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,
Sero-Epidemiology Unit, Immunisation Division, PHLS Communicable Disease
Surveillance Centre, 61 Colindale Avenue, London, UK. firstname.lastname@example.org
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%)
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.
PMID: 11803074 [PubMed - indexed for MEDLINE]
This study does not give the reason for the vaccine
failure, merely that it occurred; hence it is unknown how many of the 19.5% of
pre-school children who had below protective levels of antibody were due to
secondary vaccine failure. - SM
Immune responses to measles and measles vaccine: challenges
for measles control.
Moss WJ, Polack FP.
W. Harry Feinstone Department of Molecular Microbiology and Immunology,
Bloomberg School of Public Health, Johns Hopkins University, Baltimore,
Most strategies for reducing global measles morbidity and mortality and
eliminating measles are based on the ability to enhance immune responses to
measles virus. Challenges to measles elimination and eradication are based in
part on the need to sustain high levels of population immunity to interrupt
transmission of measles virus. We review aspects of the immunology of measles
and measles vaccination with the aim of demonstrating how knowledge of the
immune responses is essential to furthering the goals of reducing measles
morbidity and mortality and the elimination of measles.
Better understanding of the mechanisms
of immune suppression after measles, the potential for alternative vaccination
strategies to induce immunity in young infants, and the immunologic basis of
atypical measles, increased mortality after high-titer measles vaccine, and
waning immunity will lead to improved strategies for measles control and
PMID: 11792060 [PubMed - indexed for MEDLINE]
Evaluation of different measles IgG assays based on
recombinant proteins using a panel of low-titre sera.
Hartter HK, de Swart RL, Hanses F, Vos HW, Bouche FB, Osterhaus AD,
Schneider F, Muller CP.
Department of Immunology and WHO Collaborating Center for Measles, Laboratoire
National de Sante, Luxembourg, Luxembourg.
During the WHO campaign to eradicate measles, accurate discrimination between
immune and non-immune individuals will become increasingly important.
Due to waning immunity in vaccinated
populations, the performance of a measles IgG assay depends mainly on
its ability to detect reliably seronegative individuals among many vaccinees
with low antibody levels. New serological tests based on recombinant proteins
detect only a fraction of the total measles virus (MV) specific antibodies.
Therefore, several assays based on recombinant MV-haemagglutinin (ELISA and
flow cytometry) or MV-fusion protein (flow cytometry) as well as
neutralisatlon and haemagglutination test have been evaluated using a large
panel of low-titre and negative sera. Since such an evaluation is highly
dependent on threshold values for positivity, the receiver operating
characteristic curve analysis was applied. The H-FACS and the H-ELISA showed
the best performing characteristics (specificity: 97.4 and 96.1%,
respectively; sensitivity: 88.1 and 89.6%, respectively) and may be an
alternative to the neutralisation assay. The number of undefined/grey zone
sera was significantly lower compared to a commercial whole virus-based ELISA
and therefore fewer individuals would be vaccinated unnecessarily.
PMID: 10680969 [PubMed - indexed for MEDLINE]
Secondary measles vaccine failures identified by
measurement of IgG avidity: high occurrence among teenagers vaccinated at a
Paunio M, Hedman K, Davidkin I, Valle M, Heinonen OP, Leinikki P, Salmi A,
Department of Public Health, University of Helsinki, Finland.
Failure to seroconvert (primary vaccine failure) is believed to be the
principal reason (approx. > 95%) why some vaccinees remain susceptible to
measles and is often attributed to the persistence of maternal antibodies in
children vaccinated at a young age. Avidity testing is able to separate
primary from secondary vaccine failures (waning and/or incomplete immunity),
but has not been utilized in measles epidemiology. Low-avidity (LA) and
high-avidity (HA) virus-specific IgG antibodies indicate primary and secondary
failure, respectively. Measles vaccine failures (n = 142; mean age 10.1 years,
range 2-22 years) from an outbreak in 1988-9 in Finland were tested for
measles-virus IgG avidity using a protein denaturating EIA. Severity of
measles was recorded in 89 failures and 169 non-vaccinees (mean age 16.2
years, range 2-22 years). The patients with HA antibodies (n = 28) tended to
have clinically mild measles and rapid IgG response. Among failures vaccinated
at < 12, 12-15 and > 15 months of age with single doses of Schwarz-strain
vaccine in the 1970s, 50 (95% CI 1-99), 36 (CI 16-56) and 25% (CI 8-42) had HA
antibodies, respectively. When a single measles, mumps and rubella (MMR)
vaccine had been given after 1982 at 15 months of age, only 7% (CI 0-14)
showed HA antibodies. Omitting re-vaccinees and those vaccinated at < 15
months, Schwarz-strain recipients had 3.6 (CI 1.1-11.5) higher occurrence of
HA responses compared to MMR recipients. Apart from one municipality, where
even re-vaccinees had high risk of primary infection, 89% (CI 69 to
approximately 100) of the infected re-vaccinees had an HA response.
Secondary measles-vaccine failures are
more common than was more previously thought, particularly among individuals
vaccinated in early life, long ago, and among re-vaccinees.
Waning immunity even among individuals vaccinated after 15 months of age,
without the boosting effect of natural infections should be considered a
relevant possibility in future planning of vaccination against measles.
PMID: 10813152 [PubMed - indexed for MEDLINE]
Measles eradication: is it in our future?
Orenstein WA, Strebel PM, Papania M, Sutter RW, Bellini WJ, Cochi SL.
National Immunization Program, Centers for Disease Control and Prevention,
Atlanta, Ga. 30333, USA.
Measles eradication would avert the current annual 1 million deaths and save
the $1.5 billion in treatment and prevention costs due to measles in
perpetuity. The authors evaluate the biological feasibility of eradicating
measles according to 4 criteria: (1) the role of humans in maintaining
transmission, (2) the availability of accurate diagnostic tests, (3) the
existence of effective vaccines, and (4) the need to demonstrate elimination
of measles from a large geographic area. Recent successes in interrupting
measles transmission in the United States, most other countries in the Western
Hemisphere, and selected countries in other regions provide evidence for the
feasibility of global eradication.
Potential impediments to eradication include (1) lack of political will
in some industrialized countries, (2) transmission among adults, (3)
increasing urbanization and population density, (4) the HIV epidemic, (5)
waning immunity and the possibility of
transmission from subclinical cases, and (6) risk of unsafe injections.
Despite these challenges, a compelling case can be made in favor of measles
eradication, and the authors believe that it is in our future. The question is
PMID: 11029981 [PubMed - indexed for MEDLINE]
Modeling the impact
of subclinical measles transmission in vaccinated populations with waning
Mossong J, Nokes DJ, Edmunds WJ, Cox MJ, Ratnam S, Muller CP.
Department of Biological Sciences, University of Warwick, Conventry, England.
An increasing body of evidence suggests that a substantial proportion of
individuals who respond to measles vaccine display an antibody boost
accompanied by mild or no symptoms on exposure to wild virus. It is unknown
whether this emerging class of individuals can support transmission. The
epidemiologic consequences of vaccinated individuals able to transmit virus
are investigated using a mathematical model. Parameters for this model are
estimated using regression analysis on a Canadian serologic data set. The
authors confirm that neutralizing antibodies are decaying significantly in
absence of circulating virus. Based on a protective threshold plaque reduction
neutralization (PRN) titer of 120, the authors estimate the mean duration of
vaccine-induced protection in absence of reexposure to be 25 years (95%
confidence interval (CI) 18, 48).
After long-term absence of circulating virus, the mathematical model predicts
that 80% (95% CI 65, 91) of all
have titers below the protective threshold. In this case, elimination
of measles virus cannot be achieved by a single-dose routine vaccination
strategy if the basic reproduction number in vaccinated individuals exceeds
1.24 (95% CI 1.10, 1.53). For this reason, there is a need to establish the
intensity and duration of infectiousness in vaccinated individuals.
PMID: 10588085 [PubMed - indexed for MEDLINE]
Total elimination of measles in Finland.
Heinonen OP, Paunio M, Peltola H.
On average, 15,000 cases of measles occurred annually in Finland before the
initiation of a vaccination programme in 1975. Because of insufficient
activity, the vaccination coverage failed to reach the required level of over
90%, and cases continued to occur. The policy was revolutionized in 1982 by
launching a project in which the Schwarz strain was substituted by an
attenuated Enders-Edmonston strain given as a component of a trivalent
live-virus measles-mumps-rubella vaccine (MMRII). This vaccine is given twice,
at the ages of 14-18 months and 6 years. The impact of the vaccinations has
been monitored in several prospective studies. In addition to a very
favourable safety profile, good immunogenicity and excellent clinical
effectiveness have also been demonstrated. Since 1996 not a single case of
measles has been found in Finland, although cases have been searched actively
and serological confirmation has been required.
Total interruption of virus
circulation has brought a new problem: the possibility of
to acquire natural boosters is so rare that waning immunity has become a
reality. As there is a continuous risk of measles originating from a foreign
source, the only tool against an outbreak is to maintain a high vaccination
coverage and to continue the two-dose schedule as a minimum policy.
PMID: 9667790 [PubMed - indexed for MEDLINE]
Estimated susceptibility to asymptomatic secondary immune
response against measles in late convalescent and vaccinated persons.
Damien B, Huiss S, Schneider F, Muller CP.
Laboratoire National de Sante, Luxembourg, Germany.
Serological evidence indicates that measles virus (MV) could circulate in
seropositive, fully protected populations. Among individuals fully protected
against disease, those prone to asymptomatic secondary immune response are the
most likely to support subclinical MV transmission. The serological
characteristics of protected subjects who developed secondary immune response
after reexposure to measles have been described recently [Huiss et al. (1997):
Clinical and Experimental Immunology 109:416-420]. On the basis of these data,
a threshold of susceptibility was defined to estimate frequencies of secondary
immune response competence in different populations. Among measles, late
convalescent adults (n = 277) and vaccinated high school children (n = 368),
3.2-3.9% and 22.2-33.2%, respectively, were considered susceptible to
secondary immune response. A second vaccination did not seem to lower this
incidence. Even when estimates of
symptomatic secondary immune response (e.g., secondary vaccine failure) were
taken into account, susceptibility to subclinical secondary immune
response was still 5-8 times higher after vaccination than after natural
infection. Although viral transmission between protected individuals has never
been directly demonstrated, the data describe a population in which protected
but infectious persons could potentially be of epidemiological importance.
PMID: 9700638 [PubMed - indexed for MEDLINE]
Five cases of measles
secondary vaccine failure with
confirmed seroconversion after live measles vaccination.
Hirose M, Hidaka Y, Miyazaki C, Ueda K, Yoshikawa H.
Hirose Children's Clinic, Saga, Japan.
We report 5 patients with secondary
vaccine failure (SVF)
who were infected with natural measles 2, 5, 5, 7 and 12 years, respectively,
after vaccination with further attenuated live measles vaccine during infancy.
had been confirmed after vaccination. Three of the 5 patients had mild
(modified) measles, while the remaining 2 patients had typical measles. The
hemagglutination inhibition antibody titers to measles virus in paired acute
and convalescent sera showed a secondary response pattern in 4/5 patients, and
a primary response pattern was present in the remaining patient. Measles IgM
antibodies were present in all patients during the convalescent stage. The
patient with the primary response pattern may have had a decrease in the B
cell memory during the 5-year period between vaccination and infection.
This may be the first
case report that confirms the existence of completely waning immunity in
recipients of the further attenuated live measles vaccines.
PMID: 9181657 [PubMed - indexed for MEDLINE]
Immunoglobulin G avidity testing in serum and cerebrospinal
fluid for analysis of measles virus infection.
Narita M, Yamada S, Matsuzono Y, Itakura O, Togashi T, Kikuta H.
Department of Pediatrics, Hokkaido University School of Medicine, Sapporo,
We studied a variety of patients with measles virus infection by using avidity
testing for measles virus-specific immunoglobulin G (IgG) in serum and
cerebrospinal fluid samples. For the avidity testing, an Enzygnost measles IgG
enzyme-linked immunosorbent assay kit was used with an 8 M urea denaturing
method. With this method, low-avidity IgG (acute primary infection, avidity of
< 30% within 15 days of the onset of rash) and high-avidity IgG (subacute
sclerosing panencephalitis, avidity of > 75%) could be clearly distinguished
by using serum samples. One patient, who developed a typical course of measles
despite a previous vaccination, showed a positive IgM response with an initial
low titer of measles virus-specific IgG of low avidity, but a later sample
revealed a high titer of IgG of intermediate (40%) avidity, suggesting
previous immunological priming. Two
patients with breakthrough infection (secondary vaccine failure), both having
central nervous system involvement, showed a positive IgM response with
initial high titers of serum IgG of high avidity. In addition, one of the
patients had a detectable level of measles-specific IgG in cerebrospinal
fluid. In this patient, the avidity of both serum and cerebrospinal fluid IgG
decreased during the short follow-up period. This phenomenon has never before
been reported. In subacute sclerosing panencephalitis patients, the avidity of
cerebrospinal fluid IgG was consistently lower than that of serum IgG. The
difference in avidity between cerebrospinal fluid and serum IgG may be used as
a direct indicator of intrathecal production of IgG. In conclusion, the
avidity testing is simple to perform, reliable, and highly informative in the
analysis of measles virus infection.
PMID: 8991638 [PubMed - indexed for MEDLINE]
Measles encephalomyelitis in a patient with a history of
Matsuzono Y, Narita M, Satake A, Togashi T, Itakura O, Ozutsumi K, Iguchi
Department of Pediatrics, Hokkaido University, School of Medicine, Sapporo,
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 antibody 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
(x8192 in serum and x1024 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
antibodies observed at the very early stage of illness and the clinical course
indicated that this patient has an encephalomyelitis due to
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.
PMID: 7645392 [PubMed - indexed for MEDLINE]
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,
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.
PMID: 7594723 [PubMed - indexed for MEDLINE]
Waning immunity and its effects on vaccination schedules.
Rouderfer V, Becker NG, Hethcote HW.
School of Statistics, La Trobe University, Bundoora, Vic, Australia.
A relatively comprehensive age-specific transmission model is used to
determine the effect of various factors on the optimal vaccination ages in
one-dose and two-dose vaccination schedules. Motivated by the situation for
measles, the model allows the duration of immunity of newborns to depend on
the level of immunity of the mother at the time of the birth and allows for
waning immunity as well as boosting of immunity by exposure to the disease. It
is found that a significant amount of waning of disease-acquired immunity is
plausible when boosting occurs but this is not an important factor in
determining optimal vaccination schedules. On the other hand, plausible rates
of loss of vaccine-induced immunity can have a substantial effect on the
optimal vaccination schedule, particularly when there is no boosting of
immunity. For two-dose schedules the optimal vaccination ages depend
significantly on the level of vaccination coverage achieved.
In the presence of plausible rates of loss of vaccine-induced immunity for
measles, it is found that the vaccination coverage required to eradicate the
disease is substantially higher than previously suggested.
PMID: 7827424 [PubMed - indexed for MEDLINE]
The 1992 measles epidemic in Cape Town--a changing
Coetzee N, Hussey GD, Visser G, Barron P, Keen A.
Department of Community Health, University of Cape Town.
Over the last 6 years there has been a decline in the incidence of measles in
Cape Town. However, during August 1992 an outbreak occurred, with cases
reported at many schools in children presumably immunised. The objectives of
this study were to characterise the epidemic in Cape Town and to determine
possible reasons for the outbreak. The investigation consisted of two
components--a description of the epidemic and an investigation of an outbreak
at one primary school. Results indicate that during the last 4 months of the
year, 757 cases were notified in Cape Town, compared with 144 in the first 8
months. The epidemic affected mainly white and coloured children over 5 years
of age (P < 0.001). In contrast, during the period before the epidemic most
cases occurred in black children and in those aged less than 1 year (P <
0.001). There was no significant increase in hospitalised cases. Investigation
of the outbreak at one school revealed that the attack rate was 7.6% (25/329
children). Immunisation coverage (at least one dose of any measles vaccine)
was 91% and vaccine efficacy was estimated to be 79% (95% CI 55-90); it was
highest for monovalent measles (100%) and lowest for measles-mumps-rubella
(74%). The epidemiology of measles in
Cape Town has thus changed as evinced in this epidemic, with an increase in
the number of cases occurring in older, previously vaccinated children. The
possible reasons for this include both primary and secondary vaccine
failure.(ABSTRACT TRUNCATED AT
PMID: 7740350 [PubMed - indexed for MEDLINE]
Serological and clinical characteristics of measles vaccine
failure in Japan.
Hidaka Y, Aoki T, Akeda H, Miyazaki C, Ueda K.
Section of Pediatric Infectious Diseases, Fukuoka Children's Hospital, Japan.
In 1991, in Fukuoka, Japan, a measles outbreak occurred in which we observed
15 cases of measles vaccine failure (MVF). We examined these patients both
clinically and serologically. Seven of
them, with a response pattern of an early rise in and attainment of a high
inhibition (HI) antibody titre,
were considered to be secondary vaccine failures (EH group). Eight
others showed a normal (relatively late rise and low titre) HI antibody
response pattern and were considered to be primary vaccine failures (LL
group). In both MVF groups, measles-specific IgM antibody was detected by
enzyme immunoassay. The EH group had a milder rash than did the LL group and
unvaccinated controls. We believe they had an immunological memory that
modified the clinical manifestations of measles. Two cases of encephalitis
were observed in the EH group; both patients recovered without sequelae. These
data suggest that the mere presence or absence of IgM antibody is not
sufficient to differentiate primary from secondary MVFs.
A two-dose measles vaccination scheme
should be recommended to secure a booster effect, because immunity is waning
in the population in which the measles vaccination rate is not high enough and
in which natural measles still exists.
PMID: 7747097 [PubMed - indexed for MEDLINE]
Pulse mass measles vaccination across age cohorts.
Agur Z, Cojocaru L, Mazor G, Anderson RM, Danon YL.
Department of Applied Mathematics and Computer Science, Weizmann Institute of
Science, Rehovot, Israel.
Although vaccines against measles have
been routinely applied over a quarter of a century, measles is still
persistent in Israel, with major epidemics roughly every 5 years. Recent
serological analyses have shown that only 85% of Israelis aged 18 years have
antibodies. Considering the high transmissibility of the virus and the
high level of herd immunity required for disease eradication, the Israeli
vaccination policy against measles is now being reevaluated. Motivated by
theoretical studies of populations in perturbed environments, we examined the
possibility of replacing the conventional cohort vaccination strategy by a
pulse strategy--i.e., periodic vaccination of several age cohorts at the same
time. Numerical studies of a deterministic age-structured model suggest that
vaccination, which renders immunity to no more than 85% of the susceptible
children aged 1-7 years, once every 5 years will suffice to prevent epidemics
in Israel, where infection rate is highest amongst schoolchildren. The model
suggests that by using such a strategy the density of susceptible individuals
is always kept below the threshold above which recurrent epidemics will be
maintained. Analysis of simpler, non-age-structured, models serves to clarify
the basic properties of the proposed strategy. Our theoretical results
indicate that the advantages and disadvantages of a pulse strategy should be
seriously examined in Israel and in countries with similar patterns of measles
PMID: 8265611 [PubMed - indexed for MEDLINE]
Although it is note stipulated here that any of these
are due to waning immunity, since there are no estimates of primary vaccine
failure being as high as 15% one can assume that a portion of the 15% are
secondary vaccine failures. - AM
vaccine failure in healthcare workers exposed to infected patients.
Ammari LK, Bell LM, Hodinka RL.
Department of Pediatrics, Children's Hospital of Philadelphia, PA 19104.
OBJECTIVE: To describe 4 healthcare
workers who developed measles despite pre-existing
antibody levels. DESIGN: Hospital employees working in patient care
areas from July through November 1990 were screened for measles antibody
levels using a commercially available enzyme immunoassay (EIA). The clinical
course and laboratory evaluation of the 4 healthcare workers who developed
measles were reviewed. SETTING: An academic tertiary care children's hospital.
PARTICIPANTS: A convenience sample of resident physicians, nurses, ward
clerks, Child Life workers, physical and occupational therapists, radiology
technicians, and housekeeping staff were screened regardless of age,
immunization status, or history of measles infection. RESULTS: Of 1,311
employees working in patient care areas, 900 (68.6%) had sera tested for
measles antibody. Fourteen (1.5%) were negative, 338 (37.6%) had low positive
antibody levels, 372 (41.3%) were mid-positive, and 171 (19%) were
high-positive; 5 (0.6%) showed equivocal results. Four healthcare workers
vaccinated in the past developed measles.
All had positive pre-illness measles
antibody levels and all had a significant rise in measles-specific
following infection. Three of the them had received at least 2 live measles
vaccinations prior to caring for patients with measles. CONCLUSIONS:
These cases raise concerns regarding
detection of adequate protective measles immunity. We recommend that
all healthcare workers observe respiratory precautions in caring for patients
PMID: 8440884 [PubMed - indexed for MEDLINE]
Secondary immune response in a vaccinated population during
a large measles epidemic.
Ozanne G, d'Halewyn MA.
Laboratoire de sante publique du Quebec, Immunodiagnostic,
The rates of secondary immune response
(SIR) and secondary vaccine failure (SVF)
during a measles epidemic (10,184 notifications) were evaluated. A
patient with SIR was defined as a subject for whom all sera were
immunoglobulin G (IgG) positive and IgM negative with a significant increase
in complement fixation titer. A patient with SVF was defined as a vaccinated
symptomatic subject showing a SIR. Sequential sera from 898 subjects were
tested for measles antibody by enzyme-linked immunosorbent assay (IgG and IgM)
and by complement fixation. Evidence of recent anti-measles virus specific
immune response was found in 496 subjects (55.5%). The vaccination rate was
estimated at 74.6% (99% confidence interval [CI], 67.9 to 80.7%). The number
of exposed vaccinated subjects was estimated at 370 (74.6% of 496). The SIR
rate was 4.03% (20 of 496) (99% CI, 2.1 to 6.9%) among subjects with immune
response. These 20 subjects were 2 with measles (Centers for Disease Control's
definition), 6 with measles with rash of unknown duration, 8 with presumed
measles with either rash or fever, 3 asymptomatic subjects (2 with recent
contact with a measles case), and 1 undocumented subject. Since 3 patients
with SIR were asymptomatic and 2 others were documented as not vaccinated,
there was a maximum of 15 probable occurrences of SVF among the 20 patients
with SIR. The
rate among exposed vaccinated subjects was estimated at 4.05% (15 of 370) (99%
CI, 1.9 to 7.5%). In conclusion, neither prior vaccination nor detectable SIR
ensures protective immunity. Measles virus may induce asymptomatic SIR
in IgG-seropositive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
PMID: 1629334 [PubMed - indexed for MEDLINE]
[Duration of immunity and occurrence of secondary vaccine
failure following vaccination against measles, mumps and rubella]
[Article in Danish]
Trier H, Ronne T.
Epidemiologisk afdeling, Statens Seruminstitut, Kobenhavn.
The present article illustrates the extent of secondary vaccine failure after
vaccination for measles, mumps and rubella (MMR). Secondary vaccine failure
means loss of the immunity induced by vaccination to such an extent that
infection becomes possible. Serological investigations carried out with
follow-up periods of up to 16 years after vaccination for measles, 21 years
after vaccination for rubella and 12 years after vaccination for mumps reveal
that loss of antibodies occurs with the elapse of time but that the clinical
significance of this is probably very limited. Where all three types of
vaccination are concerned, secondary vaccine failure has hitherto been very
seldom. Infection with measles after secondary vaccine failure is generally
described as running a milder course. In rare cases, rubella re-infection has
resulted in infection in utero, so that a slight risk of congenital rubella
cannot be entirely excluded after successful vaccination. No extensive
systematic investigations of the effect of revaccination have been carried out
and, similarly, the optimal interval between two or more vaccinations has not
been illustrated in more detail in the literature. Subclinical infection is
not uncommon after all three vaccines.
Where measles is concerned, immunity may possibly be regarded as a continuum
which, depending upon the antibody level, protects the individual from various
degrees of clinical disease. If wild virus can be spread via individuals with
subclinical infections, it is doubtful whether population immunity (herd
immunity), which is necessary to eliminate the three diseases, can be attained
in large populations.(ABSTRACT
TRUNCATED AT 250 WORDS)
PMID: 1509566 [PubMed - indexed for MEDLINE]
[Reappearance of post-vaccination infection of measles,
rubella and mumps. Should adolescents be revaccinated?]
[Article in French]
Measles-mumps-rubella immunization has had a dramatic impact on the incidence
of these diseases and their complications. However, a partial coverage, as
seen in Belgium and France, only slows the spread of the wild virus, thus
increasing the age at infection and the risk of complications. This is to be
added to the fact that there are 5% primary vaccine failure (no antibody
production) and 5% secondary vaccine
failure (loss of antibodies over time). When introducing first
immunization at 15 months of age it is thus very important to increase quickly
the immunization coverage by immunization of all non-immune children entering
school and by re-immunization of all teenagers.
- Review, Tutorial
PMID: 1336841 [PubMed - indexed for MEDLINE]
Persistence of measles antibody after revaccination.
Markowitz LE, Albrecht P, Orenstein WA, Lett SM, Pugliese TJ, Farrell D.
Division of Immunization, Disease Control, Atlanta, Georgia 30333.
To evaluate persistence of measles antibody after revaccination, antibody
levels were measured 6 years after revaccination of 40 hemagglutination-inhibition
(HAI) antibody-negative students who had participated in a serosurvey in
Massachusetts. Twelve subjects who had been HAI antibody-positive and were not
revaccinated were included as a comparison group. Before revaccination, 7
revaccinees had no detectable plaque reduction neutralization (PRN) antibody
(group 1) and 33 had low levels of PRN antibody (group 2). Three weeks after
revaccination, all in group 1 and 30 (90%) of 33 in group 2 had developed a
fourfold or greater rise in PRN antibody. Six years after revaccination, all
subjects had PRN-detectable antibody. However, 12 in group 2 (36%) had
antibody titers less than or equal to 1:120 compared with none in group 1 (P
less than .01). Persons without PRN antibody will respond to revaccination and
maintain protective antibody titers.
In contrast, persons with low levels of PRN antibody may respond initially to
revaccination, but their antibody titers may fall again to low levels.
PMID: 1607699 [PubMed - indexed for MEDLINE]
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
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.
PMID: 2054370 [PubMed - indexed for MEDLINE]
Duration of live measles vaccine-induced immunity.
Markowitz LE, Preblud SR, Fine PE, Orenstein WA.
Division of Immunization, Centers for Disease Control, Atlanta, GA 30333.
From the article:
Similar to immunity after natural measles infection, live measles
vaccine-induced immunity has been thought to be lifelong. Vaccinees who
subsequently develop measles have been considered primary vaccine failures,
defined as the failure of the initial vaccination to elicit an appropriate
immune response. Primary vaccine failures are believed to be caused by
(1) interference by maternal antibody when vaccination occurs at a young age,
(2) technical problems, such as improper vaccine storage or administration, or
(2) other unknown reasons. Transmission of measles among older children
in the United States, most of whom have been appropriately vaccinated, has
raised the question of whether waning vaccine-induced immunity may also be
responsible for some vaccine failures. Current vaccination policy as
well as mathematical models assume that vaccine-induced immunity is life-long.
If waning vaccine-induced immunity does occur, changes in measles vaccination
strategies might be necessary. The purpose of this paper is to review
information concerning the duration and quality of measles vaccine-induced
Discussion: Several types of
studies have been applied to evaluate the duration and quality of measles
vaccine-induced immunity. The few reports of measles disease in persons
who had seroconverted after vaccination document that secondary vaccine
failure can occur. In addition two studies provide data on the potential
magnitude of the risk of secondary vaccine failure. However, most data
suggest that waning immunity is uncommon.
Many questions concerning the
duration of vaccine-induced immunity remain to be answered, including what
percentage of cases reported in previously vaccinated persons in the United
States is caused by primary or secondary vaccine failure, whether different
measles vaccine strains produce immunity which is more or less "durable",
whether reexposure to wild measles virus is important for maintenance of
vaccine-induced immunity and whether it is possible to identify individuals at
risk for waning immunity.
The consequences of waning measles
vaccine-induced immunity may be minor for individuals if secondary vaccine
failure is associated with mild disease. However, waning vaccine-induced
immunity could be of greater consequence to a population. Although
persons with subclinical reinfection have not been shown to transmit virus, it
is not known whether this is true for persons with secondary vaccine failure.
If these individuals are able to transmit disease to other susceptibles,
waning immunity, even in a small percentage of persons, may impede realization
of the goal of measles elimination. Revaccination may be successful in
decreasing the number of persons who become susceptible due to waning
immunity. However, it is not known whether revaccination of such persons
will result in sustained immunity.
Questions concerning duration of
vaccine-induced immunity and secondary vaccine failure were raised at the time
of vaccine licensure and discussed 10 to 15 years later when outbreaks
occurred in vaccinated children. Now, 26 years after licensure, many of
the same issues remain unresolved. Although waning immunity has been
documented to occur in a small proportion of vaccinees, the epidemiologic
significance of this is still unclear.
PMID: 2179836 [PubMed - indexed for MEDLINE]
[The results of multiyear observations on the duration of
the maintenance of immunity in those vaccinated and revaccinated against and
recovered from measles]
[Article in Russian]
Sliusar' LI, Sokhin AA, Radomskaia FS, Degtiareva GV, Panasenko LI,
Litvinova TP, Komarevskaia RV, Bol'shinskaia ZhI.
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
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.
PMID: 2239007 [PubMed - indexed for MEDLINE]
Mild measles and secondary vaccine failure during a
sustained outbreak in a highly vaccinated population.
Edmonson MB, Addiss DG, McPherson JT, Berg JL, Circo SR, Davis JP.
Department of Pediatrics, University of Wisconsin, Madison 53792.
A prolonged school-based outbreak of measles provided an opportunity to study
"vaccine-modified" mild measles and secondary vaccine failure. Thirty-six
(97%) of 37 unvaccinated patients had rash illnesses that met the Centers for
Disease Control clinical case definition of measles, but 29 (15%) of 198
vaccinated patients did not, primarily because of low-grade or absent fever.
Of 122 patients with seroconfirmed measles, 10 patients (all previously
vaccinated) had no detectable measles-specific IgM and significantly milder
illness than either vaccinated or unvaccinated patients with IgM-positive
serum. Of 108 vaccinated patients with seroconfirmed measles, 17 patients
(16%) had IgM-negative serology or rash illnesses that failed to meet the
clinical case definition; their mean age (13 years), age at the time of
vaccination, and time since vaccination did not differ from those of other
vaccinated patients. The occurrence of
secondary vaccine failure and vaccine-modified measles does not appear to be a
major impediment to measles control in the United States but may lead to
underreporting of measles cases and result in overestimation of vaccine
efficacy in highly vaccinated populations.
PMID: 2278542 [PubMed - indexed for MEDLINE]
The role of secondary vaccine failures in measles
Mathias RG, Meekison WG, Arcand TA, Schechter MT.
Department of Health Care and Epidemiology, University of British Columbia,
An outbreak of measles in 1985-86 in a community where measles vaccine trials
had been carried out from 1974-76 allowed the assessment of the role of
secondary vaccine failures in previously immunized children. A total of 188
children from the vaccine trial were followed. Of these, 175 seroconverted
initially while 13 (6 per cent) required re-immunization (primary failure). A
total of 13 cases of measles, eight of which were laboratory and/or
physician-confirmed, were reported in this cohort. Of these, nine cases
occurred in the 175 subjects who had hemagglutination inhibition test (HI) and
neutralizing antibody responses following the initial immunization. These nine
cases represent secondary vaccine failures. An additional four cases occurred
in the 13 subjects with primary vaccine failure.
We conclude that secondary vaccine
failures occur and that while primary failures account for most cases,
secondary vaccine failures contribute to the occurrence of measles cases in an
epidemic. A booster dose of measles vaccine may be necessary to reduce
susceptibility to a sufficiently low level to allow the goal of measles
elimination to be achieved.
PMID: 2929807 [PubMed - indexed for MEDLINE]
The use of IgM tests for analysis of the causes of measles
vaccine failures: experience gained in an epidemic in Hungary in 1980 and
Nagy G, Kosa S, Takatsy S, Koller M.
Following a period of 6 years of low measles incidence, an epidemic occurred
in Hungary with more than 11,000 reported cases between September 1980 and
August 1981. About 60% of the cases had a documented history of previous
measles vaccination. Serum samples obtained from 7815 patients were examined
for measles antibody by haemagglutination inhibition (HI). In addition to
conventional antibody titration, most of the sera or their IgM fraction
obtained by a simple ion exchange chromatography were tested for the presence
of measles-specific IgM antibodies by 2-mercaptoethanol (2-ME) treatment, and
in 300 patients also by the fluorescent antibody (FA) technique. Laboratory
results confirmed the diagnosis of measles in 5356 patients and supported it
in 685 cases. Primary antibody response was found in 96.1% of unvaccinated and
in 77.4% of previously vaccinated patients. The percentage of secondary
antibody responses increased with increasing time from vaccination only in
patients vaccinated before their first birthday, whereas in those who were
immunized when over 12 months old, the distribution of primary and secondary
antibody responses was independent from the time that had elapsed since
vaccination. Therefore, secondary
vaccine failure due to waning immunity account for only 6.2% of previously
vaccinated patients, whereas in 93.8% of patients, including the majority of
those with secondary antibody response, a primary failure of vaccination due
to unsuccessful immunization was incriminated.
PMID: 6693863 [PubMed - indexed for MEDLINE]
This abstract was put here because although most
vaccine failures were considered to be "primary", secondary vaccine failures did
occur. - SM
The measles epidemic in Calgary, 1974-1975: the duration of
protection conferred by vaccine.
- From the article:
Individual immunity to measles, derived from live vaccine, wanes with time.
PMID: 688165 [PubMed - indexed for MEDLINE]
A measles outbreak among adolescents.
Weiner LB, Corwin RM, Nieburg PI, Feldman HA.
In a May, 1975, outbreak, 147 adolescents, ages 12 to 19 years, were
identified as having measles by a physician or school nurse. One junior high
school, with an enrollment of 1,122, contributed 131 of the cases. Of the 147
students, 54 were seen by physicians who also supplied their immunization
records; 19 of 54 (35%) had received live measles virus vaccine without
measles immune globulin, after age one year. The remaining 35 received: killed
virus vaccine only (1), K + L (4), L + MIG (4), L at less than 1 year of age
(4), L + ? MIG (4), immune serum globulin only, for exposure (6), no vaccine
but history of measles previously (9); history uncertain (3). Hemagglutination-inhibition
antibody titers were consistent with the diagnosis of acute measles in 11
children. No index case was identified and no secondary cases occured within
the families of the 54 cases. This
measles outbreak among seemingly immunized adolescents raises a serious
question as to the duration of such protection.
PMID: 830888 [PubMed - indexed for MEDLINE]
Persistence of measles antibody in the absence of
circulating natural virus five years after immunization of an isolated virgin
population with Edmonston B vaccine.
Brown P, Gajdusek DC, Tsai T.
- From the abstract: In
the absence of circulating natural measles virus in an isolated Pacific atoll
community after immunization of 136
virgin individuals from 1 to 24 years of age with
B strain live attenuated measles vaccine, serum levels of HI antibody remained
stable between 1 and 2 1/2 years after immunization, but decline 2 to 3-fold
by 5 years after immunization. Sera having the highest antibody titers
at 1 year showed the greatest decline, with a resultant narrowing of the titer
range at 5 years. Individuals with even undetectable HI antibody
levels at 5 years, nevertheless showed neutralizing antibody at a serum
dilution of at least 1:2, and thus
presumably remain immune from infection.
PMID: 5362859 [PubMed - indexed for MEDLINE]
Measles vaccine effectiveness and duration of
vaccine-induced immunity in the absence of boosting from exposure to measles
Guris D, McCready J, Watson JC, Atkinson WL, Heath JL, Bellini WJ, Polloi
Center for Disease Control and Prevention, Atlanta, GA, USA.
BACKGROUND: It is unknown whether vaccine-induced immunity is lifelong in the
absence of periodic exposure to measles virus. After 27 years of no known
exposure to measles, an outbreak in Palau in 1993 offered the opportunity to
study this issue and the measles vaccine effectiveness. METHODS: Household
contacts of a sample of confirmed cases were interviewed for exposure,
symptoms and vaccination status verified by records. Serum from symptomatic
contacts was tested for measles antibodies. RESULTS: Among 78 contacts 4 of 5
(80%) unvaccinated, 4 of 35 (11%) 1-dose vaccine recipients and none of 38
(0%) > 1-dose recipients developed measles. Effectiveness of 1-dose vaccine
was 86% (95% confidence interval, 60 to 95%). An additional dose significantly
reduced the risk of measles (P = 0.048). Time since vaccination was not a
significant risk factor for developing measles (relative risk, 1.6; 95%
confidence interval, 0.3 to 9.4; persons vaccinated > 15 years ago vs. < 5
years ago). CONCLUSIONS: Similar to the estimates previously obtained in the
area, measles vaccine effectiveness in Palau was lower than the estimates
obtained in the US. A second dose of vaccine further reduced the risk for
developing measles. We found no
evidence that waning immunity was an important problem in this limited
population with no known previous exposure to measles virus. The small
number of vaccinated contacts precludes a definitive assessment.
PMID: 8970216 [PubMed - indexed for MEDLINE]
Measles epidemic in Romania, 1996-1998: assessment of
vaccine effectiveness by case-control and cohort studies.
Hennessey KA, Ion-Nedelcu N, Craciun MD, Toma F, Wattigney W, Strebel PM.
Vaccine-Preventable Disease Eradication Division, National Immunization
Program, Centers for Disease Control and Prevention, Atlanta, CA 30333, USA.
A measles epidemic occurred in Romania with 32,915 cases and 21 deaths
reported between November 1996 and June 1998, despite high vaccination
coverage since the early 1980s. Most cases were unvaccinated children aged <2
years and vaccinated school-aged children. A case-control study among
preschool children and a cohort study among primary-school children were
conducted to estimate effectiveness of Romanian-produced measles vaccine, and
to evaluate age at vaccination and waning immunity as risk factors for vaccine
failure. Both studies indicated that measles vaccine was highly effective. One
dose reduced the risk for measles by 89% (95% confidence interval (CI) 85,
91); two doses reduced the risk by 96% (95% CI 92, 98). Children vaccinated at
<1 year of age were not at increased risk for measles compared with children
vaccinated at > or =1 year. Waning
immunity was not identified as a risk factor since vaccine effectiveness was
similar for children vaccinated 6-8, 9-11, and 12-14 years in the past.
Because specific groups were not at risk for vaccine failure, an immunization
campaign that targets all school-aged children who lack two doses may be an
effective strategy for preventing outbreaks. A mass campaign followed by
increased first-dose coverage should provide the population immunity required
to interrupt indigenous measles virus transmission in Romania.
PMID: 10588086 [PubMed - indexed for MEDLINE]
Measles vaccine: a 27-year follow-up.
Ramsay ME, Moffatt D, O'Connor M.
Immunisation Division, PHLS Communicable Disease Surveillance Centre, London.
In 1964, the Medical Research Council undertook a trial of measles vaccine in
over 36,000 United Kingdom children; 9577 of whom received live vaccine,
10,625 received inactivated followed by live vaccines, and 16,328 acted as
unvaccinated controls. Participants in this study have been followed to
determine the long term protection from measles vaccine and follow-up data
were available on 4194, 4638 and 274 respectively. During the 5-year period
1986-90, the protective efficacy of live measles vaccine has remained high at
87%, but the 95% confidence interval was wide (-43 to 99%) due to the small
numbers of cases. Between 1976 and 1990, however, the overall efficacy of the
live vaccine was 92% (95% confidence interval 86 to 95%) and there was no
evidence of a decline in efficacy (P = 0.13) over the 15-year period.
study suggests that the protection from live measles vaccine persists for up
to 27 years after vaccination, and that no change in the current United
Kingdom measles immunization policy should be made on the grounds of waning
PMID: 8150015 [PubMed - indexed for MEDLINE]
Should all children receive two measles vaccinations? A
study of measles susceptibility in a suburban New Jersey private practice.
Tesoro LJ, Levin MB, Atkin MD, Katz NS, Cotton JM, Patrick-Miller T, Langer
Pediatric Group, Princeton, New Jersey.
Because of the rising incidence of rubeola, we tested all our patients who
were vaccinated prior to 15 months of age and those vaccinated after 15
months, if requested, for susceptibility to measles (IgG, ELISA). Those found
to be susceptible were revaccinated. Of 1,228 tested, 264 (21.5%) were
susceptible. In the group vaccinated before 1980, 237 of 901 (26.3%) were
susceptible, whereas only 27 of 327 (8.3%) vaccinated after 1980 were not
immune. Susceptibility was sharply divided by month of age at vaccination at
the 14-month mark. Less than 5% of those vaccinated after age 15 months in the
1980s (one of 22, or 4.5%) were susceptible.
Waning immunity (secondary vaccine
failure) was not found to be a factor in our patients. Despite
outbreaks of measles in surrounding communities and in our area, none of our
patients developed measles. Identification of high-risk groups and selective
measles revaccination should be considered as an alternative to universal
revaccination in populations such as ours, since it is more cost-effective and
may prove equally successful.
PMID: 1563191 [PubMed - indexed for MEDLINE]
[The duration and strength of postvaccinal measles
[Article in Russian]
Bolotovskii VM, Gelikman BG, Auzinia AV, Glinskaia EV.
A prolonged immunoepidemiological follow-up of a large group of children
immunized against measles revealed a high epidemiological efficacy of a single
vaccination. Cases of measles were registered only among those vaccinees in
whose blood sera no specific hemagglutinins were detectable by titration with
4 hemagglutinating units of measles antigen prior to the disease. The study
showed that groups of children seronegative with respect to measles appeared,
as a rule, after unsatisfactory immunization and not due to loss of
postvaccinal immunity with time.
Properly immunized children in whom the formation of
antibodies had occurred in response to the injection of live measles vaccine
immunity for more that 15 years (the term of observation).
PMID: 2386001 [PubMed - indexed for MEDLINE]
Measles outbreak in a vaccinated school population:
epidemiology, chains of transmission and the role of vaccine failures.
Nkowane BM, Bart SW, Orenstein WA, Baltier M.
An outbreak of measles occurred in a high school with a documented vaccination
level of 98 per cent. Nineteen (70 per cent) of the cases were students who
had histories of measles vaccination at 12 months of age or older and are
therefore considered vaccine failures. Persons who were unimmunized or
immunized at less than 12 months of age had substantially higher attack rates
compared to those immunized on or after 12 months of age. Vaccine failures
among apparently adequately vaccinated individuals were sources of infection
for at least 48 per cent of the cases in the outbreak.
There was no evidence to suggest that
waning immunity was a contributing factor among the vaccine failures.
Close contact with cases of measles in the high school, source or provider of
vaccine, sharing common activities or classes with cases, and verification of
the vaccination history were not significant risk factors in the outbreak. The
outbreak subsided spontaneously after four generations of illness in the
school and demonstrates that when measles is introduced in a highly vaccinated
population, vaccine failures may play some role in transmission but that such
transmission is not usually sustained.
PMID: 3826461 [PubMed - indexed for MEDLINE]
Risk factors for measles vaccine failure among immunized
Hull HF, Montes JM, Hays PC, Lucero RL.
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.
PMID: 4047794 [PubMed - indexed for MEDLINE]
Measles in the 1980s.
Christopher PJ, MacDonald PA, Murphy AM, Buckley PR.
We detail aspects of measles immunization programmes in several countries.
Live measles vaccine has been available in Australia for 16 years, yet, in
1981, there were outbreaks of measles in the State of New South Wales
(population 5 200 000) which led to 2200 admissions to hospital and five
deaths. In response to complaints of "vaccine failure", a survey determined
that 22.5% of children with measles seen by general practitioners and 10.3% of
those admitted to hospitals had been previously immunized.
There was no evidence of waning
immunity, and noparticular batch of vaccine was implicated. The vaccine
failures are attributed in part to failure of seroconversion in some
recipients when immunized at 12 months of age as a result of interference by
transplacentally acquired antibodies. As more of the susceptible population is
vaccinated, there will be fewer cases of measles, but among these cases will
be an increasing proportion of cases occurring in previously vaccinated
individuals. The equation to calculate this expected proportion of "vaccine
failures" is given. We support the measures to increase immunization
PMID: 6633361 [PubMed - indexed for MEDLINE]
Measles revaccination. Persistence and degree of antibody
titer by type of immune response.
Deseda-Tous J, Cherry JD, Spencer MJ, Welliver RC, Boyer KM, Dudley JP,
Zahradnik JM, Krause PJ, Walbergh EW.
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.
PMID: 629246 [PubMed - indexed for MEDLINE]
Measles vaccine efficacy: influence of age at vaccination
vs. duration of time since vaccination.
Shelton JD, Jacobson JE, Orenstein WA, Schulz KF, Donnell HD Jr.
To evaluate the recent decision of the Advisory Committee on Immunization
Practice to increase the recommended age for initial measles vaccination from
12 to 15 months, we carried out a case control study of vaccine failure in a
recent measles epidemic. Compared to children vaccinated at ages 15 months or
older, we found an increased risk of vaccine failure among those vaccinated at
12 to 14 months (relative risk = 19.2, 95% confidence interval = 4.6 to 80.1).
In order to sort out the influence of age at vaccination from elapsed time
since vaccination, we subjected the data to discriminant analysis. Age at
vaccination subsumed all of the effect of duration of time since vaccination.
Thus, we find no evidence of waning
immunity over time.
PMID: 733424 [PubMed - indexed for MEDLINE]