Reactivation of and Primary Infection with Human Herpesvirus 8 among Solid-Organ Transplant Recipients

Reactivation of and Primary Infection with Human Herpesvirus 8 among Solid-Organ Transplant Recipients

Herpetic urethritis occurs 35% to 45% of affected men and is characterized by severe dysuria and mucoid discharge. 10 days after the encounter, I got had tingling in my genital area, and when I inspected, I found what looked like a rash with cracks or slits in the skin. Not only is there no indication of whether he is infected or not, but he may not be actually positive. Although, my splenomegaly does seem to be leveling off at this point. 13 Among other findings related to infectious disease risks in the US military, DoDSR studies revealed important information about the prevalence of adenovirus infections among military recruits 17,26 and resulted in a new estimate of herpes simplex virus 1 and 2 infections in young adults. Are these antibody counts my acually antibodies or a comparison to a positive sample? None of the seroconversion events was related to the source of the donor organ.

It was like a vicious cycle. Its been pretty consistent for 3 months, although, sometimes are much better than others. If your HSV 1 and 2 were both negative. I would like to go forward with my life – I have to make a lot of work and life decisions based on my test result. Association between syphilis, antibodies to herpes simplex virus type 2, and recreational drug use and hepatitis B virus infection in the Women’s Interagency HIV Study. KS is a tumor originating from either endothelial or spindle cells that occurs in 4 forms [6]. The classic form presents in older men of Mediterranean, east European, or Jewish descent, whereas the endemic form is seen in sub-Saharan Africa and affects primarily young adults and young children.

The virus travels to nerve cells near your spine. My questions are… KS is more common among transplant recipients from those areas associated with classic and endemic forms of KS (reaching 5% in Saudi Arabia). In the United States, KS occurs in ∼0.5% of all transplant recipients. Choi MJ, Torremorell M, Bender JB, Smith K, Boxrud D, Ertl JR, Yang M, Suwannakarn K, Her D, Nguyen J, Uyeki TM, Levine M, Lindstrom S, Katz JM, Jhung M, Vetter S, Wong KK, Sreevatsan S, Lynfield R: Live Animal Markets in Minnesota: A Potential Source for Emergence of Novel Influenza A Viruses and Interspecies Transmission. Immunosuppression is known to result in the reactivation of many human herpesviruses, including herpes simplex virus types 1 and 2, cytomegalovirus, Epstein-Barr virus, varicella-zoster virus, and HHV-6 [1]. Most studies of HHV-8 among transplant recipients have focused on persons who developed KS, with an emphasis on adult renal transplants.

How before it appears ? 3. In this report, we performed a longitudinal study of HHV-8 serology in serum samples collected before and after transplantation in a cohort of 100 transplant recipients that consisted of both children and adults with different transplanted organs. Study subjects. Gonorrhea and chlamydia among women usually involve the cervix as a portal of entry, whereas other STD pathogens (including HIV) may infect women through the vagina or vulva, as well as the cervix. Aspects of some of the samples from this repository have been reported elsewhere [13]. Samples were selected to fulfill the following criteria: an approximately equal number of men and women, a broad range of ages at the time of transplantation, and a broad range of organ types transplanted.

At the time of this study (1999–2001), limited clinical datawere available on all the transplant recipients: age of the transplant recipient at the time of transplantation, sex, and type of organ transplanted. Other data—such as the race or ethnicity of the recipient, age and sex of the donor, type of immunosuppressive therapy, clinical outcome of transplant recipient, and the number of blood transfusions each recipient received—were not available for a sufficient number of the subjects to permit analyses. Healthy control subjects consisted of 101 University of Pittsburgh students. The mean age of this cohort was 22:8 ± 0:71 years (range, 17–47 years). Serologic assays. Antibodies to HHV-8 lytic antigens were determined by a modification of an indirect immunofluorescence assay (IFA) [14] with use of the body cavity-based lymphoma (BCBL)-1 cell line that contains the HHV-8 genome [15]. In brief, BCBL-1 cells were induced by 20 ng/mL tetradecanoyl phorbol acetate for 3–5 days, collected by centrifugation, rinsed with PBS, and resuspended in a small volume of PBS.

Aliquots of cells were placed in individual wells on a 12-well Teflon-coated glass slide, air-dried, and fixed with ice-cold acetone for 20 min. After fixation, the slides were again allowed to air dry and stored at −220°C. For each assay, the fixed cells were first incubated in PBS containing 10% goat serum for 1 h at 37°C, to block nonspecific binding. The blocking buffer was removed, and primary antibody was added, which was diluted in PBS containing 10% goat serum. The slides were incubated for 1 h at 37°C. Two dilutions (1:50 and 1:100) of primary antibody (participant’s serum) were tested for each serum sample. The cells were next washed extensively in PBS, treated with a 1:200 dilution of a mouse monoclonal antibody directed against human IgG (clone GG-7; Sigma), and incubated at 37°C for 0.5–1 h.

The cells were again washed in PBS, treated with a 1:100 dilution of a goat anti-mouse IgG conjugated to fluorescein isothiocyanate, and incubated at 3°-C for 0.5–1 h. The cells were washed overnight in PBS, and glass coverslips were added. For each assay, the specificity of the fluorescence was confirmed by use of cells incubated with primary but no secondary antibody and cells incubated with secondary but no primary antibody. For each batch of serum samples tested, known HHV-8-positive and -negative serum samples were included. All serum samples were tested at least twice in a blinded fashion and assessed microscopically by the same reader. Assays with the induced BCBL-1 cells were examined for the presence of whole cell immunofluorescence. The cutoff for a positive serologic result was 1:50.
Reactivation of and Primary Infection with Human Herpesvirus 8 among Solid-Organ Transplant Recipients

HHV-8 antibody titers were determined by performing the IFA on serially diluted serum samples (1:25– 1:51,200). End-point titers were reported as the reciprocal of the last positive dilution. Data analyses. Differences between the 2 HHV-8 seropositivity rate groups were examined by use of χ2 or Fisher’s exact test, as appropriate, when the risk factor variable was categoric. The Wilcoxon signed rank test was used to examine differences between matched samples. Differences in mean titer levels after transplantation (a continuous variable) by categoric risk factor variables were examined with the Mann-Whitney U test. Determination of HHV-8 seropositivity.

Tables 1 and 2 list several characteristics of the healthy adult volunteers and solid-organ transplant recipients, respectively, whose serum samples were used in this study. Serum samples from 101 healthy adult volunteers and samples from 100 solid-organ transplant recipients taken 6–7 months after transplantation were analyzed for antibodies directed against lytic HHV-8 antigens. Among the transplant recipients, those whose sample taken after transplantation (6–7 months) was negative for HHV-8 antibodies were identified as seronegative, whereas those whose posttransplantation sample was positive were identified as seropositive. As shown in tables 1 and 2, HHV-8 seropositivity was higher in transplant recipients (20%) than in healthy control subjects (9.9%; P < .05). Among the 20 seropositive transplant recipients, serum samples taken before or on the day of transplantation were available for 15 subjects. Analysis of the pretransplantation samples showed that 5 of the 15 subjects were seropositive for HHV-8 before and after transplantation and were, therefore, HHV-8 seroprevalent. The remaining 10 subjects, who were seronegative before transplantation and seropositive after transplantation, were identified as seroconverters. The identification of the 5 seroprevalent samples puts the pretransplantation HHV-8 seropositivity at 5.3% (5/95). Thus, HHV-8 seropositivity among the transplant patients increased significantly, from 5.3% to 15.8% (15/95; P < .01). Determination of HHV-8 seropositivity by age, sex, type of organ transplanted, and immunosuppressive therapy. In the United States, HHV-8 appears to be primarily sexually transmitted, and seropositive persons therefore generally have been found to be sexually active or adults [16, 17]. To determine whether the presence of HHV-8 antibodies in the samples taken after transplantation was related to the age of the transplant recipient at the time of transplantation, the cohortwas divided into age >16 years and age ⩽16 years. As seen in table 2, there was no significant difference in HHV-8 seropositivity between these groups (20.6% vs. 18.9%; P > .05).

The group ⩽16 years old was then further divided into 3 subgroups: .05). The transplant recipients were grouped according to their HHV-8 serostatus and then separated by age, sex, and organ transplanted (table 3). If the posttransplantation sample was negative for HHV-8 antibodies, the patient was classified as seronegative. Those whose pretransplantation sample was negative and posttransplantation sample was positive were classified as seroconverters. Those whose pretransplantation and posttransplantation samples were positive were classified as seroprevalent. Those whose posttransplantation sample was positive and who had no pretransplantation sample available were classified as simply seropositive after transplantation. As shown in table 3, all the known seroprevalent cases occurred in persons >16 years old at transplantation.

At least 3 of those ⩽16 years old seroconverted to HHV-8. HHV-8 seropositivity (after transplantation) was not associated with the sex of the transplant recipient (table 2; P > .05). There was also no association between sex and HHV-8 serology among the healthy adult volunteers (table 1; P > .05). HHV-8 seropositivity (after transplantation) was also not associated with the type of organ transplanted. As shown in table 2, the percentage of HHV-8-seropositive persons within each organ subgroup was not significantly different among groups (P > .05). There was limited information on the immunosuppressive therapy given to each transplant recipient. The following regimens were used for immunosuppression: FK506 plus steroids, FK506 plus azathioprine and steroids, cyclosporin A plus steroids, and cyclosporin A plus azathioprine and steroids.

This information was available for only 4 of the 20 HHV-8-seropositive and 18 of the 80HHV-8-seronegative subjects, preventing anyanalyses on the effect(s) of immunosuppressive therapy on HHV-8 reactivation or primary infection. Determination of HHV-8 antibody titers. The HHV-8 antibody titers of the 20 transplant recipients and 10 healthy HHV-8-seropositive control subjects were determined by an endpoint IFA. As shown in table 4, the mean titer of antibodies among the transplant recipients was much higher than that among the healthy control subjects (P < .001). When the seropositive transplant recipients were divided into seroprevalent and seroconverters, the mean HHV-8 antibody titer in the seroconverter group was twice as high as the mean titer in the seroprevalent group (table 4). There were no associations between posttransplantation antibody titer and type of organ transplanted (P > .05) or age group (P > .05). Serologic evidence for viral reactivation was obtained by comparing HHV-8 titers of the 5 seroprevalent subjects in the pre- and posttransplantation samples.

As shown in table 5, 4 of the 5 seroprevalent subjects demonstrated a ⩾4-fold increase in antibody titer between pre- and posttransplantation samples, indicating that viral reactivation had occurred (P < .05). Serumspecimens from donors were available from 49% of the transplant recipients, including 9 of the 10 seroconverters. None of the donor samples from seroconverters tested positive for HHV-8 antibodies (data not shown), suggesting that they did not obtain HHV-8 from the donor organ. This study reports on HHV-8 seropositivity among a cohort of 100 solid organ transplant recipients. This cohort of North American patients is unique in that it consists of both children and adults who had several different types of organ transplants. HHV-8 seropositivity increased significantly from before to after transplantation. This increase in seropositivity suggests that a number of the transplant recipients acquired a primary infection after the transplantation procedure. Although the transmission of HHV-8 from donor organ to recipient has been documented elsewhere [18–22], most of these reports have involved patients from countries where endemic KS is found and where HHV-8 seropositivity among the healthy population is higher than that seen in the United States. In our study, none of the donors for whom serum was available (49% overall and 90% of the seroconverters) was seropositive for HHV-8, indicating that infection from the donor organ was unlikely. This was further supported by evidence that the increase in seropositivity was not associated with the type of organ transplanted.

You may also like