Loss of antibody titers and effectiveness of revaccination in post-chemotherapy pediatric sarcoma patients

BACKGROUND: Little is known about the effects of chemotherapy on patient antibody titers to vaccine-preventable infectious diseases; thus, there is no standard protocol for revaccinating post-chemotherapy patients. PROCEDURES: To assess losses of detectable antibody titers due to chemotherapy, we retrospectively examined antibody titers for tetanus, varicella, measles, mumps, rubella, hepatitis B, and polio in 109 pediatric sarcoma patients. We also evaluated revaccination data to determine current practices and efficacy of revaccination. We limited our sample to osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma patients to control for the chemotherapy regimen patients received. RESULTS: Patients had pre-treatment detectable antibody titer that fell within the range of healthy children's antibody titers. However, 71% of patients had post-chemotherapy negative titers for at least one infectious disease. Patients most commonly had negative titers for hepatitis B (64%). Few patients had negative titers for measles (14%), mumps (9%), rubella (4%), polio 1 (0%), polio 2 (2.9%), polio 3 (4.8%), tetanus (5%), or varicella (11%). Revaccinations most frequently administered were hepatitis B and polio. CONCLUSIONS: Our findings suggest that post-chemotherapy patients may need to be revaccinated against certain vaccine-preventable diseases including hepatitis B, tetanus, varicella, polio, measles, mumps, and rubella. Larger studies need to be performed to establish guidelines for revaccinating post-chemotherapy pediatric patients.     

Demand for evaluation of vaccination antibody titers in children considered for renal transplantation

Vaccinations are recommended for achieving protection against vaccine-preventable infections in solid-organ transplant recipients. In order to evaluate the protection at the time of renal transplantation, the antibody titers against measles, mumps, rubella, varicella, hepatitis B, diphtheria, and tetanus were determined in 35 children one month prior to transplantation. Only 26% of patients on dialysis listed for transplantation showed protective antibodies against all tested pathogens. Particularly, low protection was found for hepatitis B. Children younger than four yr showed significantly lower protective antibody titers compared with older children for almost all vaccines. Children who completed vaccination in the last six months to six yr prior to renal transplantation showed higher rates of protective antibody titers against all pathogens compared with children who had vaccination more than six yr before transplantation. Preventive strategies in children with chronic renal failure include repeated measurements of serum antibodies and appropriate revaccination if titers decline. Our results underline the demand for continuous surveillance of specific antibody titers against vaccine-preventable diseases in the risk group of renal transplant recipients.     

疫苗时代疫苗可预防疾病流行病学和临床表现的变化

在高疫苗接种率的国家和地区，近些年来几种疫苗可预防疾病发病情况再度增多，如麻疹、水痘、百日咳、流行性腮腺炎等，引起了广泛关注。研究发现，这些疾病的临床表现和流行病学特征不同于疫苗使用以前。该文综述疫苗可预防疾病在疫苗使用前后的临床和流行病学特点，重点介绍我国情况，希望以此引起临床医生的重视，提高认识，加强防控，促进深入研究。     

Routine vaccination and vaccine-preventable infections in children born to human immunodeficiency virus-infected mothers

Information on vaccinations and vaccine-preventable infections collected in a prospective study of children born to human immunodeficiency virus (HIV)-infected mothers was analysed for reports of adverse reactions and to estimate the clinical efficacy of vaccines. No vaccinated, HIV-infected child developed measles (56 child-years'follow-up), mumps (33), rubella (33) or pertussis (239), and only one adverse reaction - to Bacillus Calmette-Guerin (BCG) - was reported. These findings provide limited evidence of the safety and efficacy of routine vaccination of HIV-infected children.     

Epidemic patterns of infectious diseases from the results of the surveillance of infectious diseases in Japan

Epidemic patterns of 12 infectious diseases based on the data derived from the surveillance system of infectious diseases in Japan are analyzed. Weekly numbers of patients per one monitor station (general clinics and hospitals) are calculated by prefecture. Based on these data, the patterns of epidemic are classified into five categories: Category 1, nationwide outbreak of short duration (rotavirus enteritis, hand-foot-mouth disease and herpangina); Category 2, nationwide outbreak of long duration (varicella); Category 3, concurrent outbreaks in several districts (rubella and erythema infectiosum); Category 4, epidemic of long duration in several prefectures at different times (measles, mumps, pertussis, streptococcal infection and atypical pneumonia); Category 5, unclear epidemic pattern (exanthema subitum).     

Combined vaccine against measles, mumps, rubella, and varicella

A combined measles, mumps, rubella, and varicella vaccine produced seroconversions for all four components similar to that found if measles, mumps, and rubella vaccine or live varicella vaccine were given separately. In addition, those exposed to varicella were completely protected or had only a mild rash. Moreover, the reaction rates were not increased if the vaccines were combined. The somewhat lower and delayed serologic response to live varicella vaccine as compared with the combined measles, mumps, rubella, and varicella may have been due to the small amount of varicella vaccine virus used or to its degree of attenuation. Persistence of antibody was observed 1 year postimmunization.     

Serological evaluation of 52 children immunized with the combined measles, mumps and rubella vaccine.

Fifty-two of 298 children vaccinated with the measles-mumps-rubella (MMR) vaccine at around the age of 16 months were evaluated for antibody titres against measles, mumps, and rubella. The seropositivity rates for measles, mumps, and rubella were 86%, 92%, and 98%, respectively. While the most prominent side effects were irritability (6.04%) and fever (4.69%), 83.55% of the vaccinated children showed no undesirable reaction to the vaccine. The MMR vaccine appeared to be immunogenic and nonreactogenic for the children in the study.     

Safety and immunogenicity of a measles, mumps, rubella and varicella vaccine given with combined Haemophilus influenzae type b conjugate/hepatitis B vaccines and combined diphtheria-tetanus-acellular pertussis vaccines

BACKGROUND: A study was conducted to assess administration of a combination measles, mumps, rubella and varicella vaccine (MMRV) with other childhood vaccines. METHODS: In this open, multicenter trial, 1915 healthy children ages 12-15 months were randomized into 3 groups: group 1, MMRV, combined Haemophilus influenzae type b conjugate-hepatitis B vaccines (Hib/HepB) and combined diphtheria-tetanus-acellular pertussis vaccines (DTaP) concomitantly; group 2, MMRV followed by Hib/HepB and DTaP 42 days later; group 3, MMR and varicella vaccine followed by Hib/HepB and DTaP 42 days later. RESULTS: Antibody responses to measles, mumps, rubella, varicella, Hib, HepB, diphtheria and tetanus were similar between groups 1 and 2 (all >95%, except varicella, 89.7% in group 1 and 90.9% in group 2). Pertussis toxin and filamentous hemagglutinin responses were significantly lower in group 1 than in group 2 (group 1, 74.1 and 67.1%; group 2, 90.4 and 86.8%, respectively). An exploratory analysis suggested that the difference in and pertussis toxin and filamentous hemagglutinin responses was likely the result of study design rather than interference among vaccine components because the groups differed in age of receipt of DTaP (group 1, approximately 12 months; group 2, approximately 13.5 months). When the groups were matched for age, sample size was sufficient for comparison only in children > or =13.5 months old. Pertussis toxin and filamentous hemagglutinin responses were similar in these children. The safety profiles for each vaccination regimen were comparable. CONCLUSIONS: The immunogenicity data support concomitant administration of MMRV with Hib/HepB. Limited data from an exploratory analysis indicate that MMRV can be administered concomitantly with DTaP. Concomitant administration of MMRV, Hib/HepB and DTaP is well-tolerated.     

Why do parents hesitate to vaccinate their children against measles,mumps and rubella?

Background: Thanks to a successful voluntary vaccination programme, measles, mumps and rubella are rare diseases in Sweden. Coverage among children 18 mo of age has been 99%, but the measles, mumps and rubella vaccination (MMR) has increasingly been questioned among parents. Aim: To study reasons why parents choose not to vaccinate their child against measles, mumps and rubella, and their opinions on vaccines and the diseases themselves. A secondary objective was to compare coverage at 18 mo of age based on parental report with the national statistics based on patient charts. Methods: The official statistics were compared with patient charts for two birth cohorts in the city of Göteborg, Sweden. Out of these children born in 1995 and 1996, 300 unvaccinated and vaccinated children were identified. Their parents received a postal questionnaire assessing the parent's views on vaccines and childhood diseases. Results: The documented vaccine coverage in this study was higher in 1995 and 1996 than official statistics indicated. The major reason, for both groups, for accepting respectively declining vaccination was strengthening the child's immune system. Parents with children unvaccinated against MMR were also more likely to have declined vaccination against diphtheria, polio, tetanus, Haemophilus influenzae and pertussis. One‐third of the parents with a child unvaccinated against MMR had not yet made their final decision 3 y after the vaccine offer. Few parents, both with vaccinated and unvaccinated children, had acquired vaccine information from the Internet. Both groups believed that insufficient time was allocated for vaccine information and discussion at the Child Health Centre. Conclusion: Our study indicates that official statistics on MMR vaccination uptake underestimate the number of vaccinated children. Vaccine safety is a major concern for many parents and needs to be addressed by healthcare professionals at institutions offering paediatric vaccinations.     

Priorix Tetra: a new combined vaccine against measles, rubella, mumps and varicella

Varicella is an infectious disease caused by a virus of the herpes virus family (VZV) affecting predominantly the pediatric age. Varicella is considered a mild disease, but in some cases, mainly in immunocompromised subjects, it can evolve towards complicated cases, even fatal. In immunocompetent subjects, however, serious complications can also arise, such as cutaneous bacterial superinfections, pneumonia, conjunctivitis or corneal infections and central nervous system (CNS) complications. The rate of hospitalization, even in developed countries, is high. Due to the epidemiological relevance of varicella, the availability of a live, attenuated, safe and effective vaccine, has prompted an international debate on the opportunity of extensive infant varicella vaccination, that could be overcome by the introduction of the combined tetravalent vaccines against measles, mumps, rubella and varicella (MMRV). Priorix Tetra, a new quadrivalent MMRV vaccine produced by GlaxoSmithKline, has demonstrated high immunogenicity, comparable to that of the separate vaccines (Priorix and Varilrix) in addition to a favorable tolerability and safety profile. This review summarizes the epidemiology of measles, mumps, rubella and varicella in Italy, encompassing the rationale for the introduction of varicella vaccination and describes the immunological, clinical and safety profile of Priorix Tetra.     

Measles, mumps and rubella infections and atopic disorders in MMR-unvaccinated and MMR-vaccinated children

Vaccinations have been incriminated in the increase of atopic disorders. Especially the measles‐mumps‐rubella (MMR) vaccination is often refused by people having a notion that these infectious diseases are beneficial for a healthy development of a child’s immune system. This practice endangers herd immunity and is the cause of repeated outbreaks. As the clinical course of infections and also its possible impact on the development of atopy may be different in vaccinated and unvaccinated individuals, we explored in vaccinated and unvaccinated children associations of MMR infection with atopic disorders. Using data from a previously conducted study on the relationship between the diphtheria‐tetanus‐pertussis‐(inactivated) poliomyelitis vaccination in the first year of life and atopic disorders, the study population of 1872 8–12‐yr‐old was divided as children MMR‐unvaccinated and children MMR‐vaccinated in the first year of life. Within each group the association between MMR infections and atopic disorders (both as reported by the parents) was assessed. We found a statistically significant positive association between measles infection and ‘any atopic disorder’ [adjusted odds ratio, OR (95% confidence interval, CI): 1.77 (1.20–2.61)] in the MMR‐vaccinated group, mainly because of the relationship with eczema. For rubella there was a negative association with eczema and food allergy in the unvaccinated group: adjusted OR (95% CI): 0.57 (0.38–0.85) and 0.23 (0.07–0.76), respectively. All other associations were not statistically significant. We found a positive relationship between measles infection and any atopy in a group of MMR‐vaccinated children and a negative association between rubella infection and eczema and food allergy in unvaccinated children. However, we cannot conclude that these relationships are causal. The negative association with rubella may be an artefact. This study shows no evidence for any protective effects from MMR diseases for the development of atopy and therefore supports conclusions found elsewhere that childhood vaccinations do not cause atopy.     

Transplacental transport of IgG antibodies to preterm infants: a review of the literature

Newborn infants, especially preterm infants, have an immature immune system, which is not capable to actively protect against vaccine-preventable infections. Therefore, the newborn is dependent on transplacental transport of Immunoglobulin G (IgG), an active, FcRn receptor mediated process. Fetal IgG rises from approximately 10% of the maternal concentration at 17-22 weeks of gestation to 50% at 28-32 weeks of gestation. If transplacental acquired IgG is lower in preterm than in term infants, preterm infants are especially at risk for these vaccine-preventable diseases.The aim of this study was to review the transplacental transfer of IgG against vaccine-preventable diseases (measles, rubella, varicella-zoster, mumps, Haemophilus influenza type B, diphtheria, tetanus, pertussis and polio) to (pre)term infants and to identify factors that influence the transplacental transfer of these antigens.After selection, 18 studies on transplacental transport to preterm infants were included. In general, these studies showed for all antibodies that preterm infants have lower antibody concentrations compared with term infants. Maternal and infants antibody concentrations showed a strong correlation in 7 of the included studies. Infant antibody concentration was not associated with parity, maternal age, height or weight. Infants of vaccinated mothers had lower anti-measles antibody titers than infants of natural immunized mothers. IgG titers of preterm infants decrease earlier in life below protective antibody titers than term infants. Combined with their immature immune system, this puts preterm infants at increased risk for vaccine-preventable diseases.     

Immunization for children treated for solid tumors: what are the guidelines?]

There is no agreement on immunization of children treated with chemotherapy (CT) for solid tumors. Based on a review of the literature, we have attempted to establish guidelines on this subject. Except for hepatitis B vaccine, there is no argument to support the use of vaccine during CT. After a standard CT, a 3-month washout period appears to be necessary before starting an immunization program for a child not previously vaccinated, or to proceed with the recommended booster injections for diphteria anatoxin, tetanus vaccine, poliomyelitis inactivated vaccine, pertussis vaccine, and haemophilus influenza type b vaccine if the child is less than 5 years old. For mumps, measles, and rubella live vaccines, a longer post-CT washout of 6 months is suggested for the initial immunization, or for a revaccination of a child proved to be negative for all three serologies. Following high-dose CT a minimal 12-months term and a normalization of the blood lymphocytes count is necessary before planning booster injections once having checked for antidiphteria, tetanic, polio, measles, mumps, rubella and +/- haemophilus antibody titles. We don't find any reason to recommend a systematic varicella immunization in pediatric oncology. Pneumococcal vaccine is recommended in case of asplenia. Any other vaccination (BCG, influenza, yellow fever) must be evaluated individually.     

Barriers to vaccination among Japanese medical students: Focus group interviews

Background: To date, medical schools and clinical training hospitals in Japan that require students to show immunity for measles, mumps, rubella, varicella (chickenpox), and hepatitis B prior to the commencement of residency are limited.
Methods: This qualitative study used focus group interviews to elucidate why medical students do not undergo vaccination. A total of three groups were identified and interviewed: group A (two men, three women), group B (two men, two women), group C (three men, two women). All recorded interviews were transcribed verbatim and analyzed according to the constant comparative method with a series of codes and categories.
Results: Findings elucidated that vaccination for medical students is not mandatory in Japan. Analysis found that the factors that influence willingness to be vaccinated can be divided into three dimensions (individual level, university/regional hospital level, governmental level) and two primary categories (cost of vaccination, awareness of vaccination) consisting of 10 codes. These factors did not exist in isolation, but have mutually overlapping areas.
Conclusions: Vaccination against vaccine-preventable diseases is essential to a hospital's infectious-disease countermeasures and cannot continue to be overlooked by physicians (at the individual level), by universities and residency programs (at the community level) nor by the government (at the national level).     

Evaluation of a quadrivalent measles, mumps, rubella and varicella vaccine in healthy children

BACKGROUND: A quadrivalent measles, mumps, rubella and varicella vaccine would facilitate universal immunization against all 4 diseases, improve compliance and immunization rates and decrease the number of injections given to children and visits to physicians' offices. OBJECTIVES: To evaluate 1- and 2-dose regimens of a combined measles, mumps, rubella and varicella vaccine (ProQuad, referred to as MMRV) manufactured with a varicella component of increased potency. METHODS: In this partially blind, multicenter study, 480 healthy 12- to 23-month-old children were randomized to receive either MMRV and placebo or M-M-RII and VARIVAX. Injections were given concomitantly at separate sites. Subjects randomized to receive MMRV and placebo received a second dose of MMRV 90 days later. Subjects were followed for 42 days after each vaccination for adverse experiences. Immunogenicity was evaluated 6 weeks after each vaccination. RESULTS: Measles-like rash and fever during days 5-12 were more common after the first dose of MMRV (rash, 5.9%; fever, 27.7%) than after M-M-RII and VARIVAX (rash, 1.9%; fever, 18.7%). The incidence of other adverse events were similar between groups. Response rates were >90% to all vaccine components in both groups. Geometric mean titers to measles and mumps were significantly higher after 1 dose of MMRV than after administration of M-M-RII and VARIVAX. The second dose of MMRV elicited slight to moderate increases in measles, mumps and rubella antibody titers and a substantial increase in varicella antibody titer (from 13.0 to 588.1 glycoprotein antigen-based enzyme-linked immunosorbent assay units/mL). CONCLUSION: A 1- or 2-dose regimen of MMRV is generally well-tolerated when administered to 12- to 23-month-old children and has a safety and immunogenicity profile similar to that of M-M-RII and VARIVAX administered concomitantly.     

Policy statement—Prevention of varicella: update of recommendations for use of quadrivalent and monovalent varicella vaccines in children

Two varicella-containing vaccines are licensed for use in the United States: monovalent varicella vaccine (Varivax [Merck & Co, Inc, West Point, PA]) and quadrivalent measles-mumps-rubella-varicella vaccine (MMRV) (ProQuad [Merck & Co, Inc]). It is estimated from postlicensure data that after vaccination at 12 through 23 months of age, 7 to 9 febrile seizures occur per 10,000 children who receive the MMRV, and 3 to 4 febrile seizures occur per 10,000 children who receive the measles-mumps-rubella (MMR) and varicella vaccines administered concurrently but at separate sites. Thus, 1 additional febrile seizure is expected to occur per approximately 2300 to 2600 children 12 to 23 months old vaccinated with the MMRV, when compared with separate MMR and varicella vaccine administration. The period of risk for febrile seizures is from 5 through 12 days after receipt of the vaccine(s). No increased risk of febrile seizures is seen among patients 4 to 6 years of age receiving MMRV. Febrile seizures do not predispose to epilepsy or neurodevelopmental delays later in life and are not associated with long-term health impairment. The American Academy of Pediatrics recommends that either MMR and varicella vaccines separately or the MMRV be used for the first dose of measles, mumps, rubella, and varicella vaccines administered at 12 through 47 months of age. For the first dose of measles, mumps, rubella, and varicella vaccines administered at ages 48 months and older, and for dose 2 at any age (15 months to 12 years), use of MMRV generally is preferred over separate injections of MMR and varicella vaccines.     

Antibody persistence for 3?years following two doses of tetravalent measles–mumps–rubella–varicella vaccine in healthy children

Two doses of a varicella-containing vaccine in healthy children <12 years are suggested to induce better protection than a single dose. Persistence of immunity against measles, mumps, rubella, and varicella as well as varicella breakthrough cases were assessed 3 years after two-dose measles, mumps, rubella, and varicella (MMRV) vaccination or concomitant MMR (Priorix™) and varicella (Varilrix™) vaccination. Four hundred ninety-four healthy children, 12–18 months old at the time of the first dose, received either two doses of MMRV vaccine (GlaxoSmithKline Biologicals) 42–56 days apart (MMRV, N = 371) or one dose of MMR and varicella vaccines administered simultaneously at separate sites, followed by another MMR vaccination 42–56 days later (MMR + V, N = 123). Three hundred-four subjects participated in 3-year follow-up for persistence of immunity and occurrence of breakthrough varicella (MMRV, N = 225; MMR + V, N = 79). Antibodies were measured by ELISA (measles, mumps, rubella) and immunofluorescence (varicella). Contacts with individuals with varicella or zoster and cases of breakthrough varicella disease were recorded. Three years post-vaccination seropositivity rates in subjects seronegative before vaccination were: MMRV-measles, 98.5% (geometric mean titer [GMT] = 3,599.6); mumps, 97.4% (GMT = 1,754.5); rubella, 100% (GMT = 51.9); varicella, 99.4% (GMT = 225.5); MMR + V-measles, 97.0% (GMT = 1,818.8); mumps, 93.8% (GMT = 1,454.6); rubella, 100% (GMT = 53.8); and varicella, 96.8% (GMT = 105.8). Of the subjects, 15–20% reported contact with individuals with varicella/zoster each year. After 3 years, the cumulative varicella breakthrough disease rate was 0.7% (two cases) in the MMRV group and 5.4% (five cases) in the MMR + V group. Conclusion: Immunogenicity of the combined MMRV vaccine was sustained 3 years post-vaccination. (208136/041/NCT00406211).     

Measles and rubella antibody status in previously vaccinated children with cancer

Measles and rubella antibody status were determined by ELISA for 115 previously vaccinated children with cancer. Seventy subjects were receiving chemotherapy, and 45 had successfully completed treatment for their malignancy. Overall, 18% of the subjects were seronegative for measles antibody and 8% for rubella antibody. Only 3% of patients lacked both. In general, seronegative individuals were over age 10 years. Subjects born before 1976 were significantly more likely to be seronegative to measles, 29% vs. 11% (P = 0.02) and to rubella, 16% vs. 4% (P = 0.03) than those born afterwards. Antibody status showed no apparent relationship to the duration of anticancer therapy. Stored serum samples were available for nine seronegative subjects, of whom five were initially seropositive and then lost antibody during or after the completion of anticancer therapy. Our observations suggest that cancer and its associated therapy interfere with antibody production. In view of the increasing survival rates for childhood cancers, additional studies are needed to assess the immune status of these subjects for all vaccine-preventable infections. Pending the outcome of further studies, we suggest that long-term survivors, particularly those born before 1976, or known to be vaccinated at less than 13 months of age, be tested after the completion of therapy for antibody to measles and rubella (and mumps). Also, immune serum globulin should be considered for any previously immunized patient with a close exposure to an active case of measles.     

Seroprevalence of mumps, varicella and rubella antibodies in children 1-16 years of age in eastern Turkey

In this study, seroprevalence of mumps, varicella and rubella was investigated in 803 unvaccinated children in eastern Turkey whose ages ranged between 1 and 16 years. Mumps IgG, varicella IgG and rubella IgG antibody levels in all children were studied by enzyme-linked immunosorbent assay (ELISA) method. Information regarding socioeconomic characteristics, number of siblings and disease history was gathered for each participant. No significant difference in seropositivity was detected between girls and boys. Seroprevalence of mumps increased with age, with a seropositivity rate of 29.9% in children aged 1-4 years and of 88.8% in those aged 13-16 years. Seroprevalence of varicella increased with age, with a seropositivity rate of 26.8% in children aged 1-4 years and of 90.3% in those aged 13-16 years. Seroprevalence of rubella also increased with age, with a seropositivity rate of 47.3% in the children aged 1-4 years and of 89.2% in those aged 13-16 years. There was a statistically significant increase in the rate of seropositivity with advancing age through the group of 13-16 years old (p < 0.05). In conclusion, in order to avoid mumps, varicella and rubella diseases and their possible complications, children should be vaccinated against these three diseases before the age of two, since seroprevalence increases with age.     

Rubella, measles and mumps antibodies following vaccination of children. A potential rubella problem

One hundred sixty-eight children immunized by one suburban Minneapolis clinic during routine pediatric visits had serum antibodies measured to determine the efficacy of rubella (HPV77 DE5 strain), measles (Edmonston B and Moraten strains), and mumps (Jeryl Lynn strain) vaccines. Serologic failure rates at the mean postvaccination times tested were as follows: rubella, 36% (4.7 years); measles, 18% (6.5 years); and mumps, 9% (4.5 years). Antibody titers shortly after vaccination were not done, so seronegative subjects may never have responded or their titers may have declined with time; our rubella data suggest the former. Children vaccinated with rubella and measles at less than 14 months of age had higher failure rates than those vaccinated at a later age. This supports postponement of rubella and measles vaccinations until at least 15 months of age. In addition to current measles reimmunization policies, consideration also should be given to reimmunizing girls who were given rubella vaccine at less than 14 months of age. Twenty-four percent (19/79) of children vaccinated with HPV77 DE5 strain rubella at 14 months or older had rubella hemagglutination-inhibiting titers less than 8. This is disturbing and, if confirmed by others, would prompt the use of a different strain of rubella vaccine for routine immunization.