bio303 lecture three: new foes, emerging infections
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Global Health and Emerging Infections 3: New Foes
Professor Mark Pallen
Bio303
Global Health and Emerging Infections1. The Global Burden of Infection and an Old Enemy, Malaria. In this
lecture I will survey the global burden of infection, including its human and economic costs, and examine the problem of neglected tropical diseases before focusing on one of the most serious infectious threats to humanity: malaria, outlining its evolutionary origins, impact on human health and wealth and the steps taken to control and treat this infection.
2. Two Old Enemies, TB and Leprosy. In this lecture I will focusing on another of the most serious infectious threats to humanity, tuberculosis, outlining its evolutionary origins, impact on human health and wealth and the steps taken to control and treat this infection. I will also discuss a related mycobacterial infection, leprosy and recent progress in its control.
3. New foes. In this lecture I will describe emerging infections, their epidemiology and ecology and the threats that they pose. I will focus on three case studies: SARS, pandemic flu and the German STEC outbreak of May-June 2011
4. Operation Eradication. In this lecture, I will celebrate the global eradication of smallpox, from the campaign's beginnings in Gloucestershire to the last tragic cases here in Birmingham. I will discuss what is required for an infectious disease to be eradicated and summarise progress on disease eradication, focusing on poliomyelitis and guinea worm.
5. Lab Diagnosis of Infectious Disease. Here I will provide an overview of how infections are diagnosed in the clinical microbiology lab, focusing not just on technologies, old and new, but on practical issues and workflows crucial to optimal use of the lab.
Emerging Infectious Diseases (EIDs) diseases caused by newly identified
species/strain e.g. SARS, AIDS, Ebola, Nipah, E. coli O104:H4
new infections resulting from variant of existing organism e.g. pandemic influenza
known infection spreads to new region or population e.g. West Nile virus
re-emerging infections due to drug resistance or breakdowns in public health e.g. tuberculosis, cholera
For a full list see http://www.nature.com.ezproxyd.bham.ac.uk/nature/journal/v451/n7181/extref/nature06536-s1.pdf
Emergence Factors Human demographics and behaviour (e.g. air
travel) Changing human susceptibility (e.g. with
AIDS, cytotoxics) Climate change Economic development and land use Microbial adaptation and change Breakdown of public health measures Abnormal natural occurrences War, bioterrorism
SARS: First pandemic of new millennium Nov 2002
Initial cases in southern China
Chinese authorities slow in reporting problems; PRC later apologises
By Feb 2003 Outbreak in Guangzhou
hospitals involving patients and health care workers.
Cumulative 305 cases (105 in health care workers) & 5 deaths from unknown acute respiratory syndrome
SARS: history of the epidemic 15 Feb: 65-yr-old
professor of nephrology from Guangdong falls unwell
21 Feb: resides at “hotel M”, Metropole Hotel in Kowloon, HK
Infects 17 residents at hotel
22 Feb: admitted to hospital
CC BY-SA 2.0 John Seb http://www.flickr.com/photos/johnseb/164756503/sizes/z/in/photostream/
SARS: history of the epidemic Hotel M contacts travel
to Hanoi, Singapore and Toronto, starting new outbreaks 26 Feb: US businessman
Johnny Chen (hotel M contact) falls ill on flight to Singapore; admitted to hospital in Hanoi, dies
4 Mar: another Hotel M contact starts HK hospital outbreak
5 Mar: another Hotel M contact dies in Toronto, five family members affected
SARS: history of the epidemic Carlo Urbani, Italian doctor and
WHO physician in Hanoi notifies WHO of explosive nosocomial outbreak in Hanoi
Urbani's description of cases
outside Guangdong alerts health
authorities throughout world and accelerates research to identify virus and combat disease, saving 1000s of lives
Urbani dies on March 29, a month after seeing his first case and 18 days after falling ill on a plane to Bangkok
"If I cannot work in such situations, what am I here for - answering e-mails, going to cocktail parties, and pushing paper?" Dr. Carlo Urbani, 2003
SARS: history of the epidemic 12-15 Mar 2003
WHO issues global alert coins name “sudden acute
respiratory syndrome” calls for global collaborative
research effort 21 March
HK Scientists isolate new coronavirus from open lung biopsy; soon confirmed in US and Germany
12 April genome sequence shows this virus
is distinct from all known human pathogens
SARS: history of the epidemic Jun 2003: virus almost identical to
SARS-CoV isolated from palm civets and other game food mammals
5 Jul 2003: Lack of transmission in Taiwan signals end of human-to-human transmission
3 Sep 2003: Lab-acquired SARS-CoV infection in Singapore
Dec 2003/Jan 2004: five cases from new animal-to-human transmission in Guangzhou
17 Dec 2003: Lab-acquired SARS-CoV infection in Taiwan
25 Mar & 17 Apr 2004: Lab-acquired infection in Beijing, with secondary and tertiary spread
16 Sep 2005: SARS-CoV-like virus in horseshoe bats
Local transmission in Toronto, Ottawa, San Francisco, Ulan Bator, Manila, Singapore, Taiwan, Hanoi and Hong KongWithin PRC spread to Guangdong, Jilin, Hebei, Hubei, Shaanxi, Jiangsu, Shanxi, Tianjin and Inner Mongolia
SARS-CoV S protein binds host
receptor angiotensin-converting enzyme 2 (ACE2)
Mutations in S protein reveal evolution of virus as epidemic progresses Adaptive changes show
increase affinity for human ACE2
Neutral changes reveal phylogeny of HK outbreak
Coronavirus Previously thought to be
benign group; 15% of all cases of common cold
large, enveloped, +ssRNA virus
Irregular shape, club-shaped spikes
Genome encodes replicase (Orf1ab) structural proteins: spike
[S], envelope [E], membrane [M], nucleocapsid [N]
SARS Case Definition and Clinical Findings Incubation period of SARS 2-14
days Clinical history & observation
flu-like symptoms : fever >38°C, myalgia, lethargy, GI symptoms, cough, sore throat, shortness of breath
≤10 days before onset of symptoms Close contact with
probable/suspected SARS patient OR
Been in area with transmission of SARS
Chest radiography: important role 70-80% patients have abnormal
chest radiographs Now "laboratory-confirmed SARS”
possible
Transmission of SARS-CoV Human-to-human transmission
direct or indirect contact of the mucosae with infectious respiratory droplets or fomites
Higher environmental stability than other human coronaviruses 2-3 days on dry surfaces; 2-4 days in stool
Explosive outbreak affecting 100s in Amoy Garden housing estate in HK due to dried U traps in sewage drains exhaust fans generate aerosols in toilets
aerosols ascend light well connecting different floors
SARS transmitted in commercial aircraft on five flights
Origins of SARS-CoV Highly probable: origination is a cross-species
jump from civets and/or horseshoe bats to humans
Second case was chef with multiple animal contact
Phylogeny from helicase sequences
Controlling SARS Principle: to break the chain of transmission
from infected to healthy person 3-step protocol of disease confinement
Case definition and detection Prompt isolation Contract tracing
Daily health check Voluntary home isolation
Treatment interferon alfacon-1 with steroids protease inhibitors with ribavirin convalescent plasma containing neutralizing
antibody
Epidemic Containment Creation of emergency operating center Institutional support
Efficient quarantine measures 1000s quarantined in HK, Canada, SG, Taiwan Schools closed in HK, SG
Legislation International collaboration—WHO
Travel alerts and restrictions controversially WHO advised only essential visits to
Toronto Airline passengers screened for fever using thermal
imaging scans Coordination for research Agreement of countries on containment protocol
SARS epidemic: the aftermath SARS epidemic involved 37
countries around the world 8,096 cases and 774 deaths
Case-fatality rate ~10% 50% for >65 yrs old
Causes of epidemic rapid economic growth in
China primed demand for exotic food animals such as civets
overcrowded cages with no biosecurity in wet markets
ability of virus to jump from animals to human
rapid global dissemination depended on capacity for human-to-
human transmission the lack of awareness in
hospital infection control international air travel
unparalleled dramatic impact on health care systems,
economies, and societies of affected countries
SARS next time: are we ready? SARS could return if
conditions are fit for the introduction, mutation, amplification, and transmission of this dangerous virus animal reservoir persists
in civets, bats etc BUT next time, we will have
wherewithal to diagnose and respond And treat and vaccinate?
4,000 publications available online
gaps still exist in understanding transmissibility
and pathogenesis in humans screening tests foolproof infection control effective antivirals and
immunomodulatory agents safe effective vaccine identifying immediate animal
host that transmitted the virus to caged civets
Swine Flu 2009: the first open-source epidemic?
Haemolytic-uraemic syndrome Shiga-toxin-producing E. coli (STEC)
bloody diarrhoea; damage to kidneys and brain anaemia; loss of platelets
German E. coli O104:H4 outbreak
May-July 2011 >4000 cases >40 deaths Link to sprouting seeds High risk of haemolytic-
uraemic syndrome Females particularly at
risk
“Calling International Rescue…”
Herr Doktor Holger RohdeUKE Universitätsklinikum Hamburg-Eppendorf
“Calling International Rescue…”
BGI-Shenzhen
UKE Hamburg
Ion Torrent
Millions of wells reading sequencesMicrochip detects release of protons~3 hour run-time~£500 cost per run
Crowd-sourcing the genome
Crowd-sourcing the genome Within 24 hours of its release, the genome is
assembled Within two days, assigned to an existing
lineage Within five days, strain-specific diagnostic test
released Within a week, two-dozen reports on the
biology and evolution of the strain had been filed on an open-source wiki
Crowd-sourcing the genome
Take away messages Pathogens don’t bother with passports!
Not a new strain something similar seen in Germany ten years ago
and in Korea closest genome-sequenced strain was isolated
from Central African Republic in late 1990s German STEC comes from a lineage
circulating in human populations rather than from an animal source
Take away messages
Bacteria evolve quickly Virulence factors in E. coli can jump from one
lineage to another on bacterial viruses Antibiotic resistance seen where no obvious prior
use of antibiotics Infection still presents a threat even in the most
advanced societies
Take away messages Open-source genomics: propitious confluence
of high-throughput genomics crowd-sourced analyses a liberal approach to data release
Social media (e.g. blogging, Twitter) can augment usual channels of academic discourse
But have we broken the mould? appropriate for public heath emergencies… …but not for “ordinary science”?
Cite or site?
Open-source genomics
Genome sequencing brings the advantages of open-endedness (revealing the “unknown
unknowns”), universal applicability ultimate in resolution
Bench-top sequencing platforms now generate data sufficiently quickly and cheaply to have an impact on real-world clinical and epidemiological problems
Addendum: Jennifer Gardy’s slides
http://creativecommons.org/licenses/by-sa/2.0/
Attribution-ShareAlike 2.0 Generic (CC BY-SA 2.0)
http://www.youtube.com/watch?v=LmAugMSJ1-Y
public health in the 21st century: the open source outbreak
dr. jennifer gardybc centre for disease controlgenome research laboratory
new technology
new attitudes
public health 2.0
open source outbreak
take-home point
technological advances shift in scientists’ attitudes
public health 2.0: rapid & collaborative
rewind to march 2009
increased flu activity in Mexico
California
CDC
WHO
pandemic!
5,000 confirmed cases100-150,000 possible cases
at June 11, 2009
open source outbreak
sharing germs,sharing data
increased flu activity in Mexico
California
CDC
WHO
pandemic!
april 25: 1st genome
april 26: international wiki13 people, 8 institutes, 4 countries
http://tree.bio.ed.ac.uk/groups/influenza
april 26: origins of the virus calculated
april 30: origins data published
5 days from sequence to open-access paper
increased flu activity in Mexico
California
CDC
WHO
pandemic!
april 25: 1st genome
may 6: 69 virus’ RNA
virus entered human population late 08/early 09
may 5: first major paper submitted
may 11: first major paper published
increased flu activity in Mexico
California
CDC
WHO
pandemic!
april 25: 1st genome
may 6: 69 virus’ RNA
june 11: 250+ papers
SARS, 2003day 0 virus isolation
day 0 virus isolationH1N1, 2009
day 19 one viral genome
day 19 100+ viral genomeswhere/when it arosemultiple papersvaccine seed strain
how?
technological advances
shift in scientists’ attitudes
genomes = easy, cheap, fast
human genome project (1990)
10 years to draft3 more to complete$3 billion100s of people
spring 2009four weeks
$48,000 worth of reagents
three-person teamstephen quake, stanford bioengineering
data = easy, cheap, fast
from flickr user amy and casey
the file-sharing generation
85% of scientists
support open
accessMann et al, Comm. of the ACM 52(3):135. (2009)
collaboration
what about H1N1?susceptible to antiviralsnot drifted from vaccine straindisplaced seasonal influenza
race between the spread of the virus and the spread of information
what about the next bug?
genome surveillance
population sampling to pick up threats before the lab or clinic
months of undiscovered circulation in people
sewage-nomics
from flickr user stuck in customs
embrace new technologies
embrace open access and collaboration
don’t embrace anyone with a fever and/or cough
from flickr user jess and colin
oink! oink!(thank you)
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