of Vaccine-Preventable Diseases Broadcast
Questions & Answers
Questions submitted during the
Surveillance of Vaccine-Preventable Diseases broadcast of December
8 , 2005
HPV a reportable disease? What methods will be used to evaluate
HPV vaccine effectiveness?
HPV is not reportable to the National Notifiable Diseases Surveillance
System (NNDSS). Discussions and plans for post licensure surveillance
and studies are underway to evaluate the roles of monitoring
HPV infections, genital warts, and cervical cancer precursors
to monitor effectiveness of HPV vaccine.
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will Tamiflu be available to take along for those who travel
in areas where there is avian influenza?
a result of increased demand for Tamiflu, Roche has decided
to proactively manage the Tamiflu inventory. Their top priority
is to ensure that the product will be available to patients
who are diagnosed with influenza, as well as those in need of
post-exposure treatment or prevention from seasonal influenza.
Therefore, Roche has temporarily suspending shipment of Tamiflu
until an increased incidence of seasonal flu is established,
as tracked by FluStar.com. Roche will then distribute product
to ensure that Tamiflu is available in the areas where flu emerges
to meet the seasonal demand.
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rubella and measles have been eradicated in the US, is it still
necessary to test for immunity and vaccinate non-immune health
When measles virus is introduced into a community, persons who
work in healthcare facilities are at greater risk for acquiring
measles than the general population (CDC. Measles, mumps and
rubella – vaccine use and strategies for elimination of
measles, rubella and congenital rubella syndrome and control
of mumps: recommendations of the Advisory Committee on Immunization
Practices (ACIP). MMWR 1998; 47 (No. RR-8):13 or http://www.cdc.gov/mmwr/PDF/rr/rr4708.pdf
Vaccination is still the best way to prevent rubella and measles
in the US. Even though there is no sustained transmission of
either measles or rubella in the US, there is always the risk
of an imported case. This would occur if a traveler from a country
where one or both of these diseases circulates visited the US
country in Latin America does not include rubella vaccine in
their national program? Does Latin America use trivalent (MMR)
or monovalent rubella vaccine?
is the one country in Latin America that does not include rubella
vaccine in their national program. This question was answered
incorrectly on the air during the satellite broadcast: instead
of the Dominican Republic, the correct answer is Haiti. Most
countries use MR (measles and rubella) though a few use MMR.
new hires are screened for rubella, how far back should they
assess rubella vaccination history?
Rubella vaccination should also be assessed back to
childhood. Clinical diagnosis of rubella is unreliable and should
not be considered in assessing immune status. Persons generally
can be considered immune to rubella if they have documentation
of vaccination with at least one dose of MMR or other live rubella-containing
vaccine administered on or after their first birthday, have
serologic evidence of rubella immunity, or were born before
1957 (except for women of childbearing age). Birth before 1957
is not acceptable evidence of immunity for women who might become
pregnant. (Pink Book, p. 153 http://www.cdc.gov/nip/publications/pink/rubella.pdf)
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the CDC Surveillance Manual the clinical case definition is
described as a cough for 2 wks, but I heard today that Dr Moran
case definition in the Surveillance Manual gives the correct
number of weeks of cough - two. When I mentioned one week of
cough I was not speaking of the case definition, I was talking
about when the diagnosis of pertussis should be suspected. Here
is what I said: "The diagnosis of pertussis should be suspected
in a person who develops a cough illness that lasts more than
7 days, or if the person has fits, or paroxysms of coughing."
long will the PCR remain to be positive in the treated and the
the length of time a PCR might remain positive after treatment,
you might want to refer to "Detection of Bordetella pertussis
by polymerase chain reaction and culture in the nasopharynx
of erythromycin-treated infants with pertussis" published
by Edelman K, Nikkari S, Ruuskanen O, He Q, Viljanen M, Mertsola
J. in the Pediatric Infectious Diseases Journal in
1996 Jan;15:54-7. Here is the abstract:
BACKGROUND: Pertussis is a highly contagious
respiratory disease and the most serious effects occur in young
infants. Recently it has been shown that rapid and highly specific
PCR can be a useful diagnostic tool for detection of pertussis
infection. To our knowledge there are no previous studies concerning
the disappearance of Bordetella pertussis DNA from the nasopharynx
during antimicrobial treatment. METHODS: We studied prospectively
how rapidly live B. pertussis organisms and DNA of these bacteria
disappear from the nasopharynx during erythromycin therapy in
unvaccinated infants. Eighty-five nasopharyngeal swabs obtained
from nine erythromycin-treated infants with pertussis on consecutive
days during hospitalization were tested by PCR and culture.
The PCR products were further analyzed by Southern hybridization.
RESULTS: On the fourth day of treatment 56% of the samples were
positive by culture and 89% by PCR, whereas after 7 days the
rates were 0 and 56%, respectively. In seven of nine patients
PCR remained positive for 1 to 7 days longer than culture. The
follow-up study also showed the semiquantitative nature of the
PCR assay. The intensity of the PCR products in agarose gel
usually weakened with time during erythromycin therapy. CONCLUSIONS:
The results of this study show that PCR assay can achieve the
specific diagnosis of pertussis infection in a large proportion
of infants even when antimicrobial treatment has killed the
organisms and culture is no longer positive. This is just a
study of unvaccinated infants but clearly the DNA can be found
days after the bacteria have been killed.
As for the length of time after cough onset that PCR remains
positive in vaccinated persons, you might be interested in "Diagnosing
Pertussis: The Role of Polymerase Chain Reaction" published
by Ellen Bamberger MD, Nitza Lahat PhD, Vladimir Gershtein PhD,
Rosa Gershtein PhD, Daniel Benilevi MD, Sara Shapiro PhD, Imad
Kassis MD, Lisa Rubin MPH, MD and Isaac Srugo MD in the Israel
Medical Association Journal 2005;7:351–354. The analysis
is a bit complicated but they report that "Cough duration
was also a statistically significant clinical marker of infection
in the pre-vaccinated group (OR 0.52, P < 0.05), indicating
that for each additional week of cough duration the likelihood
of infection declines by over 50%. A decomposition analysis
indicated that sensitivity is greatest with cough duration of
1 week or less (41.3% with a positive PCR), declining as duration
increases and eventually leveling out at 13.04% with a positive
PCR at 2–3 weeks." I would say that in most cases
it is probably no longer worth testing by PCR more than 2-3
weeks after cough onset.
comment on current prophylaxis recommendations for contacts
to pertussis cases.
You can access recommendations for pertussis
outbreaks at http://www.cdc.gov/nip/publications/pertussis/guide.htm.
For specific antibiotic regimens, see http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5414a1.htm.
has a recent influx of pertussis reports with practitioner recommending
post exposure prophylaxis based on pertussis serological testing.
What information can be used to give practitioner the best testing
Pertussis culture is considered the gold standard lab test,
but the organism is difficult to culture and many laboratories
no longer have personnel with sufficient expertise in the process.
Culture is affected by specimen collection, transport, and isolation
techniques. Isolation rates are highest in the first 3—4
weeks of illness (catarrhal and early paroxysmal stages). Cultures
are less likely to be positive in immunized individuals, later
in illness, and in individuals who have received antibiotics.
Cultures are variably positive (30-50%) and often give results
too late for clinical usefulness. Since adolescents and adults
have often been coughing for several weeks before they go to
the doctor, it is often too late. Success of culture declines
after 2 weeks of cough illness, antibiotic treatment, and vaccination.
Cultures can be negative with even one dose of antibiotic.
Due to perceived increased sensitivity and faster reporting,
DNA amplification [e.g., polymerase chain reaction (PCR)], many
laboratories have abandoned culture and started pertussis testing
by PCR. No FDA-licensed product is available and there are no
nationally recognized standardized protocols, reagents, or reporting
formats for pertussis PCR testing. Specificity can be poor with
high rates of false positives in some laboratories. Exclusive
reliance on non-standardized PCR tests resulted in overdiagnosis
in several recent large outbreaks. Overdiagnosis had important
public health consequences including unnecessary treatment of
PCR false-positive individuals and inappropriate chemoprophylaxis
of contacts, with adverse events from unwarranted antibiotic
therapy in both. PCR is also affected by specimen collection.
A poorly taken NP swab will likely be negative in both culture
and PCR. PCR is less affected by prior antibiotic therapy, but
this is a relative thing and PCR will be negative--it just takes
a little longer (and that time depends on the initial bacterial
load, the person's immune status, and the antibiotic treatment).
Previous vaccination results in some degree of immunity, which
results in a lower bacterial load, which can ultimately affect
the PCR test. Specificity can be a problem with PCR---there
are lots of reasons for false positive PCR tests.
Serologic testing could be useful in adults and adolescents.
However, there is no FDA licensed serology test. The current
serologic tests were developed for use in vaccine trials and
thus measure antibody response to vaccine antigens. So a positive
serology simply means that the person has been exposed to pertussis
(by infection or by vaccination). There are several papers that
have looked at establishing a high cut-off value above which
is suggestive of recent infection (within the last 2 years).
However, the assays that are available commercially do not differentiate
infection from vaccination. They simply show that the person
has no detectable antibody to pertussis or has detectable antibody.
These commercial assays cannot be used to determine whether
this reflects recent infection, past infection, or past vaccination.
CDC is working with the FDA to develop a serologic assay with
a cut-off that is suggestive of recent infection. Of course,
any assay with such a cut-off will misclassify a certain percentage
of individuals incorrectly (both ways). The MA DOH does have
a serology test that can be used in people >11 years old
(to eliminate some of the problems from recent vaccination).
They validated this assay with culture and established a cut-off
level that is 63% sensitive and 99% specific. The CDC/FDA assay
will be somewhat similar to the MA assay. We are looking to
develop a serologic assay that can be used by the state health
departments. We are also working with other investigators to
look at other serologic assays that would use pertussis antigens
not found in the vaccine. Obviously that is going to take a
longer amount of time to get such an assay to the point where
it could be used in the diagnostic lab.
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a child received 4 doses of IPV, all 4 weeks or more apart,
the last dose coming at 28 months (of age?), does the child
need a dose after 4 years of age?
Yes, a dose
should be administered on or after the 4th birthday to boost
antibody titers to high levels for long-lasting protection.
An extra dose before 4 years of age does not eliminate the need
for the 4-6 year old dose.
"All children should receive four doses of IPV at ages
2, 4, and 6-18 months and 4-6 years. The first and second doses
of IPV are necessary to induce a primary immune response, and
the third and fourth doses ensure 'boosting' of antibody titers
to high levels.. . . All children who have received three doses
of IPV before age 4 years should receive a fourth dose before
or at school entry. The fourth dose is not needed if the third
dose is administered on or after the fourth birthday."
(CDC. MMWR Recommendation & Report on "Poliomyelitis
Prevention in the United States: Updated Recommendations of
the Advisory Committee on Immunization Practices," published
May 19, 2000.)
preferred interval between the second and third doses of IPV
is 2-8 months. However, if accelerated protection is needed,
the minimum interval between doses of IPV is 4 weeks. Children
who receive three doses of IPV before the fourth birthday should
receive a fourth dose before or at school entry. (CDC. Epidemiology
and Prevention of Vaccine-Preventable Diseases. Atkinson
W, Hamborsky J, Wolfe S, eds. 8th ed. Washington DC: Public
Health Foundation, 2004. p. 95). Pink Book: http://www.cdc.gov/nip/publications/pink/polio.pdf.
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the many cases of varicella we still see and hear about, won’t
individual case-reporting of varicella take up a lot of time
and resources for local health departments?
it definitely can, and it can take up a lot of time for the
people who will report the cases to the health department as
well. There are two key ways to decrease the impact of implementing
case-based varicella surveillance. First, instead of collecting
all of the data on the varicella worksheet, jurisdictions that
are beginning surveillance programs may initially report three
key variables on each reported case: age, varicella vaccination
history, and severity of disease. These data will allow the
states and CDC to assess the impact of vaccination on disease
reduction in specific age groups and possible shifts in varicella
incidence to older persons as well as appropriate targeting
of vaccination programs by age; evaluate the proportion of all
cases that are vaccinated (or have breakthrough disease), and
better understand vaccine effectiveness; and assess severity
of remaining disease, and how vaccination may alter severity.
As it becomes more feasible, states should consider incorporating
additional variables into surveillance, for example, data on
source patients, and laboratory information on cases. Another
way to decrease the resources needed for varicella surveillance
is that instead of implementing state-wide surveillance, the
state may choose to implement sentinel-site surveillance. Sentinel-site
surveillance allows the state to choose either representative
reporting sites throughout the state, or select counties within
the state, or some combination. Sites can then be monitored
across time so that the state can assess trends. (Letter sent
to all state and territorial Immunization Program Managers from
CDC, September 2004)
4 year old female had chickenpox vaccine at 12 months of age
and now has a breakthrough rash with 15 maculopapulovesicular
lesions and 3 vesicular lesions after exposure to wild type
virus. What is your recommendation for her 11 ½ month-old
sibling who was exposed to her rash in the last 2 days but experienced
a fever of 102°F last evening.
the fever could be unrelated to varicella, if both the 11½
month-old and the 4 year old children were exposed to the same
case at the same time, then the 11½ month-old may also
have wild type varicella virus from that exposure. The incubation
period for varicella is at least 10 days, so it is unlikely
that the infant would have a rash from exposure to the 4 year-old
if the 4 year-old child began having rash one day before the
11½ month-old developed fever. The parents should continue
to monitor the child and consult a physician as needed. Meanwhile,
both children should be isolated and kept away from other susceptible
information related to shingles (incidence of disease and/or
death) included in the varicella data? Have there been any studies
to look at the changes in the incidence of shingles since the
recommendation for varicella immunization was implemented? Is
varicella data referred to in the presentation includes only
acute varicella cases. Yes, there have been several post licensure
studies that have looked at the effect of varicella vaccine
on zoster; however, there is not a clear conclusion on the overall
impact of varicella on zoster incidence. Some studies seem to
indicate that zoster incidence is unchanged, and others seem
to show a gradual increase over time. The problem with each
of these studies is that there are little data that show the
incidence of zoster prior to licensure of the vaccine, so there
are limited baseline data from which to measure or compare current
trends. Herpes zoster rates among persons (children) who received
varicella vaccine are lower than the herpes zoster rates in
children who were not vaccinated but had varicella. This is
also true among children with immune compromising conditions,
such as leukemia.
Jumaan AO, Jackson LA, Bohlke K, Galil K, Seward JF. Incidence
of herpes zoster, before and after varicella-vaccination –
associated decreases in the incidence of varicella, 1992-2002.
J Infect Dis 2005;191:1999-2001
WK, Brooks DR, Lett SM, Jumaan AO, Zhang Z, Clements KM, Seward
JF. The incidence of varicella and herpes zoster in Massachusetts
as measured by the Behavioral Risk Factor Surveillance System
(BRFSS) during a period of increasing varicella vaccine coverage.
BMC Public Health 2005;5:68
A new herpes zoster vaccine (ZOSTAVAX) may be available by 2006
to prevent herpes zoster and its main complication, post herpetic
neuralgia (PHN). (Oman MN, Levin MJ, Johnson GR, Schmader KE,
et al. A vaccine to prevent herpes zoster and postherpetic neuralgia
in older adults. N Engl J Med 2005; 352:2271-84).
Zoster is not currently a nationally notifiable disease reportable
through NNDSS. There has been some discussion with the Council
of State and Territorial Epidemiologists (CSTE) since 1995 about
making it reportable.
new-hires are screened for varicella, how far back should vaccination
status be assessed?
and disease history for varicella should be assessed back to
childhood since most vaccines and vaccine-preventable diseases
occur in childhood. If there is a question on whether a person
had varicella or the vaccination, that person can either have
serologic testing for immunity, or receive the 2-dose vaccination
series. (Pink Book, 2004 p.158)