The CAPiTA ILI study Monitoring of influenza-like symptoms among eldery, an observational study” Marieke Bolkenbaas, MD, PhD candidate Julius Center for.

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

Overview

• Introduction and background• Design and practical aspects• Results

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

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

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

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 >1 season• Self-reported symptoms of ILI and common cold• Weekly questionnaire• Anyone can registrate as a participant

Great Influenza Study

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

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)

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

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

The ILI study – practical aspects

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

The ILI study – practical aspects

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 ≥38°C, shortness of breath,

wheezing, chest pain or sputum production

The ILI study – Response

The ILI study – Response

• 2010-2011

• N=7511

• 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

• N=4240

• 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)

The ILI study – results – baseline

PCV13 (N=3727) Placebo (N=3784) Total (N=7511)

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 years75-84 years85 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%)

The ILI study – vaccine effects

The ILI study – vaccine effects

The ILI study – vaccine effects

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

The ILI study – GP visits

• 4317 visits in 2 seasons

The ILI study – GP visits

• 4317 visits in 2 seasons

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 -> comprehensive view on clinical course of

lower respiratory tract infections

Questions?

Reference list

1. WHO, Factsheet no. 211 Seasonal Influenza, March 2014 www.who.int2. WHO, Factsheet no. 310 The Leading 10 Causes of Death, May 2014 www.who.int3. 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 3;292(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 1;198(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 16;26(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 23;27(45):6353-7

8. ECDC. Influenza case definitions. http://www.ecdc.europa.eu/en/activities/surveillance/EISN/surveillance/Pages/influenza_case_definitions.aspx