Data were obtained by direct interview using a questionnaire with cases and controls at the time the patients were coming for follow-up on a monthly basis. Medical records of cases were also reviewed. Individuals were consi­dered to have malaria if the malaria parasite was found (at the time of visit) using light microscopy, rapid diagnostic tests or polymerase chain reaction, or the patient give history of malaria or having received anti-malarial drugs before he came to the hospital. A record was kept for each enrolled individual and data was added month by month.


   Statistical Analysis Top


Data were analyzed using the SPSS software (Statistical Package for the Social Sciences, version 17.0, SPSS Inc., Chicago, IL, USA). Differences between the two groups were evaluated using the independent sample t test, 1-way analysis of variance and the Kruskal- Wallis test. P-values lower than 0.05 were considered significant. Continuous variables were presented as mean ± standard deviation.


   Results Top


All enrolled patients successfully completed the study period. No death or loss to follow-up was reported among cases or controls. [Table 1] shows the demographic and clinical charac­teristics of the transplanted group and the con­trol group. In of the transplanted group there were 67.27% (37) males representing about two-thirds of the cases, while females repre­sented only 38.18% (21) of the control group. The duration (mean ± SD) of CKD was 9.04 ± 21.707 years in the transplanted group. The duration of hemodialysis (mean ± SD) before the transplantation was 18.45 ± 21.707 months and the duration of the post-transplantation period (mean ± SD) was 4.87 ± 4.37.
Table 1: Demographic and clinical characteristics of transplanted group versus control group.

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The methods used for diagnosing malaria is summarized in [Table 2]. [Table 3] shows the immunosuppressive drugs used by the trans­planted group. The incidence of malaria among cases and controls is given in [Table 4]. The overall malaria incidence is 464 cases/1000 population. The risk is a bit higher among cases, but with no significant difference [1.04 (0.47 < OR > 2.44)].
Table 2: Methods of diagnosing malaria.

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Table 3: Immunosuppressive drugs used by the transplanted group.

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Table 4: The incidence of malaria among cases and control groups.

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The reported malaria incidence among cases and controls looks similar (P ≥ 0.05). True inci­dence and severity of malaria among the post-transplant recipients is not completely defined. [28] In Western India, George reported that Plas­modium falciparum infected 22.5% of the renal-transplant patients and produced acute renal failure in 60%. [29] Although immunosuppression appears to increase the risk of malaria complications, particularly in renal transplant recipients, some reports have stated that cyclosporine and tacrolimus have an antimalaria effect. [30],[31],[32],[33]

In 2004, the American Society of Transplan­tation (AST) issued guidelines for vaccination of solid organ transplant candidates and reci­pients, which include influenza, hepatitis A, hepatitis B, tetanus, polio (inactivated), S. pneumonia, N. meningitides and rabies. [34] Till now, there is no available vaccination for malaria for clinical use. Antimicrobial prophy­laxis of renal transplant recipients is recom­mended for urinary tract infection. The World Health Organization recommends intermittent preventative therapy (IPT) for pregnant wo­men residing in areas of high and medium malaria transmission with sulfadoxine-pyrimethamine (Fansidar). [35] IPT is effective for redu­cing the risk of malaria infection among preg­nant women. [36] Anteyi et al conducted a small-scale study (n = 7) for eight weeks and conclu­ded that renal transplant recipients in malaria-endemic zones benefit from short-term routine malaria prophylaxis. [37] According to our finding, no specific additional means of prevention is needed for transplanted patients on mainte­nance immunosuppressive.

In conclusion, providing routine malaria pro­phylaxis probably is not necessary for renal transplant recipients on maintenance immunosuppressives. However, we feel that further studies are needed to judge whether prophy­laxis is needed in the post-transplantation period.

 
   References Top

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32.Nickell SP, Scheibel LW, Cole GA. Inhibition by cyclosporin A of rodent malaria in vivo and human malaria in vitro. Infect Immun 1982; 37:1093-100.  Back to cited text no. 32
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34.Guidelines for vaccination of solid organ transplant candidates and recipients. Am J Transplant 2004;4(Suppl 10):160-3.  Back to cited text no. 34
    
35.World Health Organization (WHO). A strategic framework for malaria prevention and control during pregnancy in the African Region. Brazzaville WHO, 2004. Available from: http://www.who.int/malaria/rbm/Attachment/2 0041004/malaria_pregnancy_str_framework.p df ([Last accessed on cited 2010 Jan 21).  Back to cited text no. 35
    
36.WHO Global Malaria Control and Elimination: report of a technical review. Geneva: WHO; 2008. p.1-47.  Back to cited text no. 36
    
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[PUBMED]    

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Correspondence Address:
Mohamed E Elsharif
Department of Nephrology, Gezira Hospital for Renal Diseases, P.O. Box 335, Khartoum
Sudan
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DOI: 10.4103/1319-2442.100970

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