Department of Pediatrics, Yale University School of Medicine, New Haven, Conn
06520-8064, USA.
BACKGROUND: A live attenuated varicella vaccine was approved for use in the
United States in March 1995 and is recommended for all susceptible persons 12
months of age or older. METHODS: To assess the effectiveness of the varicella
vaccine, we conducted a case-control study with two controls per child with
chickenpox, matched according to both age and pediatric practice. Children
with potential cases of chickenpox were identified by active surveillance of
pediatric practices in the New Haven, Connecticut, area. Research assistants
visited the children on day 3, 4, or 5 of the illness, assessed the severity
of the illness, and collected samples from lesions to test for varicella-zoster
virus by polymerase chain reaction (PCR). RESULTS: From March 1997 through
November 2000, data collection was completed for 330 potential cases, of which
243 (74 percent) were in children who had positive PCR tests for varicella-zoster
virus. Of the 56 vaccinated children
with chickenpox, 86 percent had mild disease, whereas only 48 percent of the
187 unvaccinated children with chickenpox had mild disease (P<0.001).
Among the 202 children with PCR-confirmed varicella-zoster virus and their 389
matched controls, 23 percent of the children with chickenpox and 61 percent of
the matched controls had received the vaccine (vaccine effectiveness, 85
percent; 95 percent confidence interval, 78 to 90 percent; P<0.001). Against
moderately severe and severe disease the vaccine was 97 percent effective (95
percent confidence interval, 93 to 99 percent). The effectiveness of the
vaccine was virtually unchanged (87 percent) after adjustment for potential
confounders by means of conditional logistic regression. CONCLUSIONS:
Varicella vaccine is highly effective as used in clinical practice.
Acute and long-term changes in T-lymphocyte subsets in
response to clinical and subclinical measles. A community study from rural
Senegal.
Lisse I, Samb B, Whittle H, Jensen H, Soumare M, Simondon F, Aaby P.
Department of Pathology, Hvidovre Hospital, Denmark.
To investigate the possibility of long-term suppression of T-lymphocyte
subsets, we examined children exposed to measles at home during an epidemic in
rural Senegal, at time of exposure and 1 and 6 months later. The measles case
fatality ratio was 1%. Subclinical
measles was common among vaccinated children exposed to measles (45%).
Both clinical and subclinical cases of measles showed a significant rise in
absolute CD4 count in the incubation period. In the prodromal phase and the
first week after the rash, the lymphocyte percentage, the white blood cell
count and the absolute CD4 cell numbers were significantly reduced. There was
no persistent decrease of absolute CD4 or CD8 numbers at 1 or 6 months after
exposure. Measles infection was followed by significant changes in the subset
composition, both CD4 and CD8 percentages being significantly higher in the
second month after measles than among non-seroresponders. These changes were
more marked among girls, since they had significantly higher CD4 percentages
and CD4/CD8 ratios than boys in the convalescence phase. In conclusion,
measles infection is not associated with a long-term suppression of CD4+ or
CD8+ T-lymphocytes.
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.
Subclinical
rubella reinfection during pregnancy followed by transmission of virus to the
fetus.
Aboudy Y, Fogel A, Barnea B, Mendelson E, Yosef L, Frank T, Shalev E.
Central Virology Laboratory, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
We report a documented case of rubella
reinfection during pregnancy in a previously vaccinated woman with residual
antibody titre
to rubella of 15 IU/ml.
The reinfection occurred following an exposure to rubella virus
(contact with 6-year-old daughter with clinical rubella) between the 7th and
10th week of pregnancy which resulted in transmission of the virus to the
fetus. Umbilical cord blood drawn by cordocentesis was found to be strongly
positive for rubella IgM antibody. After termination of the pregnancy rubella
virus was isolated in cell culture from fetal tissues.
Comparative efficacy of acellular pertussis vaccines: an
analysis of recent trials.
Cherry JD.
Department of Pediatrics, UCLA Children's Hospital, USA.
Diphtheria-tetanus-acellular pertussis vaccines have been licensed in the
United States since 1991. Compared with the whole cell pertussis component
diphtheria-tetanus-pertussis vaccine, the diphtheria-tetanus-acellular
pertussis vaccines were found in reactogenicity and immunogenicity studies to
be immunogenic with respect to their specific antigen content and to be
associated with less severe and less frequent adverse reactions. A case
definition of pertussis was developed by the World Health Organization for use
in vaccine efficacy trials, but this definition eliminates some
laboratory-confirmed cases from efficacy calculations. Because these cases are
more common in vaccinees than in controls, vaccine efficacy appears better
than it truly is whereas less effective vaccines seem comparable with their
more effective counterparts. In
addition observer bias may contribute to the appearance of enhanced efficacy
of the less effective vaccines, which tend to prevent typical but not mild
disease. When analyzing efficacy based on prevention of
laboratory-confirmed pertussis with cough > or = 7 days, single component
pertussis toxin (PT) toxoid vaccines were found to be less effective than
two-component PT toxoid/filamentous hemagglutinin vaccines, and three- or
four-component vaccines containing pertactin in addition to PT toxoid and
filamentous hemagglutinin were more effective than either the single-component
or two-component vaccines.
[Study on the
subclinical infection of the recipients of measles vaccine]
[Article in Chinese]
Wu T, Wang SL, Xiang YZ.
Sanitary and Anti-epidemic Station, Zhejiang Province, Hangzhou.
Through observation to subclinical infection of the 71 children who had been
inoculated against measles 12 years ago and then exposed to natural measles
from three classes at a primary school, we have noticed: (1) Subclinical
infection did exist among the crowd who were inoculation against measles;
The rate of subclinical infection of
the three classes was between 18.5%-75.0%, with an average of 45.1%.
(2) The level of the HI Ab titer was between 1:2-1:16. The peak level was
between 1:2 and/or 1:4. So the rate of subclinical infection who had been
inoculation against measles but later exposed to natural measles would depend
on the proportion of those whose titer of HI Ab was 1:2-1:4 in the crowd. (3)
The epidemiological significance of
subclinical measles infection lies in that it can actively keep and
consolidate the level of immunity to certain extent in a crowd who had been
inoculation against measles.
[Mumps vaccines: vaccination failures from an immunological
viewpoint]
[Article in German]
Hess U.
Bundesamt fur Gesundheitswesen, Bern.
The significance of mucosal and systemic immunity is illustrated with the
example of the different immune response of Poliovaccine live oral (Sabin) and
Poliovaccine inactivated parenteral (Salk).
On the occasion of rubella- and measles-outbreaks it will be demonstrated that
in vaccinated people subclinical reinfections
may much more frequently occur than clinically manifest diseases. On
the basis of these findings one may consider the large number of parotitis
cases without complications in mumps vaccinated Swiss pupils as secondary
mucosal vaccine failures at a time, when systemic immunity still was
protective. Significance for vaccination policy and consequences for handling
of vaccines shall be briefly discussed.
Department of Microbiology and Immunology, Faculty of Medicine, Ain Shams
University, Cairo, Egypt.
The present study was designed to estimate the level of measles IgG antibody
in infants early after vaccination and in preschool children to determine
their immune status. Three groups were studied: Group I, unvaccinated infants,
Group II, recently vaccinated infants and Group III vaccinated preschool
children. Measles IgG antibody was measured using the ELISA technique. The
study showed that 90% (18/20) of the unvaccinated Group I infants were
seronegative and only 10% were seropositive for measles IgG antibody
representing most probably persisting maternal antibodies. Fifty percent
(15/30) of recently vaccinated Group II infants were seropositive. A
statistically significant higher antibody level was observed in Group II
infants in comparison to those of Group I. The majority of seropositive
infants of Group II (10/15 = 66.7%) showed high antibody level representing
successful vaccination. Seropositives
represented 77.4% (24/31) of Group III preschool children and the majority of
them 75% (18/24) showed high antibody level which was significantly higher
than the comparable in Group II infants, most probably due to subclinical
infection in addition to successful vaccination. Fifty percent (15/30)
of Group II infants and 22.6% (7/31) of Group III children were seronegative,
more likely due to failure of initial vaccination.
Serologic evidence
of subclinical pertussis in immunized children.
Long SS, Lischner HW, Deforest A, Clark JL.
Department of Pediatrics, St. Christopher's Hospital for Children,
Philadelphia, PA 19134.
Incidental to a vaccine study involving 783 immunized children conducted at
two study sites, inner city children had significantly higher geometric mean
pertussis agglutinin titers compared with suburban children just before the
fourth dose of diphtheria-tetanus-whole cell pertussis vaccine (47 vs. 25; P
less than 0.001). Higher titers in the inner city were correlated with
residence in census tracts where cases of pertussis were reported. Three
hundred thirty-two children in a placebo arm of the study who were clinically
observed and had paired serum samples taken during a 2- to 4-month period were
analyzed for evidence of natural Bordetella infection. Twelve (11%) inner city
children and three (1.3%) suburban children had spontaneous 4-fold or greater
rises in at least two different pertussis antibodies measured (agglutinin,
antitoxin or enzyme-linked immunosorbent assay for IgG to pertussis toxin, IgG
and IgA to filamentous hemagglutinin). Eighty percent of these children had
IgA to filamentous hemagglutinin. Nine of 12 inner city children with
serologic evidence of pertussis lived within 6 blocks of a case of pertussis
reported within 1 month of the observed antibody rise in study subjects; none
had a household member with pertussis and none had symptomatic disease.
Subclinical measles
infection in vaccinated seropositive individuals in arctic Greenland.
Pedersen IR, Mordhorst CH, Glikmann G, von Magnus H.
Institute of Medical Microbiology, University of Copenhagen, Denmark.
Measles vaccination was performed in the arctic district of Scoresbysund,
Greenland in 1968, which had never been exposed to natural measles. More than
90% of the total population was vaccinated and a 94-100% seroconversion was
obtained. During a serological survey to examine the immunity status of the
vaccinees, it was discovered that a temporary increase in measles antibodies
took place in the majority of the population 2-4 years after the vaccination.
This was not accompanied by clinically observed measles.
Most likely, it was due to an
inapparent measles infection in a population considered highly immune after
vaccination.
Congenital rubella infection after previous immunity of the
mother.
Saule H, Enders G, Zeller J, Bernsau U.
II. Kinderklinik im Krankenhauszweckverband, Augsburg, Federal Republic of
Germany.
A newborn boy was admitted with a congenital rubella infection. Seven years
previously his mother had been vaccinated against rubella; 3 years previously
rubella immunity had been confirmed. Therefore, intrauterine transmission must
have occurred after maternal reinfection during pregnancy. Prenatal diagnosis
of rubella embryopathy with serological methods after subclinical maternal
reinfection is nearly impossible.
Challenge study on infectious bursal disease in chicks
derived from vaccinated hens.
Abdu PA, Abdullahi SU, Adesiyun AA, Ezeokoli CD.
Presence and levels of maternal antibody (MA) in broiler chicks derived from
hens vaccinated with a live infectious bursal disease (IBD) vaccine were
investigated by a quantitative agar-gel precipitin test. At day old 100% of
the chicks tested had MA; by 17 days of age it was present in only 10%. The
mean MA level at day old was 337.5 UK units/ml but decreased to 6.3 UK
units/ml at 17 days of age. Randomly selected chicks from the pool studied
were challenged at weekly intervals from day old for 29 days with an IBD virus
obtained from a natural outbreak.
Subclinical and clinical disease were observed in chicks challenged at eight
and 29 days of age respectively.
A long-term follow-up study on the efficacy of further
attenuated live measles vaccine, Biken CAM vaccine.
Isomura S, Morishima T, Nishikawa K, Hanada N, Rahman M, Terashima M, Kido
S, Ueda S, Takahashi M.
Antibody persistence was measured in 39 children in an open community 12-13
years after immunization against measles with further attenuated live vaccine,
Biken CAM. Serum samples of the children taken every two or three years after
vaccination had higher, lower, or the same HI antibody titers as those in
samples taken 6 weeks after vaccination.
These differences reflected a decrease
in the titer in some children and subclinical natural reinfection in others.
However, all the children still retained detectable antibody in 12 or
13 years after vaccination, indicating long-term persistence of immunity after
immunization with Biken CAM vaccine. For evaluation of the protective efficacy
of the vaccine, matched controls were studied during the same period.
Serological examination revealed that 97.5% of the controls were infected with
measles and contracted the disease. In contrast, none of the vaccinees
developed clinical infection after close contact with measles patients.
Duration of immunity after rubella vaccination: a long-term
study in Switzerland.
Just M, Just V, Berger R, Burkhardt F, Schilt U.
In Switzerland 319 of 594 young women seronegative for rubella antibody
vaccinated at 15-25 years of age against rubella with the Cendehill vaccine
strain were retested 15 years later with three tests (hemagglutination
inhibition, enzyme-linked immunosorbent assay, and a neutralization technique)
for the presence of rubella antibodies. For 307 women rubella antibodies were
still detectable by all three techniques. For nine women rubella antibodies
were demonstrable by only one or two tests. Only three vaccinees were
seronegative by all three tests. These three women also showed no booster
response after challenge with the vaccine strain.
The high percentage of women with
persistent rubella antibodies 15 years after vaccination might be explained in
part by the presence of subclinical reinfections
due to a wild rubella virus.
Live varicella immunization in healthy non-immune nurses.
Ndumbe PM, Cradock-Watson JE, Heath RB, Levinsky RJ.
Thirty-four varicella-zoster virus (VZV) seronegative nurses were vaccinated
with the live varicella vaccine (Varilrix) and followed for periods of up to
36 months. No major vaccine reactions were observed. At 5 and 12 months, 94%
of the nurses had seroconverted but at 3 years, only 64% retained antibody
activity. However, lymphocyte transformation to VZV antigen was positive in 7
seronegative nurses, all of whom had previously seroconverted. The one nurse
who developed chickenpox had not seroconverted after vaccination.
Two out of 11 seroconverted
nurses had a subclinical reinfection, as shown by a rise in antibody, upon
exposure to varicella.
In contrast, 4 out of 5 seronegative nurses who had refused vaccination
developed chickenpox. Varilrix is therefore safe, immunogenic, and protective
in adults and can be considered for routine use in susceptible health workers.
However, it is still uncertain whether lifelong immunity is obtained with this
vaccine. Both cell-mediated and antibody tests are needed for long-term
assessment of immunity to chickenpox.
Seven cases of asymptomatic rubella
reinfection in early pregnancy are described. In each, there was a
history of exposure to a rubelliform illness and low levels of
rubella-specific IgM subsequently appeared in the serum.
Four of the women had been immunised,
after having been shown to be susceptible to rubella, one had been immunised
at school without previous antibody screening, and two were uncertain about
immunisation.
One pregnancy was terminated and rubella virus was not isolated from the
products of conception. Six pregnancies went to term and the infants showed no
evidence of intrauterine infection. In a further case it was impossible to
discriminate between reinfection and primary infection, and termination of
pregnancy was offered.
Subclinical rubella
reinfection in vaccinated women with rubella-specific IgM response
during pregnancy and transmission of virus to the fetus.
Forsgren M, Soren L.
This report concerns 2 cases of
documented rubella reinfection during pregnancy in previously vaccinated
women. The antibody response at reinfection comprised not only
anti-rubella IgG but also IgM. In the first case the reinfection occurred
between the 13th and 19th week of pregnancy and was followed by transmission
of virus to the fetus (anti-rubella IgM in cord blood and persisting antibody
activity). The child had no clinical signs of congenital rubella and is
normally developed without hearing impairment at 41/2 years of age. In the
second case the reinfection resulted from exposure in the 15th week of
pregnancy; there were neither serological nor clinical signs of congenital
rubella in the child. The reported case of fetal infection in spite of
previous rubella vaccination of the mother does not discourage the use of
rubella vaccine. Rubella vaccine induces long lasting immunity and protection
from viremia in the vast majority of individuals.
We report a case of a patient who had a
subclinical rubella infection
in the first trimester of pregnancy which resulted in the delivery of a baby
suffering from congenital rubella. Rubella virus vaccine, liver attenuated (Cendevax)
vaccine had been administered to the mother nearly three years before, with
proven seroconversion from a rubella haemagglutination-inhibition titre of
1:10 to 1:80.
Rubella-vaccinated students. Follow-up in a public school
system.
Schiff GM, Rauh JL, Young B, Trimble S, Rotte T, Schiff BE.
In a 7 1/2-year follow-up evaluation of the duration of
rubella-vaccine-induced immunity of students who received either HPV-77 DK-12
or Cendehill vaccine, both groups showed a continous decline in
hemagglutination-inhibition antibody from seven weeks after vaccination but a
lower decline between 4 1/2 and 7 1/2 years after vaccination. However, at 7
1/2 years only 16 students (8%) receiving the Cendehill vaccine and one
student (0.5%) receiving the HPV-77 DK-12 vaccine lacked detectable antibody.
Despite the persistence of antibody
titers, there was evidence of subclinical rubella among both groups of
vaccinated students. These results emphasize the importance of
continued evaluation of the conditions of persons receiving rubella vaccine.
Rubella epidemic in an institution: protective value of
live rubella vaccine and serological behavior of vaccinated, revaccinated and
naturally immune groups.
Baba K, Yabuuchi H, Okuni H, Harima R, Minekawa Y, Taniuchi M, Otsuka T,
Takahashi M, Okuno Y.
A rubella epidemic occurred in an institutional population composed of 189
susceptible, 37 naturally immune, 35 previously vaccinated and 38
serologically uncharacterized children and nursing staff. The epidemic lasted
3.5 months and showed more than 5 waves. Detailed clinical and serological
examinations of these subjects were made. A rash appeared in 156 (52%) of 299
persons, including 145 (87%) of 166 unvaccinated and serologically
uncharacterized subjects, but not in the 72 immune persons. In the middle of
the 3rd wave urgent vaccination of 61 children aged 0 to 2 years of the
susceptible group reduced the rate of appearance of a rash to 11 of the
children (18%), as compared with 126 (98%) of 128 subjects in the unvaccinated
non-immune group. The epidemic only reached a 4th wave in the vaccinated
group, but it extended to a 5th wave or more in unvaccinated subjects.
None of the 35 subjects in a
previously vaccinated group developed rubella, although the rate of
subclinical reinfection in this previously vaccinated group was higher (35%)
than that in the naturally immune group (17%). Three cases of
subclinical reinfection were detected even among 6 previously revaccinated
subjects.
Rubella-vaccinated students. Follow-up in a public school
system.
Schiff GM, Rauh JL, Young B, Trimble S, Rotte T, Schiff BE.
In a 7 1/2-year follow-up evaluation of the duration of
rubella-vaccine-induced immunity of students who received either HPV-77 DK-12
or Cendehill vaccine, both groups showed a continous decline in
hemagglutination-inhibition antibody from seven weeks after vaccination but a
lower decline between 4 1/2 and 7 1/2 years after vaccination. However, at 7
1/2 years only 16 students (8%) receiving the Cendehill vaccine and one
student (0.5%) receiving the HPV-77 DK-12 vaccine lacked detectable antibody.
Despite the persistence of antibody titers, there was evidence of subclinical
rubella among both groups of vaccinated students. These results
emphasize the importance of continued evaluation of the conditions of persons
receiving rubella vaccine.
Long-term follow-up for immunity after monovalent or
combined live measles, mumps, and rubella virus vaccines.
Weibel RE, Buynak EB, McLean AA, Hilleman MR.
Antibody in human subjects persisted without substantial decline for 8 years
after mumps vaccine (Jeryl Lynn), for 6 years after measles (Attenuvax), for 5
1/2 years after rubella vaccine (HPV-77 duck), for 5 years after
measles-mumps-rubella and mumps-rubella combined vaccines, for 4 years after
measles and rubella, and for 2 years after measles-mumps vaccines, the longest
periods tested. Protective immunity against mumps illness persisted through
the eighth year. The patterns for antibody following vaccination parallel
those for natural infection and indicate that immunity will be lasting.
Subclinical reinfection evidenced by
antibody increase was commonly seen in persons who had been vaccinated, much
as follows the natural infection.
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.
