Cynthia F. Hinton, PhD, MS, MPH Pertussis Outbreak in a Highly-Vaccinated School Population–Faulkner County, Arkansas, 2007 Cynthia F. Hinton, PhD, MS, MPH Presented at the 42nd Annual National Immunization Conference, Atlanta, GA March 19, 2008

Background: Pertussis Outbreak in Faulkner County, Arkansas Occurred among school children from February 2007 Post-exposure antimicrobial prophylaxis given to contacts Cases reported through April Invited by Arkansas State Health Department to assist with investigation on April 24, 2007 Tdap campaign April 27, 2007 Vilonia is a small town north of the state capitol of Little Rock, about a 45 minute drive. Although still considered rural, the town is in one of the fastest growing areas of Arkansas, due to its proximity to Little Rock, and Conway a university town 14 miles west. Beginning in February 2007, the Vilonia school district in Faulkner county experienced an outbreak of cough illness affecting school-aged children, their families, school faculty and staff. Contacts received post-exposure antimicrobial prophylaxis, and as the outbreak continued the Arkansas Department of Health planned a Tdap vaccination campaign for the end of April for eligible students, faculty, and staff. Cases continued to be reported through April and on April 24, 2007, the state invited CDC to participate in an investigation of the outbreak.

Objectives Characterize epidemiology of outbreak Assess vaccine effectiveness The objectives of our investigation were to characterize the epidemiology of the outbreak and assess vaccine effectiveness in the affected school population.

Council of State and Territorial Epidemiologists (CSTE) Case Definitions Clinical case : Cough duration ≥14 days Paroxysms, whoop or post-tussive vomiting No other cause identified Probable case Meets clinical case definition with no laboratory or epidemiologic linkage Confirmed Case Cough with any duration and isolation of Bordetella pertussis Clinical case AND Positive polymerase chain reaction test (PCR) OR Epidemiologic-link to lab-confirmed case In conducting out investigation , we applied the following cases definitions: Clinical case : Cough duration ≥14 days plus one of the following symptoms: Paroxysms, whoop or post-tussive vomiting No other cause identified Probable case Meets clinical case definition with no laboratory or epidemiologic linkage Confirmed Case Cough with any duration and isolation of Bordetella pertussis OR Clinical case AND Positive polymerase chain reaction test (PCR) OR Epidemiologic-link to lab-confirmed case

Methods Corroborated PCR results from the Arkansas Public Health Laboratory at CDC Pertussis Laboratory using IS481 and ptxS1 primers Reviewed pertussis surveillance case records Accessed school vaccination records for grades K-7 We corroborated PCR results from the Arkansas Public Health Laboratory at CDC Pertussis Laboratory using IS481 and ptxS1 primers We reviewed pertussis surveillance case records collected by the state, and We accessed school vaccination records for grades K-7 to assess vaccine efficacy

Laboratory Confirmation 23 cases identified with 1-target PCR CDC corroborated 3 cases with 2-target PCR using IS481 and ptxS1 primers 19 identified by commercial laboratories 14 cases had epidemiologic-linkage No positive culture We were able to send samples collected by the Arkansas Public Health Laboratory to the CDC Pertussis laboratory for corroboration by 2-target pcr using IS481 and ptxS1 primers. CDC was able to corroborate 3 of 4 cases identified by the Arkansas Public Health Laboratory. Nineteen cases were identified by pcr from samples sent to commercial laboratories earlier in the outbreak. The samples were unavailable for further testing. 14 cases were link epidemiologically linked to theses laboratory confirmed cases Despite best efforts to collect samples via nasal swab and naso-pharyngeal aspirates, our CDC laboratorian was unable to culture bordetella pertussis

N = 88 Health Department Tdap campaign Index Case This slide shows the epidemiologic curve for the outbreak as a whole, which included school children, children under school age, family members, school faculty and staff. The cough onset of the index case was February 15, 2007. This child was not confirmed as a case until her sister tested pcr positive almost 5 weeks later. The health department identified this as a pertussis outbreak on March 30, which was the first incidence of a macrolide being prescribed for treatment. The outbreak has a broad peak during the weeks of March 22 through April 5th. In total, there were 88 occurrences of cough-illness: 42 in grades K-7 15 in grades 8-12 and 31 others, which included children younger than school-age, family members, and school faculty and staff The red arrow indicates the time of the Tdap vaccination campaign administered to eligible students, faculty and staff (April 27, 2007) Our investigation focuses on the confirmed cases in the school district, of which there were 37 confirmed cases K-12 N = 88

This figure shows the distribution of confirmed pertussis cases, grades K through 12. The week of the outbreak is on the x-axis, the number of cases on the y-axis. PCR confirmed cases are in green and epidemiologically-linked cases in yellow. N =37

Demographics 97% of cases were non-Hispanic White 57% of the cases were female 97% of cases were non-Hispanic White. This reflects the composition of the community. 57% of the cases were female

This is the age distribution of the confirmed cases This is the age distribution of the confirmed cases. The median was nine years of age. The age distribution is also reflected in the attack rate by school.

Attack Rate (AR) by School Grades # Cases AR (%) Primary K-4 11/504 2.2 Elementary 8/570 1.4 Middle 5-7 10/661 1.5 Junior High 8-9 4/440 0.9 High 10-12 4/667 0.6 The attack rates were highest in grades K through 7. The Primary school (K-4) had the highest attack rate at 2.2%.

Distribution of Symptoms Among Cases Describe slide: By case definition, 100% of cases had cough. 89% of cases reported paroxyms 47% reported postussive vomiting or gagging 42% reported apnea. Finally, 16% of cases reported whoop. The median length of cough was 21 days, with a range from 14 to 59 days. There were no complications, such as hospitalization or death, among any of the cases. N = 37

Treatment 87% cases treated with recommended antimicrobial agents Time to treatment pre-outbreak recognition: 14 days Time to treatment post-outbreak recognition: 6.5 days (p < 0.0006) 87% of the cases were treated with an appropriate antimicrobial agent, such as one of the macrolides (typically azithromycin) or co-trimoxazole. It took several weeks before it became apparent that the school was experiencing an outbreak of pertussis as opposed to another type of upper respiratory infection. The average time to from cough onset to start of appropriate antimicrobial was 14 days before recognition of a widespread outbreak. The average time to treatment after recognition was 6.5 days from cough onset. This difference is significant.

Vaccination Status by Doses, Grades K-7 Total Dose Non-cases Case AR % ≤2 4 3 19 187 5 2.6 1496 24 1.6 We were eager to explore possible differences in vaccination status, particularly considering the young ages of the affected students. We looked at vaccination status by number of doses. These were students who were eligible for 5 doses. There were 4 students whose records reported less than 3 doses. These may be students who weren’t still enrolled or up-to-date, because the minimum number of doses for school enrollment required by Arkansas state law is three. The attack rate for students with 4 doses was 2.6% and the attack rate for students with 5 doses was 1.6%.

Time Since Last Dose, K-7 P > .7038 N Days since last dose Cases 29 1783 ± 146.4 Non-cases 1706 1726 ± 30.6 Was there a difference in the time since the last doses between affected and unaffected students? The days since last does for cases was 1783 days. The days since last dose for non-cases was 1726. As you can see, there was no significant difference in the time since last vaccination dose. P > .7038

Are Doses Valid? Grades K-7 Invalid Age Non-cases Case Dose 1 5 Dose 2 7 Dose 3 Dose 4 Dose 5 33 Were the doses valid? We determined that cases had valid vaccination doses.

Attack Rate By Vaccination Status, Grades K-7 AR (%) Vaccinated 29/1506 1.9% Under-vaccinated 0/229 0% Which leads us to an attack rate among vaccinated students of 1.9%. There were no cases among under-vaccinated students. P > 0.7

Conclusions Pertussis was the cause of the outbreak Outbreaks can occur in highly-vaccinated school populations Recommend continued high levels of vaccine coverage and heightened awareness Research on disease transmission and resolution of outbreaks is needed In conclusion: Pertussis was the cause of the outbreak. This outbreak was very unusual in that it occurred among young school age children and not infants or adolescents. This serves as reminder that pertussis outbreaks can occur in highly-vaccinated school populations We recommend continued high vaccination coverage and we see a need for increased awareness of among health care providers. Lastly, there is still much we do not know about patterns of disease transmission and resolution of outbreaks. Continued research is needed on improved detection --- such as PCR and serology --- and effectiveness of prophylaxis and expanded Tdap coverage.

Acknowledgements AR DOH CDC/NCIRD/DBD Linda Gladden Andrew Baughman Terri Iacobacci Altino McKelvey Sandra Snow AR Public Health Laboratory Nurses of the Faulkner County Health Unit Vilonia School Nurses and Administrative Staff CDC/NCIRD/DBD Andrew Baughman Pam Cassiday Thomas Clark Nancy Messonier Eric Stern Tej Tiwari Lucia M. Tondella I would like to acknowledge everyone who contributed to the investigation and to the analysis of these data. In particular I want to thank the nurses of the County health unit and school nurses who did a tremendous job identifying and tracking cases and helping us obtain the data to conduct this investigation. The findings and conclusions in this presentation are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention

THANK YOU

How Many Susceptibles Could Be Expected? Vaccine Efficacy 85% Fully vaccinated students 1506 Fully vaccinated but Susceptible 226 Under-vaccinated 229 Total Susceptible 455

Are the doses valid? Invalid Interval? Unaffected Case Dose 1 late 191 4 Dose 2 14 Dose 3 12 Dose 4 52 Dose 5