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.
Duration of rubella immunity induced by two-dose measles,
mumps and rubella (MMR) vaccination. A 15-year follow-up in Finland.
Davidkin I, Peltola H, Leinikki P, Valle M.
National Public Health Institute, Helsinki, Finland. firstname.lastname@example.org
A national two-dose vaccination program with a combined measles, mumps and
rubella (MMR-II) vaccine was introduced in Finland, in 1982, immunizing
children at the ages of 14-18 months and 6 years. Antibody levels were
determined from serial samples from a group of originally 350 children during
15 years. The latest samples were taken 15.5 years after the first vaccination
and 70% of the children could still be reached. The aim of this study was to
determine the kinetics of rubella antibodies induced by the MMR-II vaccine in
these individuals. Rubella antibodies were analyzed from three different
cohorts: Group I seronegative children (n=166) vaccinated at 14-18 months and
6 years, Group II seronegative children (n=139) and Group III seropositive
children (n=16) vaccinated at 6 and 11-13 years. Samples collected 0-9 years
after vaccination were analyzed by hemolysis-in-gel (HIG) and later samples by
enzyme immunoassay (EIA) techniques. The primary vaccination induced 100%
seropositivity in vaccinees with a mean zone diameter of 10 (+/-1.3), 10.2
(+/-1.1) and 11.5 (+/-0.9) mm, in Groups I, II and III, respectively. The
seropositivity rate was still high at 15 years, 99%, 100% and 100% with the
geometric mean titer 23, 46 and 105 IU/ml, respectively.
At 15 years, antibody levels <15
which is the suggested protective level, were found in 31, 9 and 0% of
children in Groups I, II and III, respectively. Because almost a third of the
individuals in Group I now, at the age of 17 years, had low levels of rubella
antibodies, it is possible that rubella infections may re-emerge during
pregnancy. A careful surveillance including serological follow-up is therefore
Adult immunization--a neglected issue in Southeast Asia.
Isahak I; Steering Committee for Prevention and Control of Infectious
Diseases in Asia.
Department of Medical Microbiology and Immunology, Faculty of Medicine,
University Kebangsaan Malaysia, Kuala Lumpur.
Adult immunization is a neglected and underpublicised issue in Southeast Asia.
Vaccine-preventable diseases cause unnecessary morbidity and mortality among
adults in the region, while inadequate immunization results in unnecessary
costs, including those associated with hospitalization, treatment, and loss of
income. Childhood vaccination coverage is high for the EPI diseases of
diphtheria, tetanus and pertussis; however, unvaccinated, undervaccinated, and
aging adults with waning immunity
remain at risk from infection and may benefit from vaccination.
Catch-up immunization is advisable for adults seronegative for hepatitis B
virus, while immunization against the hepatitis A and varicella viruses may
benefit those who remain susceptible. Among older adults, immunization against
influenza and pneumococcal infections is likely to be beneficial in reducing
morbidity and mortality. Certain vaccinations are also recommended for
specific groups, such as rubella for women of child-bearing age, typhoid for
those travelling to high-endemicity areas, and several vaccines for high-risk
occupational groups such as health care workers. This paper presents an
overview of a number of vaccine-preventable diseases which occur in adults,
and highlights the importance of immunization to protect those at risk of
Prevalence of antibodies against rubella virus in The
Netherlands 9 years after changing from selective to mass vaccination.
de Haas R, van den Hof S, Berbers GA, de Melker HE, Conyn-van Spaendonck
Department of Infectious Diseases Epidemiology, National Institute of Public
Health and the Environment, Bilthoven, The Netherlands.
A two-dose mass vaccination programme with a combined vaccine against measles,
mumps and rubella (MMR) was adopted in the Netherlands in 1987, replacing the
selective schoolgirl vaccination strategy introduced in 1974. To obtain
insight into the effect of mass vaccination and the population's immunity, the
antibody levels against rubella were studied in the general Dutch population
and in religious groups refusing vaccination. In the national sample, we
observed a high prevalence (96.5%) for rubella antibodies in vaccinated
cohorts as well as in the older unvaccinated cohorts.
No indications of rapidly waning
immunity after vaccination were found. There are indications of low
virus circulation in the last few years.
The very high seroprevalence
in women at childbearing age is consistent with the few reported cases of
congenital rubella syndrome (CRS) at present. However, individuals in
the age group of 1-9 years who are not vaccinated for religious or other
reasons have a considerably lower seroprevalence and thus there is a potential
risk of a CRS outbreak in the future.
Expression of interleukin-2 receptor alpha and CD45RO
antigen on T lymphocytes cultured with rubella virus antigen, compared with
humoral immunity in rubella vaccinees.
Toyoda M, Ihara T, Nakano T, Ito M, Kamiya H.
Department of Pediatrics, National Mie Hospital, Tsu, Japan.
We studied the expression of interleukin-2 receptor alpha (CD25)+ CD45RO+ CD4+
T lymphocytes (T-cell activation) in response to the rubella virus (RV)
antigen (Matsuura strain, Biken, Osaka, Japan) using three-color-staining flow
cytometry. The subjects were 48 healthy children (3-14 years old, 31 boys and
17 girls), who had received either monovalent vaccine (n = 5; mean age, 13.2
years) or measles-mumps-rubella (MMR) vaccine (n = 21; mean age, 10.5 years),
had been naturally infected (n = 5; mean age, 11.4 years), or had been neither
vaccinated nor naturally infected (n = 17; mean age, 10.0 years) and 62
healthy adolescents and adults (15-37 years old; 19 males and 43 females), who
had received monovalent vaccine (n = 26, mean age, 27.4 years), had been
naturally infected (n = 8; mean age, 24.0 years), or had been neither
vaccinated nor naturally infected (n = 8; mean age, 16.5 years). Ninety-four
of 110 subjects had HI titers > or = 1:16. T-cell activation in these subjects
was significantly higher than that in 6 seronegative (HI titers < 1:8)
subjects (p < 0.05). T-cell activation did not differ significantly with the
history of exposure to RV. HI antibody titers > or = 1:16 and T-cell
activation persisted in vaccinated subjects for > or = 20 years and was
similar to those in naturally infected subjects.
Our results suggest that cell-mediated
immunity and humoral
immunity persist for at least 20 years after vaccination.
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 vaccinees
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.
Antibody persistence after primary measles-mumps-rubella
vaccine and response to a second dose given at four to six vs. eleven to
Johnson CE, Kumar ML, Whitwell JK, Staehle BO, Rome LP, Dinakar C, Hurni W,
Department of Pediatrics, Case Western Reserve University at MetroHealth
Medical Center, Cleveland OH 44109-1998, USA.
BACKGROUND: Since 1989 the American Academy of Pediatrics and the ACIP have
recommended a second dose of measles-mumps-rubella vaccine (M-M-R-II) at
either school entry or age 11 to 13 years. Unfortunately few studies are
available to compare responses to vaccine at the two ages. We performed a
prospective trial to determine the persistence of antibody to measles, mumps
and rubella vaccination in two age groups and the response to a second dose
given at either 4 to 6 or 11 to 13 years. METHODS: Thirty-eight children 4 to
6 years old and 57 children 11 to 13 years old were given a second dose of
M-M-R-II as they presented for yearly examinations. All had received the first
dose at > or = 15 months of age. Measles and rubella antibody were measured by
enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody (NT)
assay, and mumps antibody was measured by an ELISA method only. An IgM-ELISA
antibody assay for measles was used in selected children. Prevaccination and
3- to 4-week post-vaccination sera were obtained. Measles ELISA,
measles-neutralizing antibody (NT) and rubella-neutralizing antibody (NT)
assays were performed in all children. Seventy-nine of the 95 children had
sufficient sera for repeat measles tests, as well as mumps and rubella ELISA
determinations. RESULTS: Before the second dose ELISA seropositivity rates for
measles and mumps were not significantly different between the two groups.
Rubella ELISA seropositivity was 67% in 11- to 13-year-olds, compared with 90%
in 4- to 6-year-olds (P < 0.01), suggestive of waning immunity.
Rubella NT seropositivity
was also lower in 11- to 13-year-olds than in 4- to 6-year-olds (63% vs. 100%,
P < 0.01). After revaccination, 100% of the children become
seropositive for all 3 antibodies. We performed measles IgM-ELISA testing on
all 17 measles-seronegative children, as well as 15 seropositive children and
19 children who were 1 month postvaccination with the first M-M-R-II at 15
months. The purpose was to determine whether the seronegative children were
primary or secondary failures. Five of the 17 children with undetectable
pre-second dose antibody made IgM measles antibody after revaccination,
suggesting that they were primary vaccine failures. CONCLUSIONS: Because all
children became seropositive after revaccination, the age of administration
can be based on the convenience of vaccine scheduling. However, in view of
the apparent decline in rubella
antibodies at 11 to 13 years, future studies of rubella vaccination
should address the issue of whether earlier boosting leads to greater
susceptibility at the time of reproductive age.
Public Health Unit, Eastern Sydney Area Health Service, Randwick, New South
OBJECTIVE: Attention is drawn to possible disadvantages arising from the
introduction of universal varicella vaccination in infancy. METHODOLOGY:
Comparisons are made between universal infant varicella vaccination and the
current measles immunization programme, and a review of current literature on
age-specific complications of varicella and cost-benefit analyses of varicella
vaccination. RESULTS: Universal infant
vaccination will cause a greater proportion of varicella
cases to occur in adults, including pregnant women, who are at greater risk of
serious complications compared to children. Although economic costs resulting from
lost time from work will fall dramatically, health costs may rise.
CONCLUSIONS: Universal infant vaccination should only be considered if measles
is first controlled, and then only if more information on duration of
protection becomes available and combined measles-mumps-rubella-varicella
vaccines are approved.
Seroprevalence of measles- and rubella-specific antibodies
among military recruits, Canada, 1991.
Duclos P, Tepper ML, Weber J, Marusyk RG.
Childhood Immunization Division, Bureau of Communicable Disease Epidemiology,
A study of the seroprevalence of measles- and rubella-specific antibodies
among military recruits in Canada in 1991 was undertaken to: 1) determine the
proportion of military recruits who are measles and/or rubella seropositive
when they enter the military; 2) detect general problems in the immune
coverage in the young adult population; and 3) determine the proportion of
measles seronegativity attributable to non-response, waning immunity or lack
of exposure to either the disease or the vaccine. One initial blood sample was
collected from all 399 recruits enrolled in basic training during the month of
January 1991, prior to immunization with measles-mumps-rubella vaccine (MMR).
Another sample was obtained from 354 of these recruits 3 to 5 weeks following
this immunization. Only 18 (4.5%) recruits had negative measles-specific
neutralization on the first sample. Only 12 (3.0%) recruits had negative
measles-specific EIA on the first sample. All recruits had neutralization
titres 40 or higher on the second sample.
A total of 43 (10.8%) individuals had
negative results for rubella
EIA before immunization,
35 of which (81.4%) tested positive on the second sample.
[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.
[The development and duration of immunity in children
vaccinated against measles with the Edmonston-Zagreb vaccine]
[Article in Serbo-Croatian (Roman)]
Borcic B, Smerdel S, Abu Eldan J, Kolic J, Ferdebar M, Kordic D, Mohacek N.
After routine measles-rubella-mumps (MRM) vaccine, seroconversion rate for
measles heminhibiting (HI) antibodies in a group of 161 children was
determined. Of the 154 children who had no HI antibodies in the first serum
sample, 153 (99.3%) developed these antibodies in titres greater than or equal
to 1:4 and 148 (96.1%) in titres greater than or equal to 1:8 at 6 weeks
postvaccination. These results are in concord with the WHO standards. Another
study was designed to evaluate persistence of HI antibodies to measles in a
group of 123 children who were given MRM vaccine 1-6 years earlier. No
significant decrease in HI antibody titers was recorded. It is concluded that
immunity acquired through vaccination with the Edmonston-Zagreb measles virus
strain in children aged 12 months to 3 years is satisfactory and that it does
not decrease at least up to 6 years following vaccination.
PMID: 2770398 [PubMed - indexed for MEDLINE]
A contrary opinion. However, later research
indicates that HI antibodies reflect primary, not secondary vaccine failure (i.e.,
waning immunity). - SM
Studies were conducted of experimental
challenge with rubella virus in vaccinees
whose possession of vaccine-induced antibody after vaccination had been
documented and whose antibody level had become undetectable or very low over
time. The challenge virus was the Howell strain, which had been shown
to produce typical clinical and laboratory features of rubella in susceptible
persons. The challenge of the vaccinees resulted in local viral replication in
all but one; in viremia, a primary immunologic response, and a secondary
antibody response in some; and usually
in illness without a rash or in subclinical infection. The results
emphasize the importance of continuing careful clinical and laboratory
surveillance of vaccinees for determining the persistence of vaccine-induced
immunity and of considering methods for identifying and revaccinating the
minority of vaccinees who lose such immunity.
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.
"A foolish faith in authority is the worst enemy of truth."
-- Albert Einstein, letter to a friend, 1901
"I know of no safe depository of the ultimate powers of the society but the people themselves, and if we think them not enlightened enough to exercise control with a wholesome discretion, the remedy is not to take it from them, but to inform their discretion by education."
-- Thomas Jefferson, letter to William C. Jarvis, September 28, 1820
“A sacred cow will not protect the herd.”
-- Sandy Gottstein
"What's the point of vaccination if it doesn't protect you from the unvaccinated?"
-- Sandy Gottstein
"Who gets to decide what the greater good is and how many will be sacrificed to it?"