1. Nosocomial Rotavirus Gastroenteritis: Is There a Role for Targeted Immunization? Verhagen P, MD 1, Moore D, MD, PhD 1, Manges A, PhD 2,St- Martin L, BScN 1 and Quach C, MD, MSc 1 (1)Montreal Children's Hospital, Montreal, QC, Canada, (2)Department of Epidemiology and Biostatistics, McGill University, Montreal, QC, Canada

2. Background Rotavirus (RV) is the leading cause of dehydrating gastroenteritis In Quebec: Between 1350–1850 hospitalizations each year (1) Hospital acquired (nosocomial) infections around 1/3 of all RV related hospitalizations (2) No recent incidence data on nosocomial RV infections in Canada Nosocomial Rotavirus Gastroenteritis (1) Buigues RP, et al. Can J Infect Dis 2002; 13 (4): 239-244 (2) Ford-Jones EL, et al. Am J Epidemiol 1990; 131(4):711-718

3. Background Two RV vaccines licensed in Canada Currently no publicly funded immunization program for RV More epidemiological data on burden of RV disease in Canada required Universal versus targeted immunization? Nosocomial Rotavirus Gastroenteritis

4. Objectives Determine incidence of (symptomatic) nosocomial RV infections Describe patient-characteristics and possible risk factors for more severe disease Defining a possible target group for selective RV vaccination NB: RV vaccination at 2, 4 (and 6) months of age Nosocomial Rotavirus Gastroenteritis

5. Study design and Methods Setting: Tertiary Care Pediatric Hospital Period: 10 years (1998-2008) Data collection: Records from hospital’s active, prospective surveillance program for Hospital Acquired Infections (HAI) Chart review of all cases of nosocomial RV gastroenteritis (nRV GE) Nosocomial Rotavirus Gastroenteritis

6. Study design and Methods Data extracted from medical records: Patient demographic data Admission diagnosis Medical history, presence of chronic underlying health conditions Presence of perinatal morbidity Previous hospitalizations Symptoms and duration of nRV GE Therapy received for nRV GE (oral or IV hydration) Nosocomial Rotavirus Gastroenteritis

7. Study design and Methods Descriptive statistics Incidence rates: Per 100 hospital admissions Per 1000 patient-days Assessment of possible risk factors for more severe disease by multivariate logistic regression Nosocomial Rotavirus Gastroenteritis

8. Results Nosocomial Rotavirus Gastroenteritis † Reasons for exclusion: i) Criteria for acute GE not met (no diarrhea or other likely non-infectious cause of diarrhea), 12 cases; ii) Criteria for nosocomial infection not met (onset of symptoms 72 hours after discharge), 13 cases; iii) Patient’s age >18 years at the time of disease onset, 3 cases

9. Results Nosocomial Rotavirus Gastroenteritis Incidence Rate for nRV GE

10. Results Nosocomial Rotavirus Gastroenteritis PATIENT CHARACTERISTICS N=214 Male (%)118(55%) Age median (range)8 months(7 days - 17 years) Prematurity or Dysmaturity (%)61(29%) Chronic condition present (%)126(59%) Respiratory (%)19(9%) Cardiovascular (%)21(10%) Malignant /Immunodeficient (%)11(5%) Neuro-developmental (%)27(13%) Gastro-intestinal (%)25(12%) Other/Non-classifiable (%)23(11%) Perinatal Morbidity present (%)95(44%) Admitted Day-of-Life (DOL) 1 (%)32(15 %) History of previous hospitalization(s)101(47%) (% of those admitted after DOL1, n=182)(56%) History > 21 previous hospital-days60(28%) (% of those admitted after DOL1, n=182)(33%) Median duration of present hospitalization (range)23 days(4-2251 days)

11. Results Nosocomial Rotavirus Gastroenteritis Distribution of cases over age-groups

12. Results Nosocomial Rotavirus Gastroenteritis CHARACTERISTICS OF nRV GE Day of onset after admission, median (range) Day 10(Day 3 – 1326) Duration of diarrhea, median (range) 4 days(1-21 days) Fever present, number (%)118(55%) Vomiting present, number (%)121(57%) Fever and vomiting, number (%)79(37%)

13. Results Nosocomial Rotavirus Gastroenteritis 1) Catheter-days: days on which a patient had an intravenous catheter exclusively for treatment of nRV GE THERAPY FOR nRV GE N(%) Received therapy132(62) Oral hydration33(15) Intravenous hydration72(34) Combined oral and IV26(12) Catheter-days 1) per patient treated IV (95%CI) 3.3(2.9, 3.7) Readmissions26(12) Readmission length-of-stay, median (range) 4(2 – 17)

14. Results Nosocomial Rotavirus Gastroenteritis Risk factors for Therapy Requirement Excluding readmissions Multivariate Logistic Regression OR(95% CI) Vomiting5.58(2.89,10.79) Age > 6 months2.00(1.05,3.78) Chronic underlying condition 1.77(0.91,3.47) Perinatal morbidity1.68(0.86,3.29)

15. Conclusions Incidence rate nRV GE: 0.5/1000 patient-days 0.3/100 admissions comparable to recent international data Approximately 60% of patients requires rehydration therapy Therapy intravenous in 3/4 of patients 3.3 extra intravenous catheter-days Nosocomial Rotavirus Gastroenteritis

16. Conclusions Frequent presence of underlying medical conditions (59%) accompanied by recurrent and lengthy hospitalizations May predispose to therapy requirements Patients identified early in life (44%) potential target group for selective RV vaccination Nosocomial Rotavirus Gastroenteritis

17. Acknowledgements Caroline Quach Dohorty Moore Amee Manges Lynn Martin Brigitte Rouleau The Montreal Children’s Hospital Research Institute Nosocomial Rotavirus Gastroenteritis

18. Thank you

19. Targeted Vaccination Target group: Children with perinatal morbidity prematurity/dysmaturity birth defects and malformations congenital syndromes chronic diseases with onset early in life associated with frequent and sometimes lengthy hospitalizations Nosocomial Rotavirus Gastroenteritis

20. Targeted Vaccination Nosocomial Rotavirus Gastroenteritis At risk model for nRV GE

21. Targeted Vaccination Assumptions for model simulation: Vaccination at 2 and 4 months (and 6 months) Both vaccines equally effective Maximum vaccine efficacy (VE) after 2 doses Effect of vaccination-dose starts 14 days post- vaccination Nosocomial Rotavirus Gastroenteritis

22. Targeted Vaccination Nosocomial Rotavirus Gastroenteritis VE after 1 doseSourceVE after 2 dosesSource Point- estimate95% CI Point- estimate95% CI RV GE of any severity50%9-96% (2;3)74%67-84%(2;4) RV GE requiring treatment* 82%39-96%(2;3;5)89%68-96%(3;5;6) Vaccine Efficacy (VE) point-estimates and 95% Confidence Interval (CI) (1) Van der Wielen M, et al.. European Journal of Clinical Microbiology & Infectious Diseases 2008; 27(7):495-501. (2) Vesikari T, et al.The Lancet 2007; 370(9601):1757-1763. (3) Vesikari T, et.al. Archives of Disease in Childhood 2008; 93(Suppl. 2):pw 70. (4) Vesikari T, et al. N Engl J Med 2006; 354(1):23-33. (5) Ruiz-Palacios GM, et al. N Engl J Med 2006; 354(1):11-22. (6) Boom JA, et al. Pediatrics 2010; 125(2):e199-e207.

23. Targeted Vaccination Study cohort: 214 cases of nRV GE 95 patients with perinatal morbidity (44%) 23 patients onset < 2.5 months of age Nosocomial Rotavirus Gastroenteritis

24. Targeted Vaccination Potential impact of Targeted Vaccination Program: Nosocomial Rotavirus Gastroenteritis nRV GE of any severitySevere nRV GE Based on Vaccine Efficacy: point- estimate worst case-best case scenario point- estimate worst case-best case scenario PF among patients with perinatal morbidity 49%40-63%59%35- 67% PF among all nRV GE22%18-28%25%15- 29%