Immune status following measles vaccination in infants and evaluation for the need of revaccination

In this prospective study, immune status of children vaccinated in infancy was determined at age 12-18 months. In 200 children, preimmunization protective measles hemagglutination (HI) antibody titres (greater than or equal to 1:8) were present in 38.5% of children of 6-8 months, the frequency decreased to 17.6 and 14.3% in age groups 9-11 and 12-18 months, respectively followed by an increasing incidence of 52.5% in those more than 18 months of age. Paired measles HI titre was estimated in 56 children, the post vaccination sample was taken at age 12-18 months, 3-9 months after measles vaccination. Most of the children (98.0%), with no detectable antibody titre, had a protective titre. Again a significant number (p less than 0.001) of children aged 12-18 months had protective HI titres compared to non-vaccinated. These findings suggest that when vaccinated at 9-11 months in our country, there is no need for revaccination later.     

Impact of revaccinating children who initially received measles vaccine before 10 months of age

Two hundred fifty-four infants who had received measles vaccine at less than 10 months of age were revaccinated at greater than or equal to 15 months of age, and their immune responses were compared with 129 control infants who received their first doses of measles vaccine at greater than or equal to 15 months of age. Sera were collected at the time of revaccination (study infants) or primary vaccination (control infants), 3 weeks, and 8 months later and tested for antibody by hemagglutination inhibition (HI), enzyme-linked immunosorbent assay (ELISA), and cytopathic effect neutralization (CPEN). Of the 121 study infants who were initially HI negative, 116 (95.9%) made HI antibody 3 weeks postrevaccination compared with 126 (99.2%) of 127 control infants (P = 0.19). Of the 63 study infants with no initial detectable antibody by any of the three tests, 14 (22.2%) had a measles-specific IgM response 3 weeks postrevaccination compared with 37 of 50 (74.0%) randomly chosen control infants. By 8 months after revaccination, the 121 initially HI-negative study infants were significantly less likely to have detectable HI antibodies than control infants (52.1% v 97.6%) (P less than .001). However, 96.7% of these 121 study infants had detectable neutralizing antibody 8 months postrevaccination, an antibody thought to correlate best with protection. This study confirms the altered immune response to revaccination in infants first vaccinated prior to 10 months of age; however, the data suggest that most of these infants were successfully primed and are probably protected after revaccination.     

Measles revaccination response in a school-age population

Due to the dramatic upsurge in the incidence of measles, the American Academy of Pediatrics and the Immunization Practices Advisory Committee of the Centers for Disease Control revised their measles immunization policies in 1989 to include a routine two-dose schedule. The objectives of this study were the following: (1) determine the prevalence of immunologically measles-susceptible subjects in a previously vaccinated, school-age, military dependent population; and (2) assess risk factors to identify immunologically measles-susceptible subjects. Serum was collected just prior to measles revaccination and again 2 weeks later. Measles-specific IgG and IgM titers were determined by enzyme-linked immunosorbent assay. Immunologically measles-susceptible subjects constituted 9.8% of the population. The interval since previous measles vaccination was significantly related to pre- and postrevaccination IgG titers in a repeated-measures analysis of variance model. The magnitude of increase in IgG titer following revaccination and analysis of trend for proportions of measles-susceptible subjects were significantly related to the age of initial vaccination. This study supports continued measles revaccination; in addition, revaccination appears to be of greater value at 11 to 12 years of age than at 4 to 6 years of age.     

MEASLES VACCINATION

ABSTRACT. Children immunized with 4 doses of formalin-inactivated vaccine and/or purified hemagglutinin prepared from Tween 80-ether (TE) treated material were subjected to a follow-up 8–9 years after the last dose of vaccine. 11 out of 27 children had clinical and/or serological signs of infections with wild measles virus during the 8 to 9 years post-booster period. 10 out of the 11 children with infections had non-hemagglutinating-in-hibiting (HI) hemolysis-inhibiting (HLI) antibodies demonstrable hi their sera after removal of HI antibodies by absorption with TE antigen. In contrast 13 out of 16 vaccinees without detectable signs of infection lacked non-HI HLI antibodies. 10 out of these 13 children were vaccinated with further attenuated live measles virus. There were no clinical reactions to vaccination. 4 vaccinees with low pre–vaccination HI antibody titers showed significant rises of antibody titers including non-HI HLI antibodies. In the remaining children no take of the live vaccine could be demonstrated. Thus HI antibodies of a certain minimal concentration can block the replication of vaccine virus even in the absence of non-HI HLI antibodies. However, since it will be difficult to establish these conditions by use of available inactivated vaccines it is recommended that future vaccine products should include both major virus envelope surface components, the hemagglutinin and the hemolysin.     

Reduced measles immunity in infants in a well-vaccinated population.

The recommended age for measles vaccination is based in part on information gathered when most mothers had natural measles. Nowadays many mothers have received measles vaccine. To assess this change measles antibody neutralization titers (NT) were determined for 278 mother-infant pairs. One hundred sixty-four mothers, born before 1958, likely had had natural measles (Group 1). Sixty mothers received one to three killed plus one attenuated measles vaccination (Group 2) and 54 received 1 attenuated measles vaccination only (Group 3). NT were determined for the mother and for the infant at birth and in the infant during the fourth and sixth months. Group 1 mothers and infants at every age had higher geometric mean NT than those in Groups 2 or 3 (P less than 0.05). By 7 months 65% of Group 1 infants and greater than 90% of Group 2 and 3 infants had an NT less than 1:10. The rate of antibody decay was significantly faster for Group 1 infants (P less than 0.05). Earlier vaccination in the infant should be considered.     

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.     

Measles revaccination. Persistence and degree of antibody titer by type of immune response

During a measles immunization campaign 203 children were enrolled in an antibody response study. Of this group, follow-up clinical data and sera samples were available from 125 children three weeks after immunization and from 90 children ten months later. Seventy-six of the children had been previously vaccinated, ten had a history of measles and 39 denied vaccination or illness. Twenty-six of the children had prevaccination hemagglutination inhibiting antibody titers of less than 5. Of this group 12 had a primary immune response (IgM measles antibody) with geometric mean titers (GMT) of 90 and 40 three weeks and ten months respectively after vaccination. In contrast, the other 14 children with initial titers of less than 5 had secondary immune responses (only IgG measles antibody) with GMTs of 28 and 9 three weeks and ten months after vaccination. Since the antibody responses in these children who had previously been stimulated by measles antigen were modest and transient, it is suggested that booster immunization may not be effective in preventing future secondary vaccine failures. Also noted in this study was a poor correlation between historical data and actual measles antibody.     

Additional evidence against measles vaccine administration to infants less than 12 months of age: altered immune response following active/passive immunization.

Quantitative serologic responses following the inoculation of infants less than one year of age with live, further-attenuated measles virus vaccine were compared to those of infants and children inoculated after one year of age. Active/passive immunization resulted in reduced antibody formation in some infants especially those less than 9 months of age. Thirty-seven infants identified as "vaccine failures" following their initial inoculation at less than one year of age were revaccinated after one year of age. Fifty-one percent had no detectable HI antibody by eight months postrevaccination, contrasted to 6.8% of the vaccinees with no detectable HI antibody following one inoculation after one year of age; 49% responded optimally to revaccination. In face of an observed altered response in many infants less than one year of age, it would appear prudent to withhold vaccine in this age group until the consequences of such an approach are better defined.     

Risk factors for measles vaccine failure among immunized students

An outbreak of measles occurred in a municipal school system which had reported 98% of students immunized against measles. A case-control study was conducted to determine reasons for vaccine failure. Vaccine failure was associated with immunizations that could not be documented in the provider's records. Among children with provider-documented immunization, vaccine failure was associated with vaccination at 12 to 14 months of age with an odds ratio of 4.73. Among children vaccinated at 15 months or older, vaccine failure was not associated with time elapsed since vaccination. Studies should be conducted to determine whether unreliable immunization records are a more widespread problem. Further consideration should be given to routine revaccination of children previously vaccinated at 12 to 14 months of age.     

Measles Vaccination V. The Booster Effect of Purified Hemagglutinin in Children Previously Immunized with this Product or Formalin-Killed Vaccine

Two groups of children immunized at the age of 6 months to two years with three monthly doses of either formalin-killed (FK) or Tween-ether (TE) measles vaccine were submitted to clinical and serological follow-up analysis up till 17 months after vaccination and then given a booster of TE vaccine of moderate potency. Among 8 cases of clearcut exposure to measles before the booster 6 responded with mild clinical symtoms; 3 without and 3 with a faint rash. An increase in HI serum titer was recorded in 3 out of the 6 cases. All of them had received FK vaccine. Between 11 and 17 months after vaccination no change in HI titers was demonstrable. After the booster the geometric mean HI titer increased 20 times in children primarily vaccinated with TE vaccine and 83 times in children given FK vaccine. In the pre-booster serum samples only 75 antibodies were detectable, where-as the post-booster serum samples in addition to 75 antibodies contained 1 to 3% 19S antibodies.     

Measles encephalomyelitis in a patient with a history of vaccination

Secondary vaccine failure (SVF) of measles is generally believed to run a milder course of illness than an ordinary course of infection. Severe complications such as central nervous system involvement have rarely been reported. A 12 year old girl, who had received a live attenuated measles vaccine 10 years earlier, developed an encephalomyelitis in the absence of symptoms indicative of ordinary measles such as Koplik spots. Anti-measles hemagglutination inhibition (HI) titer and measles IgM and IgG anitbody titers were measured in a commercial laboratory. Measles virus genomic sequence was detected by polymerase chain reaction. Both serum and cerebrospinal fluid (CSF) samples obtained at acute phase already showed extremely high titers of HI (x 8192 in serum and x 1024 in CSF, respectively) and IgG antibody along with the presence of IgM antibody. Polymerase chain reaction detected the measles virus genomic sequence in the acute phase CSF. The patient's definite history of measles vaccination, high titers of HI and IgG antibodies observed at the very early stage of illness and the clinical course indicated that this patient had an encephalomyelitis due to SVF of measles. It is suggested that measles virus can be a pathogen of encephalitis without symptoms indicative of ordinary measles in individuals who received live attenuated measles vaccines.     

Revaccination with locally-produced vi typhoid polysaccharide vaccine among chinese school-aged children: safety and immunogenicity findings

OBJECTIVE: To evaluate the safety and immunogenicity of revaccination with locally-produced Vi polysaccharide vaccine 3 years after the first dose in Chinese children aged 9 to 14 years. METHODS: A randomized, placebo-controlled trial was conducted in Suzhou, Jiangsu, China. Six hundred and sixty-seven eligible children who had previously received a primary dose of Vi vaccine were randomly assigned to receive 1 dose of 30 mug Vi vaccine or placebo. In addition, 331 eligible children received 1 dose of Vi polysaccharide vaccine as a primary vaccination. Adverse events were followed for 28 days after vaccination. Serum samples were collected from a subgroup of participants on day 0 and day 28, and Vi antibodies were analyzed using a passive hemagglutination method. RESULTS: Revaccination was found to be safe and immunogenic. No severe adverse events were observed. A significant increase in antibody titers after vaccination was observed among children who had and had not been previously vaccinated. Twenty-eight days after injection, the seropositive rate was 79% in both revaccination and primary injection groups; the geometric mean antibody titer was 1:40 in the primary injection group and 1:29 in the revaccination group (P = 0.24). Although the difference of attained geometric mean titers in follow-up sera was not significantly different in these 2 groups, the fold-rise of these titers from baseline was significantly higher in the primary injection group than in the revaccination group (7.7 versus 3.1, P < 0.001). CONCLUSION: We found that revaccination using the locally produced Vi polysaccharide vaccine among Chinese school-aged children was safe and increased antibody titers. Revaccination can be used to extend the duration of protection provided by Vi polysaccharide vaccine.     

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.     

Seroconversion after measles vaccination at nine and fifteen months of age

BACKGROUND: Despite high vaccination coverage, single dose measles immunization programs have been unsuccessful in eliminating the disease. Because seroconversion rates are lower in infants vaccinated before 12 months of age, a second dose of measles vaccine is recommended at 15 months. The aim of this study was to determine the seroconversion rates in children after the first and second doses of measles vaccinations at 9 and 15 months of age. METHODS: Study population comprised 116 infants attending the Well Baby Clinic of Istanbul University, Faculty of Medicine. Serum specimens were obtained from children before and 1 month after the first measles (Rouvax, Schwarz strain 1000 TCID(50)) vaccine given at 9 months. A second dose was given to 72 children at 15 months of age as measles-mumps-rubella (Trimovax, Schwarz measles strain, 1000 TCID(50); Urabe Am 9 mumps strain, 5000 TCID(50); Wister RA 27/3 rubella strain, 1000 TCID(50)). Third blood samples were collected 20 months after the second vaccine. RESULTS: Passive antibody positivity rate was 5.2% at the age of 9 months. Seroconversion rate was 77.6% after the first dose and 81.9% after the second dose of measles vaccine. Of 15 children who were seronegative, 13 (86.7%) became seropositive after the immunization at 15 months. Eleven children (19.2%) seroconverted from positive to negative after the second vaccine. CONCLUSION: The two dose schedule seems to increase the seropositivity rate. Our findings also indicate that increasing vaccination coverage and revaccination at 6 years of age are important even with the early two dose schedule.     

Responses in children to measles vaccination associated with perirenal transplantation

Background:  Measles infection can be fatal in pediatric patients with chronic renal failure or in patients who have undergone renal transplantation, both of whom are in the immunosuppressed state. The efficacy of single, live measles vaccination in preventing infection was examined.
Methods:  Of 156 children with renal failure who underwent renal transplantation, the changes in antibody titer were investigated before and after renal transplantation in 125 children whose measles antibody titer could be examined, together with disease and vaccination histories. Live measles vaccine was administered to 42 children with negative antibody titer. The antibody seroconversion rate was then investigated in these children, along with rate of antibody maintenance and degree of antibody titer elevation.
Results:  Seroconversion rate was 97.6%. Antibody titers measured on HI and EIA were 72 ± 118 fold (HI) and 36.9 ± 31.3 (EIA), respectively. The geometric mean of the increase in antibody titer 6 months after vaccination was 15. No side-effects of vaccination were observed in any of the children.
Conclusions:  Live measles vaccination of children with chronic renal failure is effective and safe, because the seroconversion rate, rate of antibody titer maintenance and degree of antibody titer elevation in children with chronic renal failure were all equivalent to those of healthy children.     

Measles vaccination. VIII. The occurrence of antibodies against virus envelope components after immunization with inactivated vaccine. Effects of revaccination with live measles vaccine.

Children immunized with 4 doses of formalin-inactivated vaccine and/or purified hemagglutinin prepared from Tween 80-ether (TE) treated material were subjected to a follow-up 8-9 years after the last dose of vaccine. 11 out of 27 children had clinical and/or serological signs of infections with wild measles virus during the 8 to 9 years post-booster period. 10 out of the 11 children with infections had non-hemagglutinating-inhibiting (HI) hemolysis-inhibiting (HLI) antibodies demonstrable in their sera after removal of HI antibodies by absorption with TE antigen. In contrast 13 out of 16 vaccinees without detectable signs of infection lacked non-HI HLI antibodies. 10 out of these 13 children were vaccinated with further attenuated live measles virus. There were no clinical reactions to faccination. 4 vaccinees with low pre-vaccination HI antibody titers showed significant rises of antibody titers including non-HI HLI antibodies. In the remaining children no take of the live vaccine could be demonstrated. Thus HI antibodies of a certain minimal concentration can block the replication of vaccine virus even in the absence of non-HI HLI antibodies. However, since it will be difficult to establish these conditions by sue of available inactivated vaccines it is recommended that future vaccine products should include both major virus envelope surface components, the hemagglutinin and the hemolysin.     

The effect of live measles vaccines on serum vitamin A levels in healthy children

Abstract Objective: Serum retinol levels have been shown to be depressed during measles infection. This study aims to demonstrate whether there is any decrease in serum vitamin A level following immunization with live viral vaccine and its relation with vaccine seroconversion in children with measles. Since many children receive measles vaccine alone or in combination with measles-mumps-rubella vaccine, we studied serum vitamin A levels and antibody levels in healthy, well-nourished children before and after immunization with monovalent and combined live attenuated measles vaccine.
Methods: The first group included 21 healthy children between the ages of9–11 months who received live measles (Schwarz) vaccine. There were also 21 healthy children (range14–20 months of age) who received measles-mumps-rubella Trimovax® (Pasteur Merieux) vaccine. All children were tested for serum vitamin A levels before vaccination, on days9–14 and30–42 following both vaccinations. Measles specific antibody levels were also measured on admission and30–42 days following vaccinations.
Results: In both vaccination groups, mean serum vitamin A levels reduced significantly on days9–14, but increased slightly on days30–42 in the measles-mumps-rubella vaccinated group (P < 0.05). The baseline and follow-up levels of mean serum vitamin A did not differ between seroconverted and nonseroconverted cases within the measles vaccinated group.
Conclusion: Serum vitamin A levels are reduced following vaccination with monovalent and combined live attenuated measles vaccines.     

Persistence of measles antibodies after 2 doses of measles vaccine in a postelimination environment

OBJECTIVE: To evaluate the persistence of measles antibodies after 2 doses of measles vaccine in a setting where exposure to wild-type measles was unlikely. Measles was declared eliminated from the United States in 2000, an achievement attributed to effective implementation of a routine 2-dose vaccination policy. Some have questioned whether measles transmission could resume if immunity wanes in the absence of boosting from wild-type measles. DESIGN: Prospective, observational, volunteer cohort study. SETTING: Rural Wisconsin health maintenance organization. PARTICIPANTS: Children who received the second measles vaccine dose at kindergarten (aged 4-6 years) or middle school (aged 10-12 years) in 1994 or 1995. Serum samples were collected periodically during a 10-year period for the kindergarten group and a 5-year period for the middle school group. INTERVENTION: Second dose of measles vaccine. MAIN OUTCOME MEASURE: Measles antibody levels were assessed by plaque-reduction neutralization: titers less than 8 mIU/mL were considered seronegative and suggestive of susceptibility to measles, and titers of 120 mIU/mL or less were considered low and suggestive of potential susceptibility. RESULTS: During the study period, no measles was reported in the study area. Voluntary attrition reduced the study population from 621 at enrollment to 364 (58.6%) by study end. Before the second dose, 3.1% (19/621) had low titers, of whom 74% (14/19) were antibody-negative, with geometric mean titers being significantly higher in kindergarteners (1559 mIU/mL) than in middle schoolers (757 mIU/mL) and rates of negativity significantly lower (1.0% [3/312] vs 3.6% [11/309]). One month after the second dose, 0.2% (1/612) had low titers and none was seronegative, with geometric mean titers being significantly higher in kindergarteners (2814 mIU/mL) than in middle schoolers (1672 mIU/mL). By study end, 4.9% (18/364) had low titers and none was seronegative, with no significant difference in geometric mean titers between kindergarteners (641 mIU/mL) and middle schoolers (737 mIU/mL) when both groups were aged 15 years. Projections suggest that the proportion of persons with low antibody levels may increase over time. CONCLUSIONS: Measles antibody persisted in all vaccinees available for follow-up 10 years after a second dose of vaccine, with no seronegative results detected. Declining titers suggest the need for vigilance in ensuring disease protection for the vaccinated population.     

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.     

Successful immunization of infants at 6 months of age with high dose Edmonston-Zagreb measles vaccine. Cite Soleil/JHU Project Team

A group of 2097 Haitian infants 6 to 11 months of age were randomized to receive Schwarz or Edmonston-Zagreb strain measles vaccines containing 10- to 500-fold more vaccine viral particles than standard potency vaccines. No unusual adverse reactions were noted. Edmonston-Zagreb vaccines were more effective than equivalent doses of Schwarz vaccines as measured by the proportion of vaccinated children with measles antibody concentrations greater than or equal to 200 mIU/ml 2 months after vaccination and the persistence of antibody at 18 to 24 months of age. High titer Edmonston-Zagreb vaccine administered at 6 months of age induced antibody concentrations greater than or equal to 200 mIU/ml in 83% of infants by plaque reduction neutralization and 93% of infants by enzyme-linked immunosorbent assay with high rates of antibody persistence at 12 to 24 months of age. The World Health Organization recommends high titer Edmonston-Zagreb measles vaccines for routine use at 6 months of age in areas where measles is an important cause of mortality in young infants.