Closed captioning script for CDC *Surveillance of Vaccine-Preventable
Diseases* videotape

GOOD:

Welcome to Surveillance of Vaccine Preventable Diseases. We are coming
to you live from the Centers for Disease Control and Prevention in
Atlanta, Georgia. I am Cynthia Good, and I will be your host for this
program. During this program, we will discuss the principles and
practice of surveillance of vaccine preventable diseases in the United
States. We hope the information in this program will make your job of
investigation and reporting a little easier.

Surveillance is a key element of public health. With most vaccine
preventable diseases at an all time low in the United States,
surveillance of these diseases has become even more critical.
Introduction of new vaccines into the childhood, adolescent, and adult
immunization schedules means new challenges in surveillance as well.
That is why we are presenting this information today. We will begin with
a discussion of some of the **basic principles of disease surveillance,
case investigation, and reporting**. Our discussion of disease- specific
surveillance issues will be divided into two parts. During the first
section we will discuss issues related to the **investigation and
reporting of viral vaccine preventable diseases** -- **varicella,**
**measles, mumps, rubella, influenza, hepatitis A, and hepatitis B**.
Influenza will be discussed in the second part of the program, after the
break. Following this we will discuss the **investigation and reporting
of bacterial vaccine- preventable diseases** -- **pertussis**,
**Haemophilus influenza type b, invasive pneumococcal disease, and
Neisseria meningitidis**. Due to time constraints we will not discuss
the surveillance of polio, diphtheria or tetanus. Finally, we will
discuss **surveillance of adverse events following vaccination**, and
the very important issue of **surveillance indicators**.

We have two instructors for this part of today's program. Dr. Jane
Seward is the Chief of the Viral Vaccine Preventable Diseases Branch in
the National Immunization Program. Dr. William Atkinson is a Medical
Epidemiologist in the Immunization Services Division of the National
Immunization Program.

Now let's look at today's objectives. After this session, we hope you
will be able to do these things and much more: **identify 3 main levels
of the national surveillance system for vaccine-preventable diseases**;
**Locate the case definitions for nationally notifiable diseases**;
**List the critical information to collect for each reported case of the
disease**; and.**Describe the concept of surveillance indicators**. Our
program will begin with a discussion of the basic principles of disease
surveillance and case investigation, right after this pause.

ATKINSON:

Today's first topic is an overview of surveillance. Many of the
principles of surveillance, case investigation, and reporting are common
to almost all the diseases we will discuss today. So this is a good
place to begin. First, let me mention that the most recent edition of
the surveillance manual is the third edition, published in 2002. In
addition to being a good reference, it is also the primary text for this
course. We no longer print the manual, but it can be downloaded from the
National Immunization Program website. We will put a link to it on our
broadcast resources website. The chapters on specific vaccine
preventable diseases are arranged in alphabetical order, starting with
diphtheria, and continuing through varicella. If you have a copy of the
manual it should be easy for you to follow along with us.

As a result of effective immunization programs, diseases that once were
major causes of death and morbidity among children in this country now
occur so infrequently that many of us have never seen a case. Our
challenge now is to identify the factors that allow the remaining cases
to occur. We also want to extend our success with the elimination of
measles, rubella, and polio to other diseases that occur more commonly,
like pertussis, hepatitis A, and varicella.

We do case investigations to help us figure out if we need to take
public health action. If action is needed, exactly what do we need to
do? At the local level, we need surveillance information rapidly so we
can start **disease control activities**. This might mean providing
antibiotic prophylaxis for contacts of pertussis cases, or vaccinating
susceptible persons when outbreaks occur.

For each vaccine preventable disease, there are specific critical data
that must be collected in order to plan and implement appropriate public
health action.

For each case, we need demographic and relevant **clinical data,
vaccination history, and laboratory test results**. This is the
information needed to classify cases, and it is critical in the
evaluation of cases of vaccine-preventable diseases.

In addition to gathering information about the case, You need to try to
identify the people that the case may have passed the infection TO. And
you need to identify the person the case got the infection FROM. You
need to find out whether the case is linked to an outbreak, or is an
isolated, sporadic case. Just because no other cases have been reported,
you cannot assume that no other cases have occurred.

At the state level, we need surveillance data on vaccine preventable
diseases to **evaluate the effectiveness of disease control programs**.
When there is a case of a vaccine-preventable disease in someone for
whom there is a vaccination recommendation, it should serve as a warning
to public health officials. There may be other susceptible individuals
who should have been vaccinated, but were not. Or there may have been
waning immunity in a vaccinated individual. You need to find out
**whether the person was vaccinated**, and **if not, WHY not**? Were
there **missed opportunities** to vaccinate? Is there **a more
widespread problem**? In addition to the evaluation of disease control
programs, states have other needs for surveillance data. Surveillance
data are also needed to **formulate and evaluate immunization policy**.
At the national level, we use surveillance data to **formulate national
immunization policy** and to **evaluate the effectiveness of
immunization programs**. We also rely on surveillance data to **evaluate
the effectiveness of the vaccines** themselves, and to **document the
impact of national immunization efforts**. This is especially important
with new vaccines, such the meningococcal conjugate vaccine, and
tetanus, diphtheria, and pertussis vaccine -- or TDAP- for adolescents
and adults. New vaccine schedules also require careful surveillance and
evaluation. An example of this is the recent recommendation for
influenza vaccination of 6 to 23 month old children. What we need from
our surveillance system depends on where we are in our disease control
program. What we need early in the program or when there are large
numbers of cases is quite different than what we need when the program
is very far along with few cases. Of course, we need to ensure adequate
surveillance for vaccine adverse events for any vaccine currently in
use, regardless of the stage of disease control. We will talk about this
part of surveillance later in the program. Before we have a vaccine for
routine use, the information we need is pretty simple. We need to have a
**baseline of reported disease**. **Complete reporting is not
essential**, but we do need **year to year consistency**. e need
national data to represent the epidemiology of the disease prior to the
availability of a vaccine. But during this phase, **aggregate
reporting** of case counts is usually sufficient. When a new vaccine is
recommended for routine use and disease remains common, our goal shifts
to monitoring the impact of the national vaccination efforts. At this
point, aggregate reporting of case counts is still sufficient. When we
have extremely good disease control, as we have now with Haemophilus
influenzae type b, we need **enhanced surveillance** so we can
**document vaccine impact, evaluate effectiveness, and monitor progress
toward disease elimination**. We can use this information to figure out
why the cases that remain continue to occur. With good disease control,
we need detailed information from **individual case investigations**,
including **vaccination status and laboratory confirmation**. We also
need **highly specific case definitions**, because we really want to
make sure that the cases we are counting are real cases of the disease.
This is the phase when every case counts. When disease incidence is very
low and we are striving for elimination, the completeness of reporting
and the quality of individual case investigations are very important. At
this point, the organism may no longer even be circulating, and we can
use molecular typing methods to help document that, as you will hear
later in this program.

So in summary, surveillance activities must be designed to fit the
public health need. We need baseline data for newly vaccine- preventable
diseases. But we need detailed, individual case investigations when we
have achieved higher levels of disease control through vaccination
programs.

GOOD:

Thanks, Bill. We will begin with varicella in just a moment.

SEWARD:

Varicella, or chickenpox, is a common, highly infectious disease. It has
been vaccine preventable since 1995. Before varicella vaccine was
licensed in the United States, about 4 million cases of varicella
occurred each year, with more than 11 thousand varicella related
hospitalizations, and about 100 to 150 deaths.

The good news is that vaccination coverage among children is rising
steadily and fewer cases of chickenpox are being reported. As the number
of cases decreases, the need for more complete surveillance increases.
Currently, most of the detailed information about the change in
varicella epidemiology, including reduced disease incidence, comes from
active surveillance sites. In 1995, the National Immunization Program
and state and local health departments initiated active surveillance for
varicella in three areas of the country- Antelope Valley in southern
California, Travis County, Texas, and West Philadelphia, Pennsylvania.
Since 2000, two of these sites, Antelope Valley and West Philadelphia,
have been funded to continue active surveillance. These two active
surveillance areas have a **combined population of about 650,000 and an
annual birth cohort of about 8300**. **Vaccination coverage** in the
active sites has risen from **40% in 1997 to 89 and 90% in 2004**. This
is a little higher than the 88% coverage for varicella vaccine estimated
by the National Immunization Survey for all U.S. children 19 to 35
months of age. This graph shows data from the Antelope Valley active
surveillance site. The vertical axis shows the number of varicella cases
by month since January 1995. From 1995 to 2004, the number of varicella
cases declined by 83%. During this time vaccine coverage rose from 40%
in 1997 to 90% in 2004. Note that in 2004, at the far right of the
graph, the number of cases increased by 53% from 2003. Also notice the
typical seasonal variation that was very apparent from 1995 through
1998. Starting in 1999 and 2000, as the number of cases identified
through active surveillance dropped significantly, the seasonal pattern
has become much less apparent. The same general pattern has been seen in
West Philadelphia. However, in this site from 1995 to 2004, the number
of cases declined steadily from year to year. By 2004 cases had declined
by 93%. Vaccine coverage rose to 89%. Seasonal variation is also much
less apparent. Reduction in varicella incidence has been observed in all
age groups in both of the active surveillance sites. The greatest
reduction was in those 1 to 4 and 5 to 9 years of age, the age groups
primarily targeted by the vaccination program. But incidence has also
declined among infants, adolescents, and adults. In addition, the number
of outbreaks, the number of school days missed due to varicella, and the
number and rates of hospitalization have fallen in both active
surveillance sites.

This overall reduction in varicella since the availability of the
vaccine is not unique to the active surveillance sites. Among the states
that have consistently reported cases through the national notifiable
disease surveillance system -- NNDSS- there has also been a significant
reduction in cases compared to the pre-vaccine era.

The epidemiology of varicella has changed in the 10 years since vaccine
licensure. In recent years the **number of varicella cases has leveled
off**. Although vaccine effectiveness has been in the expected range of
80 to 85%, **outbreaks have been reported in highly vaccinated school
populations**. This raises the issue of whether a second dose of
varicella vaccine is needed routinely for children. As anticipated, the
**proportion of cases among vaccinated persons is increasing** and the
**median age of patients is shifting towards adolescence.** So it is now
increasingly important to ensure that older children, adolescents, and
adults are vaccinated.

We expect a shift in age to older children, adolescents, and adults with
the implementation of a childhood vaccination program. It is important
to track incidence of disease by age as well as proportions. As
mentioned previously, varicella incidence among adolescence and adults
is declining. Bill?

ATKINSON:

In 2002, the Council of State and Territorial Epidemiologists, or CSTE,
recommended that varicella be included in the National Notifiable
Diseases Surveillance System. States were encouraged to conduct ongoing
varicella surveillance to monitor vaccine impact on morbidity. CSTE
specifically recommended that states establish individual case-based
reporting systems for varicella surveillance by 2005. However, other
forms of surveillance such as case-based reporting in sentinel sites
were considered to be reasonable interim steps toward statewide case
reporting. As of November 2005, 19 states have implemented individual
case reporting. Connecticut was one of the first states to implement
this. Earlier this year we prepared a short video that described
Connecticut's experience with varicella case based reporting. We will
not have time during this program to show the video. But it will be
available on the broadcast resources webpage. Please have a look at it.
Aggregate reporting of case numbers provides some information regarding
the vaccination program. In contrast, case-based reporting yields data
that will allow a state to assess the epidemiology of varicella by age,
through time, and by disease severity. It will provide more complete
data to guide future immunization policy. As a result, NATIONAL case-
based varicella surveillance is needed. It is needed to continue
monitoring the impact of the varicella vaccination program on disease
incidence, morbidity and mortality, and to guide future immunization
policy. There are two options available for case-based varicella
surveillance. First, **varicella may be reported statewide**, where all
sites that currently report notifiable diseases add varicella to their
reporting list. If statewide surveillance is not yet feasible,
**sentinel site surveillance** can be used in the short term. To
implement this type of surveillance, states can identify sentinel sites
to report individual information on cases. Sites can be **located
throughout the state or in select jurisdictions**. They might include
schools, child care centers, physicians' offices, hospitals, colleges,
and other institutions. Statewide or local school nurse associations and
managed care networks may provide case-based reporting in some states.
States may consider requesting reports from sites that already
participate in other surveillance networks. States can expand their
number of sites as they develop their system with the intention of
having statewide surveillance within several years. In addition to core
demographic and clinical data, 3 key pieces of information should be
collected for each varicella case investigation: the age of the person,
the vaccination history, and the severity of disease. Data on the
**age** of the patient **allows states to monitor the impact of
vaccination on disease reduction in specific age groups** and to
**identify any shift in disease to older persons**. **Vaccination
history** allows **determination of the proportion of all cases that are
vaccinated** and **allows assessment of crude vaccine effectiveness,**
provided there is information on vaccine coverage in the population or
age group. Monitoring **disease severity** allows **assessment of the
severity of varicella in vaccinated cases**, indicating possible waning
immunity of the vaccine. This information along with vaccination history
can also be used to **monitor vaccine effectiveness against all disease
and against severe disease**. A **varicella case**, according to the
definition established in 1999, is an **illness with acute onset of a
diffuse, generalized maculopapulovesicular rash without other apparent
cause**. **Breakthrough disease** is **varicella that occurs in a
vaccinated person more than 42 days after vaccination.** Breakthrough
disease occurs in about 20% of vaccinated persons who are exposed to
varicella. In about 70 to 80% of breakthrough cases, disease is mild
with fewer than 50 lesions and has a shorter duration of illness. The
rash may also be atypical in appearance -- maculopapular with few or no
vesicles. Because of the increasing likelihood of atypical rash,
laboratory testing, whenever possible, or epidemiological linkage to a
typical case or laboratory-confirmed case will eventually be needed to
confirm -- or rule out -- varicella. **Laboratory confirmation of
varicella**, both in vaccinated and unvaccinated persons, includes
**direct antigen detection** methods; **isolation of the virus from a
clinical specimen** through virus culture; a **significant rise in serum
varicella immunoglobulin G- or IgG- antibody level;** or a **positive
varicella immunoglobulin M- or IgM- antibody** test result using capture
IgM method. Since the varicella IgM test is not yet widely available,
and because the kinetics of the IgM response in varicella infection are
poorly understood, IgM testing is currently NOT the preferred method for
laboratory confirmation.

Material from vesicular or papular skin lesions, and scabs are a readily
available clinical specimen. Polymerase chain reaction, or PCR, a direct
antigen detection method, is the recommended test for confirmation of
varicella. Direct fluorescent antibody, or DFA, is another direct
antigen detection method. State public health laboratories now have the
capacity to diagnose varicella infection either by PCR or DFA assays.
Jane?

SEWARD:

Case-based varicella surveillance will allow us to monitor the impact of
the varicella vaccination program on disease incidence, morbidity, and
mortality. Systematic national case-based varicella surveillance will
allow us to evaluate the effectiveness of our vaccination program and
policies. It is possible that in the future we will need to use the
varicella vaccine differently than we now use it. For example, a second
dose of varicella vaccine is being considered for routine immunization.
Case-based reporting will also allow for implementation of control
measures for varicella outbreaks. Because varicella vaccine coverage is
high, disease incidence has been reduced, as noted in areas from which
we have surveillance data. As a result, public health action is now
warranted in response to varicella outbreaks. The investigation of
varicella outbreaks will help determine whether the outbreak is a result
of vaccine failure or failure to vaccinate. However, what is reasonable
to do will of course vary based on the circumstances of the outbreak and
the resources available for control. Regardless, persons with varicella,
as well as unvaccinated children, should be excluded from child care or
school during outbreaks. In June 2005, the ACIP updated its
recommendation for the use of varicella vaccine for outbreak control.
ACIP recommended that persons who have received 1 dose of varicella
vaccine receive a second dose during a varicella outbreak. Guidelines
for the investigation and management of varicella outbreaks are
currently being developed at CDC, and have already been developed by
several states. One additional component of varicella surveillance is
the investigation of all varicella deaths. These deaths are a major
component of the remaining burden of disease. Varicella deaths became
nationally notifiable on January 1, 1999. There has been a **significant
decline in varicella-related mortality since the prevaccine era**. The
**greatest decline in mortality has occurred in children 1 to 4 years of
age**, the group targeted for vaccination. **Declines have also been
seen in infants, older children and adolescents, and adults 20 to 49
years of age** as a result of a combination of vaccination and herd
immunity effects. From 1998 through 2002, 231 deaths among all age
groups, with varicella listed as the underlying cause, were reported to
the National Center for Health Statistics. Only 51, or 22%, of these
deaths were reported to CDC. Varicella deaths continue to be greatly
under- reported to CDC. A varicella death in a healthy unvaccinated 10
year old girl was recently reported to CDC. This is a tragic reminder
that varicella deaths are vaccine preventable.

Varicella case-based reporting and death reporting will provide evidence
about programmatic changes that are needed, and will improve varicella
control. We cannot change policy or improve our program for vaccine
delivery without this information. Cynthia?

GOOD:

Thanks Jane. We will talk about measles after this pause.

ATKINSON:

The Healthy People 2010 Objectives for the United States established a
target of elimination of indigenous cases of measles. We have met that
objective. In March 2000 a group of experts met in Atlanta to review the
current measles situation in the United States. They concluded that
measles was no longer an endemic disease in this country. They also
warned that we should not become complacent because measles continues to
be imported into the U.S. from other parts of the world. Endemic
transmission could be re-established at any time. We must keep
immunization levels high and surveillance intact. Typical measles
disease includes a prodrome of fever and malaise, cough, coryza, and
conjunctivitis, followed by a maculopapular rash. Before the vaccine
program measles was usually a mild or moderately severe illness of
childhood. But severe complications occurred, and 1 to 3 cases per
thousand resulted in death. Measles is highly contagious and a single
importation can lead to an outbreak if not quickly identified and
contained. Measles outbreaks can occur even in the presence of high
vaccination coverage when pockets of susceptible persons are present, or
where transmission is facilitated by close living conditions. This graph
shows the number of measles cases reported in the United States by year
from 1950 through 2004. Before the introduction of measles vaccine,
there were more than 500 thousand cases of measles reported every year.
In the first 5 years following licensure of the vaccine, 1963 through
1967, the incidence of measles fell more than 90%. This graph shows the
number of reported cases of measles by year since 1980. In 1989 through
1991, there was a major resurgence of measles in the United States.
These epidemics highlighted the risks of measles among unvaccinated
preschool age children. The epidemics led to major efforts to improve
immunization coverage among young children, and to implement a routine
second measles dose in school-aged children. Since 1992, immunization
coverage among preschool age children has increased substantially, and
has been higher than 90% each year since 1996. In addition, most school
age children now receive 2 doses of measles vaccine. As a result,
measles incidence has reached an all time low in the United States. Only
37 confirmed cases were reported in 2004. Measles virus no longer
continually circulates in this country. The cases that now occur are due
to importation and subsequent limited spread of measles virus.

Sometimes cases are linked to known importations, but sometimes it can
be very difficult to identify the index case. When the index case cannot
be identified, even with extensive case investigation, we can often link
cases together by comparing the measles VIRUS from cases and
demonstrating that they are closely related. This is called molecular
epidemiology.

Identification of measles virus genotypes allows us to link apparently
sporadic cases to importations, even when the index case cannot be
found. Analysis of the virus is the only method that allows us to
differentiate between vaccine virus and wild-type virus if the suspected
case of measles was recently vaccinated. Of course, as long as measles
continues to occur anywhere in the world, we remain at risk in the
United States. The challenge is to continue to do good surveillance for
measles, now that so few cases are reported.

With vaccination coverage now at record high levels, many of the people
who remain susceptible are unvaccinated because of religious or
philosophical exemption. They are likely to have close contact with
other persons who share these beliefs. This sets up a situation where
further spread is very likely. An example of this was a measles outbreak
with 34 cases in Indiana in early 2005. This was the largest measles
outbreak in the U.S. since 1996.

The good news is that prompt recognition of the disease, with
appropriate control measures, can limit the spread of measles. So let's
move on to some guidelines that will help you recognize and contain
measles, should you suspect it. You should suspect measles when you see
or hear about a person with an illness that includes a **generalized
rash for 3 days or more, a temperature of 101 degrees Fahrenheit or
greater, which is 38 point 3 degrees centigrade**, **and either cough,
or coryza, or conjunctivitis**. Of note, some persons with measles virus
infection, especially those who have received measles containing vaccine
in the past, may have a milder disease with fewer symptoms. These cases
may not meet the clinical case definition and should be lab tested in
the context of an outbreak or if there is epidemiological linkage to a
confirmed case. Jane?

SEWARD:

Generally, a previously susceptible person exposed to either vaccine or
wild type measles virus will first develop an IgM response, followed by
an IgG response. The IgM response, shown here by the **purple line**, is
usually detectable in the first 48 to 72 hours after onset of rash, and
peaks about 2 weeks later. So if the blood specimen is drawn too early
in the course of disease it may be falsely negative and should be
repeated after 72 hours of rash onset.

IgG antibody, shown by the **yellow line**, is usually not detectable
until later in the illness. IgG peaks later than IgM, and remains
detectable for many years, probably for the rest of the person's life.
For confirmation of measles, IgG testing requires the demonstration of a
significant rise in measles antibody between the acute and convalescent
specimens, so two specimens are needed. The first serum specimen should
be drawn as soon as possible after rash onset, and at the latest within
7 days after rash onset. The second specimen should be drawn 10 to 30
days after the first one.

Because tests for IgG require two serum specimens, and because a
confirmed diagnosis cannot be made until the second specimen is
obtained, IgM tests are preferred. However, a negative IgM- even when
properly drawn- does not rule out measles in a previously vaccinated
person and acute and convalescent IgG testing, or virologic testing will
be necessary. The serologic test most commonly performed for measles
antibody is an enzyme linked immunoassay, which is also known as an
ELISA or EIA. CDC has developed a highly sensitive and specific IgM test
for measles and has trained personnel from every state public health
laboratory in its use. The CDC IgM test is the preferred reference
serologic test for measles. In addition, efforts should be made to
**obtain specimens for viral isolation from all sporadic cases, or from
at least some cases in each outbreak**. These **specimens should be
obtained at the time of the initial investigation**, not later after
serologic test results are received. Viral isolates are **essential for
tracking the epidemiology -the MOLECULAR epidemiology- of measles** now
that we no longer have ongoing indigenous transmission in the United
States. Once a suspected case is identified, contingency planning for
public health action should begin. Ideally, results from measles IgM
antibody testing would be available quickly. But if they are not, it may
be necessary to initiate public health response in the absence of
laboratory confirmation. Control activities should NOT be delayed
pending the return of laboratory results. And I will repeat that-
control activities should NOT be delayed while you are waiting for lab
results for a probable case of measles. A measles investigation
worksheet is included in your surveillance manual. Here is a picture of
it. We will put a link to the measles and other worksheets on our
broadcast resources webpage. There is specific information that is
essential to collect during a measles case investigation. In addition to
collecting **demographic and clinical data**, **laboratory
confirmation** is absolutely essential for all outbreaks and for all
isolated or sporadic cases. As we mentioned, in the United States,
endemic measles has been eliminated, so measles is now a rare disease.
Most cases of measles- like illness will not be measles. Even in
outbreaks, laboratory confirmation should be obtained on as many cases
as possible. In the context of an outbreak, a person meeting the measles
clinical case definition should be considered to have measles for
containment purposes, regardless of IgM results.

Once community awareness is increased during an outbreak, many cases of
febrile rash illness may be reported as suspected measles. The magnitude
of the outbreak will be exaggerated if these cases are classified as
confirmed in the absence of laboratory confirmation. This is
particularly important as the outbreak is ending. At that point,
laboratory confirmation should be sought on all suspected cases. During
a case investigation, it is important to obtain an **accurate and
complete immunization history** on all confirmed cases. Measles case
investigations should include complete immunization histories that
document all doses of measles- containing vaccine. Efforts should be
made to identify the **source of infection** for every confirmed case of
measles. Case patients or their care givers should be asked about
contact with other known cases. When no history of contact with a known
case can be elicited, opportunities for exposure to unknown cases should
be sought. Such exposures may occur in **schools, following contact with
international visitors**, while **visiting tourist locations, during air
travel or, unfortunately, in healthcare settings**. Unless there is a
history of exposure to a known person with measles, patients or their
care givers should be closely questioned about other exposure settings.
The next thing you should do is assess the **potential for
transmission**, and identify contacts. Transmission is particularly
likely in households, schools and other institutions, such as colleges,
prisons, and in healthcare settings. Contacts of the case patient during
the infectious period should be identified. For measles, the infectious
period is from 4 days before to 4 days after onset of the rash. In
general, contacts that have not received two valid doses of measles
containing vaccine on or after the first birthday are considered
susceptible. These contacts may be at risk for infection. These contacts
should be vaccinated- ideally within 72 hours of exposure.

Now that measles is no longer an endemic disease in this country,
importation of measles cases from outside the United States is the only
way cases can occur. Even among those cases classified as indigenous --
that is, persons infected in the U.S.- most are due to importations. The
cases we classify as indigenous are probably due to unrecognized
importations. This situation will almost certainly continue in the
future, until better measles control is achieved worldwide. Until
measles is eradicated from the planet, our best defense is a well
vaccinated population and careful surveillance. Cynthia?

GOOD:

Thanks, Jane. We will be back in just a moment to talk about rubella.

ATKINSON:

In this segment, we are going to discuss rubella. Like measles,
indigenous rubella and congenital rubella syndrome were targeted for
elimination in the United States by the year 2010. We have met that
goal. In October 2004, CDC convened a panel of experts who concluded
that rubella is no longer endemic in the US. The absence of endemic
transmission is defined as the lack of any continuous US-acquired chain
of transmission that persists for 12 months or longer in a defined
geographic area. Like measles, a diagnosis of rubella needs to be
considered when evaluating a person with a febrile rash illness. The
rash of rubella is sometimes confused with measles or scarlet fever. But
not everyone infected with the rubella virus develops a rash. Up to 50%
of persons infected with rubella virus may be asymptomatic. The major
public health importance of rubella is not the acute disease, which is
usually mild, but rather the consequences of infection of a fetus. When
**rubella virus infection occurs during early pregnancy**, especially
during the first trimester, fetal infection is very likely. Intrauterine
rubella infection can cause a **serious, and sometimes fatal, illness**
that may include **spontaneous abortion, stillbirth**, and a
constellation of **birth defects** known as congenital rubella syndrome,
or CRS. Up to 90% of the infants born to women infected during the first
10 weeks of pregnancy can have CRS. The most common clinical
manifestations of CRS are cataracts, which you see here, heart disease,
sensorineural hearing impairment and developmental delay.

A worldwide rubella epidemic occurred in 1962 through 1965. An estimated
12 point 5 million cases of rubella occurred in the United States during
this epidemic. These rubella cases resulted in more than 11 thousand
fetal deaths, more than 2 thousand neonatal deaths, and 20 thousand
infants born with CRS. This global epidemic spurred the development of
rubella vaccines and the implementation of national rubella vaccination
programs. In 1969, rubella vaccine was licensed in the United States,
and a vaccination program was established with the goal of preventing
congenital rubella infections, including CRS. This graph shows the
number of rubella cases reported by year from 1966, when rubella became
reportable, until 2004. The number of reported cases of rubella in the
United States has declined more than 99%, from more than 57 thousand
cases in 1969 to only 10 cases in 2004. The incidence of rubella has
declined dramatically in all age groups. Among the small number of cases
that have occurred between 2001 and 2005, the majority are adults.

With rubella epidemics continuing to occur in most countries outside the
United States, rubella virus can be imported into this country at any
time. The virus can spread within communities unless high population
immunity is maintained. This is especially likely when importation
occurs into an area with populations who were not vaccinated against
rubella in childhood, such as recent immigrants, or communities that
object to vaccination. A large rubella outbreak with more than 300 (311)
cases occurred in an Amish community in Ontario, Canada in 2004.
Fortunately there was no spread to the United States during that
outbreak. (no CRS cases found as of broadcast date but several infected
pregnant women had not yet delivered) Surveillance for rubella involves
the serologic and virologic evaluation of persons with febrile rash
illness, and monitoring for the typical sequelae of maternal infection,
or CRS. Whenever rubella occurs in a community, there is a risk of
subsequent CRS. We recently spoke to Dr. Susan Reef, a medical
epidemiologist in the Viral Vaccine Preventable Diseases Branch of the
National Immunization Program, about the absence of endemic rubella
transmission in the US.

REEF:

Rubella and congenital rubella syndrome, or CRS, were targeted for
elimination in the United States by the year 2010. By elimination we
mean the absence of endemic rubella virus transmission. In October 2004,
the CDC convened an independent expert panel to review available rubella
and CRS data. After a careful review, the panel unanimously agreed that
rubella was no longer endemic in the United States. The Healthy People
2010 goal had been achieved! Some of the data that supported elimination
of rubella and CRS included the fact that rubella and CRS cases have
reached historic low levels -- only 10 cases of rubella were reported in
2004; only one rubella outbreak has been reported since 2001 - this
outbreak occurred on a cruise ship with the source of the outbreak being
imported from the Philippines; during 2001-2004, all states and major
cities had at least one full year with no reported rubella cases.
Serological studies indicate that more than 90% of the population is
immune to rubella due to either vaccination or prior infection. This
immunity level is high enough to sustain the elimination of rubella;
rubella-containing vaccine coverage is very high - our first dose
coverage among children aged 19 to 35 months has been higher than 90%
since 1996 and our school coverage has been higher than 95%; and last
but definitely not least, the surveillance system was determined to be
adequate to detect endemic rubella. In summary, we did it!
Congratulations and thank you to state and local health departments and
health care providers. Your diligent efforts made this possible.

ATKINSON

Let's talk now about rubella case investigation. A mild case of measles
may mimic rubella. Measles virus infection should always be ruled out by
laboratory testing if the diagnosis of rubella is being considered.
Likewise, rubella should always be considered in the evaluation of a
febrile rash illness. If serologic testing for measles is negative,
testing for rubella should always be done. A case of rubella may be
laboratory confirmed by **isolation of rubella virus;** by demonstrating
a **significant rise in serum rubella IgG antibody** level by any
standard assay; or by the **presence of serum rubella IgM antibody**.
The laboratory criteria for confirmation of CRS are **isolation of
rubella virus from the infant; or** **detection of rubella virus by
polymerase chain reaction - PCR- or serologic confirmation**. Many rash
illnesses mimic rubella infection, and up to half of rubella infections
may be subclinical. So the only reliable evidence of acute rubella
infection is from the laboratory. Similar to measles a negative IgM test
does not rule out rubella in a vaccinated person. If the index of
suspicion is high, particularly if additional cases occur, obtain
virologic specimens as well.

Surveillance for rubella involves the serologic evaluation of persons
with febrile rash illness, and monitoring for the typical sequelae of
infection during pregnancy. Careful surveillance and continued high
vaccination coverage will help assure that congenital rubella syndrome
remains a thing of the past. Cynthia?

GOOD:

Bill, in the past Latin American has been the source of many rubella
cases imported into the United States. What is the status of rubella in
the Americas now?

ATKINSON:

You are correct that Latin America, particularly Mexico was the source
of many imported cases during the 1990s. Fortunately, all but one
country in Latin America now includes rubella vaccine in their national
immunization program. As a result, the number of cases of rubella has
been greatly reduced. Latin America is now rarely a source of imported
rubella in the U.S.

GOOD:

Thanks, Bill. We will come right back to talk about mumps surveillance.

SEWARD:

Mumps virus can cause illness with an acute onset of unilateral or
bilateral tender, self-limited swelling of the parotid or other salivary
gland, lasting more than 2 days, without other apparent cause. The
number of reported mumps cases in the US has decreased more than 95%
since mumps vaccine began to be used routinely in 1977. The Healthy
People 2010 goal for mumps is elimination of indigenous transmission of
mumps.

The combination measles, mumps, and rubella vaccine has contributed to
the same high coverage rate for mumps as we have already discussed for
measles and rubella. Although mumps is thought to be less infectious
than either measles or rubella, the reported disease rates are much
higher than for the other two diseases. In 2004, **258 mumps cases were
reported** in contrast to 37 cases of measles and 10 cases of rubella.
**32% of these cases were among children 1 through 9 years of age**.
**Vaccine history was known for only 87, or 34%** of the cases. Of
those, **50, or 57% had received at least one dose of mumps containing
vaccine**. Of the 258 cases reported in 2004, only 95, or 37% were
laboratory confirmed. It is very likely that many of the cases lacking
laboratory confirmation are actually not due to infection with mumps
virus. However, we cannot say with certainty because of our poor record
of laboratory testing.

Mumps vaccine is routinely used in only 56% of countries or areas in the
world. Importation of mumps into the United States is now increasingly
recognized. Of **171 mumps cases with known importation status** in
2004, **18, or 10% were known to be international imports**.

During 2004, a mumps **outbreak with 31 cases occurred in a New York
camp where the index case was an unvaccinated counselor from the United
Kingdom.** This illustrates the potential impact of importation.
Surveillance for measles and rubella is facilitated by the fact that
they share the same clinical syndrome and very similar case definitions.
Unfortunately, because of its unique clinical presentation, mumps
surveillance is not affected by enhanced surveillance for measles or
rubella.

Confirmed mumps cases are those that are laboratory confirmed or that
meet the clinical case definition and are epidemiologically linked to a
confirmed or probable case. Note that a laboratory confirmed case does
not need to meet the clinical case definition. Acute mumps can be
laboratory confirmed by **isolation of mumps virus in cell culture,
detection of mumps virus by PCR**, a **significant rise in serum mumps
IgG antibody**, or the **presence of serum mumps IgM antibody**.
Serologic testing is the simplest method of confirming a case of mumps.
Remember that as with measles and rubella, mumps IgM may be transient or
missing in individuals who have had any doses of mumps-containing
vaccine. Sera should be collected as soon as possible after symptom
onset for IgM testing or as the acute specimen for IgG seroconversion.
Convalescent sera should be drawn two weeks later.

The clinical samples that are acceptable for mumps virus isolation are
throat or nasopharyngeal swabs, urine, and fluid collected from the
buccal cavity. The buccal cavity is the space between the cheek and
teeth. The parotid duct drains in this space near the upper rear molars.
Fluid from this area may yield the best viral sample, particularly when
the parotid gland area just below the ear is massaged for 30 seconds
prior to collection of secretions. Virus may be isolated from the buccal
mucosa or urine from 7 days prior until 9 days after onset of parotitis.
Collection of viral samples from persons suspected of having mumps is
strongly recommended. The molecular characteristics of mumps viruses
provides important information that will help determine whether endemic
transmission is still occurring in the U.S.

Because the number of cases of mumps reported each year is low, a
detailed investigation should be conducted for EVERY case. The clinical
diagnosis of mumps is unreliable, so all cases of mumps MUST be
laboratory confirmed. In addition to **demographic and clinical data**
it is important to obtain accurate and **complete immunization
history**. Recent outbreaks have included many cases who had already
received at least one dose of mumps-containing vaccine. The **source of
infection** should be identified for each confirmed case of mumps. If
there is no history of contact with a known case, **opportunities for
exposure to unknown cases** should be identified, so that investigative
efforts can be directed to locations of possible exposure. Finally,
**potential for further transmission should be assessed**, and contacts
of the case-patient during the infectious period should be identified.
For mumps, the infectious period usually begins 3 days before, but
occasionally as early as 7 days before the onset of parotitis, and lasts
until 9 days after symptom onset. Mumps vaccine should be given to all
exposed susceptible persons. Although vaccine has not been proven to
prevent the occurrence of disease when administered after exposure, it
will provide protection for future exposures.

Measles and rubella were eliminated from the United States as a result
of major efforts at hemispheric control of these two diseases. No
hemispheric or global program for mumps control exists currently, making
the challenge of domestic mumps elimination more daunting. Documentation
of elimination of mumps in the U.S. will depend on improving mumps
surveillance, including laboratory confirmation of EVERY case. Cynthia?

GOOD:

Thanks, Jane. We will be back to discuss hepatitis A surveillance right
after this pause.

ATKINSON:

Hepatitis means inflammation of the liver. Many different viruses, as
well as many environmental toxins, chemicals, and drugs can cause
hepatitis. In this segment of the program we are going to limit our
discussion to hepatitis A, caused by infection with hepatitis A virus,
or HAV. The incidence of hepatitis A has declined since 1995, when the
vaccine was licensed. This decline was due at least in part to programs
for routine vaccination of children. In 2004, about 5 thousand 7 hundred
cases of hepatitis A were reported. This is an incidence rate of about 2
per 100 thousand population, the lowest incidence ever reported. The
true number of hepatitis A cases is actually much larger than the number
officially reported to CDC, for several reasons. First, the **likelihood
of having symptoms with hepatitis A depends on age**. Although **most
adults with hepatitis A develop jaundice**, the **majority of young
children either do not have typical symptoms or are completely
asymptomatic.** Only people with symptoms of hepatitis A are reportable
to the health department. Second, **not everyone with symptoms of
hepatitis A goes to a doctor, gets tested and gets reported**. This is
because symptoms can be very mild. Mathematical models have been used to
estimate the true number of HAV infections. It is estimated that on
average there were about 112 thousand symptomatic infections each year
during 1980 through 1999. This was more than 4 times the number of
reported cases. In 2004 when approximately 57 hundred cases were
reported, CDC estimated that there were actually more than 20 thousand
people with symptomatic hepatitis A. The incidence of hepatitis A is
currently lowest among children younger than 5 years of age. In the
prevaccine era, the highest incidence rates occurred among children, but
currently rates of disease are similar among children, adolescents, and
adults. After decades of large differences in rates among racial groups,
currently incidence rates are similar across races. Despite declines in
recent years, rates of disease remain higher among Hispanic children and
adults, compared to non-Hispanics.

HAV is transmitted by the **fecal oral route**, and is easily
transmitted through **close personal or sexual contact**. HAV is also
transmitted through **contaminated food or water**. Because the virus is
present in the blood during the acute infection, **bloodborne
transmission is also possible, but is rare**. Unlike hepatitis B,
hepatitis A virus infection does not lead to chronic infection. The
**incubation period for hepatitis A averages about 28 days with a range
of 15 to 50 days**. The most common signs and symptoms associated with
acute hepatitis A include **jaundice, fever, malaise, anorexia, and
abdominal discomfort**. The illness can be severe and **10 to 20% of
reported cases require hospitalization**. While rarely fatal in younger
persons, the **case fatality rate is approximately 1% among reported
cases who are older than 50 years**. Infected people with either
symptomatic or asymptomatic infection can transmit HAV to others.
Hepatitis A virus can be found in the blood and stool of an infected
person, especially in the 2 weeks before onset of illness. Virus is shed
in the stool of people without symptoms as well as those WITH symptoms.
Young children infected with hepatitis A virus play an especially
important role in transmission because they can transmit the virus, but
often have no symptoms of the infection. The most frequently reported
**risk factors** for HAV infection are **household or sexual contact
with a person who has hepatitis A**, and **international travel**. Other
less commonly reported risk factors include **illegal drug use**, and
being a **man who has sex with men**; however, **45 to 50% of persons
with hepatitis A have no risk factor that can be identified**. Hepatitis
A vaccines have been available since 1995. The two licensed vaccines are
available in pediatric and adult formulations and are administered in a
two dose series. The pediatric formulation of both vaccines are licensed
for children 12 months through 18 years of age. These vaccines are
highly effective in preventing disease when given before exposure.
Protection lasts at least 12 years, and likely for 20 years or longer.
Historically, the areas with the highest rates of hepatitis A were in
the Western and Southwestern regions of the United States. The reason
for this geographic distribution of HAV infection is not known. However,
in recent years, rates have been similar across all U.S. regions. We
recently spoke with Dr. Annemarie Wasley in the Division of Viral
Hepatitis in CDC, about the current epidemiology of hepatitis A and the
impact of hepatitis A vaccination in the United States.

WASLEY:

Hepatitis A vaccines were first introduced in the United States in 1995.
In 1996, the Advisory Committee on Immunization Practices, or ACIP,
recommended that people at increased risk of hepatitis A infection
should be vaccinated. These recommendations included vaccination of
travelers to areas endemic for hepatitis A virus, men who have sex with
men, and users of injecting and noninjecting drugs. However, we knew
that cases in these groups accounted for only a minority of all cases
reported. Most cases of hepatitis A were occurring as part of community
wide outbreaks with the majority of infections occurring among children
and their adult contacts. We also knew that much of the disease being
reported in the U.S. was occurring in the western regions of the
country. Cases reported by 17 predominantly western and southwestern
states accounted for more than two thirds of all cases reported in the
prevaccine era. However, these states represented less than one third of
the U.S. population. Based on this information, in 1999, ACIP
recommended that children living in the 11 states which historically had
the highest rates of hepatitis A be routinely vaccinated against the
disease. Those 11 states are shown here in blue. It was also suggested
that vaccination be considered for children in an additional 6 states,
shown in yellow. Rates in these 6 states were not as high as those in
the 11 highest incidence states, but were still consistently higher than
the national average. Since those recommendations were made, we have
seen a dramatic change in the epidemiology of hepatitis A in the United
States. This graph shows the overall rate of hepatitis A in the United
States from 1990 through 2004. It shows the decline in rate that began
in 1995 and accelerated in 1999, the year routine childhood vaccination
was recommended in the high incidence states. The rate has declined by
76% relative to the average rate seen in the prevaccine years of 1990
through 1997. The 2004 rate of 1 point 9 per 100 thousand population is
the lowest ever recorded. The decline has been greatest in the 17 states
where routine vaccination of children is recommended or suggested, shown
here by the yellow line. The rate of hepatitis A in the rest of the
country is shown in blue. For the first time rates are similar across
all regions of the country. The 1999 hepatitis A ACIP statement targeted
children in the highest incidence states. Children historically have had
the highest rates of disease. Since that time rates among children have
declined more than rates among adults. Now, also for the first time,
rates are similar across all age groups. We do not think that
vaccination is completely responsible for these declines. Hepatitis A
rates in the U.S. have historically shown a cyclic pattern every 10 to
15 years, with periodic increases followed by subsequent decreases. Some
of the decline that we are seeing now probably is a result of this
pattern. However, hepatitis A rates now are significantly lower than any
previously recorded. In addition, the decline has been greater in the
age groups and geographic locations recommended for routine vaccination.
Together, these factors indicate that the strategy of routine childhood
vaccination in areas with increased risk of infection has played a
significant role in reducing overall rates of hepatitis A in the U.S. We
are continuing to monitor the occurrence of hepatitis A. Among cases
reported in children, the disease is no longer focused in the 17 states
targeted by the 1999 recommendations. Many of the states with the
highest rates in 2004 do NOT have a recommendation for routine childhood
vaccination. Based on the changing pattern of hepatitis A in the United
States, the ACIP voted in October 2005 to expand routine vaccination of
children nationwide. It is now recommended that ALL children should
receive hepatitis A vaccine at 1 year of age. Vaccination should be
integrated into the routine childhood vaccination schedule. Children who
are not vaccinated by 2 years of age can be vaccinated at subsequent
visits. ACIP encourages states, counties, and communities with existing
hepatitis A vaccination programs for children aged 2 through 18 years to
maintain these programs. These new recommendations are expected to
increase hepatitis A vaccination levels among children throughout the
country. We expect that implementation of these recommendations will
allow us to sustain and perhaps even further reduce the current low
rates of hepatitis A in the United States.

SEWARD:

Currently, national surveillance for hepatitis A is for symptomatic
disease only. Hepatitis A disease is reportable in all states.
Asymptomatic cases though should NOT be reported to CDC. The clinical
case definition for acute viral hepatitis is an **acute illness with a
discrete onset of symptoms** and either **jaundice or elevated serum
aminotransferase levels**. But clinical information is not sufficient to
differentiate a case of acute hepatitis A from hepatitis of some other
type. To tell them apart we need some help from the **laboratory**. To
**confirm a case of acute hepatitis A**, that case **must meet the
clinical criteria** and **MUST also be positive for IgM antibody to
hepatitis A virus**. IgM antibody to hepatitis A virus is detectable in
virtually all patients with acute hepatitis A but generally disappears
within 6 months of the onset of symptoms. IgG is the other antibody
produced in response to HAV infection. IgG persists for the person's
lifetime and confers protection against subsequent infection.

There is one situation when a clinically reported case lacking serologic
information can also be reported as a confirmed case of hepatitis A.
That is when a person with hepatitis A is epidemiologically linked to
another person with laboratory confirmed hepatitis A. By epidemiologic
link, we mean household or sexual contact with a person with confirmed
hepatitis A during the 15 to 50 days before the onset of symptoms. To
**prevent secondary cases**, the two main priorities are to **identify
whether there are persons at risk of becoming infected by the case** and
second, to determine, if possible, the **source of infection for the
index case**. Identification of the source is important because there
may be other people who continue to be at risk of infection from the
same source. Prompt case investigation and follow up with the case and
contacts is important to prevent further spread of hepatitis A. There is
a viral hepatitis worksheet and report form in the surveillance manual
that can help guide your investigation. The **critical data to be
collected for a hepatitis A case investigation** includes
**demographic** information such as age and race; **clinical** data
including symptoms and the date of disease onset; pertinent **laboratory
data including serologic testing and liver enzyme levels;** **risk
factor** information; and **vaccination status** of the case. During
your case investigation, you should also develop a **list of any
susceptible contacts** who require postexposure prophylaxis. Once you
have identified contacts, post exposure prophylaxis should be offered.
This must be given as soon as possible and not more than 14 days after
the last exposure. The recommended post exposure prophylaxis for
hepatitis A in susceptible contacts is a single intramuscular dose of
immune globulin, or IG, and hepatitis A vaccine, where appropriate.
Postexposure prophylaxis is recommended for the **sexual and household
contacts** of a person with hepatitis A. Prophylaxis should be
considered for **other close personal contacts** as well. These might
include persons who shared illegal drugs with the case or had ongoing
close household like exposures, such as a regular babysitter. There are
other circumstances in which IG prophylaxis might be used. For example,
**attendees and employees of a child care center where a hepatitis A
case is identified**, or **persons who consumed food handled by a
hepatitis A virus infected food handler**, may benefit from IG. For
these types of exposures, the benefit of giving IG will vary, and must
be assessed specifically for each situation. In areas that currently
have a routine hepatitis A vaccination program, hepatitis A vaccine can
be given along with IG to contacts for whom vaccine is recommended. The
vaccine and IG may be given simultaneously, but not in the same syringe
as the IG, of course, and not at the same anatomic site.In addition to
identifying the contacts of the case for postexposure prophylaxis, it is
also important to identify- if at all possible- the SOURCE of exposure
for the case. Sources of exposure could most likely include sexual and
household contact with another person with hepatitis A, illegal drug
use, international travel, or consumption of contaminated food.

It is important to determine the sexual history of the case, including
whether they have had multiple sex partners or are a man who has sex
with other men. For hepatitis A cases, it is important to ask about
these exposures during the 2 to 6 weeks before they became ill.

Coordination of surveillance and immunization activities can focus
appropriate interventions and reduce missed opportunities. In addition,
surveillance data- especially risk factor data- will be important to
assess the effectiveness of vaccination recommendations and to identify
additional populations that should be vaccinated. **Strategies to
improve and enhance surveillance** should include **improved case
reporting**. Now that hepatitis A vaccine is recommended for all areas
of the country these recommendations for enhancing surveillance apply to
every state. **Healthcare providers** should be educated about the
importance of reporting all cases of acute hepatitis. **Hospitals and
infection control practitioners** should report all patients with the
ICD-10 diagnosis code of B 15, the code for acute hepatitis A.
Surveillance is an important tool in hepatitis A disease prevention.
Information gained through surveillance can help prevent spread of
disease from cases, and can also help define vaccination and other
prevention strategies. Cynthia?

GOOD:

Thanks, Jane. We will be back to discuss hepatitis B surveillance right
after this.

ATKINSON:

In 2004, about 6 thousand 2 hundred cases of acute hepatitis B were
reported in the United States. This is an incidence of 2 point 1 per 100
thousand population, and is the lowest incidence of hepatitis B ever
reported in the U.S. The rate of hepatitis B has declined 75% since
1990, due at least in part to the implementation of universal childhood
immunization.

Historically, acute hepatitis B has been a disease of older adolescents
and young adults 15 to 39 years old. However, as vaccination coverage
has increased among adolescents, rates of disease among older
adolescents and young adults have declined. Rates of acute hepatitis B
are now highest among persons 25 through 44 years of age. **Transmission
of hepatitis B virus, or HBV, requires percutaneous exposure to blood of
a person acutely or chronically infected with HBV**. Common **risk
factors** for infection with hepatitis B virus include **sex with
multiple partners, injection drug use, and men who have sex with men**.
Other risk factors include **occupational exposure to human blood or
medical interventions** such as surgery, blood transfusions, or organ
transplants. Number range CHAPTERThe **incubation period for acute
hepatitis B averages 120 days with a range of 45 to 160 days**.
**Infants, children younger than 10 years of age, and immunosuppressed
adults with newly acquired HBV infection are usually asymptomatic.**
Number range CHAPTER**30 to 50% of older children and adults are
symptomatic**. When present, clinical symptoms and signs might include
**nausea, vomiting, abdominal pain, and jaundice**. **Fulminant
hepatitis B occurs with a case fatality rate of zero point 5 to 1%**. In
adults with normal immune systems, most -- 94 to 98% - recover
completely from newly acquired HBV infection. In infants, young
children, and immunosuppressed persons, most newly acquired HBV
infections result in chronic infection. Infants are at greatest risk
with a 90% chance of developing chronic infection if infected at birth.

Although the consequences of acute hepatitis B can be severe, most of
the serious sequelae associated with this disease occur in persons in
whom chronic infection develops. Persons with chronic HBV infection are
often initially asymptomatic. However, chronic liver disease develops in
two-thirds of these persons, and approximately 15 to 25% will die
prematurely from cirrhosis or liver cancer.

Persons with chronic HBV infection are a major reservoir for
transmission of the virus. Any person testing positive for hepatitis B
surface antigen- or HBsAg- is potentially infectious.

Until recently, national surveillance for hepatitis B included only
acute symptomatic disease, and perinatal hepatitis B. Chronic hepatitis
B was added to the list of nationally notifiable diseases in 2003, to
monitor morbidity due to chronic disease and to guide prevention
programs. The **case definition for acute hepatitis B** includes having
**clinically compatible symptoms, jaundice or an elevation in liver
enzymes and laboratory confirmation**. The case definition for
**chronic** hepatitis B includes only **laboratory confirmation**
because symptoms are not always present. The preferred test for
**laboratory confirmation** of a case of **acute** HBV infection is a
**positive test for IgM antibody to the hepatitis B core antigen**. IgM
antibody to core antigen is a good marker for acute hepatitis B because
it is generally detectable for only the first six months after
infection. If this test is not available, a **positive test for
hepatitis B surface antigen- with a negative test for acute hepatitis A
virus infection**, if done-, is sufficient to confirm a diagnosis of
acute hepatitis B. ANTIBODY to hepatitis B surface antigen indicates
immunity to hepatitis B virus. **Chronic** hepatitis B infections are
also confirmed by laboratory criteria. Cases will be **hepatitis B
surface antigen positive, total anti-hepatitis B core antibody positive-
if the test was done -, and hepatitis B core IgM antibody negative**.
Chronic infection can also be confirmed by having **two positive HBsAg
tests at least 6 months apart**. Perinatal hepatitis B infection is a
chronic infection which results from transmission of the hepatitis B
virus from an infected woman to her infant before, during, or soon after
birth. **Perinatal hepatitis B infection** is defined as the **presence
of hepatitis B surface antigen in an infant 1 to 24 months** of age,
**born in the US or US territories to a hepatitis B surface antigen
positive woman**. Since perinatal infections are almost always
asymptomatic, there are no clinical criteria for these cases. Number
range CHAPTERPostexposure prophylaxis with hepatitis B immune globulin
and hepatitis B vaccine MUST be administered to infants born to
HBsAg-positive woman. These infants should be tested for HBsAg three
months after the third dose of vaccine. These cases should be reported
through the national notifiable diseases surveillance system. For either
acute or chronic hepatitis B, in addition to the appropriate demographic
and clinical data, there are two **priorities in conducting case
investigations**. First, you should **identify whether there are
contacts of the case at risk of becoming infected**, and second, you
should **determine, if possible, the source of infection for the index
case**. Information to be collected for a hepatitis case investigation
should include **demographic and clinical data**, **laboratory data
including serologic testing and liver enzyme levels**, **risk factor
information**, and **vaccination status**. **Pregnancy status of any HBV
infected woman** should be determined to make sure that action is taken
to prevent perinatal transmission to her infant. Number range CHAPTERFor
acute hepatitis B, the general recommendation for postexposure
prophylaxis is to give hepatitis B immune globulin, or HBIG, and to
begin the hepatitis B vaccine series within 14 days of last exposure.
Persons in need of postexposure prophylaxis include **sexual contacts of
the case** and any **infant younger than twelve months of age for whom
the case is a primary caregiver.** Also **persons who have had
identifiable percutaneous or permucosal exposure to the blood of the
case** should be given prophylaxis. Providing postexposure prophylaxis
to non-sexual household contacts of the case or others with no clear
exposure to blood of the case is not recommended. However, providing
hepatitis B VACCINE to nonsexual household contacts, especially children
and adolescents, is highly recommended.

Persons with hepatitis B infection that remain chronically infected
should be referred for clinical follow-up. These persons should be
monitored for the development of chronic liver disease and should be
evaluated for treatment. In addition, they should be advised on ways to
prevent transmission of the infection to others.

In addition to contact identification for postexposure prophylaxis, it
is also important to identify the source of infection for acute cases.
There may be other people who continue to be at risk of infection from
the same source. To identify the **source of infection** for acute
hepatitis B infections, ask about **exposure during the previous 6 weeks
to 6 months to another person with acute or chronic HBV infection,
injection drug use, occupational exposure to human blood, medical
interventions** such as dialysis, blood transfusions, organ transplants
or **use of blood products**. It is also important to determine the
**sexual history** of the case, including whether multiple sex partners
or men who have sex with men. Surveillance for hepatitis B is an
important public health tool. Identification and reporting of persons
with HBV infection assists public health professionals in reaching
contacts of cases who are at risk of infection so that vaccination and
postexposure prophylaxis can be provided, if appropriate. Surveillance
also helps public health understand the risks for infection, to provide
the appropriate programmatic resources to reduce the rates of acute and
chronic infection in the U.S.

GOOD:

Welcome back to Surveillance of Vaccine Preventable Diseases! We hope
you have had time to take a break and get ready for the second half of
the program.

We have a new instructor for this part of today's program. Dr. John
Moran is the Acting Chief of the Bacterial Vaccine Preventable Diseases
Branch in the National Immunization Program.

GOOD:

High vaccination coverage has led to all time record low levels of many
vaccine preventable diseases- but not pertussis. Pertussis remains
endemic in the United States. Sporadic cases and community wide
outbreaks continue to occur in spite of record high vaccine coverage
among children. Dr. Moran will begin our discussion of pertussis. John?

MORAN:

Thank you Cynthia. Pertussis, or whooping cough, is caused by the
bacterium Bordetella pertussis. Pertussis is characterized by severe
paroxysmal coughing sometimes followed by vomiting, in older adolescents
and adults and an inspiratory whoop in infants. Some adults experience
incontinence or rib fracture from forceful coughing. Pertussis in very
young infants can be severe but may not present with the characteristic
cough and whooping. Very young infants can start the illness with
apnea - stopped breathing, and bradycardia - slow heart rate. Infants
have high rates of complications including pneumonia and
hospitalization.

During the last 5 years, about 20 deaths due to pertussis have been
reported each year in the United States; most are among infants less
than 4 months of age, who are too young to have received 3 doses of
pertussis vaccine, and so are not yet fully protected. This graph shows
the number of reported cases of pertussis by year from 1940 through
2004. Notice the scale of the vertical axis-- 250,000 cases. Between
1940 and 1945, an average of 175 thousand cases and 2700 deaths from
pertussis were reported each year. With the widespread use of pertussis
vaccine in the late 1940s, the number of reported cases began to drop,
although not as rapidly as with some other diseases. Periodic peaks of
illness continued every 3 or 4 years. Since 1980, the reported cases of
pertussis have been gradually rising, again with periodic peaks of
illness. Since 2001, the pattern has changed, with increases in 2002,
2003, and 2004. More than 25 thousand cases were reported in 2004, the
highest number reported since 1959. Although we usually think of
pertussis as a disease of children, we are now recognizing pertussis in
older children, adolescents, and adults more frequently than in the
past. Outbreaks are being reported in middle schools and high schools.
This is probably due to both an increasing awareness of pertussis as a
cause of cough illness in this age group and the increasing availability
of sensitive diagnostic tests, such as DNA polymerase chain reaction --
or PCR.

Although infants typically have the most severe cases of pertussis,
older children and adolescents can also have severe illness. Here is a
short video of an adolescent with pertussis.

\[UNSCRIPTED VIDEO OF BOY COUGHING, WITH FRENCH VOICEOVER\]

ATKINSON:

Protection induced by pertussis vaccines, or by the disease for that
matter, is NOT life long and begins to wane after about 5 years. There
have been outbreaks in high schools where almost all the students had
received 4 or 5 doses of pertussis vaccine. In some adolescents the
disease is less severe because they were vaccinated in the past, but
these cases can still be infectious. Other adolescents have classic
cases of pertussis, even though they were previously vaccinated. Because
protection does not last, even VACCINATED children are susceptible to
pertussis by early adolescence. In fact, the proportion of cases
reported occurring in persons 10 years of age and older increased from
20% in 1990 to 67% in 2004. In contrast, outbreaks in elementary school
students are not common- probably because most children get a booster
dose of pertussis vaccine before they start kindergarten.

During May and June, 2005, the Food and Drug Administration licensed two
booster tetanus, diphtheria, and acellular pertussis -- Tdap vaccines --
that is capitol T, small d-- a-- p- for adolescents in the U.S. In June
2005, the Advisory Committee on Immunization Practices- or ACIP-
recommended the newly licensed vaccines for use in **adolescents**. The
provisional recommendation is that **adolescents 11 and 12 years of age
be given Tdap in place of the Td currently given**. The ACIP also made
other recommendations for use of these vaccines in adolescents for
**catch-up vaccination**. One of these vaccines was also licensed for
use in **adults** through 64 years of age. In October 2005, the
Committee made a provisional recommendation for adults to **use Tdap
vaccine to replace the next dose of the currently recommended
tetanus-diphtheria vaccine that is used as the adult booster vaccine**.
Use of these new vaccines in new populations is going to require careful
surveillance to monitor vaccine program impact. Collection of vaccine
history - now for all cases, not just for children - will be especially
important as we launch a national immunization program with new vaccines
in new populations. As you talk with vaccine providers, encourage them
to remind adults to keep records of their vaccination so they can avoid
extra vaccination. Recording manufacturer, type of vaccine and lot
number will make it easier to identify the type of vaccine, both for
surveillance and for physicians providing prevention services for their
adult patients. During the 1980s and 1990s, acellular pertussis vaccines
were **developed for children because of concerns about the safety of
the whole-cell pertussis vaccine**. Acellular pertussis vaccines were
approved for use as the 4th and 5th dose in 1992, and were **approved
for the first three doses of the pediatric pertussis vaccine series in
1996**. It was never proven that the whole-cell vaccine caused brain
injury. But whole-cell pertussis vaccines with diphtheria and tetanus
toxoids did often cause redness, swelling, and pain at the injection
site and systemic reactions like fever and irritability. Some of these
local reactions were actually related to the diphtheria and tetanus
portions of the vaccine. We will talk about surveillance for vaccine
adverse events later in the program.

There are now 3 DIFFERENT diphtheria, tetanus and acellular pertussis
vaccines licensed for use in infants and children. One of these vaccines
also comes in a combination with inactivated polio and hepatitis B
vaccines. The acellular pertussis vaccines for infants and children also
differ from the two new versions of diphtheria, tetanus and acellular
pertussis vaccines licensed for use in adolescents and adults in 2005.
The three pediatric versions **contain different COMPONENTS** of the
pertussis organism, **different AMOUNTS of these components**, and the
**components are made by different PROCESSES**. **Adolescent and adult
versions of the vaccines have reduced quantities of many of the
components** compared with the pediatric formulations. With so many
different vaccines, you can see the importance of getting complete
vaccine history for all cases of pertussis, both pediatric and adult.
All of the acellular pertussis vaccines are less likely to cause
reactions than the whole-cell vaccines were. The new vaccines for
adolescents and adults have about the same rates of reactions as the
currently recommended tetanus and diphtheria toxoids vaccines used for
booster doses against tetanus.

We now have had more than 10 years of experience with acellular
pertussis vaccines among infants and children, and we know that with
those vaccines immunity wanes after a few years. That is why we see
pertussis outbreaks in high schools. The new Tdap vaccines for
adolescents and adults were developed and are now recommended to provide
protection as the immunity from the childhood series wanes. But how long
does protection persist following acellular pertussis vaccines? Does it
matter? Yes it does matter. As with any vaccine preventable disease, we
must monitor disease due to waning immunity -- to identify possibly
needed changes or additions to immunization schedules.

How often would booster doses need to be given? It is expected that
additional booster doses of Tdap will be required in the future for
adults although the vaccines are currently approved ONLY for a SINGLE
dose. At this time we are not certain how long protection will last from
the booster doses in adults. But that is important for us to know.
Again, you can see that use of new vaccines in new populations requires
careful surveillance, to monitor vaccine program impact. John?

MORAN:

Now let's talk about the investigation of a suspected pertussis case.
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. Cough is the hallmark of pertussis. But
remember that in very young infants pertussis may present as apnea, or
stopping breathing. When the diagnosis of pertussis is suspected,
appropriate specimens should be obtained for laboratory testing. For
national reporting, there are two different methods by which cases can
be laboratory confirmed. These methods include **isolation of Bordetella
pertussis from a clinical specimen**, or a **positive polymerase chain
reaction assay**, PCR. Let me repeat that: for laboratory confirmation
of pertussis, we need either isolation of Bordetella pertussis from a
clinical specimen, or a positive PCR test. **Direct fluorescent antibody
testing, or DFA, has low sensitivity and variable specificity, and
should NOT be used** for laboratory confirmation. Commercial serological
tests for pertussis infection are not standardized, and there is no
absolute association between antibody levels and immunity. Results of
serologic testing are not used for case confirmation for national
reporting except in Massachusetts, where a standardized serological
assay has been in use for many years. Isolation of Bordetella pertussis
remains the gold standard for diagnosis. However, even in the best
circumstances the organism takes time to isolate. But try. Also, it is
important to remember that Bordetella parapertussis may be isolated from
a mixed infection with Bordetella pertussis and generally grows faster.
The laboratory should continue to look for Bordetella pertussis when it
finds parapertussis. The longer you wait to obtain the nasopharyngeal
swab for pertussis culture, the less likely you will be to isolate the
organism. **Cultures are most often positive if the nasopharyngeal swab
is obtained within the first week of cough onset**. **Beyond the first 3
weeks of illness, the organism is recovered less often**, except in
infants, who can remain culture positive for **more than 6 weeks**. It
is also less likely that you will be able to isolate the organism if the
patient has already been taking an antibiotic effective against
pertussis, like erythromycin, azithromycin, or trimethoprim
sulfamethoxazole.

In addition to being the gold standard for diagnosis of pertussis,
culture is important for another reason. Isolates are the only way to
evaluate for antimicrobial resistance, and are used for molecular
typing. **PCR** can also be used for pertussis laboratory confirmation.
This test is now **widely available**, and has been found in many places
to be a **rapid, sensitive, and specific** method for diagnosing
pertussis. Unfortunately **some PCR assays have not been completely
reliable**. That is why it is very important that **cultures continue to
be performed, even if PCR tests are used**. We have heard about the
importance of obtaining a nasopharyngeal swab for pertussis culture and
PCR, but many of you may not have ever OBTAINED a nasopharyngeal swab.
The quality of the specimen collection is critical to obtaining a
positive test.

Since good technique in obtaining a nasopharyngeal swab is such an
important part of pertussis surveillance, we would like to show you a
brief video on the proper technique for NP swabs. Have a look.

\[UNSCRIPTED VIDEO OF MAN OBTAINING A SWAB FROM HIS NOSE\]

MORAN:

That video was produced by Dr. Jim Nordin of Health Partners in
Minneapolis. We would like to thank Dr. Nordin for allowing us to use
it. Laboratory results, particularly cultures, are an important part of
the investigation of a suspected case of pertussis. But there is other
information you will need to collect as well. As always, we need
**demographic data** like age and gender. We also need **clinical
data**, such as the duration of cough, and the presence of paroxysms,
whoop, and post-tussive vomiting. This information is important because
laboratory testing cannot always be obtained, or may not be conclusive.
We use the clinical data to determine if the person met the clinical
case definition for pertussis. We need to know how severe the illness
is, and that is why we ask about **complications** like pneumonia, and
whether or not the patient survived. And of course, the **vaccination
history** is critical. A complete vaccination history includes the
**date, vaccine type, manufacturer, and lot number** for each dose of
vaccine. This is important for all ages now that vaccines are
recommended for all ages. However, vaccination history is ESPECIALLY
important for cases among preschool children. A pertussis surveillance
worksheet is included in the surveillance manual. The worksheet will
help you organize your case investigation so not miss any critical
information. We will include a link to the manual on the broadcast
resources webpage. How can you find out if your pertussis surveillance
system is working? One easy method is by using a surveillance indicator.
For pertussis, that means finding out if anyone is even CONSIDERING the
diagnosis. If cultures are not being done, no cases will be reported,
because no one is looking. We will talk more about surveillance
indicators later in the program. If you determine that no one is
looking, there is a lot that can be done to improve pertussis
surveillance at the community level. Most importantly, doctors need to
know that pertussis is an important cause of severe cough illness in
adolescents and adults. They may think of pertussis as a disease only of
children. Some adults undergo extensive and unnecessary evaluations for
prolonged cough without the diagnosis of pertussis even being
considered. Increasing awareness of providers about this infection is
very important. We have begun a new era in prevention and control of
pertussis, with new vaccines available and changes in the recommended
vaccination schedules. Surveillance will be essential to evaluate the
impact on pertussis incidence in the United States. Cynthia?

GOOD:

Thank you, John. We will be back in a moment to discuss influenza.

ATKINSON:

Influenza viruses are responsible for respiratory illness in people of
all ages throughout the world. The usual symptoms of uncomplicated
influenza are fever, muscle aches, headache, sore throat, nasal
congestion, cough, and extreme tiredness. Some people can become very
ill from influenza. Influenza can exacerbate underlying chronic
diseases, and lead to viral or bacterial pneumonia. The risk for
complications of influenza is highest in persons 65 years of age and
older and in those with chronic health conditions. In most years, an
average of about 36 thousand people in the United States die because of
complications of influenza. Among adults, influenza is generally more
severe than illness caused by other respiratory viruses. Even so,
influenza infection often cannot be distinguished from other respiratory
virus infections based on clinical information alone. As a result,
**laboratory testing is necessary to confirm the diagnosis of
influenza**. Methods for confirming the diagnosis of influenza include
**virus culture, detection of viral antigens, and serologic testing**.
However, only a virus culture can give information about the antigenic
variant of influenza that is causing an illness. There are **two types
of influenza** that cause epidemics in humans- **type A and type B**.
Influenza **type A viruses, but not influenza B viruses, are grouped
into SUBTYPES on the basis of two surface proteins, hemagglutinin and
neuraminidase**. The two subtypes of influenza A currently circulating
worldwide among humans are subtype H3N2, and subtype H1N1. Influenza A
subtypes and influenza B viruses are **further characterized as specific
strains**. One of the most striking features of the influenza virus is
its tendency to change its antigenic structure, particularly the
hemagglutinin protein. Influenza A and B viruses undergo **gradual,
continuous antigenic change**, known as **drift**, **resulting in new
antigenic variants**. Because of this constant antigenic change, a prior
influenza infection or vaccination may not protect a person from the
particular influenza virus variant that is circulating each year. This
is why influenza epidemics occur almost every year. These antigenic
changes also mean that each year's influenza vaccine can be different
from the previous year. Influenza type A viruses also undergo a more
dramatic antigenic change known as **shift**. Antigenic shift **produces
a new human influenza A subtype** with a new hemagglutinin protein or
new hemagglutinin and neuraminidase proteins. Antigenic shift **occurs
because of an exchange of gene segments between an animal and human
influenza virus, or by adaptation of an animal virus to a human host**.
Some scientists believe that the increased prevalence of the H5N1 strain
of avian influenza in Asia and Europe may increase the chance of a
genetic recombination. This might happen if a human or other animal were
to be infected with both this and a human influenza virus strain
simultaneously. When a new strain of influenza A appears, almost
everyone is potentially susceptible to infection, setting the stage for
a world wide influenza epidemic, known as a pandemic. Fortunately,
antigenic shifts do not occur very frequently. The last shift that
resulted in a pandemic was the appearance of Hong Kong influenza, - or
H3N2- in 1968. No one can predict when the next shift will occur,
although influenza surveillance can help to identify new subtypes of
influenza A when they do occur. Influenza surveillance is important for
**detecting antigenic shifts as well as the more frequent antigenic
drifts**. It is also important for **monitoring the impact of influenza
each year in terms of illness and mortality**. Influenza surveillance
provides information needed to document the epidemiology and public
health impact of the virus. Individual cases of influenza are usually
NOT investigated by public health personnel. The only cases that need to
be investigated are those that are unusual in some way, such as cases
caused by an unusual viral isolate as part of the investigation of a
defined outbreak. All influenza deaths in children and adolescents
should be investigated in detail.

In the U.S. we do not try to count the actual number of cases of
influenza that occur each year. This is because many infected
individuals are asymptomatic or experience only mild illness, do not
seek medical care, and laboratory testing is rare in less severe cases.
Instead, we conduct surveillance that allows us to determine when,
where, and what type of influenza viruses are circulating, identify
significant changes in circulating viruses, track influenza related
illness, and assess the overall impact that influenza has on illness and
death. **Virologic data** from surveillance **help guide decisions about
the strains of influenza to be included in each year's vaccine,** and
**detect the emergence of viruses** with pandemic potential. These data
also can **assist healthcare providers in making treatment decisions**.
For example, if influenza activity has been confirmed in a community, a
physician can be more confident that a patient with influenza-like
illness actually has influenza. This can allow the physician to begin
treatment with antiviral drugs, if indicated. If started within 48 hours
of onset of symptoms, these drugs can reduce the duration of influenza
symptoms. Knowledge of the type of viruses that are circulating can also
help physicians choose which antiviral to prescribe because some
antivirals treat influenza type A and B and other antivirals treat only
influenza A.

Influenza viruses can spread very rapidly, and have no respect for the
borders of states or countries. As a result, knowledge of influenza
virus activity in other countries is critical.

So, how do we do influenza surveillance in the United States? Influenza
surveillance in the United States consists of seven surveillance
systems: the influenza **sentinel provider surveillance system**, which
tracks the%age of physician office visits due to influenza-like illness;
the **Emerging Infections Program** and the **New Vaccine Surveillance
Network,** which track laboratory confirmed influenza associated
hospitalizations and Emergency Department visits in children; the **122
Cities Mortality Reporting System**, which monitors influenza and
pneumonia deaths in 122 cities in the United States; and **nationwide
reporting of pediatric deaths** associated with laboratory confirmed
influenza infection. You may recall that influenza deaths among children
received a lot of media attention during the early influenza season of
2003 -- 2004. During that influenza season CDC requested that states
report laboratory confirmed deaths among children younger than 18 years.
The Council of State and Territorial Epidemiologists made these deaths
reportable beginning in 2004. Influenza deaths among children are
important to highlight the severe health effects of this disease. A
better understanding of influenza-related death in this age group will
help us evaluate and perhaps revise our current influenza vaccination
recommendations for children. Additional influenza surveillance in the
U.S. includes **state and territorial epidemiologists** who report
influenza activity levels. This gives an overall weekly estimate of
influenza activity within each state during the influenza season; and,
finally, the **World Health Organization and national respiratory and
enteric virus laboratory surveillance system**, from which virologic
data are obtained. Traditionally, influenza surveillance in the United
States has been conducted from October through mid-May but we are now
moving to year round reporting from as many sites and systems as
possible.

**State and local health departments** play a vital role in annual
influenza surveillance in numerous ways. State and local health
departments **oversee all influenza surveillance components;** **enroll
and maintain contact with the influenza sentinel providers;** and
**promote year round surveillance for all relevant influenza
surveillance components**. They also **report influenza associated
pediatric deaths;** **determine and report the state's overall weekly
estimate of influenza activity;** perform **laboratory testing** for
influenza and report results to CDC; and **submit a subset of influenza
isolates to CDC for antigenic characterization**. During an influenza
pandemic some surveillance enhancements might be instituted to improve
geographic and demographic coverage, and increase the amount of detail
captured by particular components of the surveillance system. In
particular, we know that it will be necessary to enhance surveillance by
testing more specimens during the early stages of the pandemic, report
data more frequently, and perhaps collect additional data. State and
local health departments will play a critical role in implementation of
these pandemic surveillance enhancements. Cynthia?

GOOD:

Bill, the possibility of a new pandemic of influenza has been in the
news a lot in the last few months. What can states do to get ready for
another pandemic?

ATKINSON:

Yes, there has been a lot of news about avian and pandemic influenza
lately. The increasing spread of avian influenza is certainly a concern.
Fortunately the Department of Health and Human Services released their
long-awaited pandemic influenza plan in November 2005. This is a very
useful document that can help states and localities prepare for pandemic
influenza. We will put a link to the HHS pandemic plan on our broadcast
resources webpage.

GOOD:

Thanks, Bill. We will be back to discuss Haemophilus influenza
surveillance right after this.

MORAN:

Among young children, invasive disease due to Haemophilus influenzae
type b has virtually disappeared in the last few years. With widespread
use of conjugate Haemophilus influenzae type b vaccines, this disease
has changed from the most common cause of bacterial meningitis in
infants, to a medical rarity. The bacterium Haemophilus influenzae can
be either **encapsulated or unencapsulated**. The **capsule is composed
of polysaccharide**, of which there are **six antigenically distinct
types**. The capsular types are **designated by the letters a through
f**. Nontypable, or unencapsulated strains may also cause invasive
disease, but are generally less virulent than encapsulated strains.
Nontypable strains are rare causes of serious infection among children
but are a common cause of ear infections in children and bronchitis in
adults.

Before introduction of effective vaccines, the type b encapsulated
strain, or Hib for short, accounted for more than 95% of invasive
Haemophilus influenzae disease among children. In the **prevaccine
era**, there were an **estimated 20,000 cases of invasive Hib disease
annually among children less than 5 years of age** in the United States.
Hib was the **leading cause of bacterial meningitis in the United States
among children in that same age group**. Nearly **two thirds of cases
were among children younger than 18 months of age**. Conjugate vaccines
against the Hib bacterium were first licensed for use in infants in the
United States in 1990. Invasive Haemophilus influenzae infections became
nationally notifiable in 1991. Since then, vaccine coverage increased
rapidly, and Hib disease DECREASED rapidly. This graph shows the
incidence of invasive Hib disease among children younger than 5 years of
age since 1989, shown by the **yellow line**. Rates fell rapidly after
introduction of the conjugate vaccine. By 1994, the incidence of Hib
among children younger than 5 years of age had decreased by 95% compared
with the prevaccination era. Rates have remained very low since then.
Notice that rates of non-type b disease, shown by the **green line**
have remained basically unchanged. In 2004, among children younger than
5 years of age, 19 cases of invasive disease due to Haemophilus
influenzae type b were reported in the United States. In addition,
another 177 cases of unknown serotype were reported, so the actual
number of Hib cases could be anywhere between 19 and 196. Most cases are
occurring among unvaccinated or incompletely vaccinated children. Let's
talk now about the surveillance and investigation of Haemophilus
influenzae type b disease. Invasive Haemophilus influenza disease
includes a number of clinical syndromes, including meningitis,
epiglottitis, periorbital and buccal cellulitis, septic arthritis,
sepsis, and pneumonia. Of course, these syndromes can be caused by other
bacterial and viral agents as well, so case confirmation requires
isolation of Haemophilus influenzae from a normally sterile body site.
But isolation of the organism is not the end of the laboratory
investigation. The next step is serotyping. This is an extremely
important laboratory procedure that **should be performed on EVERY
isolate of Haemophilus influenzae from a normally sterile site**.
Serotyping is especially important for isolates from children younger
than 15 years of age. Serotyping is the **only way to determine if an
isolate is type b**. This is important because only type b is
preventable by vaccination. Serotyping provides critical information to
those in public health who need to decide whether or not the contacts of
the case require chemoprophylaxis. The serotype also has clinical
implications for evaluating the immunological status of the patient.
That is, a case who had been vaccinated may indicate that the person may
not have responded normally to the Hib conjugate vaccine.

Laboratory support for Haemophilus influenzae serotyping should be
readily available through your state laboratory. For advice on
serotyping capability within your state, contact your state health
department.

Other than getting the isolate for serotyping, what else needs to be
done for case investigation? After you hear about a possible case, you
need to review laboratory, hospital, and other clinical records to
obtain the critical information needed on every case. This includes
**demographic** and relevant **clinical data**. Clinical data needed
includes the **clinical syndrome, dates of hospitalization, date of
first positive culture, and outcome of the illness**. **Results of**
**laboratory testing** are critical. The **serotype of the isolate, body
fluid source of the isolate, and antibiotic susceptibility** are all
important. **Vaccination status** should be obtained for every case.
Since there are several types of Hib vaccines, this means the **date,
manufacturer, and lot number** of each Hib vaccine dose. This
information tells us whether the case occurred as a result of vaccine
failure, or failure to vaccinate. Finally, we need information on **risk
factors for Hib disease**. One of the most important of these is whether
or not the child attended childcare and whether the child was premature.
If the child attended childcare, control measures may be needed for
other center attendees. How can surveillance for Hib disease be
improved? Hib is a laboratory- based diagnosis and virtually all cases
are hospitalized for the first few days of the illness. As a result,
reporting can be virtually complete if all clinical microbiology
laboratories and all hospitals report the cases that they see.

With so few cases of Hib disease now occurring, how can we be sure that
our surveillance is good enough to detect the few cases that may still
be out there? Remember, only type b disease is preventable by
vaccination. That means that disease that LOOKS like Hib, but is caused
by non- type b strains, is still occurring at the same rate it always
did. Although rates vary in different populations, data from active
surveillance suggest that non-b cases continue to occur at a rate of
about 1 or 2 cases per 100 thousand children younger than 5 years of
age, per year. If cases of invasive Haemophilus influenzae disease are
being serotyped and reported among children, and these cases are NOT due
to type b, surveillance is probably good enough to detect type b cases.

If you are not finding type b cases, but you ARE finding NON-type b
cases, that is good evidence that type b disease is probably not present
in your community. This is an example of a surveillance indicator. We
will be talking more about surveillance indicators later in the program.
Cynthia?

GOOD:

Thank you, John. We will be back in a moment to discuss pneumococcal
surveillance.

ATKINSON:

The heptavalent pneumococcal conjugate vaccine-- PCV7 - was licensed by
the Food and Drug Administration in February 2000. It was made a part of
the recommended childhood immunization schedule in October of that same
year. However, because of vaccine cost and some manufacturing shortages,
national coverage rates are not as high as for the other routinely
recommended pediatric vaccines. National Immunization Survey data for
2004 indicate that national coverage is about 73%, with coverage in
states and metropolitan areas ranging from 44% to higher than 90%.

As with other vaccine preventable diseases, we need to establish
surveillance to monitor the impact of our vaccination program. Before we
talk about what such a program might look like, a little background on
pneumococcal disease. Streptococcus pneumoniae are **gram- positive
bacteria. There are 90 known serotypes. As with other encapsulated
organisms, the polysaccharide capsule is an important virulence factor,
and capsular type specific antibody is protective**. Although all
serotypes may cause serious disease, a relatively limited number of
serotypes cause the majority of invasive infections. Overall, the 10
most common serotypes are estimated to account for about 60% of invasive
disease worldwide. But the ranking and serotype prevalence differs by
age group and by geographic area.

Among children younger than 5 years of age in the U.S., seven serotypes
accounted for 80% of isolates from blood or cerebrospinal fluid at the
time the pneumococcal conjugate vaccine was licensed. In contrast, these
same 7 serotypes accounted for only about 50% of isolates from older
children and adults. Currently, five years after vaccine licensure, the
seven vaccine serotypes account for about 20% of cases in children
younger than 5 years of age. Pneumococcus is a frequent inhabitant of
the upper respiratory tract and may be isolated from the nose, throat,
or both of about 10% of people at any given time. Carriage rates among
children may be even higher. All persons probably carry pneumococci at
some time during the course of a year. Transmission can probably occur
as long as the organism is present in respiratory secretions. We do not
understand why some of these people go on to develop invasive disease.
Host factors, such as underlying illness, are probably important. But
persons without any underlying illness may also develop invasive
pneumococcal disease. **Bacteremia without a known site of infection is
the most common clinical presentation of invasive disease among children
younger than 2 years of age**. Bacteremia accounts for about 70% of
invasive disease in this age group. With the decline of invasive Hib
disease, pneumococcus has become the **most common cause of bacterial
meningitis in the United States**. The **highest rate of meningitis are
among children younger than 1 year of age**, approximately 10 cases per
100 thousand population. This graph shows the incidence of invasive
pneumococcal disease by age group prior to use of PCV7, based on data
from CDC's Active Bacterial Core Surveillance. The vertical axis shows
incidence, expressed as rates per 100 thousand population. The
horizontal axis shows age groups in years. The highest rates are in
children younger than 2. Incidence falls to its lowest point among
children 5 to 17 years of age. After age 34, the incidence of
pneumococcal disease then rises steadily with increasing age. But the
incidence of invasive pneumococcal infection in persons 65 and older is
less than half of that in young children. Although pneumococcal
infections occur in healthy children, there are medical and other
factors that significantly increase the risk. Children with **functional
or anatomic asplenia**, **sickle cell disease** and other sickle
hemoglobinopathies, and children with **HIV infection** are at extremely
high risk of invasive disease. Some studies estimate rates more than 50
times higher than the rates among children of the same age without these
conditions. **Out-of-home group child care** has been shown to increase
the risk of invasive pneumococcal disease and acute otitis media. The
risk for children in these settings is increased 2 to 3 fold among
children younger than 5 years of age. Finally, children of **certain
racial and ethnic groups** have increased rates of invasive pneumococcal
disease. These include Alaska Natives, certain American Indian groups,
and African Americans. The reason for this increased risk is not clear.
Much of our knowledge of the incidence and risk factors for invasive
pneumococcal disease comes from special studies and surveillance
systems. One such surveillance system is the CDC's Active Bacterial Core
Surveillance- or ABCs. We asked Dr. Chris Van Beneden, the medical
director of ABCs to describe this system for us.

VAN BENEDEN:

CDC's Active Bacterial Core Surveillance -- or ABCs - is an active,
laboratory and population- based surveillance system for invasive
disease due to 6 bacterial pathogens: groups A and B streptococcus,
*Haemophilus influenzae*, *Neisseria meningitidis*, *Streptococcus
pneumoniae*, and methicillin-resistant *Staphylococcus aureus,* or MRSA.
The principal objectives of ABCs are to accurately measure the incidence
of these 6 bacterial pathogens; to determine their epidemiologic
characteristics; to track trends over time; and to provide an
infrastructure for further public health research. ABCs is a core
component of the Emerging Infections Program Network-or EIP -- and is
conducted at 10 EIP- sites across the United States. These sites
represent a population of over 38 million persons. ABCs is managed by
staff in the National Center for Infectious Diseases. For each case of
invasive disease in the surveillance population, a case report with
basic demographic and clinical information is completed. The bacterial
isolate is sent to CDC and other reference laboratories for additional
evaluation. ABCs also provides an infrastructure for further valuable
public health research, including special studies aimed at identifying
risk factors for disease, post-licensure evaluation of vaccine efficacy
and monitoring effectiveness of prevention policies. For *Streptococcus
pneumoniae*, the main objectives of surveillance are to measure the
burden of invasive pneumococcal disease among persons of all ages; to
track emerging antibiotic resistance; and to study the impact of
pneumococcal vaccines. The principal objectives for *Neisseria
meningitidis* are to provide baseline data related to the meningococcal
conjugate vaccine; to evaluate vaccine impact on disease burden, herd
immunity, and molecular epidemiology; and to determine appropriate
verification and validation criteria for current and potential
serogrouping methods. Data from ABCs has been particularly useful in
documenting the impact of pneumococcal conjugate vaccine among children
and the indirect benefit of this vaccine for older persons. Data for all
six diseases included in ABCs, as well as estimates of disease burden
extrapolated to the U.S. population are available on the Active
Bacterial Core Surveillance web site.

MORAN:

Data from ABCs have been invaluable for documenting the burden of
invasive pneumococcal disease among children, and for identifying groups
of children at increased risk of disease. The ABCs data have also been
valuable in documenting the impact of pneumococcal vaccination of
children. In fact, since implementation of PCV7 vaccination, the ABCs
indicate that rates of invasive pneumococcal disease have fallen very
significantly. In 2004, the rate of invasive pneumococcal disease in
children younger than 2 years was 38 cases per 100 thousand population,
down from 191 cases per 100 thousand population before the vaccine was
licensed.

But ABCs only operates in 9 selected locations. We cannot rely on it to
document the impact of each state's program for vaccination of children
with pneumococcal conjugate vaccine. To monitor the impact of state's
vaccination programs, each state must evaluate the impact of invasive
pneumococcal disease with time and within populations. These national
data, based on each state's surveillance, should be used to look at
rates between groups\... to see if state programs are appropriately
reaching individuals and groups recommended for vaccination.

Passive surveillance does not yield the same type of data as the ABCs
related to tracking vaccine impact or projecting real numbers of cases.
But each state's data would allow comparisons among states to see if
funding differences or immunization program differences are leading to
differences in disease rates. This would help identify inequalities that
need to be addressed at the national level. Fortunately, we have a good
model for how to go about doing this from surveillance for Haemophilus
influenzae invasive disease. Invasive disease due to either of these
organisms is a laboratory- based diagnosis. Laboratories usually provide
very complete case reporting. With a requirement for reporting of
laboratory- confirmed cases, and infection control staff backing up that
system by reporting hospitalized cases, national reporting for invasive
pneumococcal disease can be virtually complete. In 1999 the Council of
State and Territorial Epidemiologists voted to make invasive
pneumococcal disease among children younger than 5 years of age
nationally notifiable. That is not to say that invasive disease in older
age groups is not important. But our national immunization program is
directed at young children, so that is the focus of our efforts in
surveillance, at least for now. Currently, however, only 31 states and
the District of Columbia have requirements for reporting invasive
pneumococcal disease among children younger than 5 years of age. Once we
identify a case of invasive pneumococcal disease in a child less than
five years old, what information should we collect? We need the core
information that should be collected for every case of vaccine
preventable disease, including **demographic and clinical data**, and
**risk factors** for invasive disease. For pneumococcal disease risk
factors include underlying medical conditions such as asplenia or HIV
infection, and out-of-home childcare. And of course, we are interested
in **vaccination history**. Most cases will be among unvaccinated or
incompletely vaccinated children. But there will be cases reported among
vaccinated children. These vaccinated cases could represent vaccine
failure -disease caused by a serotype included in the vaccine. They
could also represent disease caused by a serotype NOT included in the
vaccine. Remember that prior to PCV7 implementation, about 20% of
invasive disease in children was caused by serotypes that are not in the
vaccine. However, currently about 80% of invasive disease is caused by
nonvaccine serotypes. The ABCs serotyping study that was set up to
monitor possible vaccine failures has been completed, and in March 2005,
CDC and CSTE notified states that serotyping was no longer available
through CDC for this purpose.

To differentiate vaccine failure in a vaccinated child from disease
caused by a serotype not included in the vaccine, the isolate would have
to be serotyped. Unfortunately, serotyping of pneumococcal isolates is a
specialized laboratory procedure that is currently not commonly
performed except by facilities conducting research studies. CDC
laboratorians and epidemiologists, together with their colleagues, are
working to develop a cost-efficient, more routinely available testing
system for serotyping pneumococcal isolates. But what should we do right
now? At this time, the focus of **state-based surveillance** should be
to **compare state rates to rates elsewhere** to see if they are within
expected range, and to **compare among populations within the state** to
make sure their vaccination programs are reaching all groups adequately.
If states' rates are increased, the next step would be to determine the
cause. In the special situations of an outbreak or increased rates, the
CDC laboratory may be able to provide serotyping. It is possible that
with vaccine-types going out of circulation, there could be more
outbreaks of nonvaccine type disease. In this situation you should
contact the Respiratory Diseases Branch of the National Center for
Infectious Diseases to discuss your specific situation. Contact
information for the Respiratory Diseases Branch is on our broadcast
resources webpage. If you identify a child with invasive pneumococcal
disease who has received one or more doses of pneumococcal conjugate
vaccine, you should **request the laboratory to save the isolate**. If
stored, these isolates would be available if needed in case of
outbreaks, unexplained increases in rates, or inequity in rates between
subsets of states' populations. Remember that as use of the vaccine has
increased, we have seen the disease burden decrease dramatically- a
decrease of about 80%. That is why, at the national level, we will be
relying on your help in conducting national surveillance. Cynthia?

GOOD:

Thanks, John. We will be right back to discuss meningococcal disease
surveillance.

ATKINSON:

With the dramatic reductions in Streptococcus pneumoniae and Haemophilus
influenzae, Neisseria meningitidis has become a leading cause of
bacterial meningitis in the United States. In January 2005, a
**tetravalent meningococcal polysaccharide-protein conjugate vaccine --
MCV4** -- was **licensed for use among persons 11 to 55 years of age**.
This new vaccine provides protection for **serogroups A, C, Y, and
W-135**. ACIP **recommends this vaccine for routine vaccination of young
adolescents 11 to 12 years of age**. In addition, for those people who
have not previously received MCV4, ACIP recommends vaccination for
**children at** **approximately 15 years of age before high school
entry**. Routine vaccination with meningococcal vaccine is also
recommended for **college freshman living in dormitories** and for
**other populations at increased risk**, such as persons with anatomic
or functional asplenia, military recruits, and certain international
travelers. Before this conjugate vaccine was licensed, the ACIP
recommended a polysaccharide vaccine for protection against the same
four serogroups. The older vaccine was recommended only for persons at
increased risk of disease and was not recommended for routine use among
either college freshman living in dormitories or among 11 and 12 year
olds. The reason for the wider recommendation for the new conjugate
vaccine is that it is expected to produce longer lasting protection and
to reduce carriage of Neisseria meningitidis. This will protect not only
the vaccinated individual but the community as well. We now have a
recommendation for routine use of meningococcal vaccine, so it is
important to establish national surveillance to monitor the impact of
the vaccination program. Before we discuss the components of
surveillance, lets go through some background information about
Neisseria meningitidis. **Neisseria meningitidis** is **transmitted
through respiratory secretions** from a person with invasive disease or,
much more commonly, from an asymptomatic carrier. Invasive meningococcal
disease occurs in three common **clinical forms**: **meningitis**, in
about 50% of cases, **blood infection,** or meningococcemia, in about
30% of cases and **pneumonia** in about 10% of cases. Other forms
account for the remaining ten% of cases. Fewer than one-fifth of
patients develop **purpura fulminans**, the skin manifestation of
meningococcemia. Approximately **1400 to 2800 cases occur each year** in
the United States, with a **case-fatality ratio of 10 to 14%**. In
addition, **serious sequelae occur in 11 to 19% of survivors** including
deafness, neurologic deficit, or limb loss. Although the **highest rate
of disease is among children younger than 2 years of age**, **62% of
meningococcal disease in the U.S. occurs among persons 11 years of age
or older**. Serogroups B, C, and Y are the major causes of meningococcal
disease in the U.S., each currently being responsible for about one
third of cases. The proportion of cases caused by each serogroup changes
with time and varies by age group. For example, serogroup B accounts for
more than 50% of cases among infants younger than 1 year of age. There
is no serogroup B vaccine available in the U.S. at this time. Among
persons 11 to 19 years of age, 75% of cases are caused by serogroups C,
Y, or W-135, which are included in U.S.- licensed vaccines. The majority
of these cases are sporadic single cases. Although outbreaks cause
tremendous public concern and disruption, they accounted for less than
3% of all cases.

This graph, from the ABCs active surveillance system, shows rates of all
reported meningococcal disease- not just vaccine serotypes- by age
group. The overall rate in the United States is about 1 case per 100
thousand population, shown here in the **pink line**. Rates are highest
in infancy with a second peak in adolescence, around 18 years of age.
About 20% of cases occur among adolescents and young adults ages 14 to
24. About 16% of cases occur among infants younger than 1 year of age.
College freshmen living in dormitories are at higher risk than the
general population of similar age. Disease is seasonal, with cases
peaking in December and January. In the U.S., invasive Neisseria
meningitidis is nationally notifiable. The states report cases to the
CDC as part of the **National Notifiable Diseases Surveillance System or
NNDSS**. The NNDSS includes case reports from healthcare providers and
laboratories in all 50 states. In addition, active surveillance for
meningococcal disease is conducted by the CDC **Active Bacterial Core
surveillance** project, known as ABCs. You heard about the ABCs system
earlier in the program. Because invasive meningococcal disease is quite
rare in the United States, and because all states should monitor the
impact of their vaccination programs, ABCs surveillance data will not be
adequate for surveillance purposes. It is critical that every state
investigate, lab confirm, serotype, and report every case of invasive
disease.

As with Haemophilus influenzae and Streptococcus pneumoniae, diagnosis
of invasive disease due to Neisseria meningitidis is based on isolation
of the organism from a normally sterile site. A diagnosis based on
culture is quite specific, with infrequent false positives. With the
national requirement for reporting, laboratory confirmation, and
hospital staff reporting cases, reporting can be virtually complete.
Information that should be collected for a case of invasive Neisseria
meningitidis is similar to other diseases we have discussed today. We
need the core data, including **demographic, clinical, and risk
factors**. We need to know the person's age and risk factors because the
current vaccine is only recommended routinely for certain age groups,
and for persons with specific risk factors. **Vaccination history** is
important, and **laboratory** data provides critical information. To
determine whether a case could have been prevented by vaccination,
testing must be performed to determine the serogroup of the isolate.
Serogroup testing of Neisseria meningitidis isolates is performed by
hospital and state public health laboratories. Cases of serogroup A, C,
Y, or W-135 in persons eligible for vaccination may represent either a
vaccine failure or a failure to vaccinate. Cases that are type B are not
vaccine preventable. With the licensure of meningococcal conjugate
vaccine, and the new recommendations for its routine use among
adolescents, a new era has begun in the prevention of this terrible
disease. Surveillance will play an important role as we monitor
meningococcal immunization programs and assess progress toward our
prevention goals. Cynthia?

GOOD:

Thanks Bill. We will be right back to discuss the surveillance of
vaccine adverse events.

MORAN:

During this program we have talked about the surveillance of vaccine
preventable diseases- why it is important, and how surveillance differs
based on the level of control we have achieved. But in our business,
surveillance for DISEASE is only part of the story. We also need to
perform surveillance for the vaccines themselves- for vaccine coverage,
effectiveness and safety. We focus this section of the program on the
surveillance of adverse events following vaccination. We need to ensure
adequate surveillance for vaccine adverse events for any vaccine
currently in use, regardless of the stage of disease control. But
surveillance for adverse events following vaccination is especially
important for newly licensed vaccines. We usually give vaccines to
healthy people- including very young children- and vaccines often are
required by state immunization laws. So vaccines are held to a higher
standard of safety than other medications. But like any medication, no
vaccine is perfectly safe or effective. Some vaccines cause minor
adverse events like local reactions or fever. And, rarely, they can
cause serious adverse events, like seizures, encephalopathy, or severe
allergic reactions. But, until vaccine preventable diseases are
eradicated, we will continue to use vaccines. So it is critical that all
of us do everything we can to ensure that vaccines are as safe as
possible and to maintain public confidence in vaccines. To do this, we
need to monitor closely the occurrence of adverse events, evaluate
possible associations, and respond appropriately to those risks. Before
licensure, vaccines undergo extensive **testing and review for safety,
immunogenicity, and efficacy**. Prelicensure studies **usually include
unvaccinated comparison- or control- groups**, so we can determine which
reactions were actually caused by the vaccine. However, prelicensure
trials include a **relatively small number of participants**. Usually,
the vaccine has been given to only a few thousand people, and usually
they are monitored for a limited time period. And the studies are often
conducted in **homogenous populations, meaning groups that are less
diverse** than those in which the vaccine is ultimately used. And
finally, because the number of participants is relatively small the
**sensitivity for detection of uncommon or rare adverse events before
licensure is low**. Because of the inherent limitations of prelicensure
testing, we cannot rely on prelicensure studies to identify all the
reactions that may occur once a vaccine is more widely used. For that,
we rely on postlicensure surveillance, which is the continuous
monitoring of vaccine safety in the general population after licensure.
The **National Childhood Vaccine Injury Act** was passed in 1986. This
law **required that healthcare providers who administer vaccines and
vaccine manufacturers report certain serious adverse events following
specific vaccinations**. The Act **stipulates that the vaccines, the
adverse events, and the time of occurrence of the adverse event after
vaccination be reported**. It also requires that any event listed in the
manufacturer's package insert as a contraindication to subsequent doses
of the vaccine be reported. The Vaccine Adverse Event Reporting System,
or VAERS, is a national passive surveillance system that was established
to provide a single system for the collection and analysis of reports of
adverse events following vaccination. CDC and the FDA work together on
the system. The VAERS form, shown here, is included in the surveillance
manual. It can also be downloaded from the VAERS website. Healthcare
providers can complete and submit paper report forms, or may choose to
submit a web-based report. Additional report forms, assistance in
completing the form, or answers to other questions about VAERS are
available 24 hours a day by dialing the toll-free number
**800-822-7967**. You can also **Email VAERS at inf@vaers.org**.

The objectives of VAERS are **to detect previously unrecognized
reactions to vaccines**, **to detect increases or decreases in
previously reported events**, **to detect pre-existing conditions that
may predispose to adverse events**, and **to detect vaccine lots with
unusual numbers and types of reported reactions**. The Food and Drug
Administration reviews reports of death and other serious events each
week and conducts analyses of reports by vaccine lots. CDC conducts
additional analyses as needed to address specific vaccine or adverse
event concerns, and to evaluate trends in reporting. VAERS has
**limitations**. It **only contains reports of people who experienced
specific health events following a dose of vaccine**. The system does
not contain information on ALL people who were vaccinated, so it
**cannot be used to estimate the rates of adverse events**. It also
**cannot be used to determine whether the event was actually caused by
the vaccine**. Analysis of VAERS data is intended to identify patterns
of adverse events that occur following the vaccine. However, population
based databases, such as the Vaccine Safety Datalink -- or V-S-D, must
also be used to evaluate whether these events are causally associated
with vaccine, or occurred coincidentally. The VSD is a collaborative
project involving CDC and several large managed-care organizations and
contains medical and immunization information on more than seven million
people. The postlicensure vaccine safety monitoring system in the United
States has proven to be an extremely valuable resource. A good example
of the utility of the system was the 1999 detection by VAERS of cases of
intussusception occurring among children who recently received rotavirus
vaccine. A major public health response followed identification of this
signal, which ultimately led to the removal of that rotavirus vaccine
from the market. VAERS data indicated a possible problem which led to a
more definitive study, which led to policy action. The system worked
exactly the way it was intended to work. A more recent example was the
2005 detection of Guillain Barre syndrome occurring in recent recipients
of meningococcal conjugate vaccine. An investigation of these reports is
in progress now. No changes have been made to ACIP recommendations for
this vaccine. All vaccine providers can contribute to the success of
this system by reporting any adverse event that might be related to
vaccination in either children or adults. The system works because YOU
make it work.

GOOD:

Thanks, John. We will be back in a moment to discuss surveillance
indicators.

ATKINSON:

We rely on surveillance to monitor the effectiveness of our immunization
programs. But how can we monitor the effectiveness or quality of our
surveillance? We have already talked about the difficulties of doing
surveillance when the disease for which we are doing surveillance is
rare. How do we know if there were no cases because there really WERE no
cases, or because no one was looking? We rely on surveillance indicators
to monitor the quality of national surveillance. We have already talked
about the critical elements that need to be collected during
investigation of cases of vaccine preventable diseases. These include
demographic information, relevant clinical and laboratory data, and
vaccination status. Monitoring whether or not these data are reported
lets us track the quality of case investigation, and we do this
routinely. But that does not tell us whether or not zero cases reported
REALLY means zero disease or infection. This year in the United States
we had the first case of poliomyelitis- a case of imported vaccine
associated polio- reported since 1999 in an unvaccinated young adult. We
have also documented a vaccine-derived poliovirus circulating in an
unvaccinated Amish community in Minnesota. We must maintain our
vigilance and surveillance for polio and other now extremely rare
vaccine preventable diseases. We recently spoke with Sandy Roush,
Surveillance Officer in the Epidemiology and Surveillance Division of
the National Immunization Program, about measuring the quality of
national surveillance.

KROGER

Surveillance is a critical component of public health. Sandy, what is
the importance of using surveillance indicators to measure the quality
of vaccine preventable disease surveillance?

ROUSH

National surveillance for vaccine-preventable diseases traditionally
relies on passive reporting, which is often incomplete. In spite of this
limitation, national surveillance data are useful for routine
surveillance because they are used primarily for monitoring trends in
disease occurrence rather than in response to individual cases. However,
for diseases with very few remaining cases, as with most of the vaccine
preventable diseases, surveillance data must be very complete. Every
case counts. We need to know whether zero reported cases means that
there is really no disease. Surveillance indicators have been developed
to assess the quality of national surveillance - that is, the ability of
our surveillance system to identify all cases, if and when they are
present. In addition, surveillance must be specific enough to exclude
non-cases by adequate case investigation and laboratory testing.

KROGER

How long have we been using surveillance indicators for vaccine
preventable diseases?

ROUSH

Methods to monitor surveillance quality were first developed in 1988 by
the Pan American Health Organization as part of the polio eradication
effort in the Western Hemisphere. In the polio eradication effort,
surveillance was performed not just for paralytic poliomyelitis, but for
a syndrome including both paralytic polio and other clinically
compatible conditions. In the absence of polio, these other conditions
causing acute flaccid paralysis -- or AFP - remain constant over time.
So, if the reported AFP rate remained constant without confirmed or
compatible polio, there was confidence that the absence of reported
cases of polio in fact meant the absence of polio. The system was
sensitive enough to find AFP- and polio - if it were present. This
surveillance indicator used an external standard -- AFP -- to measure
the quality of surveillance.

KROGER

Indigenous transmission of measles and rubella has been eliminated in
the U.S. Do we have specific surveillance indicators for these diseases?

ROUSH

Yes, we do. Surveillance indicators for measles and rubella are quite
similar. Both include completeness of data, timeliness of reporting,
proportion of cases that are laboratory confirmed, and the proportion of
chains of transmission that have an imported source. If our surveillance
system can identify imported cases of measles and rubella, we have
confidence that the system could identify indigenous cases, too, if they
were present. For rubella, we also measure the proportion of cases among
women of child-bearing age with known pregnancy status. For measles, we
measure the proportion of chains of transmission for which a clinical
specimen is submitted for virus isolation.

KROGER

That makes sense. Is there a measles surveillance indicator related to
cases that were ruled out through case investigation?

ROUSH

Yes. Discarded measles-like illness -- or MLI - surveillance was
established in 1997 to document the ability of the US surveillance
system to identify cases, if present. The MLI data collected by the
states helped to document the elimination of endemic measles in the U.S.
Now that elimination of indigenous transmission has been documented,
surveillance quality can be monitored using indicators based on data
routinely collected through the national surveillance system. In fact,
the National Immunization Program recommends that states discontinue
collection of MLI data, as of January first, 2006.

KROGER

Are there surveillance indicators for any other vaccine preventable
diseases?

ROUSH

Yes. We have also developed indicators for Haemophilus influenzae and
pertussis surveillance. For Haemophilus influenzae, we measure the
timeliness and completeness of case information for children younger
than 5 years of age, including vaccination history and serotype. We can
also track the incidence of non-type b disease among children younger
than 5 years of age. Based on active surveillance data, we expect 1 or 2
cases of NON-type b Haemophilus influenzae per 100 thousand children per
year. So, if no cases of NON-type b disease are being found,
surveillance for type b disease may be inadequate. For pertussis, we
measure completeness of data for vaccination history and duration of
cough, as well as the proportion of cases that are laboratory confirmed
or epidemiologically linked to another confirmed case. We are working
with federal and state partners to develop surveillance indicators for
other vaccine preventable diseases as well, including mumps, varicella,
and meningococcal disease.

KROGER

Sandy, thank you for discussing surveillance indicators with us today.

ROUSH

My pleasure.

ATKINSON:

These are a few approaches to monitoring the quality of surveillance. We
do surveillance to monitor the quality of our immunization program. We
use surveillance INDICATORS to monitor the quality of our surveillance.
With the incidence of many of the vaccine preventable diseases at all
time record lows, we CANNOT be sure that zero means zero unless we can
document that someone is looking.

GOOD:

This brings us to the close of this edition of Surveillance of Vaccine
Preventable Diseases. Before we say goodbye, a comment about any
unanswered questions you may have. If you have any questions about
disease surveillance procedures, case investigation, or the availability
of laboratory support, you should FIRST contact your state immunization
program. They will be able to answer most of your surveillance
questions. You can use the Internet to Email questions, comments, or
requests to the National Immunization Program. Our Email address is
**nipinfo@cdc.gov**. Throughout this program we have mentioned several
immunization resources, including the Surveillance Manual. You will find
links to these and much more on the National Immunization Program
website at www.cdc.gov/nip. Click on the Healthcare Professional tab,
and go to the Education and Training section. There you will find a link
to Broadcast Updates and Resources. Finally, if you would like to find
out more about upcoming Public Health Training Network courses, visit
the PHTN website at www.cdc.gov/phtn. Thank you for joining us today. It
has been our pleasure to bring this program to you. Goodbye

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