1. Background
Infections are a major cause of morbidity and mortality among solid organ transplant patients as more than 80% of these patients suffer at least one episode of infection during the first year after transplantation. The concurrent administration of immunosuppressive drugs to prevent acute allograft rejection further increases the risk of morbidity and mortality among these patients (1, 2). Although cytomegalovirus is the most important, and one of the most common infections seen in renal transplant recipients, numerous other viruses have also affected outcomes (3-11). Herpes simplex virus (HSV) is an alpha herpes virus with a double stranded DNA core. According to previous studies, the seroprevalence of HSV in the adult population is as high as 60% (12, 13). Therefore, donor and recipient candidates for kidney transplantation are also at risk of this infection. Although, there are many studies about the prevalence of HSV infection in the general population or transplant candidates in developed countries, yet only a few studies have been done in developing countries regarding this issue.
2. Objectives
The aim of this study was to evaluate the role of screening and the prevalence of HSV infection in donor and recipient candidates for kidney transplantation in Ahvaz city of Iran.
3. Materials and Methods
In this cross sectional study, from October 2012 to November 2013, we investigated all candidates for receiving renal allograft and living donors who had referred to our kidney transplant center before transplantation. The study was approved by the chronic renal failure research center of Ahvaz Jundishapur University of Medical Sciences.
A standardized questionnaire was used to collect socio-demographic data (for donors and recipients) including causes of end stage renal disease (ESRD), date of onset and length of time before receiving renal replacement therapy and history of a kidney transplantation (for recipients).
Blood samples were taken from recipients and donors to test for IgG and IgM anti-HSV antibodies (Trinity Biotech, New York, USA). The levels of antibodies were determined by using a commercially available direct fluorescent antibody (DFA) method. The recipients and donors were also screened for human immunodeficiency virus (HIV) (Pishtaz Teb Zamen, Tehran, Iran), HBsAg and hepatitis C antibody (anti-HCV) (Pasto kit, Pasteur Institute, Iran) by using the sensitive enzyme-linked immunosorbent assay (ELISA). All samples were also tested for liver function including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels by a colorimetric method. Liver function tests including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were also determined by a colorimetric method. Medical laboratory tests were performed for the recipients and donors free of charge by the hospital.
3.1. Hemodialysis Methods
Hemodialysis (HD) was performed during six to 16 hours, two, three or four times a week according to clinical grounds. The rate of ultrafiltration rate during each hemodialysis (HD) session was also determined by the nephrologist. We used Fresenius machines, synthetic (polysulfone) dialyzer membranes and bicarbonate-buffered dialysate for our patients.
3. 2. Statistical Analysis
At the end of the study, we performed statistical analysis using the statistical package for social sciences (SPSS) software version 15. Results are expressed as mean ± SD. Prevalence rates and 95% confidence intervals (CI 95%) were calculated. Chi-square tests were performed to evaluate the distribution of variables associated with herpes simplex virus infection. A P value of less than 0.05 was considered statistically significant.
4. Results
Overall, 37 candidates for kidney transplantation were enrolled in this study. There were 22 candidates for kidney donation with mean age of 30 ± 5 years with most being males; 20 males (90.90%) and two females (09.09%). Our recipients included 15 dialysis patients; eight males (53.33%) and seven females (46.66%) with mean age of 45 ± 6 years.
The minimum and maximum ages of the candidates were 21 and 60 years for donors and 19 and 66 years for recipients, respectively. All of our recipients were on maintenance intermittent hemodialysis. Herpes simplex virus IgG antibody was positive in 93.33% of recipients (n = 14) and 77.27% of donors (n = 17). Although the prevalence of positivity for HSV IgG antibody was higher in recipients, there was no statistically significant difference between the two groups (P = 0 .33). Herpes simplex virus IgM antibody was positive in 33.33% of recipients (n = 5) and 13.63% of donors (n = 3) and there was no statistically significant difference between the two groups (P = 0.15). The liver function tests indicated that AST and ALT were at normal ranges in both recipients and donors. The markers of HBV and HCV infection were also negative in all recipients and donors.
5. Discussion
Herpes simplex virus infection is a well-known opportunistic pathogen among immunocompromised patients including kidney transplant recipients. This infection is usually caused by reactivation of latent virus among these patients; however, it has also been recognized as a potential donor-to-host transmission infection after transplantation. In the absence of prophylaxis, HSV may be seen early, even during the first post transplant month (14-16). Although it usually presents oral or genital lesions, it can also be a life threatening disease with high morbidity and mortality among infected patients (14, 15).For example in some instances, it can cause life threatening diseases including esophagitis, hepatitis, encephalitis or pneumonitis. It may be difficult to differentiate between an infection acquired from the allograft, and an infection due to reactivation of latent disease in the recipient (14).
The results of our study show that, the prevalence of HSV IgG antibody and therefore exposure to the HSV infection in candidates for kidney transplantation in Khuzestan province of Iran, is high and almost all of the recipients (93.33%) and most of the donors (77.27%) had the HSV IgG antibody before transplantation. Similar to the result of our study, the incidence of HSV in renal transplant recipients was also high and estimated to be approximately 53% (15). Other studies have reported that HSV can cause pneumonia, which may lead to a mortality rate of up to 75% despite treatment with acyclovir (16, 17). Walker et al. in a prospective study of HSV disease in renal transplant recipients, reported that HSV infection was diagnosed in about 52% of the studied patients (18).
Regarding the prevalence of HSV infection among donors and recipients, due to probability transmission of infection from seropositive donors to seronegative recipients, and the potential of reactivation of the latent virus among recipients, it is recommended for recipients and donors of kidney transplantation to be routinely tested for IgM and IgG anti–HSV antibodies before transplantation while recipients should be followed to monitor for reactivation of latent virus following immunosuppressive treatments (14, 15, 19, 20).
In addition, post-transplant prophylaxis against reactivation of HSV is also recommended to prevent severe recurrences of this infection. In patients who need cytomegalovirus (CMV) prophylaxis, ganciclovir is adequate against both CMV and HSV infections. Among kidney transplant patients who do not require CMV prophylaxis, valacyclovir or acyclovir should be administered for approximately one to three months post transplantation (21-26). Herpes simplex virus infection is a well-known opportunistic pathogen among kidney transplant recipients. It may become a life threatening disease among these patients. This infection is usually caused by reactivation of latent virus or by transmission from seropositive donors to seronegative recipients.
The results of our study show that, almost all of the recipients and most of the donors for kidney transplantation in Khuzestan province Iran had HSV IgG antibody and exposure to the infection. The incidence of HSV infection in other countries is also high and therefore it is recommended that both the recipients and donors for kidney transplantation should be routinely tested for IgM and IgG anti–HSV antibodies before transplantation while recipients should be monitored for reactivation of latent virus following immunosuppressive treatments.
