STC talk

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Francis A. Plummer,Senior Advisor, Public Health Agency of Canada and

Distinguished Professor, University of Manitoba

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Anticipating where the puck is going to be:

Using advanced technologies to keep ahead in the evolutionary struggle with the microbial world

• Emerging infections are those that are new or newly discovered in humans – mainly come from animals (H1N1, measles, plague, tuberculosis, influenza, HIV, SARS)

• Infections re-emerge when old microbial foes acquire new weapons through genetic exchange or mutation –resistance to drugs or vaccines, escape from the human immune defences

Emerging and Remerging Infectious Diseases

Bacteria

• Legionairre’s disease• E.coli H7:O157• Clostridium difficile colitis• Helicobacter pylori• Chlamydia trachomatis and C.

pneumonia• Staphylococcus toxic shock• Flesh eating disease• Methicillin resistant S. aureus• Penicillin resistant gonorrhea and

Hemophilus influenza• Extremently drug resistant

tuberculosis• Vancomycin resistant enterococcus

Emerging and Re-emerging Infectious Disease Over My

Career Viruses

•Ebola virus•HTLV-I•HIV-1•HIV-2•Nipah virus•Borna virus•West Nile virus•SARS•H5N1 Avian influenza•H1N1 pandemic influenza•Hepatitis B & Hepatitis C•Delta agent•Prion disease (mad cow)•NERS

Are Infectious Diseases Threats Increasing?

• Probably “yes”• 35+ “new” diseases over the past 40 years• Of all microbial species, we have characterized

less than 1% and the unknown 99% represent constant source of new threats.

• Most new infections come from animals • Organisms mutate in response to human tactics:

drugs, vaccines, disinfectants ...

Why Is This Happening?• Ecologic changes• Human demographic/behavioural changes• Globalization• Rapid growth in technology• Microbial adaptation and change• Gaps in public health programs/infrastructure

Anticipating the Puck

The Katrina Lesson

____ _______ _________ __ _____ _______ _________ _______

Using Advanced Technology to Combat Emerging Infectious Diseases

Tactic 1:

Rapid Detection & Alerting of Infectious Disease

New Tools to Increase Speed of Detection and Alerting

• Previously: Countries reported new & emerging diseases to WHO – take weeks

• Now: advanced computer based technologies

– Canadian Network for Public Health Intelligence

– Monitors news, internet etc.

• Examples: SARS, H1N1, Listeria

Data Collection/Exchange

Surveillance/Program ‘Watches’

Alerting

Event Management

Respo

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urce M

anagem

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Centr

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nadian

Integr

ated O

utbrea

k Surv

eillanc

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Program Management

Syndromic SurveillanceNESP

CBRN Watch WNV

Prov/TerrEpi SchoolsLabs Hospitals OTC Telehealth

DND/RCMP OthersEnvironmental Data CFIA

Manual Data Entry

FluWatch

Automated Data Collection

Public Health Alerts

GPHIN RespiratoryZoonotic

Phone Fax Email Pager

ReferencesProtocols

Training Materials Resource Inventory

Knowledge Management Resources

- Targeted alerting- Role based- Respect jurisdictional accountabilities- Program driven; configurable & flexible

- Command and control - Real-time data collection and integration- Intelligence organization, display, and decision making tools - Integration of organic and external expertise- Connectivity of external command centres and capabilities- Data recovery and long-term analysis

- Program/Businesss centres - Communication and coordination - Program driven; configurable and flexible

Inter-Jurisdiction Case Management

- Intelligence presentation using maps, charts, etc.- Supported by algorithms and other decision support tools- Program driven; configurable and flexible

- Manual and automated targeted data collection - Respects privacy issues- Program driven; configurable and flexible

CNPHI at a Glance January 1, 2005

CNISP

iPHIS/EHR

TravelNosocomial CBRN EntericSTD

Secure role-based registration system

Program Specific Surveillance

Intelligence Exchange ResourcesDiscussion Forum News Board

Document Manager SchedulerGroup Chat

Web-cast

ETEAM

Web SurveysOther

ModelingGIS

Statistics Algorithms

Decision Support Resources

Web-Data Web-Data

Copyright © 2005, Canadian Network for Public Health Intelligence. Reproduction in whole or in part in any form or medium withoutexpress written permission is prohibited.

Other

Outbreak Summmaries Outbreak Summmaries

Inter-Jurisdiction Case Management

Canadian Integrated Outbreak Surveillance Centre (CIOSC)Public Health Alerts

Nurses

ER physicians General practitioners

Custom Officers

Veterinarians

Laboratorians

FNIHB health care

professionals

Law Enforcement

ParamedicsMilitary

Social Workers

Others

Provincial/Territorial AuthoritiesPublic Health

Agency of Canada

Other Federal

Agencies

Regional Health

Authorities

Enteric (launch Apr 2001)

Respiratory (launch Dec 2004)

Travel (launch Apr 2005)

Zoonotic (launch Apr 2005)

- Targeted alerting- Role based

- Respect jurisdictional accountabilities- Program driven

- Configurable & flexible- Secure web-technology

Phone

Fax

Email

Pager

December 2004

General* (launch Apr 2005)

First Responder (proposed)

*General Alerts will accommodate disease areas not specifically addressed in other modules until program areas define disease specific user requirements

First Responders

Alert Modules

Epi-X

2005

Copyright © 2005, Canadian Network for Public Health Intelligence. Reproduction in whole or in part in any form or medium withoutexpress written permission is prohibited.

Laboratory Feature of CNPHI

CASAI.0022CASAI.0014CASAI.0023CASAI.0017CASAI.0021CASAI.0013CASAI.0002CASAI.0001CASAI.0004CASAI.0011CASAI.0003CASAI.0007CASAI.0015CASAI.0016CASAI.0005CASAI.0006CASAI.0018CASAI.0010CASAI.0019CASAI.0020CASAI.0024CASAI.0012

1 0 0908 07 06 05 04 03 0

Patterns enteredinto Bionumericsand analyzed

Clusters identified Is this a new pattern? Is this a common pattern?

Each lab analyzes the image and replies to listserv:Any pattern matches?Any known sources of infection?What is known about the pattern?

PFGE tiff file Dendrogramcreated in Bionumerics

Patterns designated

Patient 3

Dice (Opt:1.50%) (Tol 1.5%-1.5%) (H>0.0% S>0.0%) [0.0%-100.0%]PFGE-AscI

100

90807060

PFGE-AscI

PNC__08-5596/#1

PNC__08-6206

PNC__08-6567

PNC__08-6568

PNC__08-6569

PNC__08-6570

PNC__08-6571

PNC__08-6573

PNC__08-5587

PNC__ID097603

PNC__08-5599/#1

PNC__08-3083

PNC__08-5374

PNC__08-5379

PNC__08-6538

PNC__08-5579

PNC__08-6506

PNC__08-2768

PNC__08-5586

PNC08228,02

PNC08260,03

PNC08287,06

PNC08287,07

PNC08287,08

PNC08287,09

PNC08287,11

PNC08287,13

PNC08224,04

QC-08-159,09

PNC08228,05

PNC08147,10

PNC08201,05

PNC08201,12

PNC08287,04

PNC08212,07

PNC08287,02

PNC08138,08

PNC08224,02

How DNA fingerprinting* was used to identify and investigate the 2008 listeriosis outbreak, example:

not outbreak strainPatient 1Patient 2

Patient 4Patient 5

Food Product 1Food Product 2

Patient 6Patient 7Patient 8Patient 9

Food Product 3Patient 10

outbreak strainoutbreak strainoutbreak strainoutbreak strainoutbreak strainoutbreak strain

not outbreak strain

not outbreak strainnot outbreak strainnot outbreak strainnot outbreak strainnot outbreak strain

Source Listeria DNA Fingerprint Result

* Pulsed-field gel electrophoresis (PFGE)

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01-J

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ul

20-J

ul

27-J

ul

03-A

ug

10-A

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17-A

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24-A

ug

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07-S

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14-S

ep

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05-O

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12-O

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Date Results Available/Analyzed by NML

Num

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of L

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Isol

ates

Listeria monocytogenes DNA fingerprints analyzed by the National Microbiology Laboratory (NML), June – October, 2008 Includes all human, food, and environmental samples from the 2008 national Listeriosis outbreak investigation

Outbreak strainLMACI.0040/LMAAI.0003



NOT Outbreak strain

Tactic 2:

Rapid Containment - Sending the Lab to the Specimen!

Microbiologic Emergency

Response Teams• use of portable CL3 units to create safe work environment• isolator for basic microbiology• isolator for specialized techniques• equipment needed to perform testing

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Arrival In Uige

Mobile Laboratory Equipment

Uige Airfield

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Operations for Ebola in DRC 2007

Second team to newlocation –> breakdown laband transport, second teamsets up again.

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High Containment in the Bush

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Perfectly Functional Laboratory

Tactic 3:

Using Viruses to Fight Viruses!

Viral Hemorrhagic Fevers

Scary Viruses !

• Ebola• Marburg• Lassa• CCHF• Machupo

Why Feared?

• Zoonotic• Mortality as high as 80%• No treatment, no vaccines• “A list” of bioterrorism

threats

Ebola Vaccine Development• Uses a Vesicular

Stomatitis Virus to fool the immune system into thinking it’s Ebola.

• Effective in non-human primates, seemingly proved effective for human use in West Africa

These Vaccines Could Help Save the Great Apes

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Article published on the 2009-05-05 Latest update 2009-05-05 11:34 TU

Tactic 4:

Using High Throughput Machines To Understand

Genetics

H1N1

Mexican Health Officials Request Assistance from NML

April 17

PHAC-NML

MX16 H1

MX21 H1

MX10 H1

MX39 H1

MX24 H1

MX17 H1

MX47 H1

MX49 H1

MX25 H1

MX26 H1

MX2 H1

MX51 H1

MX9 H1

MX29 H1

A-California-04-2009 HA EPI176470

MX4 H1

A-Brisbane-59-07 CY030230.seq

A-Solomon Islands-3-06 ISDN220951.seq

87

99

49

39

27

0.01

April 24

NML determines outbreak in Mexico is H1N1 Influenza A (human swine flu)

North AmericanSwine Origin

Eurasian Swine Origin

North America (A/Mexico/ /2009 [H1N1]), Influenza A virus, April 2009:- Reassortment H1N1: An unusual mix of genetic sequences- 4 unique virus sources

North American Avian Origin

North American Human Origin

R. Cordero

April 29200 clinical samples

Mexico City direct to Winnipeg

Tactic 5:

Using Systems Biology to Understand Infectious

Disease

Solutions for the HIV Pandemic

HIV Prevention With The Old Science

Finding Time Lag to General Acceptance

Women were readily infected with HIV through sex

2 years

Other STD promote HIV transmission 5 yearsBreast feeding is a major route of mother to child HIV transmission

5 years

Male circumcision reduces HIV susceptibility 19 yearsHormonal contraception enhances susceptibility to HIV

?

Behavioural interventions targettedat “core groups” reduced HIV in the general population

?

Highly-exposed persistently seronegative.

3 years follow, HIV-1 serology and PCR negative, Active in sex work.

10% of highly exposed sex workers resistant to HIV-1.

Years of Followup

2 01 81 61 41 21 086420

Surv

ival

Pro

babi

lity

1 .0

.8

.6

.4

.2

0 .0 Decline in HIV-1 Incidence with follow up in the Pumwani Cohort. Adapted from Fowke et al Lancet 1996; 348: 1347–51

Resistance to HIV-1 Infection

Nature of HIV Resistance

Res Negs

CD4 T cellsGene expression profiling in HIV Resistant

WomenResNeg

Whole Blood

The Human Genome Project• Two efforts, one publically funded and one

privately funded, resulted in publication first full draft human genome sequence in 2003.

• 13 year efforts costing $100 M.• 1 genome generates 1.5 Gbytes of data.• Related fields of proteomics and

transcriptomic are advancing apace.

Towards New Technologies for HIV Prevention

Frank Plummer, May 1, 2015Objective: To undertake an exhaustive analysis of mucosal factors involved in protection against HIV

infection

The Future of Genomics• Within two years ability to generate whole

human genome for around $100 dollars.• Using a device the size of a memory stick.• Our ability to understand the enormous

amount of data produced has lagged the ability to produce it.

Analyzing the Data• Conventional statistical analysis has

yet to yield the ability to fully exploit these very powerful tools.

• Does machine learning offer the solution to this and other big data problems?

What Is Machine Learning?– A type of artificial intelligence that provides

computers with the ability to learn from data without specific programming.

How Will This Be Disruptive?• New diagnostics, new disease markers.• New treatments.• Personalized medicine.• New products.• New businesses with tremendous

economic potential.• Huge societal implications.

Conclusion

• Microbial threats are growing and ever changing

• In the evolutionary standoff with the microbial world we are like the Red Queen: needing to run faster to keep pace with the threats

• Advanced technologies help us to anticipate where they are going to be and be ready for them

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Health & Medicine

STC talk