Influenza and TB:Influenza and TB:Challenges in 21Challenges in 21stst Century IrelandCentury Ireland

Dr Joan O’DonnellDr Joan O’DonnellApril 3April 3rdrd 2008 2008

Overview Overview InfluenzaInfluenza

– Seasonal Influenza-Epidemiology– Challenges – National influenza and pneumococcal vaccine

uptake telephone survey – Avian and Pandemic Influenza– Challenges

TuberculosisTuberculosis– Context and epidemiology– Challenges– Future Directions

Influenza VirusInfluenza VirusAn RNA virus of the orthomyxovirus family

Three types: Type A that causes moderate to severe illness

Human and animal reservoirs Unstable - antigenic shift likely (epidemics likely)

Type B causes milder epidemics-Humans only reservoir

Primarily affects children, relatively stable, immunogenic

Type C: Humans only reservoir, Not associated with epidemics (Sub clinical infection)

Serious illness and mortality in those with co-morbidity and older people

EISS Weekly surveillance reportHPA Dept Public Health

NVRLICGP Departments of Public Health

HPSC

Sentinel GP ILI consultations Hospital admissions

School absenteeism

Enhanced influenza surveillance

Other

GRO-Mortality data

HSE-Influenza vaccine uptake

International-EISS, HPA, etc

ILI outbreaks

Influenza notifications

Sources of Influenza DataSources of Influenza Data

Sentinel specimens

Non-sentinel specimens

GP Co-Ops

ILI rate per 100,000 population and the number of ILI rate per 100,000 population and the number of positive influenza specimens positive influenza specimens detected by the NVRL detected by the NVRL during the 2000/2001, 2001/2002, 2002/2003, 2003/2004, during the 2000/2001, 2001/2002, 2002/2003, 2003/2004, 2004/2005, 2005/2006 & 2006/2007, 2007/2008 seasons2004/2005, 2005/2006 & 2006/2007, 2007/2008 seasons

0

10

20

30

40

50

60

70

80

90

100

0

20

40

60

80

100

120

140

Num

ber o

f pos

itive

spe

cim

ens

ILI r

ate

per 1

00,0

00 p

opul

atio

n

Season (2000/2001 - 2007/2008)

Influenza A Influenza B ILI Rate

Sentinel General PracticesSentinel General Practices

Number of sentinel GPs increased – Aim 5%

population coverage

– 2004/2005: 2.7%– 2005/2006: 3.8%– 2006/2007: 4.0%– 2007/2008: 4.8%

Current ChallengesCurrent Challenges Maintain sentinel surveillance network

– Exploring surveillance using GP co-ops (NHS Direct) Enhanced surveillance of hospitalised

children aged 0-14 years– Guide influenza vaccine policy for 0-4 year olds

Measurement of influenza vaccine uptake ILI/influenza outbreak surveillance and

management protocol Influenza baseline estimation

– Public health action re antiviral use in high risk groups Mortality Project –EU MoMo

– Early warning system for influenza epidemic and pandemic and other public health emergencies

The uptake of Influenza The uptake of Influenza and Pneumococcal and Pneumococcal Vaccine in Ireland Vaccine in Ireland

2005/20062005/2006

Influenza vaccine annually – Recommended for risk groups– Influenza vaccine recommended for all healthcare

workers (HCWs) Pneumococcal vaccine once usually

– Recommended for risk groups Limited influenza vaccine uptake data

available No pneumococcal vaccine uptake data

available Population aged <65 years with

health risk unknown

Influenza and pneumococcal Influenza and pneumococcal vaccination policy in Irelandvaccination policy in Ireland

Study ObjectiveStudy Objective

To estimate – The proportion of the population aged 18-64

years in at-risk groups for influenza or pneumococcal infection

– Uptake of influenza and pneumococcal vaccine in all risk groups

in order to provide baseline information, to improve targeted immunisation programmes and to prevent morbidity and mortality

Methods and MaterialsMethods and Materials Study design

– Cross-sectional retrospective telephone survey Study population

– Over 18 years– Age and sex– Resident in Ireland – Landline telephone

Sample size – 1500 respondents

Data collection – Standardised questionnaire

Interviews– June 2006

ResultsResults

Population with health risk Population with health risk

18-64 years18-64 years

No risk89%

Health risk11%

0 1 2 3 4 5 6 7 8 9

Other

Heart

Immunosupression

Diabetes

Respiratory

% risk group and 95% CI

Influenza vaccine uptakeInfluenza vaccine uptake

0

10

20

30

40

50

60

70

80

Over 65 18-64 with healthrisk

HCWs Total

% v

acci

ne

up

atke

Pneumococcal vaccine Pneumococcal vaccine uptakeuptake

0

5

10

15

20

25

30

35

40

45

50

Over 65 18-64 with health risk Total

% v

acci

ne

up

take

ConclusionsConclusions Vaccine uptake

– For those over 65 years Meets national target for influenza (69%) Low for pneumococal vaccine (41%)

– For those aged 18-64 years with health risk Low (28% influenza, 11% pneumococcal)

– For influenza among HCWs Very low (20%)

First national estimate of health risk groups (11%)

Study LimitationsStudy Limitations Selection bias

– 88% have a fixed line phone – Persons with limited mobility – Excluded

Non-English speakers Institutional settings, non-private dwellings

Recall bias – Questions cover quite a long period of time

Self reported information– Not validated

RecommendationsRecommendations Continue to promote influenza vaccination

among those aged 65 years and over Endeavour to increase vaccine uptake

– In risk groups aged 18-64 years for both vaccines– HCWs

Telephone surveys are feasible options during a pandemic to determine morbidity, vaccine uptake and absenteeism in the population

National Information system for vaccine uptake statistics

Chronic Disease Registers

AvianAvian InfluenzaInfluenza

Avian influenza Avian influenza (bird flu)(bird flu)

Avian influenza (AI) -identified in the early 1900s. Usually affects only birds, and pigs, but rarely can cross the species barrier to infect humans

Vast majority of AI viruses found in birds do not infect humans

Current strain of concern, AH5N1 has infected humans

Why is there Why is there concern about concern about avian influenza avian influenza

A/H5N1?A/H5N1?

H5N1 has caused the largest outbreak in birds on record, since late 2003

Despite culling >200 million birds, it has become endemic in parts of SE Asia, Africa

Current Situation-Current Situation-H5N1H5N1

H5N1 is now present in birds in over 60 countries – migratory birds spreading it to Europe

Virus has crossed species barrier on multiple occasions to infect 376 persons in 14 countries

It causes severe disseminated disease affecting multiple organs and systems with death in 63% of those affected

Most cases have occurred in previously healthy children and young adults

As no virus of H5 subtype has ever circulated widely in humans, all will be susceptible to infection

AI control strategy in IrelandAI control strategy in Ireland Strategy is: Prevention of introduction to poultry

via:– bio security measures– ban on import of poultry from

infected areas Early detection via surveillance and

rapid diagnosis If AI outbreak occurs, stamp out via

culling Joint working response plan with

public health to protect contacts of avian influenza source and workers at risk

Available at http://www.ndsc.ie/hpsc/A-Z/Respiratory/AvianInfluenza/

Guidance/

The threat posed by avian influenza: The threat posed by avian influenza: WHO assessment (2005)WHO assessment (2005)

The risk of a pandemic is great The risk will persist Evolution of the threat cannot be predicted The early warning system is weak Preventable intervention is possible, but

untested Reduction of morbidity and mortality globally

will be impeded by inadequate medical supplies Although AH5N1 is the current strain of concern,

the next pandemic might not come from AH5N1

What is pandemic flu? What is pandemic flu? 

Pandemic flu is a global epidemic of a newly emerged strain of flu (a new influenza A subtype)

Three pandemics in the last century– 1918 ‘Spanish flu’– 1957 ‘Asian flu’– 1968 ‘Hong Kong flu’

Worst killed 40+ million worldwide

WHO Alert LevelsWHO Alert Levels

Low risk of human cases 1Higher risk of human

cases2

No or very limited human-to-human transmission

3

Evidence of increased human-to-human

transmission

4

Evidence of significant human-to-human

transmission

5

Pandemic Efficient and sustained

human-to-human transmission

6

Inter-pandemic phase New virus in animals,

no human cases

Pandemic alert New virus causes

human cases

Lessons from past pandemicsLessons from past pandemics   Can occur at any time of year - not

only in winter In each pandemic you can have

very different– Death rates, severity and patterns of

illness, age most severely affected You get a rapid surge in number of

cases over brief period of time, often measured in weeks

Tend to occur in waves - subsequent waves may be more or less severe

    Key lesson – unpredictability 

How pandemic flu may affect IrelandHow pandemic flu may affect Ireland Impossible to predict when it

will begin Difficult to predict impact with

any accuracy Great deal of uncertainty over

estimates of scale of illness, death rates and those most likely to have severe illness

Will also depend on the availability and effectiveness of antiviral drugs and vaccines

Impact on Business, Schools, Impact on Business, Schools, ServicesServices

25% of the workforce will take 5-8 working days off over a three-month period

Likely to spread rapidly in schools and other closed communities leading to potential closure

Impact on all services including gardai, fire, the army, fuel supply, food production, distribution and transport, prisons, education and business

Reduce impact throughReduce impact throughSurveillanceDiagnosisAntiviral drugsVaccines (once they become

available)Public health interventions

ChallengesChallenges Surveillance systems and early warning system

– Alternative e.g. GP OOH, cluster surveillance, internet Health Service Response

– Clinical management, human resources, infection control Anti-virals

– Emergence of Oseltamivir resistance– Supply

Vaccines– Availability

Implementation of public health measures– Multidisciplinary, intersectoral approach– Out of hours

Tuberculosis:Tuberculosis:An old and new problem…An old and new problem…

In Giacomo Puccini's 1896 opera, La Bohème, Mimi dies from consumption

100 years later, in John Larson’s musical remake, RENT, the bohemians suffer from AIDS

Some Messages still Some Messages still prevail..Some May Not!!prevail..Some May Not!!

Current Situation (1)Current Situation (1) Case-based surveillance since 1998 Marked decline in the number of cases since 1950s Lowest rate in 2001 (9.7/100,000)

HOWEVER Still a Problem

Decline not sustained with slow increase since:– 2005: 10.6/100,000 (450 cases)– 2006: 10.8/100,000 (458 cases) – 2007:474 cases

Inner city pockets of high incidence– HSE-East (North Inner City): 24.5/100,000– HSE-South (North Inner City): 21.5/100,000

0

1000

2000

3000

4000

5000

6000

7000

8000

52 54 56 58 60 62 64 66 68 70 72 74 76 78 80 82 84 86 88 90 92 94 96 98

Non-respiratoryRespiratory

National Notifications in IrelandNational Notifications in IrelandDept. of Health Statistics 1952-1998Dept. of Health Statistics 1952-1998

National TB notifications, rate & 3 National TB notifications, rate & 3 year moving average 1991-2006*year moving average 1991-2006*

0.0

2.0

4.0

6.0

8.0

10.0

12.0

14.0

16.0

18.0

20.0

19

91

19

92

19

93

19

94

19

95

19

96

19

97

19

98

19

99

20

00

20

01

20

02

20

03

20

04

20

05

20

06

*

Year

Rat

e p

er 1

00,0

00 p

op

ula

tio

n

0

100

200

300

400

500

600

700

Nu

mb

er o

f ca

ses

Number of cases Crude Rate per 100,000 population 3 year moving average

*2006 provisional data only

Source: WHO, 2008

No report

0–24

25–49

50–99

100 or more

* Notified TB cases (new and relapse) per 100 000 population

Tuberculosis notification rates (1)World, 2006*

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO 2006. All rights reserved

Tuberculosis notification rates (2)WHO European Region, 2006

TB cases per 100 000 population

Not includedNot reporting to EuroTB< 11 11 – 20 21 – 50> 50

AndorraMalta Monaco San Marino

TB cases with positive culture, 2006*

(28-100%) (28-63%) (4-36%)Andorra

Malta

Monaco

San Marino

Percentage of TB cases with positive culture

Not included or no culture data reported to EuroTB< 40% 40% – 54% 55% – 74%> 74%

* Data from 2005 for Ireland and Romania (culture results incomplete in 2006)

Outcome data, 2005Outcome data, 2005

Outcomes reported for 392 (87.1%) of the 450 cases notified in 2005

Total cases Smear positive cases

Treatment outcome Number % Number %

Completed 304 67.6 98 69.5

Lost to follow up 32 7.1 12 8.5

Died (attributed to TB) 10 2.2 2 1.4

Died (not attributed to TB) 27 6.0 10 7.1

Still on treatment 10 2.2 6 4.3

Interrupted (>2mths) 8 1.8 1 0.7

Defaulted 1 0.2 0 0.0

Unknown 58 12.9 12 8.5

Total 450 100 141 100

Treatment Outcomes 2000-2005Treatment Outcomes 2000-2005

0

10

20

30

40

50

60

70

80

Success Died LTFU Interrupted Still on rx Unknown

2000

2001

2002

2003

2004

2005

15

Treatment outcome, EU & West*, 2005 (1)New pulmonary culture positive TB cases, by country

* Including only countries with nationwide, complete data (Bulgaria: smear or culture positive).† Defaulted, Transferred and Unknown.

0%

20%

40%

60%

80%

100%

Hu

ng

ary

Cyp

rus

An

do

rra

Be

lgiu

m

Sw

ed

en

Cze

chR

epu

blic

Ge

rma

ny

Un

ite

d Kin

gdo

m

Au

str

ia

Lith

ua

nia

Esto

nia

Ire

lan

d

La

tvia

Po

lan

d

Isra

el

Slo

ven

ia

De

nm

ark

Ro

man

ia

Bu

lga

ria*

Ne

the

rlan

ds

Po

rtu

ga

l

Ma

lta

Slo

va

kia

No

rwa

y

Ice

lan

d

Success Died Failed Still on treatment Other †

Treatment outcomeNew definite pulmonary cases, 2001-2005*

* Countries with representative outcome data. EU & West (culture positive): Andorra, Austria, Belgium, Czech Rep, Denmark, Estonia, Germany, Hungary, Iceland, Ireland, Israel, Latvia, Lithuania, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Sweden, United Kingdom. Balkans (smear positive): Albania, Macedonia F.Y.R. East (smear positive): Kazakhstan, Kyrgyzstan

0%

20%

40%

60%

80%

100%

2001 2002 2003 2004 2005 2001 2002 2003 2004 2005 2001 2002 2003 2004 2005

EU & West Balkans East

% cases

Success Died Failed or Still on treatment Defaulted, Transferred or Unknown

Current ChallengesCurrent Challenges

Migration PatternsMDR-TB/XDR-TBTB cases associated with HIV

infection

Migration PatternsMigration Patterns (1)(1)

Proportion of immigrant cases has doubled since 2001 – 2001: 16.5% of cases. 2005: 34%

In 2005:– The majority of cases from Asia (46%) with– 22% from Africa and 19% from Europe

In 2005– The rate in the indigenous population was

8.3/100,000– The rate in foreign born population was

24.8/100,000

0.0

5.0

10.0

15.0

20.0

25.0

30.0

35.0

1998 1999 2000 2001 2002 2003 2004 2005 2006*

Year

Rat

e p

er 1

00,0

00 p

op

ula

tio

n

Irish-born Foreign-born

*2006 provisional data only

TB rates per 100,000 population by geographic origin, TB rates per 100,000 population by geographic origin, 1998 to 2006*1998 to 2006*

Percentage of TB cases of foreign origin, 2006

AndorraMalta Monaco San Marino

Not included or not reporting to EuroTB0% – 4% 5% – 19% 20% – 49%> 49%

TB cases and rates by age group and TB cases and rates by age group and geographic origin: 2005geographic origin: 2005

0

50

100

150

200

250

300

350

0-14 15-24 25-34 35-44 45-54 55-64 65+ Total

Age group

Cas

es

0

5

10

15

20

25

30

35

40

45

Rat

e

Cases - Irish born Cases - Foreign born Rate - Irish born Rate - Foreign Born

9

TB notifications by age-group and geographic origin, EU & West*, 2006

* Excluding countries with missing data (Monaco, San Marino)

0

10

20

30

40

50

60

70

0-4 5-14 15-44 45-64 65+

% TB cases

National

Foreign

TB mortality rates, 2001-2006*

Not includedNo data or data incomplete< 1.1 1.1 – 5.0 5.1 – 10.0> 10.0

TB deaths per 100 000 population

AndorraMalta Monaco San Marino * Source: WHO Mortality Database, October 2007. Data shown for latest available year.

Including only deaths from TB coded ICD-9 010-018 or ICD-10 A15-19.

Migration PatternsMigration Patterns (2)(2)

Voluntary screening offered to asylum seekers

Screening of non-asylum seekers– No formal structures– Increase awareness among healthcare

professionals – ? See at joint clinical and public health

clinics

Drug Resistant CasesDrug Resistant Cases

Percentage of drug resistant cases is still low.

In 2005: – 2.9%(13) of cases resistant to isoniazid– MDR: 0.4% (2 cases) of total cases– 1 XDR TB case reported

An increasing challenge due to migration patterns

In 2005: – Baltic States: MDR (18.3%) Isoniazid R (30.5%)– EU and Western Europe: MDR (2%) Isoniazid R (9%)

Proportion of TB cases with isoniazid resistance and Proportion of TB cases with isoniazid resistance and multidrug resistance, 2000 to 2006*multidrug resistance, 2000 to 2006*

*2006 provisional data only

0

2

4

6

8

10

12

14

16

2000 2001 2002 2003 2004 2005 2006*

Year

Nu

mb

er o

f ca

ses

Isoniazid resistance MDR

12

Multidrug resistance (MDR), EU & West, 2005 (1)Mean combined MDR, Baltic States & Other countries*

* Vertical lines denote country range of % MDR; including only countries with nationwide, representative data -Baltic States : Estonia, Latvia, LithuaniaOther countries : Andorra, Austria, Belgium, Cyprus, Denmark, Finland, France, Germany, Iceland, Israel, Luxembourg, Netherlands, Norway, Romania (2003-2004), Slovenia, Sweden, Switzerland, United Kingdom

0%

3%

6%

9%

12%

15%

18%

21%

Baltic States Other countries

% MDR

TB cases with primary MDR, 2006*

Andorra

Malta Monaco

San Marino

Percentage of new TB cases with MDRNot included or not reporting to EuroTB

No nationwide data on drug resistance reported0.0% – 0.9%

1.0% – 1.9%2.0% – 5.9%

6.0% – 19.4%

**

*

*

*

*

*

Showing only countries with nationwide data.Data from 2004 for Poland and Romania and 2005 for Ireland.

Data representativeness unknown in countries marked with an asterisk.

MDR TB cases- 2000 to 2006MDR TB cases- 2000 to 2006

15 cases of MDR-TB

Previous History of TB• Yes in 7 cases

Place of birth•8 foreign born•7 Irish

TB cases associated with HIV TB cases associated with HIV

InfectionInfection Notification of HIV/AIDS not

mandatoryData on HIV status of TB cases is

incomplete and an underestimateUnable to link TB and HIV casesNew guidance recommends

improving this surveillance

HIV associated cases 2000-HIV associated cases 2000-2006*2006*

YearHIV

Positive% HIV

Positive% Unknown or Not specified

2002 19 4.7 95.1

2003 2 0.5 97.5

2004 13 3.0 94.4

2005 11 2.4 93.8

2006* 7 1.5 94.1

*2006 provisional data only

Estimated HIV prevalence in new adult TB cases

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO 2005. All rights reserved

HIV prevalence in TB cases, 15-49 years (%)

0 - 45 - 1920 - 4950 or moreNo estimate

Current Situation (2)Current Situation (2)

Updating National TB guidelines HSE subgroup for TB control strategy Universal BCG programme to continue National Reference Laboratory assigned Development of new TB clinical and

laboratory centreo Research Programme

Revision of National TB Revision of National TB

GuidanceGuidance In process of completion– Clinical management– Screening methods– Laboratory – Public health –contact tracing– Screening of special groups– Latent TB Infection– BCG Vaccination – TB and HIV – Epidemiology and surveillance – Research and Training

Future Directions (1)Future Directions (1) Foster a multidisciplinary approach to TB control Increase awareness among primary care and the

public– Training, information materials etc

Investment in strengthening public health infrastructure and capacity– Key workers, DOTs etc– Target Blackspots and high risk groups e.g. immigrants

Investment in laboratory and clinical services Continue to improve surveillance

– TB cases associated with HIV infection

Training and research – Diagnositics, treatment and vaccines

Future Directions (2)Future Directions (2)

Elimination of TB Move towards elimination as proposed by

STOP TB strategy– (< 1 case per million population)– 4 cases of of TB annually by 2050

Global TB control is required to achieve TB elimination in countries with low incidence– Borgdorff MW et al. Emerging Infectious

Diseases Vol 11 (No. 4) April 2005– World TB day Theme 2008: “I am stopping

TB”

AcknowledgmentsAcknowledgments

HPSC: Ms. Sarah Jackson, Drs. Kate O Donnell, Lorraine Hickey, Lisa Domegan, Derval Igoe and Darina O FlanaganDepartments of Population HealthLaboratoriesEuroTB and WHO colleagues

THANK YOUTHANK YOU