**Section 2**

**Nominal mean *Campylobacter* cases in the U.S. population**

+-------+-------------------------------------------+------------------+
| **Sym | **Description**                           | **Formula**      |
| bol** |                                           |                  |
+-------+-------------------------------------------+------------------+
| p     | Probability a person with                 | Beta             |
| ~mn~, | campylobacteriosis seeks care             | distribution     |
| p~mb~ |                                           | based on data    |
|       | (non-bloody, bloody enteric cases)        |                  |
+-------+-------------------------------------------+------------------+
| p     | Probability a person with                 | Beta             |
| ~cn~, | campylobacteriosis who has sought care is | distribution     |
| p~cb~ | then requested to supply a stool and      | based on data    |
|       | complies                                  |                  |
|       |                                           |                  |
|       | (non-bloody, bloody enteric cases)        |                  |
+-------+-------------------------------------------+------------------+
| p~t~  | Probability a lab tests a stool sample    | Beta             |
|       | for *Campylobacter*                       | distribution     |
|       |                                           | based on data    |
+-------+-------------------------------------------+------------------+
| p~+~  | Probability a stool with *Campylobacter*  | Beta             |
|       | is cultured positive                      | distribution     |
|       |                                           | based on data    |
+-------+-------------------------------------------+------------------+
| λ2~n~ | Nominal mean number of *Campylobacter*    | =                |
|       | cases in U.S. population (non-bloody,     | λ1~n~/(p~mn~\*p~ |
| λ2~b~ | bloody, invasive and total)               | cn~\*p~t~\*p~+~) |
|       |                                           |                  |
| λ2~I~ |                                           | =                |
|       |                                           | λ1~b~/(p~mb~\*p~ |
| **λ2  |                                           | cb~\*p~t~\*p~+~) |
| ~T~** |                                           |                  |
|       |                                           | =λ1~i~           |
|       |                                           |                  |
|       |                                           | =λ               |
|       |                                           | 2~n~+λ2~b~+λ2~i~ |
+-------+-------------------------------------------+------------------+

**Parameter estimations**

[2.1]{.underline} (p~mn~, p~mb~) -- [Probability a person with
campylobacteriosis seeks care]{.underline}

Two estimates were provided for this proportion, one for the probability
that a person with enteric illness would seek care if they reported
having no blood in their stool (p~mn~) and one (p~mb~) for bloody
diarrhea.

The proportion of cases that sought care for "diarrheal illness" is
based upon a 1998-9 population survey of 12,755 persons. The people
interviewed were from the general population of the FoodNet sites
(selected counties in California, Connecticut, Maryland and New York and
the states of Georgia, Minnesota and Oregon), representing 8.6% of the
U.S. population (26). The survey was conducted for the entire year.
Approximately 150 persons per site were interviewed per month. People
were randomly selected using a random digit dialing, single stage,
Genesys-ID sampling method and were interviewed using methods similar to
those used in the Behavioral Risk Factor Surveillance System. Cases
excluded from the survey included persons with chronic illness, colitis,
prior surgery to remove part of their stomach or intestine and irritable
bowel syndrome (n=680); resulting in a total number of 12,075 usable
interviews. Of the 12,075 usable interviews, **645** individuals
reported having a "diarrheal illness," defined as three or more loose
stools within a 24-hour period, or diarrhea lasting for more than one
day or which resulted in an inability to perform normal activities. Of
the 645 persons with a diarrheal illness, 30 reported bloody stools, 609
reported non-bloody stools and 6 were unknown.

(p~mn~) *Probability a person with campylobacteriosis and **non-bloody**
diarrhea seeks care*

Of those **609** cases with a diarrheal illness and non-bloody stools,
**20.5%**, a weighted estimate (131/609), sought care (26). The estimate
was adjusted to account for unequal probabilities of selection to allow
population estimates to be made. Factors that affected selection
probabilities included the number of people in a household. Age and sex
were also weighted, creating an "external weight" so that the sample
population resembled that of the U. S[^1]. Because a confidence interval
was not available for the estimate, uncertainty about the parameter was
modeled using a Beta distribution as follows:

p~mn~ = Beta(609\*0. 205+1, 609\*(1-0.205)+1)

(p~mb~) *Probability a person with campylobacteriosis and **bloody**
diarrhea seeks care*

The same population survey identified **30** people who reported bloody
diarrhea. Of the thirty persons with bloody diarrhea, nine sought care
and an adjusted estimate of **33.2%** for p~bm~ was given (26).
Uncertainty about the parameter was modeled using a Beta distribution as
follows:

p~mb~ = Beta(30\*0. 332+1, 30\*(1-0.332)+1)

*Invasive disease*

No information is available to estimate this parameter, see Section 1.3.
It was assumed that, due to the severity of illness, 100% of people with
invasive *Campylobacter* illness sought care.

DISCUSSION: These estimates are for diarrheal illness, and not
campylobacteriosis specifically. Data describing care seeking behavior
for campylobacteriosis was not available. Bacterial foodborne disease is
typically more severe than viral foodborne disease (42) and rates of
seeking care may differ by pathogen.

In the population survey, factors that were most important in
influencing the decision to seek care were fever, vomiting, "how sick
they felt," stomach cramps, reporting blood in stool and duration of
diarrhea (26). Some of these factors were evaluated for diarrheal
illness in the telephone survey and compared with the same
characteristics in individuals who had culture-confirmed *Campylobacter*
infections or diarrheal disease (Table 2.1). Comparing the groups, a
greater proportion of people with culture-confirmed *Campylobacter*
cases were affected by fever and blood in the stool than the people
seeking care for diarrheal illness. Therefore, the actual rate of
seeking care for campylobacteriosis may be underestimated by the 20.5%
for persons with non-bloody and 33.2% for persons with bloody stools.
However, because a greater proportion of people with fever and bloody
stools would be cultured and enrolled in the case control study, such
comparisons are difficult.

ASSUMPTION(s): The rate at which people reporting bloody stools seek
care is similar to the rate at which people with campylobacteriosis
reporting bloody stools seek care. The rate at which people with
non-bloody stools seek care for diarrheal illness is similar to the rate
at which people with campylobacteriosis reporting non-bloody stools seek
care.

DATA GAP: Additional studies to define the rate at which people with
campylobacteriosis seek care (123) would be helpful and would provide a
more accurate estimate. These data would require very large
community-based surveys.

Table 2.1. Comparison of characteristics of illness most important in
seeking care between the telephone population survey of all diarrheal
illness (26) and culture confirmed campylobacteriosis and a survey of
diarrheal disease

+---------------+--------------------+-------------------+------------+
| C             | Diarrheal Illness  | Culture-confirmed | CCCC       |
| haracteristic |                    | *Campylobacter*   |            |
|               | Seeking Care &     | Cases             | 1980-1^c^  |
|               | Submitted Cultures |                   |            |
|               | -- 1998-9^a^       | \(CCCC\) 1998^b^  |            |
+---------------+--------------------+-------------------+------------+
| Sample size   | 21                 | 1461              | 239        |
+---------------+--------------------+-------------------+------------+
| Fever         | 48%                | 83%               | 74%        |
+---------------+--------------------+-------------------+------------+
| Vomiting      | 50%                | 30%               | 38%        |
+---------------+--------------------+-------------------+------------+
| Stomach       | 75%                | 86%               | 79%        |
| Cramps        |                    |                   |            |
+---------------+--------------------+-------------------+------------+
| Blood in      | 15%                | 46%               | 46%        |
| stool         |                    |                   |            |
+---------------+--------------------+-------------------+------------+

^a^Population Survey,(Ref. 26)

^b^*Campylobacter* Case Control Study (Ref. 28)

^c^Survey conducted in eight hospitals in the National Nosocomial
Infections Study (Ref. 17, Table 2).

[2.2]{.underline} (p~cn~, p~cb~,) -- [Probability a person with
campylobacteriosis who has sought care is then requested to submit a
stool and complies, for non-bloody and bloody diarrhea]{.underline}

Two estimates were provided for this proportion, equivalent to the
probability that a person with an enteric illness would be requested to
submit a stool sample and comply, if they reported having no visible
blood (p~cn~) or having visible blood (p~cb~) in their stool.

The probability that a specimen was requested and submitted was
determined from the same population survey of the seven FoodNet sites as
listed in Section 2.1.

##### (p~cn~) Non-bloody diarrhea

From the CDC population survey that identified 18 people reporting
non-bloody diarrhea that were requested to submit and did submit a stool
sample for culture of **128** persons reporting non-bloody diarrhea and
seeking care and responding to the survey question, CDC provided an
adjusted estimate of **15.1%** for p~cn~ (26). The estimate was adjusted
to account for the number of people in a household, see Section 2.1.

Confidence intervals were not available with the weighted population
estimates and in the absence of confidence intervals, uncertainty about
the parameter was modeled using a Beta distribution as follows:

p~cn~ = Beta(128\*0.151+1, 128\*(1-0.151)+1).

(p~cb~) *Bloody diarrhea*

In the population survey, the proportion of persons with a diarrheal
illness that reported blood in their stools were requested to submit a
stool sample and did submit was **26.1**% (weighted estimate based on
3/**9**)(26)[^2].

Confidence intervals were not available with the weighted estimates and
in the absence of confidence intervals, uncertainty about the parameter
was modeled using a Beta distribution as follows:

p~cb~ = Beta(9\*0.261+1, 9\*(1-0.261)+1).

Invasive disease

There is no information on the rate of physician requests for diagnostic
testing or rate of sample submission for cases of invasive disease
caused by *Campylobacter*, see Section 1.3. In this assessment, we have
assumed a rate of 100%.

ASSUMPTION: The probability that a stool specimen was requested among
people with diarrheal illness reporting bloody stools is similar to the
probability that a stool specimen was requested among people with
campylobacteriosis reporting bloody stools. The probability that a stool
specimen was requested among people with diarrheal illness reporting
non-bloody stools is similar to the probability that a stool specimen
was requested among people with campylobacteriosis reporting non-bloody
stools.

[2.3]{.underline} (p~t~) -- [Probability a lab tests a stool sample for
*Campylobacter*]{.underline}

##### Non-Bloody Stool and Bloody Stool

In a survey of 309 laboratories in the five original FoodNet sites (CA,
CT, GA, MN, OR, population 14,281,096 million persons), **389,255**
stools were submitted during 1996. In the laboratories surveyed, **367,
846** (94.5%) of submitted stool specimens were tested for
*Campylobacter* (115).

Thus, this parameter was modeled using a Beta(367846+1, 389255-367846+1)
distribution which is essentially a single point estimate of 94.5%
because of the very large data set.

*Invasive disease*

No information is available for an estimate, see Section 1.3. The
proportion is assumed to be 100% for invasive disease.

[2.4]{.underline} (p~+~) -- [Probability a stool with *Campylobacter*
cultures positive]{.underline}

The problems with the lack of sensitivity of stool culture are two-fold.
First, stool culture techniques lack sensitivity as *Campylobacter* are
fastidious microaerophillic organisms that, when exposed to oxygen or
other stress, may enter a non-culturable state. Secondly, sensitivity of
stool culture is limited by the amount of *Campylobacter* present in the
stool. Finally, handling of the specimen is important and contributes to
the lack of sensitivity of culture of *Campylobacter*. Sub-optimal
specimen handling and storage may allow competitive growth by other
bacteria or result in low numbers of *Campylobacter* in the stool that
could reduce the likelihood that *Campylobacter* will be identified
during culture. In addition, there are no standardized methods for
isolation of *Campylobacter* and the increased costs associated with
enrichment procedures and the utilization of highly selective media that
would improve isolation discourages their routine use.

In an outbreak at a camp in New Zealand of *Campylobacter* enteritis, in
1990, associated with exposure to spring water, of 116 persons attending
or resident at the camp, 44 showed clinical symptoms. Of the 44 clinical
cases, 14 showing signs of enteric disease submitted stools for culture.
Of the **14** specimens submitted from clinically affected individuals
only **11** (78.6%) cultured positive for *Campylobacter* (55). Serology
was not conducted to determine if rising titers of immunoglobulins were
evident in persons ill and culture negative to determine if they may
have been exposed to the pathogen.

Because another, U.S. related, estimate of the sensitivity of stool
culture was not available and to assess whether this estimate was a
close approximation to the true value for the sensitivity of stool
culture, Dr. Fred Angulo, from CDC and Dr. Irving Nachamkin, from the
University of Pennsylvania Medical Center, were surveyed for their
expert opinions of the sensitivity of stool culture for *Campylobacter*
(personal communications). Their estimates of 70% and 75%, respectively
were close to the mean value of the parameter modeled.

DISCUSSION: There is little information on the sensitivity of stool
culture methods and the methods for culturing stools are extremely
diverse. Specimen handling is another factor that can greatly decrease
the sensitivity of stool culture methods. In a review of non-typhoidal
salmonellosis, an assumed estimate of the sensitivity of culturing
*Salmonella* was 70% and was used to estimate the burden of
salmonellosis in the U. S. (117). This estimate was adopted for
determining the burden of campylobacteriosis in a recent review of
foodborne disease (70).

DATA GAP: There is incomplete knowledge of the sensitivity of culturing
specimens for *Campylobacter* and an estimate with a large degree of
uncertainty was used from the literature. A study to estimate the
sensitivity of stool culture as commonly practiced in labs testing stool
for *Campylobacter* would provide a more precise estimate.

Thus, this parameter was modeled:

p~+~= Beta (11+1,14-11+1).

[2.5]{.underline} (λ2~n~, λ2~b~, λ2~i~, **λ2~T~**) -- [Nominal Mean
number of *Campylobacter* cases in the U.S.]{.underline}

[Estimate of expected number of people in U.S. population ill with
enteric *Campylobacter* infection and bloody and non-bloody diarrhea and
with invasive disease *Campylobacter* in year in population and the sum
of the three]{.underline}

Calculation of the estimate of illness caused by *Campylobacter* in the
U.S. population is done by combining the results determined by category
of disease, enteric without observable blood in stools, enteric with
observable bloody stools and invasive disease.

(λ2~n~, λ2~b~, λ2~i~): *The estimates of illness caused by Campylobacter
in the U.S. population*

The estimate of expected number of people in U.S. population ill with
enteric disease was modeled separately for non-bloody and bloody
diarrhea. Invasive disease caused by *Campylobacter* in a year is
determined as equal to λ1~i~. This assumes that, due to the severity of
the illness, all invasive cases of campylobacteriosis would seek care
and provide a stool sample. The estimates, by category of disease,
enteric with observable bloody stools and enteric without observable
blood in stools and invasive disease are calculated as follows:

For non-bloody stool:

λ2~n~ = λ1~n~/(p~mn~\*p~cn~\*p~t~\*p~+~)

For bloody stool:

λ2~b~ = λ1~b~/(p~mb~\*p~cb~\*p~t~\*p~+~)

For invasive disease:

λ2~i~ = λ1~i~

  ----------- ----------------- -------------- -------------- --------------
  **Year**    **Model output**  **5^th^        **Mean**       **95^th^
                                percentile**                  percentile**

  **1998**    **λ2~n~**         822,273        1,307,500      1,999,114

              **λ2~b~**         158,991        460,951        1,065,573

              **λ2~i~**         433            567            715

  **1999**    **λ2~n~**         641,837        1,016,954      1,559,694

              **λ2~b~**         124,414        358,581        829,404

              **λ2~i~**         420            538            668
  ----------- ----------------- -------------- -------------- --------------

Therefore the sum of the total number of cases in the U.S. population
is:

**λ2~T~** = λ2~n~+ λ2~b~ + λ2~i~

The statistical characteristics of the distribution of the sum of the
total number of cases in the U.S. population are given below:

  -------------- -------------- -------------- ----------- -------------- -----------
  **Year**       **Model        **5^th^        **Mean**    **95^th^       
                 output**       percentile**               percentile**   

  **1998**       **λ2~T~**      1,113,895      1,769,018   2,773,268      

  **1999**       **λ2~T~**      867,090        1,376,073   2,156,934      

  **Difference                                 -392,945                   
  (99-98)**                                                               
  -------------- -------------- -------------- ----------- -------------- -----------

![](media/image1.wmf)

**Figure 2.1**. The confidence distribution (distribution of
uncertainty) for the nominal mean total number of cases of
campylobacteriosis in the U.S. for 1998 and 1999. *Note that the
vertical axis for this and all other figures showing histogram (relative
probability) representations of probability distributions have no scale:
this is because the y-axis scale simply normalizes the curve to contain
an area equal to unity. Values associated with higher likelihoods are
more probable* *than values associated with lower likelihoods, but the
height does* *not represent* *a* *probability for any given value.*

# Section 2 Summary

The expected total number of cases of campylobacteriosis is then
estimated as **λ2~T~** = λ2~i~ + λ2~n~ + λ2~b.~ The estimates for 1998
and 1999 using this model are given in Figure 2.1. The mean estimate of
the distribution for 1998 is 1.77 million cases, with a 5^th^ percentile
estimate of 1.11 million and a 95^th^ percentile estimate of 2.77
million. The mean estimate of the distribution for 1999 is 1.38 million,
the 5^th^ percentile estimate is 0.867 million and the 95^th^ percentile
estimate is 2.16 million. Relative contributions of the various
components of the model to the model uncertainty will be presented in
Section 5, Sensitivity Analysis.

[^1]: In the draft risk assessment the 1996-7 population survey (25, 49)
    was used to estimate the probability of seeking care and submitting
    a stool. A second population survey was conducted in 1998-9 (26) and
    was used to update these parameters in the model. The 1998-9 data
    were considered more relevant to the years modeled.

[^2]: From the draft version of the risk assessment the physician survey
    (27,48) was dropped because reponses to the physician survey
    questionnaire were not data-driven, but rather based on physician
    recall.