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Varicella infections pose serious challenges for organ transplant recipients. To determine the safety and immunogenicity of the OMVV and determine the maintenance of OMVV responses in transplanted subjects at varying periods of immunosuppression within the first two yr following transplantation. Eligible subjects given a two-dose OMVV pretransplantation were monitored for AE. Antibody levels were assessed at baseline, six wk post-OMVV, pretransplantation and up to 24 months post-transplantation. Seroprotection was defined as >or=5 gpEU. Twenty-one seronegative children were vaccinated. Following 42 doses, no vaccine-related serious AE occurred. Mab&#95;titer were 17.8 (5.7-910.2) and 183.5 EU (18.8-8116.4) at six and 12 wk, respectively (p < 0.0001). Fourteen (66.7%) participants were transplanted at a median of 16 months (1.5-56) following OMVV and had Mab&#95;titer of 27.2 EU (9.0-236.2) just prior to transplantation. Of 11 who had post-transplantation serology, seroprotection was sustained at three, six and 12 months post-transplantation in 10/11, 12/12 and 8/10 subjects. In five of six subjects with two-yr follow-up, antibody levels remained seroprotective. No breakthrough varicella infections occurred. The receipt of OMVV prior to transplantation induced humoral responses which persisted in the early months following transplantation and up to two yr post-transplantation and was not associated with any serious adverse consequences.

Objectives: To determine the safety and immunogenicity of the conjugate pneumococcal vaccine (PCV7) in pediatric solid organ transplant recipients., Patients and Methods: Pediatric solid organ transplant recipients were prospectively enrolled at > or =4 months following transplantation. Eligible pneumococcal vaccine-naive subjects received 3 doses of PCV7 at 8 week intervals, followed 8 weeks later by a dose of the 23-valent vaccine (PV23). Serology was done at baseline, 8 weeks following doses 2 and 3 of PCV7 and 8-12 weeks after PV23. Repeated measures analyses were done using SAS 9., Results: Eighty-one recipients commenced immunization at a median age of 7.8 (0.6-17.5) years and a median time from transplantation to immunization of 1.3 (0.3-6.0) years. There were 31 heart, 18 liver, 5 lung, and 27 kidney recipients. Reported adverse events following vaccine doses included local reactions (PCV7: PV23 = 19%:16%) and fever (PCV7: PV23 = 3.8%:4.9%) and there were no serious reactions. Two doses of PCV7 induced > or =2 fold increases in geometric mean concentrations (GMCs) in all organ groups. Cardiac and lung recipients demonstrated additional benefit from a third dose of PCV7. The cardiac recipients showed most benefit from boosting with PV23 with significant increases in GMC's (P < or = 0.008). The time of initiation of the vaccine strategy posttransplantation predicted seroprotection., Conclusion: PCV7 was safe and immunogenic in solid organ recipients. Three doses of this vaccine appear beneficial for selected organ groups. PV23 when administered at >/=1 year posttransplantation was useful in boosting antibody responses in patient groups demonstrating lower rates of responsiveness.

In the present study, the effect of heat stress, which is commonly observed in the animals of Upper Egypt area in summer, as well as the effect of antioxidant treatment as a thermo-protective was examined. In this study, the animals (n = 120) were divided into winter group (n = 40, bred during winter) and summer group (n = 80, bred during summer) as well as, animals in the summer group were divided into first subgroup animals (n = 40) and injected with Viteselen intramuscularly (15 ml) twice weekly for 10 weeks and second subgroup animals (n = 40) were not treated (as control). Serum levels of progesterone (P4), oestradiol (E2), cortisol, superoxide dismutase (SOD), lipid peroxidase (LPO) and nitric oxide (NO) were measured. The pregnancy rate of all animals was detected rectally. The levels of oestradiol and the activity of the antioxidant SOD were decreased in serum of animals in behavioural oestrus during summer as compared with those in winter. During the same time period the levels of oxidants such as LPO and NO were increased in the serum of animals again in the phase of oestrus. In another group of animals treated by intramuscular injection with 15 ml viteselen (antioxidant) twice weekly for 6 weeks during hot months, the activities of serum SOD showed an increase and the levels of oxidants and cortisol decreased. Moreover, the levels of oestradiol were increased during the oestrous behaviour. The pregnancy rate was decreased in animals under heat stress and the pregnancy rate was enhanced dramatically when these animals received antioxidants during the heat stress. This means that the heat-stress in Upper Egypt may affect the fertility of animals and pregnancy rate and this effect may be through an increased production of free radicals and decreased production of antioxidants as well as increased levels of cortisol. Treatment of animals or supplementation with antioxidants before the beginning of months of heat-stress and also during the stress period may correct the infertility due to heat-stress through the decrease in cortisol secretion and a decrease in the oxidative stress. These results resulted in an increase in pregnancy rate in treated animals.

Post-transplant Lymphoproliferative Disorder (PTLD) because of the Epstein-Barr Virus (EBV) is a major concern after pediatric transplantation. The group at greatest risk is EBV-seronegative recipients who receive EBV-seropositive organs. Additional risk factors remain to be determined, including those among EBV-seropositive recipients. In this case-control study, PTLD cases were biopsy-proven over a period of 4 yr (1997-2000, inclusive). Each case was matched with 2 controls, based on the type of organ transplanted and the period of transplantation (+/-1 yr). Variables compared between cases and controls included those relating to the clinical and virologic profiles and immunosuppressive therapy. Twenty-two cases of PTLD were diagnosed during the study period. PTLD cases occurred at a median of 22.8 months post-transplantation (range 1-131). The median age of cases was 26.2 months (range 6.1-194) compared with 47.4 months (range 0.8-202.2) for controls (p = 0.93). Cases had a higher mean baseline EBV load compared with controls (3.1 log(10) (s.d. +/- 1.0) vs. 1.6 log(10)/10(6) PBMCs (s.d. +/- 1.4), with every 1 log increase in viral load resulting in a three times increase in the likelihood of PTLD (p < 0.007). Close to one in four cases of PTLD were EBV-seropositive pretransplantation. These seropositive recipients tended to be older patients with a trend to a worse outcome compared with their seronegative counterparts. The occurrence of PTLD was not associated with the use of any specific immunosuppressants. A significant proportion of PTLD cases occurred among EBV-seropositive transplant recipients, with a tendency towards an unfavorable outcome. Besides EBV-seronegative recipients who receive seropositive organs, some EBV-seropositive pediatric patients are at risk of PTLD. Additional studies are warranted to further define the factors associated with PTLD in EBV-seropositive transplant recipients.

Aim: The objective of this study was to assess the sensitivity and specificity of a newly developed parameter: the ankle peak systolic velocity (APSV) to provide an objective assessment of the degree of peripheral ischemia., Methods: In phase 1 of the study: data was prospectively collected for 21 ischemic limbs and 5 healthy volunteers. APSV was calculated as the mean value of the distal anterior and posterior tibial arteries peak systolic velocities (PSV). Ankle brachial index (ABI) was calculated for the anterior tibial and posterior tibial arteries. A mean ABI for both tibial arteries was also calculated. APSV was correlated with the mean ABI. Cut off values were calculated to differentiate critical, moderate and no ischemia. In phase 2 of the study data was prospectively collected for 37 ischemic limbs and 5 healthy volunteers, to assess the sensitivity and specificity of the cut off values of the APSV to identify limbs with critical ischemia, moderate ischemia, and no ischemia., Results: APSV correlated strongly with the mean ABI (r=0.8, p<0.01). The sensitivity and specificity of APSV in identifying critical ischemia were 90% and 87%, for moderate ischemia they were 75% and 88%, and for differentiating limbs with any degree of ischemia from normal limbs they were 100% and 100%, respectively., Conclusions: APSV can be used as an alternative to ABI for the assessment of degree of peripheral ischemia.

Background: Data are lacking on the pneumococcal serotypes present in many developing regions, including the Caribbean. We examined the serotypes of nasopharyngeal (NP) isolates of pneumococci obtained from Jamaican children., Methods: We obtained NP samples from children seen in the Emergency Department at the Bustamante Children's Hospital. The samples were transported to Canada for isolation and serotyping of pneumococci., Results: We obtained 94 isolates from 276 children; median age 3.4 years. The majority (57%) had symptoms of acute respiratory infection at the time of sampling. The main serotypes carried were 6B (20.5%), 19F (14.5%), and 14 (8.4%). Non-typable isolates accounted for 10.8% of the isolates. Fifty-nine per cent of the serotypes were present among the 11 being considered for candidate pneumococcal conjugate vaccines (95% CI 48-70%); the corresponding proportion present in the recently licensed 7-valent vaccine was 57% (95% CI 45-67%). A significant proportion of the serotypes found is absent from those to be included in future conjugate vaccines (P<0.0001; reference=85% expected serotype representation). Less than 5% of isolates were non-susceptible to penicillin (3.2%), cefotaxime-ceftriaxone (3.2%) and cefuroxime (3.2%), while 8.4% and 1.l% of isolates were resistant to trimethoprim-sulfamethoxazole and erythromycin respectively. There were three isolates with resistance to two or more classes of drug. These isolates were all resistant to penicillin (MIC 2 micro g/mL); the serotypes were 14, 23F, and 19F., Conclusion: A significant proportion of the serotypes found is absent from those to be included in future conjugate vaccines.

Introduction: The number of antiretroviral agents available for children who are failing existing therapy is limited. Data are lacking on the use of various combination regimens and the resulting viral load dynamics in such children., Methods: Between March 1998 and March 2000, HIV-infected children younger than 18 years of age were studied in an open trial. The study regimen included ritonavir, with at least two drugs to which the virus was known or presumed to be sensitive. Subjects were ritonavir-naive and were included if they had high viral loads while receiving antiretroviral therapy. Patients had clinical assessments, CD4 counts and viral load monitoring., Results: Fifteen antiretroviral-experienced HIV-infected children were enrolled. Approximately 87% (13 of 15) had perinatally-acquired HIV; median age was 7.9 years (range 1.6 to 14.8). At enrolment, the median CD4 count was 557 cells/mm(3) (range 57 to 1702) and the median viral load was 72,600 copies/mL (range 3626 to 796,440). The majority of children (73.3%) had increases in CD4 counts within 12 weeks. During this period, the median increase in CD4 counts over baseline was 30.0%. Approximately 73% (eight of 11) of subjects with initial improvements in CD4 counts had sustained increases at 32 to 48 weeks. Over the first 12 weeks, 60% (nine of 15) had greater than 0.5 log(10) decreases in viral load. The improvement was sustained in 88.9% (eight of nine) of these patients at 32 to 48 weeks. Three patients discontinued therapy due to taste aversion., Conclusions: Among pediatric patients with high viral loads while on existing therapy, the ritonavir-containing regimen was generally well tolerated. In a significant proportion of patients, modification of therapy was associated with sustained improvements in viral loads and CD4 counts over 32 to 48 weeks.

We examined the utility of Epstein-Barr virus (EBV) load as a test for the presence of posttransplant lymphoproliferative disease (PTLD). A semiquantitative (SQ) EBV polymerase chain reaction (PCR) on peripheral blood mononuclear cells (PBMC) was used to determine virus load. We compared the values from pediatric patients, both with and without PTLD, with those from healthy pediatric and adult subjects. The virus loads for asymptomatic healthy subjects had a range of 0-1 log10 cells/10(6) PBMCs. Among transplant recipients (n=135), the mean virus load (+/- standard deviation) at the time of diagnosis of PTLD was 3.1+/-1.2 log(10) cells/10(6) PBMCs versus a baseline value of 1.3+/-1.4 log(10) cells/10(6) PBMCs in children without PTLD (P<.0001). A cutoff of > or =3 log10 cells/10(6) peripheral blood leukocytes resulted in the following values for use of virus load as a test for PTLD: sensitivity, 69%; specificity, 76%; positive predictive value, 28%; and negative predictive value, 95%. We conclude that determination of EBV load by use of SQ PCR is more useful in ruling out than in indicating the presence of PTLD.

The aim of this work was to obtain information on the magnitude of the problem, disease characteristics, and clinical practices relating to post-transplant lymphoproliferative disease (PTLD) in Canadian institutions. Adult and pediatric Canadian solid organ transplant groups were sent a questionnaire between July and October 1998. Analyzable data were obtained from 33 transplant groups. For the period 1988-97, 90 cases of PTLD were seen among 4283 solid organ transplant recipients. The incidence of PTLD varied from 0 to 14.6%, with the highest rates in children. Lymph nodes were the sites most frequently affected. Among the classifiable lesions, the majority were monoclonal. The lesions were of B-cell origin in 42.2% and of T-cell in 15.6%. The lesions were classified as monomorphic in 31.1%, polymorphic 18.9%, and hyperplastic in 1.1%. Tumors were reported as low grade in 26.7% and high grade in 10%. The majority of patients (71.1%) received reduced immunosuppression. Anti-viral agents were used in 52.2%. Chemotherapy was used in 27.8%, while immune globulin was used in 22.2%. Surgical resection was used in 20.0%, radiotherapy in 14.4%, and interferon-alpha therapy in 12.2%. The results showed that 48.9% of the patients had died, while 25.6% and 8.9% were regarded as having complete remission and partial remission, respectively. In conclusion, the incidence of PTLD varies widely across Canadian centres. Children are disproportionately affected and the mortality rate is high. Management practices vary significantly, and the need for information sharing was identified as one way of optimizing management.

We reviewed 58 cases of varicella-zoster infection that occurred between 1988 and 1998 in 47 pediatric solid-organ transplant recipients. The median age of patients at the time of admission with varicella-zoster infection was 8.0 yr (range 1-17 yr). The median interval between transplantation (Tx) and varicella-zoster virus (VZV) infection was 1.6 yr (range 0.06-9.3 yr). Varicella infection occurred at a rate of one case for every seven transplant recipients. Among the 58 cases of VZV infection, 53% were varicella while 47% were herpes-zoster. Varicella infection occurred despite treatment with varicella-zoster immune globulin (VZIG) in 17 of 31 cases of varicella infection. However, the disease was generally mild with severe disease occurring in only two patients. One patient (1.7%) died as a result of bacterial sepsis. There was no significant relationship between VZV infection and specific immune suppressants. Episodes of rejection were more likely to be temporally associated with the occurence of herpes zoster than with varicella infection (p = 0.02). The data generated provide useful background information in our population in the prevaricella vaccine era.

The prevalence of antibody to parvovirus B19 was assessed in two populations. In a group of 494 residents from Ontario and the Maritimes, virus-specific immunoglobulin (Ig) M antibody, a marker of acute infection, was found throughout the year but was most prevalent during the late winter and early spring months. The overall prevalence of IgG antibody in this group was 30.3%. In an effort to examine age-specific prevalence in this population, a second group of sera from 210 pediatric patients at The Hospital for Sick Children, Toronto, Ontario and from Red Cross blood donors was tested for the presence of B19-specific IgG, and of these, 31.4% of the samples were positive. This prevalence varied from 3.3% in the under five-year-old age group to 66.7% in the 35- to 45-year-old age group. Eighty per cent of sera from females of this group were seropositive. This study provides insight into the prevalence of parvovirus B19 IgG antibody in the population.