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HOW TO PREPARE FOR A PANDEMIC
WONCA 2015: THE PRIMARY CARE ROLE Workshop
INTRODUCTION
 Infectious diseases contribute to high morbidity and mortality
across the globe due to their nature of spreading through
populations and due to varied susceptibility of individual patients.
 Mass vaccinations, public health measures, general awareness in
keeping hygienic measures, modern diagnostics and treatments
made a progress in infections disease control and management.
 However, in a globalised community any outbreak in any region of
the world is actually an outbreak of the doorstep of any country or
any practice.
 Recent history tells us how quick a stable situation in infectious
disease control can break down.
PREPARE PROJECT
 PREPARE is a EU funded network for harmonized large-
scale clinical research studies on infectious diseases (IDs),
prepared to rapidly respond to any severe ID outbreak,
providing real-time evidence for clinical management of
patients and for informing public health responses.
 PREPARE aims to be at the basis of establishing a paradigm
shift in clinical research in response to severe ID outbreaks.
AIMS OF THE WORKSHOP
 To bring some key information on how to approach these
challenges from human and biomedical perspective.
 To discuss primary care role and responsibility in
infectious diseases control and possible pandemic.
TIMETABLE
 Introduction: Aims of the course, a brief outline of PREPARE,
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introducing each other – Zalika Klemenc-Ketis /10 min/
Common infectious diseases in a pandemic: rational decision
making in family physicians – Jean-Pierre Jacquet /15 min/
Group work – Experiences with management of infectious
diseases and epidemic outbreaks in the participant practices /25
min/ reporting back /5 min/
Traditional and new pathogens in the Middle East immigrants –
Mehmet Ungan /15 min/
Summing up /5 min/
Common infectious diseases in a
pandemic: rational decision making in
family physicians
Pr. Jean-Pierre Jacquet Department of General
Practice Grenoble University France
Pr. Jean-Pierre Jacquet Department of General Practice
Grenoble University France
No conflict of interest
Pr. Jean-Pierre Jacquet Department of General Practice
Grenoble University France
Seasonal flu
Pr. Jean-Pierre Jacquet Department of General Practice
Grenoble University France
Remember some definitions.
 Epidemic.
 Pandemic.
 Public Health.
 Prevalence.
 Incidence Rate.
 Virulence.
 Transmission and Communicable disease
Pr. Jean-Pierre Jacquet Department of General Practice
Grenoble University France
What are the potential tasks of the
General practitioner/Family? Physician as
a researcher?
Pr. Jean-Pierre Jacquet Department of General Practice
Grenoble University France
Four steps:
Vaccination
Decrease transmission of the
virus
Identify early cases.
Prevent complications.
Pr. Jean-Pierre Jacquet Department of General Practice
Grenoble University France
Vaccination:
Rationale
Pr. Jean-Pierre Jacquet Department of General Practice
Grenoble University France
Vaccination, research question:
How to increase the
percentage of vaccinated
people into the risk groups ?
What are your proposals?
Pr. Jean-Pierre Jacquet Department of General Practice
Grenoble University France
Vaccination, research question:
What are the factors
influencing the choice of
the patients ?
What are your proposals?
Pr. Jean-Pierre Jacquet Department of General Practice
Grenoble University France
Lower transmission of the virus.
 Rationale
Pr. Jean-Pierre Jacquet Department of General Practice
Grenoble University France
Lower transmission of the virus.
Research question:
 How to change behaviour of the patients to reinforce rules of
prevention of inter-human transmission?
o What are your proposals?
Pr. Jean-Pierre Jacquet Department of General Practice
Grenoble University France
Identify early cases quickly
 Rationale
Pr. Jean-Pierre Jacquet Department of General Practice
Grenoble University France
Identify early cases quickly, research
question:
 What are the sensitivity, specificity, positive predictive value
and negative predictive value of each symptoms of flu ?
What are your proposals?
Pr. Jean-Pierre Jacquet Department of General Practice
Grenoble University France
Identify early cases quickly, research
question:
 How can you set-up a sentinel network ?
What are your proposals?
Pr. Jean-Pierre Jacquet Department of General Practice
Grenoble University France
Prevent complications
Rationale
Pr. Jean-Pierre Jacquet Department of General Practice
Grenoble University France
Prevent complications, research
question:
 What are the criteria to hospitalise a patient with flu illness?
What are your proposals?
Pr. Jean-Pierre Jacquet Department of General Practice
Grenoble University France
Conclusion:
 A GP can and must do research, even if as
non academic it is more difficult.
 White-Williams-Greenberg diagram, also
called the square of White is still relevant,
but we have to accept the challenge to
produce more scientific data in the field of
primary care.
Pr. Jean-Pierre Jacquet Department of General Practice
Grenoble University France
Pr. Jean-Pierre Jacquet Department of General Practice
Grenoble University France
Bibliography
 http://www.who.int/influenza/resources/documents/extr


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
act_PIPGuidance09_phase5_6.pdf
http://www.who.int/mediacentre/factsheets/fs211/en/
:http://www.who.int/influenza/vaccines/virus/recommen
dations/en/
http://www.who.int/ith/diseases/influenza_seasonal/en/
http://www.lecmg.fr/livreblanc/sommaire.html
Pr. Jean-Pierre Jacquet Department of General Practice
Grenoble University France
TOPICS FOR SMALL GROUP WORK
 Name and describe your experiences with management of
infectious diseases and epidemic outbreaks in your
country/practice
TB CONTROL AND PRIMARY CARE EXAMPLE–WONCA
Workshop 2015
Need for Screening?

An overview of the region and TB
Movement of TB across borders, regional?
•
Relevant characteristics unique to TB
Acknowledgement: Some of the slides are from a CDC tarining presentation in CapeTown by Dr Justin Waring, Medical Director, Western
Australian TB Control Program, Chair, National TB Advisory Committee, Australia. Thanks to Dr Waring.
WHO 2013 TB REPORT
Entry to Turkey-2009
From 2.3 millon to 25.5 million entry
to Turkey
 Entrance to Turkey from Former Soviet Union was 200 000 in 1990
=> 5 400 000 in 2009.
 Balkan countries from 900 000 => 2.6 million

 Middle East , 400 000 => 2.2 million
 Entry to Turkey in total was 2.3 million in 1990 => 25.5 million in
2009
Regional Refugee & Resilience Plan
UNHCR (3RP) 2015-2016
The projected number of
Syrian refugees in Turkey
in 2015 is 2.5 million of
whom 300,000 will reside
in 25 camps and 2.2
million people will live
among communities.
In addition, it is estimated
that 8.2 million people
in refugee hosting areas
will be impacted.
Everyday More and More in Turkey, more than 3 000 000, and
impact on at least 8 500 000 in 2015 and 2016 Turkey does a
lot….and alone !
U.N.: 850,000 Refugees Are Expected to Reach Europe During
2015 and 2016
Ongoing TB Treatment in Turkey, n=200
other-african
14%
other-european
16%
Adzerbeijan
18%
Bulgaria
10%
Turkmenistan
9%
other-asia
33%
This is only air traffic around the world !
What about the cars, buses, trains and cruises ??
A single country is not able to isolate TB as millions travel in
each day and night !
TB transmission
The only risk factor for TB is breathing!
TB transmission
 Passive:
 Individual plays no active part in acquiring the infection
 Onus for preventing transmission is with health providers
 Often Unrecognized:
 Individual does perceive the transmission
 Individuals often don’t perceive a risk
Not the primary reason for screening, but adds weight to
the argument for it.
Sub-acute & non-specific presentation
 Individual often doesn’t realize: cannot rely on symptoms for the
decision on screening
 “Healthy Migrant Effect” doesn’t apply
 Difficult to avoid
TB
Caused by bacteria Mycobacterium tuberculosis
 Spread by respiratory secretions
 Two categories of TB: Latent and TB Disease

Latent TB
TB Disease
• Infected with M. tuberculosis
• Also called “Active TB”
• No signs (except reactive test) or
symptoms--infected but not ill
• Usually symptomatic
• Cannot transmit tuberculosis
• Can transmit to others
Exposed individual
TB Infection
Latent TB
Primary Disease eg
pleural effusion,
dissemination
Reactivation
(~10 – 15%)
Natural
eradication
TB Disease
XPTB (~30%)
Pulmonary (~70%)
Smear positive
(advanced)
Spontaneous cure (25%)
Death (50%)
Chronic (25%)
Migration
400 - 200 years ago:
 Industrialization & urbanization led to TB rise:
25% deaths in Western
Europe due to TB
 Grand migration through trade & colonization
 Wars, invasions in Europe &....
Now:
 Since ~1980 unprecedented human migration:
150 million people are long term residents of a country other than their
COB (country of birth)
 Short term travellers 50 x as much
 Most migrants travel from high TB-incidence countries (> 40 / 105)
to low TB-incidence countries (< 20 / 105)

Tuberculosis Cases, United States,
1993-2009
2010 U.S.TB rate:
3.6 per 100,000
Are migrants specifically more at risk of TB reactivation?
• Some specific groups clearly are e.g. refugees, migrants from
war-torn countries
• Age of TB reactivation
migration coincide
&
Figure 5: Tuberculosis rate by Population subgroup and Age
group, Australia, 2010
Australian-born Indigenous
60
Australian-born non-Indigenous
Overseas-born
50
Notifications
40
30
20
10
• … but why does TB seem to reactivate just after migration?
0
– stress, Vit. D deficiency, increased
0-4
5 to 14
15 to 24
25 to 34
35 to 34
45 to 54
55 to 64
co-morbidity e.g. diabetes
Year
65+
They achieved the Goal
 They screen in the source country before coming to USA, or
to Australia, or to UK, or to Canada !
 They invest to overseasTB screening in migration programs
 They invest and promote DOT treatment programs in the
common countries of origin (born)-COB
Who do they screen?
 The best predictor of TB is TB incidence in the COB
 Focus screening on high incidence countries
 Dependant on accuracy of rate estimates
and correlation of
country rate & rate in refugees
 Looking at the work done up to now could they do better? Discussion is
about it,
 Targeting recognized risk factor e.g. past history, contact history, relevant
co-morbidity: probably not.
 Close feedback loop (?)
 Targeting recognized risk groups from arrival country data (?)
How do they screen?
On the 24th March 1882, Robert Koch showed that
TB was due to bacteria seen in sputum – Nobel
Prize for Physiology or Medicine, 1905.
On 8th November 1895, Wilhelm Röntgen,
German Physicist, demonstrated x-rays –
1st Nobel Prize for Physics, 1901.
How do we screen?
Mobile x-ray unit, Gaziantep
Find & Treat Service, Adana VSD, 2014
Tuberculosis Handbook, WHO, 1998:
• “…two mandatory steps for detecting pulmonary TB: assessment of
symptoms and microscopy examination.”
• “… an optional second screening filter, chest radiography … alone
should never be considered adequate…”
X-rays in TB
Chest x-ray: general
– Sensitive: active pulmonary TB rarely not apparent
Miliary or laryngeal TB potentially infectious but missed
– Latent TB infection usually not seen (75%)
–
– Not specific - distinguishes poorly between:
• TB and other diagnoses
• Active and inactive TB
– Protean manifestations
– Changes often out of proportion symptoms
– Lateral rarely adds anything,
– Apical (lordotic) view can help
CT rarely adds anything
X-ray screening of migrants for TB
Advantages:
 Easy for migrant and clinician
 Allows remote review
 Sensitive: rarely misses active pulmonary TB
 Lesions from LTBI can predict reactivation risk
Disadvantages:
 Nonspecific: must be backed up by good microbiology
 Cost: financial, radiation
How to screen ?
sputum microbiology
 How do we screen? Smears ! Need both ! S&C
 Sputum smear has been the main stay:
 Diagnoses most important TB
 Culture now routine and required
 Smear too insensitive
 Drug resistance becoming more important
 QA improvements in culture important
A Dedicated Induced Sputum Facility Improves Early
Diagnosis of Tuberculosis
Wong J, Waring J. 2014
• Audit: 21 months, dedicated induced sputum facility
• Patients suspected of PTB, no spontaneous sputum
• Induced sputum x 3, 6% hypertonic saline
Results
• n = 137
• 98 (72%) asymptomatic
• 81 (60%) identified through x-ray screening
• M.TB cultured in 33 (24%);
– 26 (72%) with typical x-ray changes
– 27 (82%) asymptomatic.
• 97% positive results with first 2 samples
• Minimal adverse events
How do they screen – LTBI (?)
Denholm J, McBryde E. Aust NZ J Public Health. 2014;38:78-82
• Screening for & treating LTBI in all new
permanent immigrants would reduce TB incidence
34.5 / 106 to 16.9 – 23.8 / 106
• Need to screen 136 – 427 new arrivals for each
case prevented
Should we screen for LTBI?
Debatable!! But USA asks screening for LTBI, age 2-15
 TB in low incidence countries: LTBI reactivation after arrival
 Minimal missed active TB at the border
 Minimal evidence of transmission within low incidence countries
 Problems:
 Very large cohorts: > 50% applicants in high incidence countries
 Crude screening tests
 IGRAs no better: improved specificity not relevant and still doesn’t predict
future active TB
 Crude treatment: most would receive potentially dangerous drugs un-necessarily
 Cost: many screened & treated for few cases avoided
Why screening matters
Migration is the crux of TB control in low incidence countries
Australian-born Indigenous notifications
1400
Australian-born non-Indigenous
notifications
Overseas-born notifications
1200
86 – 88%TB cases are born
overseas = 20 - 22 / 105
20
800
15
600
10
400
200
5
0
0
2002
2003
2004
2005
2006 2007
Year
2008
2009
2010
Rate (per 100,000 population)
25
1000
Notifications
30
2011
Data to 2009: Commun Dis Intell. 2012:36(1);82 2010 – 2011 data: personal communication, Dr Justin
Waring, Medical Director, Western Australian TB Control Program, Chair, National TB Advisory Committee,
Australia
Tuberculosis cases, Europe, 2000 - 2010
Falzon D. et al. Italian J Pub Health. 2012;9(3)
Tuberculosis rate, United States, 1993 - 2010
Falzon D. et al. Italian J Pub Health. 2012;9(3)
Managing TB globally, not within borders
New Engl J Med 2005;353(10):1008-20
Schwartzman et al. New Engl J Med 2005;353(10):1008-20
• Decision analysis model: multiple Markov processes
• Est. active TB, TB-related death & associated costs in US
• Done in relation to migrants (legal, undocumented & temporary
visitors) from Mexico, over 20 years.
Results
1. Current x-ray screening of legal migrants + usual TB control
program:
–
2.
35.4m migrants, 47 610 TB cases & 5245 TB deaths, costing $1.985 billion
& $632 million respectively
Adding LTBI screening to legal migrants
–
401 fewer cases of TB, costing an extra $329 million
Schwartzman et al. New Engl J Med 2005;353(10):1008-20
Results
3. Adding expansion of DOTS program in Mexico

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
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Cost to US = $34.9 million
2591 fewer cases & 349 fewer deaths,
in undocumented migrants
NET discounted saving over 20 years = $108 million
Cost saving still if:




… 88%
initial investment doubled,
US paid for allTB drugs in Mexico or
decline in TB incidence in Mexico was less than projected
Works by reduced LTBI in Mexican migrants once expanded DOTS
improves TB incidence in Mexico
New Engl J Med
2005;353(10):
1008-20