The association of class I HLA alleles and antibody levels
after a single dose of measles vaccine.
Jacobson RM, Poland GA, Vierkant RA, Pankratz VS, Schaid DJ, Jacobsen SJ,
St Sauver J, Moore SB.
Department of Pediatric and Adolescent MedicineMayo Clinic, Rochester, MN, USA
Despite the success of the current
measles vaccine in controlling disease in industrialized countries, the
importance of vaccine failure has become increasingly apparent. Our
objective was to determine if associations exist between
seronegativity
after measles vaccination and class I human leukocyte antigen (HLA)
alleles. We undertook a cross-sectional observational study in Rochester,
Minnesota, with 242 school-age children previously recruited from a
communitywide seroprevalence study. We studied two groups of subjects: 72 were
seronegative (EIA </=0.8 after a single dose of measles vaccine) and 170 were
seropositive (enzyme immunoassy [EIA] >/=1.0 after one dose). We used the
resources of Mayo Clinic's tissue typing laboratory for serotyping class I HLA-A
and HLA-B alleles via microlymphocytotoxicity assays. We found no
statistically significant associations with class I HLA-A but did find
associations with class I HLA-B, which includes alleles associated with
seronegativity (B8, B13, and B44) and those associated with seropositivity (B7
and B51). Elucidation of the specific peptide-HLA complex interactions that
lead to varying or failed immune responses may provide fertile groundwork for
improved vaccines that can overcome limitations of the current live,
attenuated measles vaccine.
Younger age at
vaccination may increase risk of varicella vaccine failure.
Galil K, Fair E, Mountcastle N, Britz P, Seward J.
Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. kgalil@cdc.gov
To determine vaccine effectiveness (VE), a varicella outbreak in a highly
vaccinated day-care center (DCC) population in Pennsylvania was investigated.
In Pennsylvania, proof of immunity is required for children >or=12 months old
for DCC enrollment. Questionnaires were administered to parents of children
who had attended the DCC continuously during the study period (1 November
1999-9 April 2000) to determine history of varicella disease or vaccination
and for information about any recent rash illnesses. VE was calculated for
children >or=12 months old without a history of varicella. There were 41 cases
of varicella among 131 attendees, with 14 cases (34%) among vaccinated
children. VE was 79% against all varicella and 95% against moderate or severe
varicella. Vaccination at <14 months was associated with an increased risk of
breakthrough disease (relative risk, 3.0; 95% confidence interval, 0.9-9.9).
Despite varicella vaccination coverage of 80%, a sizeable outbreak occurred.
Early age at vaccination may increase the risk of vaccine failure.
Concentration and avidity of anti-Haemophilus influenzae
type b (Hib) antibodies in serum samples obtained from patients for whom Hib
vaccination failed.
Breukels MA, Jol-van der Zijde E, van Tol MJ, Rijkers GT.
Department of Pediatric Immunology, Wilhelmina Children's Hospital, University
Medical Center, 3584 EA, Utrecht, The Netherlands. m.breukels@azu.nl
Haemophilus influenzae type b (Hib) conjugate vaccines are extremely effective
in protecting infants and children from invasive Hib infections; however,
vaccine failures do occur. The anti-Hib antibody production was studied both
quantitatively and qualitatively in 12 patients who experienced Hib failure,
all of whom had normal serum immunoglobulin concentrations and all of whom
were without clinical risk factors for invasive Hib disease. Both anti-Hib
antibody concentration and immunoglobulin-G2 anti-Hib antibody avidity were
significantly lower in patients who experienced Hib failure, at onset of
disease and after reconvalescence, when compared with controls.
This finding suggests that the
patients who developed invasive Hib
disease--despite having received 3-4 Hib
conjugate vaccinations--were inadequately primed by these vaccinations.
HISTORY AND CLINICAL FINDINGS: A 59-year-old woman, her 55-year-old husband,
their daughter, son and the son's girlfriend were admitted with acute icterus
32-34 days after a dinner when they had eaten shellfish. The father had been
immunised against hepatitis A and B with a combined vaccine (Twinrix(R)) and
had completed the full vaccination schedule 47 days prior to this meal. His
wife had been incompletely vaccinated with one injection 16 days prior and a
second injection 13 days after the dinner. The other three participants of the
dinner had not been immunised. The incubation time and clinical picture did
not differ between the vaccinated and non-vaccinated patients. INVESTIGATIONS,
TREATMENT AND COURSE: All 5 patients were anti-HAV IgM-positive, had high
serum aminotransferases and serum bilirubin. All patients had an uneventful
recovery. There was no difference in
the clinical course between the vaccinated and non-vaccinated patients.
CONCLUSION: Combined hepatitis A/B
vaccination according to the recommended schedule does not guarantee
protection in elderly persons. Before travelling in endemic areas,
their antibody response after basic hepatitis A/B vaccination should be
determined.
Reduced efficiency of influenza vaccine in prevention of
influenza-like illness in working adults: a 7 month prospective survey in EDF
Gaz de France employees, in Rhone-Alpes, 1996-1997.
Millot JL, Aymard M, Bardol A.
EDF GDF Services Annecy Leman, 5 boulevard Decouz, BP 2334, F-74011 Annecy
Cedex, France. jean-louis.millot@edfgdf.fr
The efficiency of influenza vaccine was evaluated in the working population by
comparing the percentage of people presenting with an influenza-like illness (ILI)
according to their influenza immunization status, drug expenses and workdays
lost. A self-completed questionnaire about the vaccination was sent to 5785
people randomly chosen among 18 249 workers. When any sick leave was incurred
amongst the respondents (63.3%), of whom 301 were vaccinated and 3362
unvaccinated, a clinical form was completed by the private physician and the
medical adviser of the firm (Electricite de France and Gaz de France). A final
self-completed questionnaire was sent to people whose sick leave was not
documented by a physician's reported diagnosis. In total, we obtained complete
data for 90.9% of the sampling. The vaccine coverage rate of 8.2% [95%
confidence interval (95% CI) = 7.4-9.0%] was higher in men than in women,
increasing with age and professional category.
Among the 775 subjects with a medical
diagnosis, the vaccine effectiveness was not significant: 27.3% (95% CI
= -13.8 to 53.5%). In the unvaccinated group, 9.6% had days absent from work,
versus 7.0% in the vaccinated group; the two populations were comparable in
terms of clinical symptoms, smoking habits, exposure to respiratory risk
factors and chronic pathology. The average duration of sick leave for ILI was
not significantly different between vaccinated (0.5 days) and unvaccinated
workers (0.6 days). Despite the large
size of the population and the occurrence of an epidemic due to a virus
closely related to the vaccine strain (A/Wuhan/359/95),
the vaccine did not effectively protect the small vaccine group nor result in
an economic benefit, whatever the professional group.
Immunological characterization of conjugated Haemophilus
influenzae type b vaccine failure in infants.
Breukels MA, Spanjaard L, Sanders LA, Rijkers GT.
Department of Immunology, Wilhelmina Children's Hospital, University Medical
Center Utrecht, Utrecht, The Netherlands. m.breukels@azu.nl
Infant vaccination with conjugated
Haemophilus influenzae
type b (Hib)
vaccine is highly effective in protecting against invasive Hib
infections, but vaccine failures do occur. Twenty-one vaccine failures are
reported since the introduction of the Hib
conjugate vaccine in The Netherlands. Of the 14 evaluable
patients, 6 children showed no antibody response to Hib polysaccharide
in convalescent-phase serum (immunoglobulin [Ig] G anti-Hib level <1.0 microg/mL),
including 1 child with hypogammaglobulinemia and 1 child with IgG2 deficiency.
After revaccination, almost all children developed anti-Hib antibodies. In
case of Hib vaccine failure, case investigation should be performed, including
measurement of serum Ig concentrations as well as specific anti-Hib
antibodies. Invasive Hib disease after infant conjugate Hib vaccination may be
the presentation of an underlying immunodeficiency, but more often, only a
decreased antibody response to Hib is found; revaccination with conjugated Hib
vaccine is advised.
Prevalence of vaccine-induced escape mutants of hepatitis B
virus in the adult population in China: a prospective study in 176 restaurant
employees.
He C, Nomura F, Itoga S, Isobe K, Nakai T.
Department of Clinical Pathology, Institute of Clinical Medicine, Tsukuba
University, Ibaraki, Japan.
BACKGROUND AND AIM: Hepatitis B virus (HBV) variants with mutations in the S
gene would pose a substantial risk to the community as current HBV vaccines
are not effective in preventing infection with them. The majority of such
vaccine escape mutants so far reported have been found while studying vertical
transmission of HBV; the vaccine failure rate in connection with vaccine
escape mutants in adults is not clear at the moment. The purpose of this study
was to evaluate the efficacy of immunization against HBV in the adult
population by analysis using polymerase chain reaction (PCR) to detect HBV-DNA,
and also to elucidate the type of mutation encountered in vaccine failure
cases. METHOD: A total of 176 adult restaurant employees in China, who had
been vaccinated according to the food epidemic law, were enrolled in a
standard vaccination program. Their serum HBV-DNA was determined before and 1
year after the completion of the vaccination program. In those infected with
HBV, despite having received the HBV vaccine, direct sequencing within the S
gene of the amplified samples was conducted. RESULTS: Although only two cases
were found to be hepatitis B surface antigen (HBsAg) positive 1 year after the
completion of the vaccination program, six subjects (3.4%) were found to be
HBV-DNA positive assessed by a nested PCR. Four out of these six cases had a
point mutation within the 'a' determinant; they were Gly-145-Ala, and Ile/Thr-126-Asn/Ser.
CONCLUSION: The HBV
vaccine failure rate assessed by using PCR
analysis was 3.4% (six of 176) in the Chinese adult population undergoing the
HBV
vaccination program. Hepatitis B virus variants with missense mutation
within the 'a' determinant were responsible in most cases.
Invasive disease due to Haemophilus influenzae type b
during the first six years of general vaccination of Swedish children.
Garpenholt O, Hugosson S, Fredlund H, Giesecke J, Olcen P.
Department of Clinical Microbiology, Orebro Medical Centre Hospital, Sweden.
orjan.garpenholt@orebroll.se
Since 1992-93 vaccination against Haemophilus influenzae type b (Hib) has been
included in the general Swedish childhood vaccination programme. The aim of
the present study is to describe the epidemiology, identify and describe
vaccine failures and calculate vaccine effectiveness during the first 6 y
after introduction of vaccination against Hib. Laboratory reports of blood and
cerebrospinal isolates to the Swedish Institute for Infectious Disease Control
were used as the source for identifying the patients. Additional information
was subsequently obtained from physicians and parents of children who had
developed the disease during the study period. Vaccine failures were
identified and vaccine effectiveness calculated. During the study period, 152
cases of invasive H. influenzae were identified in the age group 0-14 y.
During the 6-y period, 6 true vaccine
failures, 6 apparent vaccine failures and 1 possible vaccine failure were
found in nearly two million vaccinated child-years. The effectiveness
of the Hib vaccination in the birth cohort of children 1993 to 1997 in Sweden
was calculated to be 96.1% (95% confidence interval 94.2-97.5). The study
supports earlier studies from several countries that conjugated Hib
vaccination introduced in general childhood vaccination programs is effective
and substantially decreases suffering from invasive Hib diseases.
Widespread paralytic poliomyelitis in Pakistan: A
case-control study to determine risk factors and implications for
poliomyelitis eradication.
Hennessey KA, Marx A, Hafiz R, Ashgar H, Hadler SC, Jafari H, Sutter RW.
Vaccine-Preventable Disease Eradication Division (E-nn05), Centers for Disease
Control and Prevention, Atlanta, GA 30333, USA. keh7@cdc.gov
Despite substantial efforts to eradicate poliomyelitis by administering oral
poliovirus vaccine through routine immunization and annual national
immunization days (NIDs), Pakistan reported 22% (1147) of the worldwide cases
in 1997. Reasons for continued high
poliomyelitis incidence include failure to vaccinate, vaccine failure, or
inadequate immunization strategies. A case-control study was conducted
to measure vaccination status and reasons for undervaccination among 66
poliomyelitis cases and 130 age- and neighborhood-matched controls. Cases were
undervaccinated through routine immunization (matched odds ratio [MOR], 0.3;
95% confidence interval [CI], 0.1-0.5); however, NID immunization was similar
for cases and controls (MOR, 0.6; 95% CI, 0.3-1.2). Reasons for
undervaccination included not being informed, considering vaccination
unimportant, and long distances to vaccination sites. Failure to vaccinate
through routine immunization was a major risk factor for poliomyelitis in
Pakistan. Successful NIDs alone will not interrupt poliovirus circulation in
Pakistan, and children remain at risk unless routine immunization is
strengthened or additional supplementary immunization is provided.
Secondary measles vaccine failures identified by
measurement of IgG avidity: high occurrence among teenagers vaccinated at a
young age.
Paunio M, Hedman K, Davidkin I, Valle M, Heinonen OP, Leinikki P, Salmi A,
Peltola H.
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.
Measles epidemic in Israel-successful containment in the
military.
Gdalevich M, Ephros M, Mimouni D, Grotto I, Shpilberg O, Eldad A, Ashkenazi
I.
Medical Corps, Israel Defense Forces, Haifa, Israel. drlena@netvision.net.il
BACKGROUND: Measles vaccination at ages 12-15 months is a routine part of
standard health care in developed countries. Nonetheless, the prevention and
control of measles outbreaks remain a challenge, owing to incomplete or
variable compliance with immunization programs and
primary vaccine failure (approximately
5%). In Israel, vaccination coverage against measles is high, yet sero-epidemiological
studies conducted in the early 1990s showed that 15% of 18-year-olds were
unprotected. METHODS: 1994 there was a countrywide epidemic of measles, which
spread to the military. The Israel Defense Forces Medical Corps immediately
launched a wide-scale vaccination campaign, targeting primarily field units
and training bases, where crowded living conditions are the rule. RESULTS: The
immunization campaign led to an abrupt cessation of morbidity in the military.
In the civilian sector, where no intervention was undertaken, the epidemic
continued for another 4 months. CONCLUSIONS: Institutional measles outbreaks,
especially in the presence of crowded conditions or high contact rates, may be
effectively controlled by mass vaccination. Copyright 2000 American Health
Foundation and Academic Press.
Resurgence of measles in Singapore: profile of hospital
cases.
Goh D, Chew F, Khor S, Lee B.
Department of Paediatrics, National University of Singapore.
OBJECTIVE: To ascertain the profile of cases of measles seen at a general
hospital during a recent outbreak that occurred despite a measles vaccination
program. METHODOLOGY: A retrospective study from January 1991 to March 1998.
All patients with measles (ICD code 055. 9) seen at the emergency unit or as
inpatients were included. RESULTS: There were 87 cases identified. The
diagnosis was clinical in all and proven serologically in 71%. Eighty-five per
cent of the cases occurred between January 1997 and March 1998. There was a
bi-modal age distribution with peaks in the very young (</= 18 months) and
those aged 16-20 years. The majority was unvaccinated (58/87).
A proportion (11/87) demonstrated
vaccine failure, most likely primary failures. CONCLUSION: This
changing measles epidemiology suggests lowering of herd immunity. 'Catch up'
vaccinations in July- October 1997 given to school children aged 12-18 years
(200 000 individuals or 82% of cohort), may have helped contain the outbreak.
These results substantiated the need for a two-dose policy and 'catch-up'
immunization program.
Department of Epidemiology, Ministry of Health, Jerusalem, Israel.
BACKGROUND: Measles-mumps-rubella (MMR) vaccine replaced monovalent measles
vaccine in the routine childhood vaccination schedule in Israel in December
1988, primarily to achieve the elimination of the congenital rubella syndrome.
In this observational study, we report on changes in reported mumps incidence
in Israel from the time of the introduction of MMR vaccine until the end of
1998. METHODS: The report is based upon passive national surveillance of mumps
incidence, which has been notifiable in Israel since 1977. RESULTS: Reported
mumps incidence in Israel is now less than 2% the pre-vaccine incidence.
CONCLUSIONS: In the decade since the introduction of routine mumps vaccination
in 1-year-olds in Israel, mumps control has been achieved. Although small
outbreaks occur and may continue to occur in future years, because of
under-vaccination of children, primary
vaccine failure and waning immunity, it can tentatively be said that
mumps is no longer a public health problem in Israel.
A district survey of vaccine cold chain protection in
general practitioners' surgeries.
Finn L, Crook S.
Dorset Health Authority, Ferndown.
Failure to ensure that vaccines are
kept within a prescribed temperature range at all times can reduce their
potency and cause primary vaccine failure. A postal survey of 103
general practices in a health district to assess vaccine handling and storage
yielded 75 responses (73%). Poor practice was identified in receipt and
storage of vaccines, temperature monitoring and control, management of
vaccines during immunisation sessions, and disposal of partly used vaccines.
The data suggest that the vaccine cold chain is not maintained with the degree
of care necessary for safe practice. National guidelines need to be
implemented conscientiously by all those involved with immunisation programmes
if the effectiveness of vaccines is to be guaranteed.
Loss maternally derived measles immunity in Argentinian
infants.
Nates SV, Giordano MO, Medeot SI, Martinez LC, Baudagna AM, Naretto E,
Garrido P, De Wolff CD.
Instituto de Virologia Dr. J. M. Vanella, Facultad de Ciencias Medicas,
Universidad Nacional de Cordoba, Ciudad Universitaria, Argentina. snates@cmefcm.uncor.edu
BACKGROUND: Measles immunization of children at 1 year of age with a single
dose of the current vaccine has successfully reduced measles incidence in
Argentina. However, the optimal
schedule of measles vaccination of young infants would balance the risk of
early loss of maternal antibody in the majority of infants with the risk of
primary vaccine failure because of passive measles immunity. This study
is the first to document a significant association between loss of passive
measles antibody and age among infants born in 1995 and 1996 in Cordoba City,
Argentina. METHODS: This is a seroprevalence study of 340 infants to
investigate the duration of transplacentally derived measles antibody, assayed
by a neutralization test, during the first 8 months of age in Cordoba City,
Argentina. RESULTS: The proportion with detectable neutralizing measles
antibodies decreased from 85% at 1 month of age to 8% at 8 months of age. The
simple logistic model with age (in weeks) as the only variable showed that the
decline in the proportion of infants with a positive antibody titer was
sharpest during the second and fifth months of age (6.6 and 6.8% per week
during a 4-week period, respectively). CONCLUSIONS: These findings suggest
that 80% of infants are susceptible to measles infection for at least 3 months
before routine immunization at 12 months of age.
Immune response to a new hepatitis B vaccine in healthcare
workers who had not responded to standard vaccine: randomised double blind
dose-response study.
Zuckerman JN, Sabin C, Craig FM, Williams A, Zuckerman AJ.
Academic Unit of Travel Medicine and Vaccines, Royal Free Hospital School of
Medicine, London.
OBJECTIVE: To evaluate the immunogenicity
and reactogenicity
of a new triple S recombinant hepatitis B vaccine in a cohort of healthy
people in whom currently licensed hepatitis B vaccines had persistently not
induced an immune response. DESIGN: Single centre, randomised, double
blind, dose-response study. SETTING: Research vaccine evaluation centre at a
teaching hospital. SUBJECTS: 100 healthcare workers aged 18-70 years with a
history of failure to seroconvert after at least four doses of a licensed
hepatitis B vaccine containing the S component. INTERVENTION: Each subject was
randomly allocated two doses of 5, 10, 20, or 40 micrograms of a new hepatitis
B vaccine two months apart. MAIN OUTCOME MEASURES: Immunogenicity of the four
doses. Seroconversion and seroprotection were defined as an antibody tire > 10
IU/l and > 100 IU/l respectively against an international antibody standard.
RESULTS: 69 subjects seroconverted after a single dose of the vaccine. After
the booster vaccination one other subject seroconverted, bringing the overall
seroconversion rate to 70%. Fifteen subjects given 5 micrograms of vaccine, 19
given 10 micrograms, 16 given 20 micrograms, and 20 given 40 micrograms
seroconverted. Seroconversion rates in the four antigen dose groups were 60%
(15/25), 76% (19/25), 64% (16/25), and 80% (20/25). After the booster dose
there was no significant dose-response effect on the overall seroconversion
rate, although the small sample size meant that a clinically important
dose-response could not be ruled out. CONCLUSION: A single dose of 20
micrograms of the vaccine was as effective as two doses of either 40
micrograms or 20 micrograms of this vaccine formulation in terms of
seroconversion, seroprotection, and geometric mean titres.
Twenty-three-year follow-up study of rubella antibodies
after immunization in a closed population, and serological response to
revaccination.
Asahi T, Ueda K, Hidaka Y, Miyazaki C, Tanaka Y, Nishima S.
Department of Pediatrics, Faculty of Medicine, Kyushu University, Fukuoka,
Japan.
Twenty-six institutionalized children immunized with a Japanese rubella
vaccine, Matsuba strain, have been observed for 23 years and the persistence
of vaccine-induced rubella immunity documented. All vaccinees were shown to
have seroconverted to rubella virus in a haemagglutination inhibition (HI)
test, and the geometric mean titre (GMT) of rubella HI antibody rose to 2 5-8
months after vaccination (Ueda et al., Acta Paediatrica Japonica, Overseas
Edition 1978, 20, 8-14). The GMT then declined gradually to 2 23 years after
inoculation, except in four cases (15.4%) which had reverted to negative.
However, three of the four maintained a rubella HI antibody titre of 1:4.
Twelve of the 26 vaccinees were revaccinated 24 years after primary
vaccination, and all ten cases having initial titres of < or = 1:16
demonstrated secondary responses. Rubella immunity induced by vaccination had
persisted, so routine booster immunization did not seem necessary.
However, a second immunization programme
should be considered to achieve high antibody-positive rates and to protect
against primary vaccine failure.
Evliyaoglu N, Altintas D, Kilic NB, Alhan SE, Onenli N, Guneser S,
Bahcebasi T.
Department of Pediatrics, Cukurova University Faculty of Medicine, Adana.
The incidence of measles has declined in our country since the routine
administration of measles vaccination was initiated. However, measles
outbreaks have been observed even among previously vaccinated children. The
objective of this study was to evaluated the measles antibody response of
children vaccinated at nine months of age. Measles-specific IgG antibodies
were determined by enzyme-linked immunosorbent assay. Of 345 children tested,
20.3 percent were immunologically measles-susceptible. When measles-specific
antibody titers were analyzed with respect to the elapsed time since prior
vaccination, the result was found to be insignificant (p > 0.05).
These data suggest that the
underestimated seropositivity
rate of measles antibody may be related to both primary vaccine failure and
inappropriate vaccination age.
Large outbreak of pertussis among young children in
Chicago, 1993: investigation of potential contributing factors and estimation
of vaccine effectiveness.
Kenyon TA, Izurieta H, Shulman ST, Rosenfeld E, Miller M, Daum R, Strebel
PM.
Communicable Disease Division, Chicago Department of Health, IL, USA.
BACKGROUND: An outbreak of pertussis from July, 1993, to April, 1994, in
Chicago was investigated to identify potential contributing factors. METHODS:
Surveillance was enhanced to identify cases. Information from a vaccination
coverage survey was used to define a retrospective cohort to estimate vaccine
effectiveness of three or more doses of pertussis vaccine. RESULTS: The median
age of 218 reported cases was 8 months, 46% had Hispanic surnames and cases
were clustered geographically. Vaccination status was known for 173 of 191
(91%) children younger than 6 years of age. Of these 173, 90 (52%) were
younger than 7 months, and 35 (20%) children at least 7 months of age had
received fewer than 3 doses of pertussis vaccine. Pertussis vaccine
effectiveness was 76% (95% confidence interval, 29 to 92). CONCLUSIONS:
The limited ability of the current
pertussis
vaccination schedule to protect young infants accounted for 52% of cases,
primary vaccine failure accounted for 28% of cases and failure to vaccinate
children on time accounted for 20% of cases in young children. Low
vaccine effectiveness did not appear to be a contributing factor.
Measles control in the United States: problems of the past
and challenges for the future.
Wood DL, Brunell PA.
Ahmanson Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles,
California 90048, USA.
Elimination of indigenous measles from the United States has been a public
priority since 1978. To assess the progress made toward this goal, we review
the epidemiology of measles from 1963 to the present. From the 1970s through
early into the recent measles epidemic, the majority of measles cases were in
highly vaccinated, school-age children.
This was due primarily to a 1 to 5%
primary measles-mumps-rubella vaccine failure rate and nonrandom mixing
patterns among school-age populations. To eliminate susceptible individuals in
the school-age populations, a second dose of measles vaccine is now
recommended between 5 and 6 years or 11 and 12 years by both the Advisory
Committee on Immunization Practices and the American Academy of Pediatrics.
Later in the epidemic, measles cases surged among unimmunized preschool
children, especially among the poor in inner-city areas. Immunization rates
have been documented to be low among preschool populations because of missed
opportunities to administer vaccines at all health visits and barriers to
access to immunizations. To raise immunization rates, the age for the first
measles-mumps-rubella immunization was lowered to 12 to 15 months of age,
federal immunization funding has increased, and new standards for immunization
delivery have been developed and promulgated.
Division of Field Epidemiology, Centers for Disease Control and Prevention,
Atlanta, Georgia.
From January to July 1991, an outbreak of mumps occurred in Maury County,
Tennessee. At the primarily affected high school, where 98% of students and
all but 1 student with mumps had been vaccinated before the outbreak, 68 mumps
cases occurred among 1116 students (attack rate, 6.1%). Students vaccinated
before 1988 (the first year mumps vaccination was required for school
attendance in Tennessee) may have been at greater risk of mumps than those
vaccinated later (65[6.1%] of 1001 vs. 2[2.2%] of 89; risk ratio, 2.9; 95%
confidence interval, 0.7-11.6). Of 13 persons with confirmed mumps who
underwent serologic testing, 3 lacked IgM antibody in well-timed acute- and
convalescent-phase serum specimens.
Vaccine failure accounted for a sustained mumps outbreak in a highly
vaccinated population. Most mumps cases were attributable to primary vaccine
failure. It is possible that waning vaccine-induced immunity also
played a role.
Risk factors for lack of detectable antibody following
hepatitis B vaccination of Minnesota health care workers.
Wood RC, MacDonald KL, White KE, Hedberg CW, Hanson M, Osterholm MT.
Acute Disease Epidemiology Section, Minnesota Department of Health,
Minneapolis 55440-9441.
OBJECTIVE--To assess the presence of antibody to hepatitis B surface antigen
(anti-HBs) at postvaccination testing in Minnesota health care workers
receiving recombinant hepatitis B vaccines, and to identify risk factors for
lacking anti-HBs following hepatitis B vaccination. DESIGN--Retrospective
cohort study. SETTING--Ten acute care hospitals in Minnesota. PARTICIPANTS--A
total of 595 health care workers who had received hepatitis B vaccine (Recombivax
HB or Engerix-B) between June 1987 and December 1991 and who underwent
postvaccination testing for anti-HBs within 6 months after receiving the third
dose of vaccine. MAIN OUTCOME MEASURE--Presence or absence of anti-HBs
following hepatitis B vaccination. RESULTS--Five variables were independently
associated with lacking anti-HBs by multivariate analysis: vaccine brand,
smoking status, gender, age, and body mass index. Stratifying by vaccine brand
demonstrated that age (P = .01), body mass index (P < .01), and smoking status
(P < .01) were associated with lacking anti-HBs only for Recombivax HB
recipients; and gender (P = .03) was associated with lacking anti-HBs only for
Engerix-B recipients. After controlling for smoking status, age, gender, and
body mass index, recipients of Recombivax HB were more likely to lack anti-HBs
than recipients of Engerix-B (relative risk, 2.3; 95% confidence interval, 1.1
to 4.7; P = .02). CONCLUSIONS--Results
indicate that certain populations of health care workers are at increased risk
of not responding to hepatitis B vaccination. Further studies evaluating
immunogenicity
of currently available recombinant hepatitis B vaccines in persons at high
risk for primary vaccine failure are needed.
Uptake of hepatitis B vaccination amongst West Midlands
radiologists.
Holland P, Hutchinson CE.
X-ray Department, General Hospital, Birmingham.
A postal survey of 150 radiologists within the West Midlands Regional Health
Authority was undertaken to obtain information about hepatitis B vaccination
uptake and its relationship, if any, to their involvement in interventional
radiology. Overall, 64% were vaccinated, the rate being higher amongst
trainees (81%). No significant relationship existed between vaccination and
regular involvement in interventional radiology. Few side effects were
reported by radiologists (11%).
Failure to seroconvert occurred in 3.5%. A telephone survey throughout
the region suggests that many Occupational Health Departments still believe
radiologists are not at risk from hepatitis B and therefore do not warrant,
and are not invited for, vaccination.
[Reappearance of post-vaccination infection of measles,
rubella and mumps. Should adolescents be revaccinated?]
[Article in French]
Malengreau M.
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 cellular basis for
lack of antibody response to hepatitis
B vaccine in humans.
Egea E, Iglesias A, Salazar M, Morimoto C, Kruskall MS, Awdeh Z, Schlossman
SF, Alper CA, Yunis EJ.
Division of Immunogenetics, Dana-Farber Cancer Institute, Boston,
Massachusetts.
We had previously obtained evidence
that among normal subjects the
humoral antibody response to
hepatitis B surface antigen (HBsAg)
was bimodally
distributed with about 14% of subjects producing less than 1,000 estimated
radioimmunoassay RIA
units. From the study of major histocompatibility complex (MHC) markers
in the very poor responders who produced less than 36 estimated RIA units of
antibody, it appeared that there was an excess of homozygotes for two extended
haplotypes [HLA-B8, SC01, DR3] and [HLA-B44, FC31, DR7]. This finding
suggested that a poor response was inherited as a recessive trait requiring
nonresponse genes for HBsAg on both MHC haplotypes and was strengthened by
finding a much lower antibody response among prospectively immunized
homozygotes for [HLA-B8, SC01, DR3] compared with heterozygotes. In the
present study, we have analyzed the cellular basis for nonresponse to this
antigen by examining antigen-specific proliferation of T cells from responders
and nonresponders in the presence and absence of autologous CD8+ (suppressor)
cells. Peripheral blood cells from nonresponders to HBsAg failed to undergo a
proliferative response to recombinant HBsAg in vitro, whereas cells from
responders proliferated vigorously. This failure of cells from nonresponders
to proliferate was not reversed in cell mixtures containing CD4+ and
antigen-presenting cells devoid of CD8+ cells. There was no difference between
responders and nonresponders with respect to the number of circulating T cells
or their subsets, or the proliferative response to mitogens such as pokeweed
or phytohemagglutinin or another antigen, tetanus toxoid. Our results indicate
that our HBsAg nonresponding subjects have a very specific failure in antigen
presentation or the stimulation of T helper cells, or both. Our evidence is
against specific immune suppression as the basis for their nonresponsiveness.
The failure of antigen presentation or T cell help is consistent with
recessive inheritance of nonresponsiveness and suggests that response is
dominantly inherited.
Reported measles immunisation and serological immunity in
children attending general practitioners.
Barrand J, Chapman J, Jeffs DA, Jack I, Wenzel WA, Bridges-Webb C, Levy MH.
Department of Community Medicine, University of Sydney.
To determine the feasibility of serological testing for measles immunity in
children attending general practitioners and to assess the validity of
establishing immune status by reported immunisation history compared with
serology, a cross-sectional descriptive study was conducted in general
practices in the Illawarra area south of Sydney, New South Wales. Participants
were 234 children under 15 years attending general practitioners. 87 per cent
of children were reported to have been immunised against measles, but 46 per
cent of these children were seronegative for measles antibody using an ELISA
test on finger-prick blood. This could not be explained by inaccurate
reporting of immunisation. No causes
other than failure to seroconvert or inadequate specificity of the test on the
blood samples were evident. Failure to seroconvert as a result of inadequate
adherence to cold chain requirements is a possibility that needs further
investigation. The results
further question whether a single vaccination is adequate to achieve the
public health aims of measles
immunisation programs.
Center for Prevention Services, Centers for Disease Control, Atlanta, GA
30333.
Immunization practice in 32 countries in Europe, North America,
Japan, and Australia is reviewed. in most countries, immunization practices
are set by the federal government which sometimes works with the private
sector. Almost all countries routinely immunize against diphtheria, tetanus,
whooping cough, polio, and measles. About half try to prevent rubella, several
try to prevent mumps, usually in combination with measles and rubella (MMR).
More than half use bacillus Calmette-Guerin (BGG) vaccine to prevent
tuberculosis, and a few give Hemophilus Influenza type B polysaccharide.
Poliomyelitis vaccine comes in 2 forms: 1) oral live attenuated (OPV) or
injectable inactivated (IPV). OPV is more used, but there is a new "enhanced
potency IPV." All countries except Japan give DPT in 3 doses during the 1st
year of life. OPV is usually given at the same time that DPT is. Measles
vaccine or MMR is usually given between 12 and 18 months of age.
Primary vaccine failure occurs in 2-5% of people who get measles vaccine, but
this may be enough to "sustain transmission." In most countries, the
government provides for immunizing children. An exception in the US. In the
UK, low coverage has taken place because of concern for adverse reactions
(whooping cough) or lack of appreciation of the disease's impact (measles).
Coverage against both measles and pertussis has improved in the UK lately. In
each developed country, vaccines have had "spectacular" effects. However,
there are too many contraindications and there is "undue fear of adverse
events." Also, there are surveillance deficiencies, a lack of coordination,
and countries vary in their commitment to "reduction/elimination targets."
Varicella vaccine, respiratory syncytial virus vaccine, and rotavirus vaccine
are being considered for universal use. Attempts are being made to improve the
safety of some vaccine.
The role of secondary vaccine failures in measles
outbreaks.
Mathias RG, Meekison WG, Arcand TA, Schechter MT.
Department of Health Care and Epidemiology, University of British Columbia,
Vancouver.
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.
Separating the factors in measles vaccine failure.
Ekunwe EO.
Three possible reasons for failure of measles vaccine were identified as
follows: (a) circulating maternal antibodies, (b) administration of non-viable
vaccine, and (c) misdiagnosis. A study designed to test the role played by
each of these in the high measles vaccine failure rate was carried out at the
Oguntolu Street Clinic, Lagos, from October 1982 to February 1983.
Failure to seroconvert was the cause
of 67.7% of measles vaccine failure, particularly at ages 6-7 months, though
this was not associated with high prevaccinationtitres.
In 32.3% incorrect diagnosis was responsible. Non-viable vaccine was
found not to be a reason because all vials of measles vaccine were potent at
the time of administration.
Rubella, measles and mumps antibodies following vaccination
of children. A potential rubella problem.
Balfour HH Jr, Amren DP.
One hundred sixty-eight children immunized by one suburban Minneapolis clinic
during routine pediatric visits had serum antibodies measured to determine the
efficacy of rubella (HPV77 DE5 strain), measles (Edmonston B and Moraten
strains), and mumps (Jeryl Lynn strain) vaccines.
Serologic failure rates at the mean
postvaccination
times tested were as follows: rubella, 36% (4.7 years); measles, 18% (6.5
years); and mumps, 9% (4.5 years). Antibody titers shortly after vaccination
were not done, so seronegative
subjects may never have responded or their titers may have declined with time;
our rubella data suggest the former. Children vaccinated with rubella
and measles at less than 14 months of age had higher failure rates than those
vaccinated at a later age. This supports postponement of rubella and measles
vaccinations until at least 15 months of age. In addition to current measles
reimmunization policies, consideration also should be given to reimmunizing
girls who were given rubella vaccine at less than 14 months of age.
Twenty-four percent (19/79) of
children vaccinated with HPV77 DE5 strain rubella at 14 months or older had
rubella hemagglutination-inhibiting
titers less than 8. This is disturbing and, if confirmed by others,
would prompt the use of a different strain of rubella vaccine for routine
immunization.
The response to oral poliovaccine in persons aged 16-18
years.
Smith JW, Lee JA, Fletcher WB, Morris CA, Parker DA, Yetts R, Magrathe DI,
Perkins FT.
Serum neutralizing antibodies to polioviruses were titrated in serum samples
from 182 police cadets aged 16-18 years before and, in 168 of the cadets, 6
weeks after vaccination with a single dose of oral polio vaccine (OPV). Faecal
excretion of poliovirus was also followed. Vaccination histories were obtained
and confirmed whenever possible. Pre-vaccination antibody could not be
detected against type 1 in 9-3% cadets, against type 2 in 2-7% and against
type 3 in 7-7%. Absence of antibody to at least one virus type was found in
14-3% of the cadets. In 93 cadets in whom vaccination histories could be
confirmed 40 had received only inactivated polio vaccine (IPV) previously; of
these 23% lacked antibody to at least one virus type, and they had less
intestinal immunity to a challenge dose of OPV than those previously given OPV.
Only two of the cadets known to have had OPV were non-immune - both had
received a single dose following full courses of IPV. However, cadets who had
received OPV had their last dose of vaccine more recently (average 4-6 years)
than those who had received only IPV (all 12 years or more). The serum
antibody response to a single booster dose of OPV, and the faecal excretion of
each type of virus after vaccination, showed an inverse relation to the
corresponding pre-vaccination antibody concentration. A single dose of OPV did
not reliably boost the immunity of those who possessed adequate immunity, and
a failure to respond was also observed
in a proportion of the cadets with no detectable antibody, mostly in the case
of type 3 antibody and particularly if antibody to types 1 or 2 virus was also
absent. No evidence was obtained that intestinal immunity could be
expected in the absence of detectable circulating antibody. The reasons for
the absence of a serological response to OPV in some subjects are discussed
and consideration is given to the practical significance of the findings. It
is suggested that reinforcement of polio immunity at school-leaving is
important, particularly at the present time when many of those aged 16-18
years will have been vaccinated only with IPV. A single dose of OPV is not
ideal for this purpose, not only because a small proportion of persons are
liable to be left unprotected, but also because failure to produce a reliable
boost in persons with adequate immunity at the time of vaccination gives rise
to the possibility that they may become susceptible later in adult life.
DISCLAIMER: All
information, data, and material contained, presented, or provided here is for
general information purposes only and is not to be construed as reflecting the
knowledge or opinions of the publisher, and is not to be construed or intended
as providing medical or legal advice. The decision whether or not to vaccinate
is an important and complex issue and should be made by you, and you alone, in
consultation with your health care provider.
