According to a study from England, repeated immunization using meningococcal
polysaccharide vaccines may actually reduce antibody response.
"This
confirms that revaccination with MACP vaccine, six months following the initial
dose, results in a reduced immunological response to A polysaccharide in
adults," concluded Borrow et al. "Repeated vaccination with MACP vaccine may be
ineffective."
Immunogenicity of second dose measles-mumps-rubella (MMR)
vaccine and implications for serosurveillance.
Pebody RG, Gay NJ, Hesketh LM, Vyse A, Morgan-Capner P, Brown DW, Litton P,
Miller E.
Sero-Epidemiology Unit, Immunisation Division, PHLS Communicable Disease
Surveillance Centre, 61 Colindale Avenue, London, UK. rpebody@phls.org.uk
Measles and mumps, but not rubella, outbreaks have been reported amongst
populations highly vaccinated with a single dose of measles-mumps-rubella
(MMR) vaccine. Repeated experience has shown that a two-dose regime of measles
vaccine is required to eliminate measles. This paper reports the effect of the
first and second MMR doses on specific antibody levels in a variety of
populations.2-4 years after receiving a first dose of MMR vaccine at age 12-18
months, it was found that a large
proportion of pre-school children had measles (19.5%) and mumps (23.4%) IgG
antibody below the putative level of protection. Only a small
proportion (4.6%) had rubella antibody below the putative protective level. A
total of 41% had negative or equivocal levels to one or more antigens. The
proportion measles antibody negative (but not rubella or mumps) was
significantly higher in children vaccinated at 12 months of age than at 13-17
months. There was no evidence for correlation of seropositivity to each
antigen, other than that produced by a small excess of children (1%) negative
to all three antigens. After a second dose of MMR, the proportion negative to
one or more antigens dropped to <4%.
Examination of national
serosurveillance data, found
that following an MR
vaccine campaign in cohorts that previously received MMR, both measles and
rubella antibody levels were initially boosted but declined to pre-vaccination
levels within 3 years.Our
study supports the policy of administering a second dose of MMR vaccine to all
children. However, continued monitoring of long-term population protection
will be required and this study suggests that in highly vaccinated
populations, total measles (and rubella) IgG antibody levels may not be an
accurate reflection of protection. Further studies including qualitative
measures, such as avidity, in different populations are merited and may
contribute to the understanding of MMR population protection.
Is Bacillus Calmette-Guerin revaccination necessary for
Japanese children?
Rahman M, Sekimoto M, Hira K, Koyama H, Imanaka Y, Fukui T.
Department of General Medicine and Clinical Epidemiology, Kyoto University
Graduate School of Medicine, Kyoto, Japan. rahman@kuhp.kyoto-u.ac.jp
BACKGROUND: Bacillus Calmette-Guerin (BCG) revaccination has been implemented
in Japan among tuberculin-negative first grade primary and first grade junior
high school students for decades. Controversies regarding the effectiveness of
BCG revaccination and low incidence of tuberculosis (TB) among Japanese
children prompted this study. METHODS: Cost-effectiveness and cost-benefit
analyses were conducted for a cohort of schoolchildren who underwent
revaccination during 1996. The study population was a hypothetical cohort
comprising 1.35 million first grade primary school and 1.51 million first
grade junior high school students enrolled in 1996 at locations throughout
Japan. Assuming 50% vaccine efficacy
for revaccination, a 10-year duration of protection, and 5% annual
discount rate, we calculated the total hypothetical number of TB cases
averted, the cost and number of immunizations per TB case averted, and the
benefit-cost ratio for the program. RESULTS: The revaccination program for
1996 schoolchildren cohort would prevent 296 TB cases over a 10-year period at
a cost of US$ 108,378 per case averted. About 4,963 immunizations would be
required to prevent one child from developing TB. The benefit-cost ratio
remained at 0.13 with baseline assumptions and ranged from 0.05 to 0.29 and
from 0.02 to 0.74 for one-way and two-way sensitivity analyses, respectively.
CONCLUSION: BCG revaccination among schoolchildren is not supported by
available scientific and economic data. Based on the results of this study,
current BCG revaccination policies in Japan and other countries should be
reexamined.
Rethinking recommendations for use of pneumococcal vaccines
in adults.
Whitney CG, Schaffner W, Butler JC.
Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases,
National Center for Infectious Diseases, Centers for Disease Control and
Prevention, Atlanta, GA 30333, USA. cgw3@cdc.gov
Streptococcus pneumoniae remains a major cause of disease worldwide; the
emergence of antibiotic-resistant strains emphasizes the importance of disease
prevention by use of vaccines. Recent studies have provided information that
is useful for the evaluation of current vaccine recommendations.
Recommendations target most people who are at high risk for invasive
pneumococcal disease. However, higher risk has also been identified for
African Americans and smokers, but these groups are not specifically targeted
by current recommendations. The vaccine is effective against invasive disease
in immunocompetent people, although studies in immunocompromised subjects have
found few subgroups in which the vaccine appears to be effective. Questions
with regard to optimal timing and indications for revaccination remain a
challenge, because the duration of protection and effectiveness of
revaccination remain unknown. New pneumococcal vaccines appear promising but
will need to be tested against the performance of the polysaccharide vaccine.
Improving delivery of the currently available pneumococcal polysaccharide
vaccine to adults who will benefit should be a high priority.
The clinical effectiveness of pneumococcal vaccination: a
brief review.
Fedson DS.
Pasteur Merieux MSD, Lyon, France. fedson@fr.pmmsd.com
Randomized controlled trials have shown that pneumococcal polysaccharide
vaccine is efficacious in preventing pneumococcal bacteraemia and pneumococcal
pneumonia in young adults. Clinical trials in older adults, however, have been
inconclusive, usually because the studies have been too small. Retrospective
studies have shown that pneumococcal vaccination is approximately 50-80%
effective in preventing invasive pneumococcal disease among older persons.
Vaccination in this age group is also very cost-effective. These findings are
the basis for the recent expansion of immunisation policies and the growth in
vaccine use in many developed countries.
Serologic and clinical studies,
however, suggest that vaccine-induced protection declines after 3-5 years,
leading to widespread concern about the need for routine revaccination.
Because pneumococcal polysaccharide vaccine does not induce immunologic
memory, the benefits of revaccination can also be expected to be relatively
short-lasting. Alternative strategies of immunological priming of
adults with pneumococcal conjugate vaccine followed by boosting with
polysaccharide vaccine, or perhaps vaccination with one of the newer protein
vaccines, should be considered. Because these new generation pneumococcal
vaccines could provide a foundation of life-long protection against
pneumococcal infection, their widespread use among adults could have an
immense impact on public health worldwide.
[The effect of the initial level of immunity on the
efficacy of antidiphtheria inoculations in children and adults]
[Article in Russian]
Sliusar' LI, Romanenko TA, Besedina EI, Radomskaia FS, Erokhina EV,
Martynenko IV.
Based on results of examination in the passive hemagglutination test of 1440
subjects at different ages, several distinguishing features were revealed of
formation of artificial active antidiphtheria immunity depending on the basic
level of immunity. Single
revaccination of those subjects presenting with the basic immunity of less
than 0.03 IU/ml
provides defence
against diphtheria in only 33.3 percent of adults and 50 percent of children,
in those subjects presenting with immunity between 0.03 to 0.99 IU/ml it is
highly effective, in the immunity 1 IU/ml and beyond the effect of further
immunization is very low since 25 to 33.3 percent of subjects demonstrate
enhancement of immunity, whereas 16.7
to 25 percent show lowering of it. The analysis of the immunological
structure of the population shows that 45 to 60 percent of adults in different
age groups need to be exposed to single revaccination, 14 to 37 present will
find it insufficient, 3 to 36 percent redundant. We suggest that revaccination
against diphtheria be conducted under control of the level of antitoxic
immunity.
Response to measles revaccination among Bolivian
school-aged children.
Bartoloni A, Cutts FT, Guglielmetti P, Brown D, Bianchi Bandinelli ML,
Hurtado H, Roselli M.
Clinica Malattie Infettive, Universita di Firenze, Italy. infdis@cesit1.unifi.it
The response to measles revaccination was evaluated in 1994 among 202 Bolivian
school-aged children whose antibody levels were below 200 miu (milli-international
units) by haemagglutination inhibition (HI) in a large-scale serosurvey
conducted in Santa Cruz one year earlier. Of the 202 revaccinated children,
164 (82%) had seroconverted between the 1993 serosurvey and the
pre-revaccination blood sample. A measles outbreak occurred in Santa Cruz 6
months before the revaccination. Among the seroconvertors, only 6% gave a
history of measles, and 15% a history of contact with a case of measles. All
20 children with undetectable HI antibody pre-revaccination, and all 6
children with levels below 100 miu, seroconverted after revaccination. The
geometric mean titres by HI at 4 weeks after revaccination were 2018 miu (95%
confidence limits [95% CL] 1143, 3564) and 398 miu (95% CL 254, 625) in the 2
groups, respectively. Six of 9 children with pre-revaccination antibody titres
of 100-199 miu also seroconverted. No child demonstrated a measles-specific
immunoglobulin M response. Among the 29 children who seroconverted and were
followed up at one year after revaccination, 15(52%) showed a fourfold or
greater decline in antibody levels, which in 8 fell to levels below 200 miu.
This study confirmed the observation
that revaccination is successful in producing an antibody response in children
with low or undetectable pre-revaccination titres,
but it also confirmed that vaccine-induced immunity wanes rapidly.
Cellular immunity in measles vaccine failure: demonstration
of measles antigen-specific lymphoproliferative responses despite limited
serum antibody production after revaccination.
Ward BJ, Boulianne N, Ratnam S, Guiot MC, Couillard M, De Serres G.
McGill Centre for the Study of Host Resistance, Montreal General Hospital,
Quebec, Canada.
Measles antigen-specific immune responses were evaluated 1 and 6 months after
revaccination in 60 previously vaccinated subjects (9.4 +/- 3.4 years of age)
who had either undetectable or low plaque reduction neutralization (PRN)
titers (< 200). PRN titers were increased in all subjects at 1 month (590 +/-
61; range, 129-2513) but fell again in 66% of subjects by 6 months (214 +/-
29; range, 30-794). At 6 months, 23 (38%) had subprotective (< 120) or
borderline (< 200) PRN titers. Lymphoproliferative responses to measles virus
antigens were low overall before revaccination (mean stimulation index [SI],
2.6 +/- 0.4; range, 0.5-13.5) but were readily detectable at 1 (SI, 145.8 +/-
2.6; range, 1.4-80) and 6 months after revaccination (SI, 9.4 +/- 1.8; range,
1.1-87). Before revaccination, 10 of the subjects (50%) with low positive PRN
titers had SIs > or = 3. At 6 months after revaccination, 18 subjects (78%)
with PRN titers < or = 200 had SIs > or = 3.
These data suggest that cellular
responses to measles virus may be better sustained than antibody titers after
vaccination and revaccination in some subjects.
[Long-term efficacy of hepatitis B vaccine in newborn and
revaccination study]
[Article in Chinese]
Cheng H, Guo Z, Zhang Y.
Zhejiang Provincial Hygiene and Epidemic Prevention Station, Hangzhou.
Two-hundred and sixty-nine newborns were followed up for 4 and 5 years after
completion of vaccination (10 micrograms x 3). The anti-HBs positive rates
remained 82.54% and 72.03%, respectively. The low-level titer (> or = 10-99
mIU/ml) made up 44.61%, and the medium-level titer (> or = 100-99mIU/ml)
32.34%. The highest titer was 857 mIU/ml. A 10 micrograms dose of hepatitis B
vaccine was given to these children. The anti-HBs level went up greatly in the
first month after revaccination, but started to drop in the third month,
decreased rapidly in the sixth month, and in the twelveth month the level
trended to restore the level before revaccination. This paper indicated that
the home-made hepatitis B vaccine was effective. Revaccination was not
necessary within 5-7 years after initial vaccination.
Revaccination to children whose anti-HBs
level was < 10mIU/ml was beneficial but the anti-HBs
persistence was short.
Measles outbreak in 31 schools: risk factors for vaccine
failure and evaluation of a selective revaccination strategy.
Yuan L.
Department of Preventive Medicine and Biostatistics, University of Toronto,
Ont.
OBJECTIVE: To examine the risk factors for measles vaccine failure and to
evaluate the effectiveness of a selective revaccination strategy during a
measles outbreak. DESIGN: Matched case-control study. SETTING: Thirty-one
schools in Mississauga, Ont. SUBJECTS: Eighty-seven previously vaccinated
school-aged children with measles that met the Advisory Committee on
Epidemiology's clinical case definition for measles. Two previously vaccinated
control subjects were randomly selected for each case subject from the same
homeroom class. INTERVENTIONS: All susceptible contacts were vaccinated, and
contacts who had been vaccinated before Jan. 1, 1980, were revaccinated. When
two or more cases occurred in a school all children vaccinated before 1980
were revaccinated. MAIN OUTCOME MEASURES: Risk of measles associated with age
at vaccination, time since vaccination, vaccination before 1980 and
revaccination. RESULTS: Subjects vaccinated before 12 months of age were at
greater risk of measles than those vaccinated later (adjusted odds ratio [OR]
7.7, 95% confidence interval [CI] 1.6 to 38.3; p = 0.01). Those vaccinated
between 12 and 14 months of age were at no greater risk than those vaccinated
at 15 months or over. Subjects vaccinated before 1980 were at greater risk
than those vaccinated after 1980 (adjusted OR 14.5, 95% CI 1.5 to 135.6). Time
since vaccination was not a risk factor.
Revaccination was effective in
reducing the risk of measles in both subjects vaccinated before 1980 and those
vaccinated after 1980 (adjusted OR reduced to 0.6 [95% CI 0.1 to 5.3] and 0.3
[95% CI 0.13 to 2.6] respectively). However, only 18 cases were estimated to
have been prevented by this strategy. CONCLUSIONS: Adherence to routine
measles vaccination for all eligible children is important in ensuring
appropriate coverage with a single dose. The selective revaccination
strategy's high labour intensiveness and low measles prevention rate during
the outbreak bring into question the effectiveness of such a strategy.
Investigation of a measles outbreak in a fully vaccinated
school population including serum studies before and after revaccination.
Matson DO, Byington C, Canfield M, Albrecht P, Feigin RD.
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030.
A measles outbreak in early 1989 among approximately 4200 students at a high
school and two intermediate schools in suburban Houston, TX, was investigated
to evaluate reasons for vaccine failure and to predict the efficacy of a
booster dose of measles vaccine. Seventy-seven cases occurred (71 at the high
school, 6 at intermediate schools; attack rate, 3.2 and 0.3%, respectively).
Vaccination in the first year of life an 13 to 14 years since last vaccination
were independent risk factors for being a case. Forty-three (18%) of 239 sera
collected from students just before revaccination during the outbreak were
negative by enzyme immunoassay; a neutralization assay confirmed these 43
lacked antibody predicting protection against measles infection. Of 43 enzyme
immunoassay-negative students 24 gave another blood sample 9 to 10 months
after revaccination. Revaccination
appeared to reduce the portion of all students with neutralization titers
predicting susceptibility to measles illness with rash from 7.9% to 3.0% and
left the portion predicted to be susceptible to illness without rash unchanged
(45%).
[Immune response to hepatitis B revaccination in children]
[Article in Chinese]
Qiu Y.
Institute of Infectious Diseases, Zhejiang Medical University, Hangzhou.
In this report, we investigated the efficacy of revaccination with hepatitis B
vaccine in thirty-eight children after primary immunization. The results
showed that anti-HBs immune response developed in 37 children after
revaccination. with a response rate of 97.4% (37/38). The geometric mean
titres (GMTs) of anti-HBs at 3rd weeks, 3rd and 6th month after the booster
dose reached 824.1, 407.7 and 193.6IU/L, which were 24.5, 12.1 and 5.8 times
higher than those before the booster dose (33.6IU/L), respectively.
The peak levels reached at 3rd week
after revaccination. However anti-HBs
levels declined rapidly, the percentage of antibody decrease were 50.5%, 76.5%
at 3rd and 6th month after booster dose respectively. The immune
response to revaccination gave a strong correlation to the primary
immunization. In conclusion, our findings indicated that a good response to
revaccination with a dose of 10 micrograms of hepatitis B vaccine in children
were observed.
Serological response to measles revaccination in a highly
immunized military dependent adolescent population.
Veit BC, Schydlower M, McIntyre S, Simmons D, Lampe RM, Fearnow RG, Stewart
J.
Department of Clinical Investigation, William Beaumont Army Medical Center, El
Paso, Texas 79920-5001.
In the spring of 1986, there was a measles outbreak in the city of El Paso,
Texas, with 92 cases reported to the City-County Health Department. Of those
92 cases, 31 (32%) occurred within a public high school's student population
of 2524. A mass measles vaccination program was undertaken at that high school
in order to limit the outbreak. The student enrollment included a military
dependent population of 368 students. Despite documented histories of prior
measles immunizations in this military dependent subgroup, three individuals
contracted the disease. Since this subgroup of students represented a highly
immunized adolescent population, it was of interest to serologically determine
their immune status prior to and following reimmunization with the expectation
that such a study would provide information relating to the level of
"protective" immunity. Prevaccination and postvaccination sera were obtained
from 95 students. Results of measuring
anti-measles antibody activity by ELISA indicate that 13 (14%) students
responded to revaccination and experienced a fourfold or greater rise
in IgG antibody levels. There were no detectable IgM responses. All of the
students who responded to revaccination produced an anamnestic response (IgG
boost only). Since most of these individuals had received first immunizations
at 15 months of age or older, these findings suggest that secondary vaccine
failure (waning immunity) was responsible for the putative "lowered" immunity
in these individuals, instead of primary vaccine failure (maternal antibody
suppression). These findings support current recommendations for measles
booster revaccination of school-age children and adolescents.
[The results of multiyear observations on the duration of
the maintenance of immunity in those vaccinated and revaccinated against and
recovered from measles]
The results of 5-year observations on the duration of immunity to measles
virus in persons vaccinated and revaccinated against measles, as well as in
persons having had this infection, are presented. The intensity of immunity
was determined in the same persons with the use of the passive
hemagglutination test. The study
revealed differences in the formation, intensity and duration of postvaccinal
immunity. A significant decrease in the concentration of antibodies over the
period of 5 years was established in 50.0-52.3% of vaccines.
Revaccination with live measles vaccine is an effective measure for enhancing
immunity to measles virus in persons with initial antibody titers less than
1:10-1:20, but revaccination made in a single injection is not sufficient for
the stable maintenance of measles morbidity at the sporadic level.
Postinfectious immunity is characterized by stability and has no tendency
towards decrease. Persons having had measles have no need in additional
measures irrespective of the time elapsed after the disease.
Measles immunity after revaccination: results in children
vaccinated before 10 months of age.
Linnemann CC Jr, Dine MS, Roselle GA, Askey PA.
Measles immunity was studied in children in a private pediatric practice who
had been revaccinated because they had received their primary measles
vaccination before 1 year of age. Antibody was measured in 72 of these
children who had received the first injection of live measles virus vaccine at
less than 10 months of age, and the second at greater than 1 year of age. Of
the 72 children, 29 (40%) had no detectable antibody and the geometric mean
titer for the group was approximately 1:4. Of the children with low antibody
titers, 15 were given a third injection of measles vaccine and five (33%)
still did not respond. Cell-mediated immunity as indicated by lymphocyte
transformation to measles antigen was measured in 11 of the children. Five
(45%) had responses to measles antigen, but the responses did not correlate
with the presence or absence of antibody.
This study confirms the observation
that revaccination is unsuccessful in many children who received measles
vaccine in the first year of life, and shows that even a third injection of
vaccine may fail to produce a significant antibody response.
The authors studied the efficacy of measles revaccination in children in whose
serum no specific antihemagglutinins were revealed in titration with 1 GAE
antigen (the first group) and having no specific antibodies in titration with
4 GAE antigen (the second group). Investigations demonstrated that children in
whose blood serum no measles antibodies were revealed in the presence of 1 GAE
antigen were subject of vaccination.
Repeated vaccination used at present in persons who produced minimal antibody
concentrations in response to vaccination is not recommended.
[Results of a study of the reactogenicity and
epidemiological effectiveness of a 2d revaccination against whooping cough]
[Article in Russian]
Baeva EA, Burgasov IuA, Kolontarova II, Glinskaia EV, Auzinia AV.
The reactogenicity and epidemiological effectiveness of the second
revaccination against pertussis were studied in conformity with all the
conditions of a controlled epidemiological trial. The character of the
distribution of local and fever reactions in children aged 6 years after the
second revaccination with adsorbed DTP vaccine suggests the presence of high
sensitivity to the pertussis component of absorbed DTP vaccine in children of
this age group. The results obtained
from the study of epidemiological effectiveness (in 15,621 children) indicated
that the second revaccination of children aged 6 years (at an interval of 3 or
more years after the first revaccination) was not advisable as it did not
influence noticeably the pertussis incidence.
The development, pharmacology, effectiveness, adverse reactions and clinical
use of polyvalent pneumococcal vaccines are reviewed. Patients with sickle
cell anemia, asplenic and elderly patients, infants and closed populations are
particularly susceptible to Streptococcus pneumoniae infections. Polyvalent
pneumococcal vaccine induces a satisfactory antibody response wihin about two
weeks which declines with time but generally remains elevated for at least 20
months after infection. The vaccine has been reported to reduce the incidence
of pneumococcal disease by 76 to 100% and to reduce the carrier rate of
pneumococci covered by the vaccine; however, infants younger than two years of
age repond inconsistently. Local reactions to the vaccine (soreness at
injection site, erythema, induration and tenderness) occur in 86% of adults
and nearly all children. The incidence
of adverse reactions increases on revaccination. The recommendations of
the U.S. Public Health Service and Center for Disease Control on use of the
vaccine are presented. Mass immunization with the vaccine is not recommended,
but the vaccine may be of benefit in sickle cell, asplenic and elderly
patients, and in closed populations.
[Response of the body to smallpox vaccination in persons
with repeated negative vaccinal antecedents]
[Article in Romanian]
Mihailescu R, Pop C, Mihancea N, Voiculescu R, Merca V, Alexandrescu N,
Iancu V, Georgescu C.
A study was carried out on the humoral response and vaccinal reaction after
repeated administration of the smallpox vaccine (1 to 3 times), at ten days
interval, to 97 subjects with a past history of repeated vaccination failures.
Revaccination ended in 52.6% failures. After revaccination the antibody titer
increased in 97.8% of the cases of successful vaccination and in 43.5% of the
negative cases. In 29.5% of the latter cases a decrease in the antibody titer
by 1--3 binary dilutions was found.
The results suggest that the repeated application at short intervals of an
antigenic stimulus perturbs the immune response.
In-vitro demonstration of cell-mediated immunity to
vaccinia virus in man.
Koszinowski U, Volkmann B, Thomssen R.
Cell mediated immunity to vaccinia virus in man was studied by lymphocyte
transformation. Vaccinia antigen, propagated on BHK-21 and Vero cells, could
be used successfully for in-vitro testing after partial purification as well
as crude infectious homogenates. Vaccinia antigen preparations were effective
both in the infective and the inactivated state. Inactivation was usually
accompanied with a certain loss of stimulating activity. Development of cell
mediated immune response in-vitro after first vaccination was investigated in
17 adults. Vaccinia virus specific lymphocyte transformation was seen in the
second week after vaccination in all cases.
Following revaccination no increase of lymphocyte transformation ratio could
be observed in 11 persons studied. At the same time the titers of humoral
antibodies were elevated.
[Unsuccessful and successful nodular and vesicular
reactions after revaccination against smallpox. IV. Number of cuts, early and
late reactions, persistency, vaccination time interval, individual and
collective protection, minimal success
and discussion of the results from reports I to IV]
DISCLAIMER: All
information, data, and material contained, presented, or provided here is for
general information purposes only and is not to be construed as reflecting the
knowledge or opinions of the publisher, and is not to be construed or intended
as providing medical or legal advice. The decision whether or not to vaccinate
is an important and complex issue and should be made by you, and you alone, in
consultation with your health care provider.
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