Response to measles-mumps-rubella vaccine in children on dialysis

Ten children receiving maintenance dialysis were immunized with the standard dose of measles-mumps-rubella vacine between 15 and 33 months of age. Immune responses to vaccination were determined using commercially available enzyme-linked immunosorbent assays for measles, mumps, and rubella viruses. Eight children responded to measles vaccine, 5 to mumps vaccine, 8 to rubella vaccine, and only 3 children to all three vaccines, compared with a seroconversion rate of over 90% to all three vaccines in healthy children (P<0.0001). We contend that the relatively poor immunocompetence of our dialysis patients explains their less than optimal vaccine response and suggest that children vaccinated while undergoing dialysis be tested to confirm serological evidence of immunity.     

Immunization practices in children with renal disease: a report of the North American Pediatric Renal Transplant Cooperative Study

 To determine the current immunization recommendations of practicing pediatric nephrologists, a questionnaire was sent to the members of the North American Pediatric Renal Transplant Cooperative Society. Sixty-two percent of the centers responded. The results of the survey suggest that although consensus for approaching immunization does exist, recommendations do vary from center to center. Virtually all centers recommend standard vaccines [DTP, oral poliovirus (OPV), hepatitis B (Hep B), and Haemophilus influenzae B (Hib)] for their renal insufficiency and dialysis patients. Despite the fact that they are not infectious, standard killed vaccines (DTP, Hep B, Hib) are recommended less frequently for transplanted patients (86%) than their renal insufficiency (98%) and dialysis (near 100%) counterparts. Additionally, OPV and measles/mumps/rubella (MMR), both live viral vaccines, are rarely recommended post transplant. Almost 90% of centers recommend the use of influenza vaccine, while only 60% of centers recommend pneumococcal vaccine for children with renal disease. Over 70% of centers recommend the newly licenced varicella vaccine for patients on dialysis and those with renal insufficiency. Between 5% and 12% of centers recommend live viral vaccines, including OPV, MMR, and varicella vaccine, for immunosuppressed patients post renal transplant. Received July 11, 1996; received in revised form and accepted November 19, 1996     

Efficacy and safety of immunization for pre- and post- liver transplant children

BACKGROUND: Infection is a serious complication after liver transplantation. Immunization is one means of controlling infections. The objective of this study was to investigate the efficacy and safety of simultaneous administration of several vaccines before transplantation and the efficacy and safety of administration under immunosuppressive conditions after transplantation. METHODS: Fifty-eight patients who underwent living-related liver transplantation between April 1994 and March 2000 were included in this study. Simultaneous administration of a maximum of six vaccines was performed in a short period of time before transplantation. We also readministered vaccines to 15 patients with waning antibody titers after transplantation from June 1999. We investigated whether patients could seroconvert for measles, rubella, mumps, and varicella after immunization and how long antibody titers could be retained by measuring them several times throughout the period before and after transplantation. We also examined side effects caused by immunization. RESULTS: The rates of seroconversion against measles, rubella, mumps, and varicella after the pretransplantation vaccination were 82%, 100%, 90%, and 95%, respectively. The rates of reseroconversion against measles, rubella, mumps, and varicella after the posttransplantation revaccination were 85%, 100%, 100%, and 71%, respectively. Although antibody titers against these viruses generally waned with time, no patient exhibited any serious illness or side effects. CONCLUSION: Although 12 of 58 patients (21%) had an infection, pretransplantation immunization was effective to prevent serious illness, especially for the 6 months after transplantation. Posttransplantation live-vaccine administration under immunosuppressive conditions is effective and safe.     

Immunization in children with chronic renal failure: a practical approach

The prevention of systemic viral and bacterial infections by effective vaccination represents an essential task of pediatric nephrologists caring for children with chronic renal failure (CRF) undergoing renal transplantation (RTPL) with life-long immunosuppression. This review addresses three issues: risk of vaccine-preventable diseases, safety, immunogenicity, and clinical efficacy of available vaccines, and implementation of immunization guidelines. Infections (including vaccine-preventable infections) represent the leading cause of morbidity and mortality in children on dialysis and after RTPL. Vaccination in children with CRF and after RTPL is safe and does not cause reactivation of an immune-related renal disease or rejection after RTPL. Children with CRF generally produce protective serum antibodies to primary vaccinations with killed or component vaccines and live virus vaccines; some children on dialysis and after RTPL may not respond optimally, requiring repeated vaccination. Proof of vaccine efficacy is absence of disease, which can only be confirmed in large cohort studies. A few observational studies provide evidence that vaccination has contributed significantly, at least in the western hemisphere, to the low prevalence of vaccine-preventable diseases among children with CRF. Close cooperation between the local pediatrician/practitioner and the pediatric nephrologist is essential for successful implementation of the vaccination schedule.     

Vaccine recommendations for patients on chronic dialysis. The Advisory Committee on Immunization Practices and the American Academy of Pediatrics

Pediatric patients on dialysis should receive all the vaccines currently recommended by the ACIP and the AAP for healthy children, except the oral polio vaccine (34, 35). Adult patients should receive the hepatitis B vaccine series, pneumococcal vaccine, yearly influenza vaccinations, tetanus-diphtheria toxoids, and varicella vaccine, if they are susceptible (33, 48, 69). Vaccines are well tolerated by these patients (33), but higher doses and/or additional boosters may be required periodically to adequately protect dialysis patients from vaccine-preventable diseases (33, 36, 37, 82, 83). Following vaccination, antibody concentrations for hepatitis B vaccine should be measured annually and booster doses administered when antibody concentrations fall below protective levels (33, 38). Although both children and adults on dialysis may show an impaired and/or delayed immunologic response to certain antigens, particularly hepatitis B virus and S. pneumoniae, appropriate immunizations can significantly reduce the risk of serious complications from vaccine-preventable diseases (11, 84). Because the protection these vaccines provide may be incomplete or transient, infection control strategies at hospitals and other health care facilities should be implemented simultaneously. Health care providers are encouraged to assess each patients need for vaccinations individually and formulate immunization strategies early in the course of progressive renal disease, ideally before the patient requires dialysis.     

Vaccination of solid organ transplant candidates and recipients: Guidelines from the American society of transplantation infectious diseases community of practice

These updated guidelines of the AST IDCOP review vaccination of solid organ transplant candidates and recipients. General principles of vaccination as well as the use of specific vaccines in this population are discussed. Vaccination should be reviewed in the pre‐transplant setting and appropriate vaccines updated. Both inactivated and live vaccines can be given pre‐transplant. The timing of vaccination post‐transplant should be taken into account. In the post‐transplant setting, inactivated vaccines can be administered starting at 3 months post‐transplant with the exception of influenza which can be given as early as one month. Inactivated vaccines can be safely administered post‐transplant. There is accumulating data that live‐attenuated vaccines can also be given to select post‐transplant patients. Close contacts of transplant patients can receive most routine live vaccines. Specific vaccines including pneumococcal, influenza, hepatitis B, HPV, and meningococcal vaccines are discussed. Newer vaccines for seasonal influenza vaccine and herpes zoster are highlighted. Live‐attenuated vaccines such as measles, mumps, rubella, and varicella are also discussed. Emerging data on live‐attenuated vaccines post‐transplant are highlighted.     

Vaccine information statements. Revolutionary but neglected educational advances in healthcare in the United States

The purpose of this report is to provide further information about vaccine information statements (VISs) that are revolutionary but neglected educational advances in the United States. Because the use of VISs is mandated by the Federal Government in every individual being immunized, it is the goal of this report to further awaken health professionals and society to the mandatory use of these superb educational statements. With the passage of the National Childhood Vaccine Injury Act of 1986, the Federal Government required that VISs would be given to all vaccine recipients. As of September 2001, the VISs that must be used are diphtheria, tetanus, pertussis, (DTaP); diphtheria, tetanus (Td); measles, mumps, rubella (MMR); polio (IPV); hepatitis B; Haemophilus influenzae type b (Hib); varicella; and pneumococcal conjugate. Copies of the VISs are available at www.cdc.gov/nip/publications/VIS. The National Childhood Vaccine Injury Act of 1986 mandated that all health care providers report certain adverse events that occur following vaccination. As a result, the Vaccine Adverse Events Reporting System (VAERS) was established by the FDA and the Centers for Disease Control and Prevention (CDC) in 1990. In order to reduce the liability of manufacturers and healthcare providers, the National Childhood Vaccine Injury Act of 1986 established the National Vaccine Injury Compensation Program (NVICP).This program is intended to compensate those individuals who have been injured by vaccines on a no-fault basis. While the use of VISs has been mandated since 1996, a national survey of private practice office settings has revealed that many immunized patients do not receive the VISs. When these forms were used, physicians rarely initiated discussions regarding contraindications to immunizations or the National Vaccine Injury Compensation Program. Fortunately, the state boards of medical examiners, like the one in Oregon, are taking a strong stand for the use of VISs, with the warning that failure to use a VIS may result in disciplinary action. Our nation and practicing physicians must be awakened to the importance of the use of VISs to ensure that every vaccinated individual receives this statement at the time of vaccination.     

Age at childhood infections and risk of atopy

BACKGROUND: It has been proposed that early age at exposure to common childhood infections is associated with a decreased risk of allergy. Previous studies on the possible association between allergy and infection with measles, mumps, rubella, and varicella have not been conclusive as most did not include information on exact age at exposure. The objective of our study was to investigate whether early age at exposure to these infections was associated with a decreased risk of atopy using information on exact age at infection. METHODS: The study population consisted of 889 pregnant women who participated in a national birth cohort study in Denmark and for whom detailed information on history of measles, rubella, varicella, and mumps before school entry (age 7 years) was available from school health records from Copenhagen. Atopic status was assessed serologically by a specific response to 11 common inhalant allergens using serum samples obtained from the women during pregnancy. RESULTS: Measles in the first year of life was associated with a higher risk of atopy than no measles before age 7 years (OR 3.36, 95% CI 1.47 to 7.68). There was no association between atopy and mumps, rubella, or varicella in the first 7 years of life or with measles acquired after the first year of life. The risk of atopy increased significantly with increasing number of childhood infections in the first 2 years of life (p(trend)=0.01). CONCLUSIONS: These findings do not support the suggestion that childhood exposure to measles, rubella, varicella, or mumps protects against atopy, even if acquired very early in life.     

Attenuated varicella virus vaccine in children with renal transplants

The long-term efficacy of varicella vaccine was studied in 34 children aged 2–18 years who were either on chronic dialysis (n=17) or were renal transplant recipients (n=17). Live attenuated virus (OKA line) was inoculated in a single 0.5-ml subcutaneous dose, without modification of the immunosuppressive therapy protocol for renal transplant recipients. The majority of children (85%) developed antibodies within the first 6 months, with IgG titres (enzyme-linked immunosorbent assay) greater than 140 (geometric mean 1640). Of those children who were followed for longer than 2 years, 76% maintained their antibody titres. Reactions to the vaccine were minimal and the immunological protection was effective. Only 3 children developed a mild form of varicella in the post-vaccination period. We consider that seronegative children who are candidates for renal transplantation must be protected against varicella by attenuated varicella vaccination. When vaccination is performed after transplantation, no modification of immunosuppressive therapy is needed.     

Lack of serologic immunity against vaccine‐preventable diseases in children after thoracic transplantation

We investigated whether children after heart‐ (HTx) or heart–lung transplantation (HLTx) show protective antibody levels against recommended vaccinations, whether vaccination schedules are completed and which factors influence serologic immunity. We performed a cross sectional ELISA – quantification of specific antibodies in 46 patients after pediatric thoracic Tx. Findings were correlated to vaccination history, age at Tx, clinical course and immunosuppressive regimen. We found protective antibody levels against diphtheria in 74% of patients, against tetanus in 22%, against Haemophilus influenzae type b in 30% and against Streptococcus pneumoniae in 59%. Antibody concentrations against live attenuated vaccines were significantly lower in children transplanted in the first 2 years of life. Antibodies were absent for measles in 55% of late – and 81% of early transplanted children, for mumps in 66%/94%, for rubella in 30%/56% and for Varicella in 34%/63%. We found significant correlation of low antibody concentrations and age at Tx. Patients without protective antibody concentrations had significantly longer use of steroids. Vaccination schedules were incomplete or delayed in the majority of patients associated with more days in hospital pre‐Tx. Our study shows that closer adherence to pretransplantation vaccination schedules and also post‐transplantation monitoring of antibody levels are required in transplant patients.     

Varicella vaccination in children with chronic renal failure

Children with kidney disease are at risk for serious varicella-related complications. To evaluate the safety and immunogenicity of a two-dose regimen of varicella vaccine in children (aged 1-19 years) with chronic renal insufficiency and on dialysis, the Southwest Pediatric Nephrology Study Group (SPNSG) undertook an open-label, multi-center, prospective 3-year clinical trial. Ninety-six patients without history of varicella were enrolled. Fifty (mean age 4.2 years) had no detectable varicella zoster virus (VZV) antibody; 98% seroconverted after the two-dose regimen. At 1, 2, and 3 years' follow-up, all patients studied maintained VZV antibody, including 16 who received a transplant. No significant vaccine-associated adverse events were seen. One subject developed mild varicella (10-50 maculopapular lesions) 16 months post transplant. In multivariate regression analysis, patients vaccinated after age 6 years had VZV antibody levels 73% (95% confidence interval 33%-89%) lower than patients vaccinated before age 6 years after controlling for gender, estimated glomerular filtration rate, and dialysis treatment. Adjusted analysis also showed that VZV antibody levels were lower after kidney transplantation, but this appeared to be a transient phenomenon. In this study, varicella vaccination with a two-dose regimen of varicella vaccine was generally well tolerated and highly immunogenic in children with chronic kidney disease.     

Active hepatitis B vaccination of dialysis patients and medical staff

One hundred six patients with terminal renal insufficiency and 29 medical personnel were given three doses of hepatitis B vaccine at an interval of 0, 1, and 6 months (Merck, Sharp and Dohme, West Point, Pennsylvania, part of a joint study no. 649). Chronic hemodialysis patients (N = 99) received 40 micrograms vaccine (V) i.m. Uremic patients, who were just about to start chronic dialysis treatment (N = 7), were given 40 micrograms V, and at the first vaccination 3 ml hyperimmune globulin (HBIG) in addition. The medical personnel was alternately vaccinated with 20 micrograms V (N = 8), 40 micrograms (N = 11), 40 micrograms V, and 3 ml HBIG at the first vaccination (N = 10). After 12 months, 50% of the male dialysis patients, 66% of the female dialysis patients, and 95% of the medical staff developed anti-HBs antibodies. The anti-HBs titer of the dialysis patients was ten times lower than in the medical staff. The simultaneous passive immunization did not lead to any impairment of the anti-HBs titer in the dialysis patients and staff. The type of renal disease, length of time on dialysis, hematocrit, and immunoglobulin concentration did not influence the rate of immunization. After 12 months, 43 patients without antibody response were vaccinated a fourth time. Sixteen of these patients then developed anti-HBs, improving the immunization rate from 56.5 to 71.7%. A fifth vaccination only led to seroconversion, when brief or borderline anti-HBs could already be demonstrated previously. In dialysis patients who fail to develop anti-HBs after three doses of vaccine, a fourth vaccination is recommended after 12 months.     

Active immunization against hepatitis A in dialysis patients.

BACKGROUND: This study investigated the feasibility, immunogenicity, and reactogenicity of hepatitis A vaccination in end-stage renal failure patients who were on chronic intermittent haemodialysis. METHODS: Forty-three subjects were vaccinated with an inactivated hepatitis A vaccine according to a 0-, 1-, and 6-month immunization schedule. Two groups were established who received the vaccine either intramuscularly (group A, n=30) or subcutaneously (group B, n=13). RESULTS: All patients in group A and 12/13 in group B developed antibodies against hepatitis A. The geometric mean titres (GMT) were high and similar to those observed in healthy subjects. There was a tendency to higher GMT in the group who received the vaccine subcutaneously. No clinically significant adverse events were observed, and the liver enzyme profile showed no abnormalities. CONCLUSIONS: We showed that hepatitis A vaccination of dialysis patients is feasible, well tolerated and immunogenic and that the vaccine can be given subcutaneously in those patients where intramuscular administration is contra-indicated.     

The duration of hepatitis B vaccine immunity in pediatric dialysis patients

Background

Dialysis patients are at risk for hepatitis B infection, a serious but preventable disease. Long-term hepatitis B protection has not been defined in pediatric patients with chronic kidney disease stage 5 on dialysis (CKD 5D) who were vaccinated as infants or children.

Methods

Annual hepatitis B antibody surveillance data were collected retrospectively on a cohort of pediatric CKD 5D patients (n?=?202) at a single institution and analyzed by survival analysis to assess hepatitis B immunity duration.

Results

Median duration of immunity by Kaplan–Meier analysis since primary vaccination was 106.3 [95 % confidence interval (CI) 93.9, 124.4] months. After the initiation of dialysis, the median duration of hepatitis B immunity was 37.1 (95 % CI 24.2, 72.3) months. Multivariate adjusted analysis showed that there was a significant difference in the duration of hepatitis immunity based on the timing of hepatitis B vaccination (p?p?Conclusions After dialysis initiation, protective hepatitis B antibody levels wane rapidly, with a shortened duration of immunity. In our cohort of pediatric patients with CKD 5D, this decline was more pronounced in children who were immunized after starting dialysis than in those who received hepatitis B immunizations during childhood. Both groups of patients should be monitored with serial antibody titers.     

Vaccinations for adult solid organ transplant recipient: current recommendations

The need for immunization in solid organ transplant recipient can arise from three factors: immune deficit owing to underlying disease, rejection of the organ graft, and immunosuppressive therapy given after transplantation. As a general rule, primary immunizations should be given as early as possible before transplantation because the immune response to vaccines is decreased in patients with end-stage organ disease. There are three categories of vaccines: Live vaccines--oral polio, vaccinia, bacillus Calmette-Guerin, live oral typho?d, and intranasal influenza vaccines--are contraindicated in solid organ transplant recipients. The use of varicella vaccine remains controversial. The use of rubella vaccine is recommended in young women of childbearing age. Of the killed vaccines or genetically engineered vaccines, the following are recommended: pneumococcal vaccine, influenza vaccine, hepatitis A vaccine, hepatitis B vaccine, diphtheria, and tetanus vaccine. Vaccination of household contacts and health care workers in transplant centers is recommended. However, live vaccine (with the exception of varicella vaccine) should be avoided in these contacts.     

Hepatitis B virus vaccination of recipients and donors of allogeneic peripheral blood stem cell transplantation

Abstract: Background: The aim of this study was to determine the role of hepatitis B virus (HBV) vaccination as defined by the seroconversion to hepatitis B surface antibody (anti‐HBs) positivity in peripheral blood stem cell transplants. Methods: A total of 65 recipients and their donors were enrolled in this study. Recipients were divided into four distinct groups. Group 1 consisted of individuals who were vaccinated, group 2 consisted of individuals who were naturally immunized, group 3 consisted of individuals who were HBs‐Ag positive, and group 4 consisted of individuals who were HBV naïve and not vaccinated. Results: Eighty‐eight percent of the HBV‐vaccinated recipients (14 of 16), who had vaccinated‐donors, seroconverted to anti‐HBs positivity. Eighty‐three percent of HBV‐naïve recipients (five of six), who received stem cells from HBV‐immune donors, seroconverted to anti‐HBs positivity. Two of the four HBs‐Ag positive recipients with HBV‐immune donors seroconverted to anti‐HBs positivity after transplantation. Fifty‐seven percent of previously vaccinated‐recipients (eight of 14) lost detectable anti‐HBs antibody following transplantation. Finally, 31% of HBV‐naïve recipients with HBV‐naïve donors acquired a de novo HBV infection. Conclusions: (i) Hepatitis B virus immunization of recipients of allogeneic hematopoietic cell transplantation results in an effective antibody response. (ii) The HBV‐immune status of the donor plays an important role in post‐transplantation HBs‐Ab on seroconversion. (iii) Systematic re‐immunization of recipients will be necessary to maintain HBV immunity in long‐term serving recipients.     

Immune status of children on continuous ambulatory peritoneal dialysis

Immunological parameters including serum IgG, IgA and IgM, lymphocyte phenotypes (CD3, CD4, CD8, HLA-DR+CD3-), natural killer cell activity and lymphocyte proliferation with phytohaemagglutinin were assessed in 10 children on continuous ambulatory peritoneal dialysis (CAPD) and 10 control subjects. Live vaccines were injected into 6 of the 10 children on CAPD (4 had a combined measles-mumps-rubella vaccine and the other 2 mumps vaccine). Serum antibody titres to these viruses were measured before and after vaccination. The serum IgG level was statistically lower in the CAPD group than in the control group (P<0.01), but there was no difference in the percentage of HLA-DR+CD3-cells and in the ratio of CD4 to CD8 between the two groups. There were no differences in the other parameters between the two groups. All of the 6 vaccinated children seroconverted, and serious side effects were not noted. Our results suggest that children on CAPD have no significant immune impairment.     

Reinforced intradermal hepatitis B vaccination in hemodialysis patients is superior in antibody response to intramuscular or subcutaneous vaccination

Since 1960, hepatitis B virus-associated chronic liver disease has been considered an important problem in dialysis units in both Europe and North America. Separate dialysis facilities for hepatitis B-infected patients, the implementation of universal precautions for the prevention of transmission, and the active immunization against hepatitis B have now reduced the yearly incidence to less than 0.05% in Western countries. However, only 50% to 60% of patients with renal insufficiency develop sufficient immune response after intramuscular hepatitis B vaccination. The aim of the current study was to determine whether the mode of vaccine application plays a role in vaccination response and whether increasing the vaccine dose of primary intradermal hepatitis B vaccination can reduce the number of vaccine injections in hemodialysis patients. We designed a prospective, randomized study of antibody responses to hepatitis B vaccine given intradermally, subcutaneously, or intramuscularly in 81 hemodialysis patients. Outcome measures were rates of seroconversion, mean levels of anti-Hbs antibodies, and antibody levels 8 years after vaccination. The results show that intradermal hepatitis B vaccination response with a higher vaccination dose than previously used in hemodialysis patients is superior to conventional intramuscular and subcutaneous vaccination and is also well tolerated. Five intradermal injections of 20 microg each induced the development of sufficient anti-Hbs antibody titer, which persisted in 70% of the patients over 3 years.     

Safety and Immunogenicity of Varicella-Zoster Virus Vaccine in Pediatric Liver and Intestine Transplant Recipients

Primary varicella‐zoster virus (VZV) infections following organ transplantation may cause significant morbidity. We examined the safety and immunogenicity of Varivax^® after transplantation as a potential prophylactic tool. Pediatric liver and intestine transplant recipients without history of chickenpox received one dose of Varivax^®. VZV humoral and cellular immunity were assessed before and ≥12 weeks after vaccination. Adverse events (AE) and management of exposure to wild type VZV were monitored. Sixteen VZV‐naïve subjects, 13–76 months of age, at 257–2045 days after transplantation were immunized. Five children developed mild local AE of short duration. Four subjects developed fever and four developed non‐injection site rashes, three of whom received acyclovir. Liver enzymes did not increase during the month after vaccination. Eighty‐seven percent and 86% of children developed humoral and cellular immunity, respectively. There were five reported exposures to varicella in four children, none of which resulted in chickenpox. One subject received VZV‐immunoglobulin and another subject with liver enzyme elevations after exposure received acyclovir; all remained asymptomatic. Varivax^® was safe and immunogenic in pediatric liver and intestine transplant recipients. Larger studies are needed to establish the efficacy and role of varicella vaccination after transplantation.     

Disseminated varicella infection in adult renal allograft recipients: four cases and a review of the literature

Disseminated varicella-zoster (VZV) infection is a rare complication after renal allotransplantation in adults. We report four patients, among them one with combined VZV and cytomegalovirus infection. The main complications were hepatitis, pneumonitis, and disseminated intravascular coagulation. A review of the literature from 1981 to 2000 revealed 34 additional cases of disseminated varicella infection in adult renal allograft recipients with an overall mortality of 34%. Among these patients 82% suffered from primary varicella, 18% had a reactivation. High-dose acyclovir therapy combined with reduction of immunosuppression lead to reduction of mortality from 53% before 1990 to 22% after 1990. No immunosuppressive drug is significantly associated with a higher risk of disseminated VZV infection. Immunization against VZV in adults is still a matter of controversy. Whereas passive immunization is performed only for prophylactic but not therapeutic purpose, active immunization is routinely performed in children and may also be recommended for adults before renal transplantation.