The CAPiTA ILI study

1
The CAPiTA ILI study

• Monitoring of influenza-like symptoms among
  eldery, an observational study
• Marieke Bolkenbaas, MD, PhD candidate
• Julius Center for Health Sciences and Primary
  Care,
• UMC Utrecht, The Netherlands

2
Overview

• Introduction and background
• Design and practical aspects
• Results

3
Introduction and background

• Influenza, influenza-like illness (ILI) and
  lower respiratory tract infections (LRTI) are
  common and represent an important health care
  problem worldwide
• Influenza global annual attack rate 5-10 in
  adults, 20-30 in children 3-5 million severe
  cases, 250-300k deaths1
• 3.2 million people die of LRTI worldwide each
  year (ranking no. 4 in the WHO top 10 of death
  causes)2
• At highest risk for a worse outcome are children
  and elderly3

4
Introduction and background

• Respiratory viruses and pneumococci are often
  found simultaneously during respiratory tract
  infections
• It is widely assumed that respiratory viruses
  like influenza facilitate secondary bacterial
  infection of the (lower) respiratory tract4

5
Introduction and background

• Viral and bacterial respiratory tract infections
  often show a similar complex of symtoms and
  cannot easily be distinguished based on clinical
  signs
• Unknown is to what extent pneumococci play a role
  in the symptomatology of milder respiratory tract
  infections
• 80 of Dutch elderly receives annual flu
  vaccination5
• Pneumococcal vaccination is not (yet) recommended
  for 65 year olds in The Netherlands6

6
Monitoring of influenza-like symptoms

• Two ways of ILI monitoring in The Netherlands
• GP surveillance (sentinel network)
• Diagnosis by GP
• Max 2 nasopharynx/throatswabs each week for
  typing
• Internet-based monitoring
• Since 2003/2004, Great Influenza Study7
• Over 50,000 participants, most participating gt1
  season
• Self-reported symptoms of ILI and common cold
• Weekly questionnaire
• Anyone can registrate as a participant

7
Great Influenza Study
8
Internet surveillance vs GP surveillance

• ILI results from both systems correlated well
• GIS detected weekly ILI incidence trends 1 week
  before GP sentinel network
• Only 1 in 6 patients with ILI symptoms visits GP,
  in elderly 1 in 4
• Elderly and very young relatively
  underrepresented in GIS
• Influenza vaccination in elderly in GIS
  comparable with general population

9
Introduction and background

• CAPiTA trial 2008 - 2013
• Double-blind randomized controlled trial
• 84,496 participants of 65 year old
• Pneumococcal vaccine (PCV13) or placebo
• 56 hospitals and 2,200 GPs
• ? Demonstrated effectivity of pneumococcal
  vaccination with PCV13 in preventing
  hospitalisation or death due to VT pneumococcal
  CAP (Bonten et al, NEJM, accepted)

10
The ILI study - design

• Observational study nested in the CAPiTA trial
• Aims
• Explore the effect of pneumococcal vaccination on
  self-reported symptoms of ILI and LRTI
• Determine the incidence of ILI and self-reported
  symptoms of LRTI (srLRTI)
• Determine the proportions of episodes for which a
  GP is consulted

11
The ILI study design

• Computer-based random selection of candidates
• Participation during autumn/winter seasons
  2010/11 and 2011/12
• Letter with instructions and login code to
  secured website, digital informed consent
• Single time questionnaire on comorbidity,
  influenza vaccination status, smoking, contact
  with young children
• Weekly questionnaire on symptoms type, duration,
  perceived severity, GP visit, reasons to visit,
  treatment by GP, use of OTC drugs
• Missing weekly questionnaires allowed
• Not possible to fill in older questionnaires

12
The ILI study practical aspects

• Help and information
• Telephone
• E-mail
• Website
• Paper user manual
• Weekly reminders with hyperlink

13
The ILI study practical aspects
14
ILI study - definitions

• ILI - Criteria European Centre for Disease
  Control (ECDC)
• Sudden onset of symptoms AND
• At least one of the following symptoms fever or
  feverishness, malaise, headache, myalgia AND
• At least one respiratory symptom cough, sore
  throat or shortness of breath
• Self reported (possible) LRTI
• Acute cough or acute worsening of cough 3 days
  AND
• At least one of the following symptoms fever
  38C, shortness of breath, wheezing, chest pain
  or sputum production

15
The ILI study Response
16
The ILI study Response

• 2010-2011
• N7511
• No. of questionnaires 95.954
• Median no. of questionnaires 15
• No. single questionnaires 548
• Median interval questionnaires 8 days
• Median study duration 126 days (7-188)

• 2011-2012
• N4240
• No of questionnaires 72.589
• Median no. of questionnaires 20
• No. single questionnaires 161
• Median interval questionnaires 8 days
• Median study duration 170 days (7 212)

17
The ILI study results baseline
PCV13 (N3727) Placebo (N3784) Total (N7511)
Male 2578 (69.2) 2697 (71.3) 5275 (70.2)
female 1149 (30.8) 1087 (28.7) 2236 (29.8)
age 72.5 (66 94.6) 72.4 (66.1 95.6) 72.4 (66 95.6)
65-74 years 75-84 years 85 years and older 2770 (74.3) 887 (23.8) 70 (1.9) 2860 (75.6) 878 (23.2) 46 (1.2) 5630 (75.0) 1765 (23.5) 116 (1.5)
Asthma/COPD 394 (10.6) 382 (10.1) 776 (10.3)
Diabetes 395 (10.6) 397 (10.5) 792 (10.5)
Heart disease 720 (19.3) 749 (19.8) 1469 (19.6)
Smoking (daily) 188 (5.0) 224 (5.9) 412 (5.5)
Influenza vaccination 3337 (89.5) 3416 (90.3) 6753 (89.9)
18
The ILI study vaccine effects
19
The ILI study vaccine effects
20
The ILI study vaccine effects
21
The ILI study vaccine effects - conclusion

• There is no statistically significant effect of
  PCV13 vaccination on the incidence of ILI and
  self-reported LRTI symptoms

22
The ILI study GP visits

• 4317 visits in 2 seasons

23
The ILI study GP visits

• 4317 visits in 2 seasons

24
The ILI study what next?

• Duration of symptoms
• Effects of ILI and srLRTI on daily activity level
• Coupling of data with pneumonia/LRTI data of GP
  practice and hospital pneumonia data -gt
  comprehensive view on clinical course of lower
  respiratory tract infections

25
Questions?
26
Reference list

1. WHO, Factsheet no. 211 Seasonal Influenza, March
   2014 www.who.int
2. WHO, Factsheet no. 310 The Leading 10 Causes of
   Death, May 2014 www.who.int
3. Voordouw AC, Sturkenboom MC, Dieleman JP, Stijnen
   T, Smith DJ, van der LJ, et al. Annual
   revaccination against influenza and mortality
   risk in community-dwelling elderly persons. JAMA
   2004 Nov 3292(17)2089-95.
4. Morens DM, Taubenberger JK, Fauci AS. Predominant
   role of bacterial pneumonia as a cause of death
   in pandemic influenza implications for pandemic
   influenza preparedness. J Infect Dis 2008 Oct
   1198(7)962-70.
5. Jansen AG, Sanders EA, Nichol AL, Van Loon AM,
   Hoes AW, Hak E. Decline in influenza-associated
   mortality among Dutch elderly following the
   introduction of a nationwide vaccination program.
   Vaccine 2008 Oct 1626(44) 5567-74
6. Health Council of the Netherlands. Pneumococcal
   vaccine in elderly adults and risk groups. Health
   Council of the Netherlands . 18-8-2003.
   18-8-2003.
7. Friesema IH, Koppeschaar CE, Donker GA, Dijkstra
   F, van Noort SP, Smallenburg R, et al.
   Internet-based monitoring of influenza-like
   illness in the general population experience of
   five influenza seasons in The Netherlands.
   Vaccine 2009 Oct 2327(45)6353-7
8. ECDC. Influenza case definitions.
   http//www.ecdc.europa.eu/en/activities/surveillan
   ce/EISN/surveillance/Pages/influenza_case_definiti
   ons.aspx