This document outlines the lectures in a course on global health and emerging infections. The first three lectures discuss existing threats like malaria, tuberculosis, and leprosy. The third lecture focuses on new threats posed by emerging infections and examines case studies of SARS, pandemic flu, and a 2011 E. coli outbreak in Germany. The fourth lecture discusses disease eradication efforts for smallpox and current efforts for polio and guinea worm. The fifth lecture provides an overview of infectious disease diagnosis in clinical microbiology laboratories.
Couples presenting to the infertility clinic- Do they really have infertility...
Bio303 Lecture Three: New Foes, Emerging Infections
1. Global Health and Emerging
Infections 3: New Foes
Professor Mark Pallen
Bio303
2. Global Health and Emerging Infections
1. 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.
3. 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
4. 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
5.
6. SARS: First pandemic ofnew 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
7. SARS: history of the epidemic
15 Feb: 65-yr-old
professorof 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/photostrea
8. 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
9. SARS: history of the epidemic
Carlo Urbani, Italian doctor and WHO
physician in Hanoi notifies WHO of
explosive nosocomial outbreakin
Hanoi
Urbani's descriptionof casesoutside
Guangdong alerts healthauthorities
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
10. 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
11. 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
12. Local transmission in Toronto,
Ottawa, San Francisco, Ulan
Bator, Manila, Singapore, Taiwan,
Hanoi and Hong Kong
Within PRC spread to Guangdong,
Jilin, Hebei, Hubei, Shaanxi,
Jiangsu, Shanxi, Tianjin and Inner
Mongolia
13. SARS-CoV
Coronavirus S protein binds host receptor
Previously thought to be benign angiotensin-converting enzyme
group; 15% of all cases of 2 (ACE2)
common cold
Mutations in S protein reveal
large, enveloped, +ssRNA virus evolution of virus as epidemic
Irregular shape, club-shaped progresses
spikes Adaptive changes show
Genome encodes increase affinity for human
replicase (Orf1ab) ACE2
structural proteins: spike [S], Neutral changes reveal
envelope [E], membrane [M], phylogeny of HK outbreak
nucleocapsid [N]
14. 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
15. Transmission of SARS-CoV
Human-to-human transmission
direct or indirect contact of the mucosae with
infectiousrespiratory droplets or fomites
Higher environmentalstability 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
16. 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
17. 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
18. 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
19. SARS epidemic: the aftermath
SARS epidemic involved 37 rapid global dissemination
countries around the world depended on
8,096 cases and 774 deaths capacity for human-to-human
Case-fatality rate ~10% transmission
50% for >65 yrs old the lackof awareness in hospital
infection control
Causes of epidemic
internationalair travel
rapid economic growth inChina
primed demand for exotic food unparalleled dramatic impact on
animals such as civets health care systems,economies,
and societies of affected countries
overcrowdedcages with no
biosecurity in wet markets
ability of virus to jump from
animals to human
20. SARS next time: are we ready?
SARS could return if conditions gaps still exist in
are fit for the understanding transmissibility and
introduction,mutation, pathogenesis in humans
amplification, and transmission screening tests
of this dangerousvirus foolproof infection control
animal reservoir persists in effective antivirals and
civets, bats etc immunomodulatory agents
safe effective vaccine
BUT next time, we will have
identifying immediate animal host
wherewithal to diagnose and
that transmitted the virus to caged
respond civets
And treat and vaccinate?
4,000 publications available
online
22. Haemolytic-uraemic syndrome
Shiga-toxin-producing E. coli (STEC)
bloody diarrhoea; damage to kidneys and brain
anaemia; loss of platelets
23. 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
31. 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
35. 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
36. 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
37. 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?
38. 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
73. what about H1N1?
susceptible to antivirals
not drifted from vaccine strain
displaced seasonal influenza
race between the spread of
the virus and the spread
of information