1. An Outbreak of Pertussis in an Amish Community Delaware, 2004-2005
March 6, 2006
KATHY KUDISH, DVM, MSPH
Delaware Division of Public Health
CDC / Office of Workforce and Career Development
Good afternoon. My name is Kathy Kudish. I am an Epidemic Intelligence Service officer with the Centers For Disease Control and Prevention. I am a field assignee based at the Delaware Division of Public Health. I am going to discuss with you today findings from an investigation of a pertussis outbreak that occurred in the Amish community in Delaware during September 2004 through February, 2005.

2. Background
Bacterial respiratory tract infection caused by Bordetella pertussis
Incubation period commonly 7–10 days
Illness spectrum
Classic illness: paroxysmal cough with whoop
Less “classic” illness: mild respiratory infection with persistent cough
Subclinical
Complications include pneumonia, seizures, encephalopathy, death
As a quick review:
Pertussis, which is also known as “whooping cough”, is a bacterial infection caused by Bordetella pertussis. An incubation period which is commonly 7-10 days is followed by the onset of an upper respiratory infection, with a pronounced cough that may become severe. The cough may last for several months. However, less severe illness or subclinical infection can also occur, especially in those that have partial immunity. Complications occur more commonly in infants and include pneumonia, seizures, and in rare cases encephalopathy or death.

3. Reported Pertussis: U.S. 1922–2004
All ages
DTP
<7 yrs
This is a graphical description of the number of pertussis cases in the US from , borrowed from a CDC publication.
In the pre-vaccine era, pertussis was a major cause of morbidity and mortality among infants and children in the U.S.
A dramatic decline in the number of reported cases began after the introduction of whole cell pertussis vaccines, and later, widespread use of diphtheria-tetanus-pertussis trivalent vaccine, or DTP, in the 1940’s.
On the next slide I will discuss the inset graph.
MMWR February 1, 2002 / 51(04);73-6

4. Reported Pertussis: U.S. 1980–2004
All ages
Number of
Cases
<7 yrs
In the 1980s and ‘90s, the number of reported cases began to gradually increase again; most of this increase has been in older age groups. In 2004, 25,827 cases were reported in the U.S., the highest number since 1964.
Year

5. Amish Community: Delaware
Religious community
Population ~1,700
323 households
9 church districts, each led by a bishop
Children aged 6–14 years attend one of ten one-room school houses
Vaccine clinics held at Amish homes since 1980
For a bit of background on the Amish:
The Amish in Delaware reside primarily to the west of Dover. Most of the families live within a 200 square mile area. The map to the right depicts the Amish households in the state, each blue dot represents one family. An estimated population of 1,700 people live in 323 households. The community is divided geographically into nine church districts, each led by a bishop. Children aged 6–14 years attend one of 10 community run schools. Vaccination coverage is presumed to be low, as it has been in other Amish communities. Nurses at Delaware Division of Public Health, which I will refer to as DPH, have held fixed outreach vaccine clinics at two Amish homes since 1980 to encourage vaccination. An outbreak of pertussis occurred in this same community in 1984.
Map of Delaware
Represents a single Amish
household

6. Pertussis Outbreak, 2004–2005
October 2004: 5 Polymerase Chain Reaction (PCR) positive samples reported from Amish persons
December 2004: 7 additional PCR positive samples reported from Amish persons
Increased clinical case reports in the Amish community
Families requesting medication
In late October 2004, 5 Polymerase Chain Reaction, or PCR positive samples were reported from Amish persons by the state laboratory. By late-December, 7 additional PCR positives were reported from Amish persons. There were anecdotal reports to DPH of many clinical pertussis cases in the Amish. Families began calling DPH to request medication.

7. Outbreak Control Measures
Health alert notices (HAN) sent to local physicians
Specimen collection kits distributed
Clinics at Amish schools
Dispense antibiotics and vaccinate
Test suspected cases
Educate about pertussis
Intensified contact tracing and medication delivery
DPH initiated outbreak control measures which included the following: We sent notification to physicians to inform them of the outbreak in the form of Health Alert Notices; we distributed specimen collection kits to local physicians with instruction on proper specimen collection; we held two “pertussis clinics” at Amish school houses to dispense antibiotics, offer vaccination, test suspected cases, and educate about the disease; and we conducted active surveillance in the community, going door to door and asking about cough illness and delivering medication to Amish homes.
In January, the state of Delaware requested an Epi-Aid from CDC, and a formal investigation was initiated.

8. Objectives Describe the outbreak Evaluate control measures
Understand reasons parents declined vaccination
Identify culturally appropriate and effective means to prevent pertussis outbreaks
Objectives of the outbreak investigation included: To describe the outbreak in this unique community, to evaluate control measures, to understand reasons parents declined vaccination for their children, and to identify culturally appropriate and effective means to prevent future pertussis outbreaks.

9. Methods: Overview Laboratory Data Case finding Population Estimate
Active surveillance
Cross-sectional survey
Household survey
Population Estimate
Immunization Registry
The methods utilized during the investigation include information from laboratory results, case finding, a household interview survey, a population estimate, and data on vaccination status of children in the Amish community against diphtheria-tetanus-pertussis, which I will refer to as DTP, from a query of the state immunization registry.

10. Methods: Laboratory Pertussis PCR testing Pertussis Culture
Nasopharyngeal (NP) swabs collected from suspected cases
Delaware DPH Laboratory
Pertussis Culture
Centers for Disease Control and Prevention
Select number of samples cultured
Laboratory testing was performed on nasopharyngeal, or NP swabs collected from suspected cases early in the outbreak, and later from select individuals to verify continued transmission in the community. PCR was performed at Delaware DPH laboratory. The state laboratory no longer routinely performs pertussis cultures. Because pertussis PCR is not standardized, several samples were sent to CDC for culture confirmation of the outbreak.

11. Case Finding Outreach, active surveillance Cross-sectional survey
Determine magnitude of outbreak
Self-administered
Enrollment: all families in the Amish community
Household survey
Case finding was accomplished through community outreach and active surveillance by DPH. We used a cross-sectional survey of the Amish community to identify emergent cases and determine the magnitude of the outbreak. We asked that every family complete the survey. We distributed and collected the survey through the bishops in each church district.
A second, more detailed survey was administered by interview with an Amish household representative, which in nearly all cases was the mother.

12. Household Survey Survey administration Household member information
Enrollment: Households with cough illness
Interview using standard questionnaire
Household member information
Illness and exposure information
Beliefs and attitudes about pertussis and vaccines
Household survey interviews were completed where there was a cough illness reported. We gathered information about the members of the household regarding cough illness symptoms, medication use, and vaccination status. We also asked questions about household beliefs and attitudes regarding pertussis and vaccines.

13. Population Estimate Amish directory created by community members
Updated for
2005
Contains birth
dates of all
members
We estimated the Amish population using an Amish directory published by a community member. This directory was updated in In addition to residence address, the directory also contains the birth dates of each family member, as well as other genealogical information.

14. Delaware Immunization Registry
DTP status queried for children aged 6 months–5 years
Mandatory physician reporting since 1999
> 90% of children aged < 6 years are enrolled in the registry
We queried DTP status of children aged 6 months–5 years in the Delaware Immunization Registry. Physician reporting to the registry became mandatory in State public health care providers have been reporting to the registry since approximately >90% of children in Delaware less than 6 years of age are purportedly enrolled in the registry.

15. Pertussis Case Definitions
Clinical Case
– Acute cough illness of >14 days duration with onset during September 2004–February 2005
Confirmed case
Clinical case that is either
Laboratory confirmed by PCR or culture OR
Epidemiological link to a lab confirmed case
Probable Case
All other clinical cases
During the investigation, a clinical case of pertussis was defined as an acute cough illness of >14 days duration with onset of illness during September 2004 through February A confirmed case of pertussis was defined as a clinical case that was either laboratory confirmed or epi linked by common household residence to a lab confirmed case. All other clinical cases were considered probable.

16. Household Transmission
Primary case
First symptomatic person in household
Co-primary case
Cough onset within 6 days of primary case in household
Secondary case
Onset 7–42 days after primary case
Second primary case
Onset greater than 42 days after primary case in household
Person to person transmission was classified according to the time of symptom onset within a household. The first symptomatic person in a household was classified as the primary case. Cases in the same household with onset within 6 days of the primary case were defined as co-primary cases. Cases among household members with cough onset 7–42 days after a primary case were defined as secondary cases. Cases that occurred greater than 42 days after the primary case were defined as second primary cases.

17. Results

18. Laboratory Results PCR Culture
47 NP swabs obtained from Amish suspected cases; 30 (64%) PCR positives
7 non-Amish PCR positive cases from persons with no epidemiologic links to Amish during outbreak time period
Culture
8 NP swabs from Amish persons cultured
2 culture positive for B. pertussis
We will begin with the laboratory results.
We tested 47 NP swabs obtained from Amish suspected cases by PCR. 30 of these samples tested positive. There were an additional 7 non-Amish PCR positive cases in Delaware residents from persons with no epi links to the Amish during the outbreak time period. Eight samples from Amish persons were submitted for culture; 2 of these were positive.

19. Cross-sectional Survey Results
183 / 323 households = 56% response rate
195 probable cases from 1006 individuals
83 households reported a case
We received 183 completed self-administered surveys, for an overall response rate of 56%. 195 probable cases were reported from a total of 1006 individuals residing in the respondents homes’. 83 households reported a case.

20. Household Survey Results
109 / 323 (34%) household interviews
6 / 323 (2%) interview refusals
96 / 323 (30%) Amish households reported at least one case
272 cases (63 confirmed, 209 probable)
DPH conducted interviews at 109, or 34% of Amish households. A representative from 6 homes refused to be interviewed. Cases were reported from 96, or 30% of households.
272 cases, of which 63 were confirmed and 209 were probable, were reported.

21. Case Finding Results 343 total cases identified
63 confirmed, 280 probable
124 identified by both surveys, 71 by cross-sectional survey only, 148 by household survey only
130 households with a case
Community attack rate (AR) 20% (343 / 1,711)
Median age 6 years (range 0–75 years)
Cough onset ranged from September 12, 2004–February 12, 2005
When we combine the case count from both the self-administered and household interview surveys, there were 343 total cases, 63 confirmed and 280 probable. 124 cases appeared in both surveys, 71 in the cross-sectional only, and 148 in the household survey only. There were 130 households with a case. The community attack rate was 20%. The median age of cases was 6 years, with a range of 0-75 years. Onset of cough ranged from September 12, 2004 to February 12, 2005.

22. Cases of Pertussis by Week (n=321)*
Primary and Co-primary
Secondary
Second Primary
*Missing onset date
in 22 cases
This the epidemic curve generated from the combined surveys. We were able to determine the temporality of cough onset in 321 cases. The cough onset of the first cases occurred during the week of September 12-18, which corresponds to week 1. Primary and co-primary cases are shown in pink, secondary cases in light blue, and second primary cases in purple. The last week cases were detected was week 21, which ended on February 5. Our final interviews were conducted in week 22. Surveillance and testing for new cases continued through the month of March. ↑
Dec 25
Sept
12-18
Feb

23. Cases by District Confirmed cases Probable cases
34%
Confirmed cases
Probable cases
33%
* District attack rate
21%
Cases
17%
22%
13%
13%*
13% 5%
Cases were reported from all 9 geographic districts; the middle north district reported the highest number of cases, at 76, as well as the highest attack rate, at 34%. No confirmed cases were reported from the Midwest or South districts.

24. Household Transmission
Members
Primary Cases
Secondary Cases
No.
AR (%)
<1 year 73 11 15 9
1–5 years
318 94 30 48 21
6–10 years
246 52 29
11–14 years
160 19 12 8 6
> 15 years
914 39 4 27 2
All
1711
215 13
121
This chart depicts the household transmission patterns obtained from combining the surveys. The column containing primary cases includes all primary, co-primary, and second primary cases. Of note is that children aged 1–5 years had the highest primary and secondary attack rates in the community, at 30 and 21% respectively. Children aged 6–10 years had the second highest primary attack rate at 21%; children under 1 year and children aged 6–10 years had the second highest secondary attack rates, each at 15%.

25. Proportion of cases by age group, Amish Outbreak and U.S., 2004
If we were to compare the proportion of cases by age group in this outbreak to the 2004 U.S. data, the contrast is striking.
While 72% of cases in the Amish outbreak occurred in children under age 11, only 35% of U.S. reported cases were younger than age 11.
While the contrast in age related proportion of cases is striking, there are some inherent age related reporting biases in U.S. surveillance data that may exaggerate this comparison.

26. Household Survey Results
During the remainder of the results slides I will be discussing data generated from the survey done by household interview only.

27. Immunization Status DTP Status Total (%) All cases (%) no DTP 106 (65)
DTP vaccination status among children aged 6 months–5 years enrolled in household survey
DTP Status
Total (%)
All cases (%)
no DTP
106 (65)
88 (72)
1 or 2 doses DTP
8 (5)
6 (5)
> 3 doses DTP
49 (30)
29 (24)
Total
163
123
Children aged 6 months–5 years are all eligible to have received 3 doses of DTP. This table shows the DTP vaccination status of children aged 6 months–5 years from case households and their disease status. Of 163 children, 106, or 65% had no DTP doses on record with the state registry. Only 49, or 30%, had 3 or more DTP doses. Of 123 children that met the clinical case definition, 88, or 72% had no recorded DTP doses.

28. Antibiotic Use
352 / 618 (57%) case-patients and household contacts reported obtaining an antibiotic
324 / 352 (92%) antibiotics provided by DPH
Erythromycin only
116 / 324 (36%) reported taking the antibiotics < 5 days
Antibiotics were used to treat and prevent pertussis cases by DPH and a handful of private physicians sought out by Amish patients. 352, or 57% of case-patients or household contacts of cases reported obtaining antibiotics; 324, or 92% of those that obtained antibiotics received them from DPH at no cost. Erythromycin was the only antibiotic provided by the state. 36% of those that obtained antibiotics from DPH took the medication for less than 5 days.

29. Antibiotics, con’t Reason for taking antibiotics
199 / 352 (57%) : treatment
111 / 352 (32%): prophylaxis
42 / 352 (12%): no reason cited
Results of prophylaxis
13 / 111 contacts became symptomatic and developed clinical pertussis after taking
7 during course of antibiotics
6 after taking antibiotics for >7 days
199, or 57% reported taking antibiotics for treatment, while 111, or 32% reported taking them for prophylaxis. 42, or 12% did not cite a reason. 13 people that took antibiotics for prophylaxis went on to become clinical cases...7 of the 13 had cough onset while taking antibiotics; 6 became symptomatic some time after completing 7 or more days.

30. Clinical Characteristics
Median duration of cough 4 weeks (range 2.0–18.0 weeks)
Associated symptoms
Coughing fits: 139 / 272 (51%)
Whoop: 99 / 272 (36%)
Post-tussive emesis: 91 / 272 (33%)
The median duration of cough was 4 weeks, with a range of 2–18 weeks. 51% reported coughing fits, 36% reported a “whoop” during coughing, and 33% reported post-tussive emesis.

31. Complications of Pertussis
Number (%)
(n=274)
Sleep disturbance
59 (22)
Apnea
11 (4)
Breathing difficulty
10 (4)
Weight loss
9 (3)
This is a summary of the complications reported by case-patients. Sleep disturbance was most commonly cited, at 22%. Apnea, breathing difficulty, and weight loss were also reported at 4, 4, and 3% respectively.
No seizures, pneumonia, hospitalizations, or deaths were reported.

32. Reasons for Not Vaccinating (n=47)
Fear of side effects
21 (44)
Didn’t think about it
14 (30)
Don’t feel that it is effective
3 (6)
Philosophical
2 (4)
Religious
5 (10)
No response
Medical reason
Among parents who reported that their children were not vaccinated, the most common reason cited was “fear of side effects” at 44%, followed by “didn’t think about it” at 30%. Other reasons such as “religious reason”, “don’t think it is effective”, and “philosophical reason” were less commonly sited.

33. Summary Epidemic was widespread in community
Cases of pertussis in every district
Peaked during the week of the Christmas holiday
Age distribution of cases during Amish outbreak resembles U.S. prevaccine era pertussis epidemiology
Young children had highest attack rates
In summary:
The pertussis epidemic was widespread in the community, with cases occurring in every district. The epidemic peaked during the week of the Christmas holiday. Numerous transmission settings are probable and they include Sunday religious services and social gatherings in the month leading up to Christmas including weddings and holiday celebrations.
The age distribution of cases in this epidemic closely resembled the U.S. prevaccine era epidemiology of pertussis.
Pre-school aged children had the highest attack rates in this epidemic.

34. Limitations Clinical case definition Recall bias Two different surveys
Immunization Registry
may be incomplete
Limitations of the study include the following:
The first is reliance on a clinical case definition. While we used the CDC case definition appropriate in an outbreak setting, persons can have cough of >14 days duration from other illnesses. The reliance on the clinical case definition to classify probable cases may have led to an overestimation of the size of the outbreak.
The survey data was collected retrospectively, so recall bias may have affected the quality of the data.
Also, some of the results were generated from combining surveys, so it is possible that answers varied by survey method.
Lastly, the immunization registry may be incomplete, leading to an underestimation of the actual proportion of vaccinated children in the community.

35. Conclusions Erythromycin compliance was suboptimal
Illness was relatively mild with no severe complications reported
A large proportion of Amish children are undervaccinated against pertussis
Fear of vaccine side effects may be an important reason for parents’ failure to vaccinate
In conclusion, erythromycin compliance was suboptimal, with over 1/3 of people taking less than 5 days of medication.
Illness was relatively mild in the community, with no severe complications reported.
A large proportion of children in the Amish community are undervaccinated against pertussis.
The fear of side effects may be an important reason for parents’ failure to vaccinate their children.

36. Recommendations Enhance immunization coverage in the Amish community
Increase awareness of the clinics in the community
Provide educational materials regarding immunizations to Amish families
Community outreach to discuss benefits of immunization versus side effects
Recommendations following the outbreak include:
Enhancing immunization coverage by increasing awareness of the existence of the Amish vaccine clinics in the community, by providing educational materials regarding immunization to Amish families, and by community outreach to discuss benefits of immunization versus side effects.

37. Acknowledgements Delaware DPH CDC
– Farhad Ahmed – Deri Austin – Fred Bailey
– Haima Bhat – Robin Cahall – Betty Jo Charles
– Carylon Comegys – Paula Eggers – Donna Felty
– Laura Gannon – Leroy Hathcock – Blenda Irwin
– Holly Lipko – Martin Luta – Jo Ann Moore
– Emily Outten – Marjorie Postell – Lorraine Rouse
– Paul Silverman – Laura Tobias – Joyce Waring
CDC
– Pamela Cassiday – Amanda Cohn – Katrina Kretsinger
– Christina Mijalski – Pekka Nuorti – Diana Bensyl
– Patricia Wilkins
I would like to acknowledge the following people for their contributions to this work.

38. Thank you
Thanks!
Ideal conditions pertussis culture only 80% sensitive. Unfortunately, only 3 or the PCR samples from DE were also submitted for culture. Two of those were positive by both means, only one was PCR positive and culture negative.

39. Self Reported Year of Past Pertussis

40. Relative Risk of Pertussis in Unvaccinated Children
Case
Non-Case 26 18 11 21
0 doses DTP
This is a 2X2 table comparing the relative risk of pertussis disease in vaccinated and unvaccinated children. The table includes only children aged 6 months-5 years, and all primary and co-primary cases are excluded. As we would expect, pertussis vaccination was protective; Children with 0 doses of DTP were 1.7 times as likely to develop pertussis compared with vaccinated children.
> 3 doses DTP
Relative risk = 1.7 (CI 1.0, 2.9)

41. Delaware Immunization Registry
Immunization status for children aged 6 months–5 years from households with pertussis cases
DTP Status*
Total (%)
All cases (%)
no DTP†
106 (65)
88 (72)
1 or 2 doses DTP
8 (5)
6 (5)
3 doses DTP
9 (6)
7 (6)
4 doses DTP
39 (24)
22 (18)
5 doses DTP
1 (1)
0 (0)
Total
163
123
* DTP/DTaP status
† No DTP or no match in registry

42. No history of pertussis
Cases
Non-cases
Total
History of pertussis 11 25 36
No history of pertussis
184 61
245
195 86
281
A verbal history of previous pertussis disease was obtained during interviews from mothers for children aged 6 months-10 years. Mothers reported past pertussis disease in 36/281 children aged 6 months-10 years. Of the 36 that reported past pertussis, 11, or 31% reported pertussis dz during this epidemic. Of those not reporting a history of pertussis, 184/245, or 75% met the case definition during this epidemic. Self-reported history of pertussis was found to have a protective effect; children with a past pertussis were 0.4 times as likely to become a pertussis case as those children without a history of pertussis.
Relative Risk = 0.4 (Confidence Interval 0.3–0.7)

43. Incidence Comparison, U.S. 2004 and Amish Outbreak
Cases
*U.S. Incidence
Amish Cases
*Amish
Incidence
<1 year
3,357
88.2 20
27,397.3
1–5 years
2,969
15.4
143
44,968.6
6–10 years
2,472
11.9 85
34,552.8
11–14 years
5,414
33.3 27
16,875.0
15–19 years
3,768
18.6 11
6,358.4
> 20 years
7,196
3.6 57
7,692.3
All
25,176
8.9
343
20,046.8
This chart depicts the household transmission patterns obtained from combining the surveys. The column containing primary cases includes all primary, co-primary, and second primary cases. Of note is that children aged 1–5 years had the highest primary and secondary attack rates in the community, at 30 and 21% respectively. Children aged 6–10 years had the second highest primary attack rate at 21%; children under 1 year and children aged 6–10 years had the second highest secondary attack rates, each at 15%.
* Per 100,000 Population