Download An Update on Emerging Infectious Diseases

An Update on Emerging
Infectious Diseases
WF Schlech, MD
9th Travel Health Conf
Winnipeg
April 2011
Infectious disease is one of the few genuine
adventures left in the world. The dragons are all
dead and the lance grows rusty in the chimney
corner . . . About the only sporting proposition
that remains unimpaired by the relentless
domestication of a once free-living human species
is the war against those ferocious little fellow
creatures, which lurk in the dark corners and
stalk us in the bodies of rats, mice and all kinds
of domestic animals; which fly and crawl with the
insects, and waylay us in our food and drink and
even in our love.
- (Hans Zinsser,1934 quoted in Murphy 1994)
…J Keystone
Want them protected!
Emerging Infectious Diseases
(EID) Defined
• “New, reemerging or drug-resistant
infections whose incidence in humans
has increased within the past two
decades or whose incidence threatens
to increase in the near future.”
Institute of Medicine, 1992
Definitions
• New infectious disease
Newly identified & previously unknown
infectious agents that cause public health
problems either locally or internationally
eg HIV infection, Nipah virus, P.knowlesi
Definition
• Re-emerging infectious disease
Infectious agents that have been known for
some time, had fallen to such low levels that
they were no longer considered public health
problems & are now showing upward trends in
incidence or prevalence worldwide
eg tuberculosis, diptheria
Definition
• Drug resistant organisms
Infectious agents that have developed
resistance to antimicrobials and subsequently
spread to many geographic areas
eg MDR tuberculosis, resistant
gonorrhea, MRSA, VRE, NDM-1
NDM-1
NEWLY IDENTIFIED INFECTIOUS
DISEASES AND PATHOGENS
Year
1993
1992
1991
1989
1988
1983
1982
1980
Disease or Pathogen
Hantavirus pulmonary syndrome (Sin Nombre
virus)
Vibrio cholerae O139
Guanarito virus
Hepatitis C
Hepatitis E; human herpesvirus 6
HIV
Escherichia coli O157:H7; Lyme borreliosis;
human T-lymphotropic virus type 2
Human T-lymphotropic virus
Source: Workshop presentation by David Heymann, World Health Organization,
1999
NEWLY IDENTIFIED INFECTIOUS
DISEASES AND PATHOGENS
Year
2009
2004
2003
1999
1997
1996
1995
1994
Disease or Pathogen
H1N1
Avian influenza (human cases)
SARS
Nipah virus
H5N1 (avian influenza A virus)
New variant Creutzfelt-Jacob disease;
Australian bat lyssavirus
Human herpesvirus 8 (Kaposi’s sarcoma
virus)
Savia virus; Hendra virus
Source: Workshop presentation by David Heymann, World Health Organization,
1999
Examples of Re-Emerging
Infectious Diseases
• Diphtheria- Early 1990s epidemic in
Eastern Europe(1980- 1% cases; 199490% cases)
• Cholera- 100% increase worldwide in 1998
(new strain eltor, 0139)
• Human Plague- India (1994) after 15-30
years absence. Dengue/ DHF- Over past
40 years, 20-fold increase to nearly 0.5
million (between 1990-98)
Dr. KANUPRIYA CHATURVEDI
Percent Fever in Returned Travelers
N=3907
NEJM 2005;354:119-30
etiology
Carib CAm SAm
SSA
malaria
<1
13
13
dengue
23
12
14
62 14 13
<1 14 32
mono
rickettsia
7
0
7
0
8
0
6
2
1
Salmon.
2
3
2
<1
14 3
1
SA
SEA
3
2
Chikungunya:
“that which bends up”
17
17
Chikungunya
Dengue
www.healthmap.org/dengue/
18
DISEASE EMERGENCE AND
RE-EMERGENCE: CAUSES
• GENETIC/BIOLOGIC FACTORS
– Host and agent mutations
– Increased survival of susceptibles
• HUMAN BEHAVIOR
– POLITICAL
– SOCIAL
– ECONOMIC
• PHYSICAL ENVIRONMENTAL FACTORS
• ECOLOGIC FACTORS
– Climatic changes
– Deforestation
– Etc.
Convergence
Model
FACTORS CONTRIBUTING TO
EMERGENCE OR RE-EMERGENCE OF
INFECTIOUS DISEASES (1)
• Human demographic change by which persons
begin to live in previously uninhabited remote
areas of the world and are exposed to new
environmental sources of infectious agents,
insects and animals
• Unsustainable urbanization causes
breakdowns of sanitary and other public
health measures in overcrowded cities (e.g.,
slums)
FACTORS CONTRIBUTING TO
EMERGENCE OR RE-EMERGENCE OF
INFECTIOUS DISEASES (2)
• Economic development and changes in the use of
land, including deforestation, reforestation, and
urbanization
• Global warming - climate changes cause changes in
geographical distribution of agents and vectors
• Changing human behaviours, such as increased use
of child-care facilities, sexual and drug use
behaviours, and patterns of outdoor recreation
• Social inequality
FACTORS CONTRIBUTING TO
EMERGENCE OR RE-EMERGENCE OF
INFECTIOUS DISEASES (3)
• International travel and commerce that
quickly transport people and goods vast
distances
• Changes in food processing and handling,
including foods prepared from many
different individual animals and
countries, and transported great
distances
6
Days to Circum navigate (
the Globe
350
)
400
5
300
4
250
200
3
150
2
100
50
1
0
0
1850
1900
Year
1950
World Population in billions (
)
Speed of Global Travel in Relation to
World Population Growth
2000
CDC
FACTORS CONTRIBUTING TO
EMERGENCE OR RE-EMERGENCE OF
INFECTIOUS DISEASES (4)
• Evolution of pathogenic infectious agents by
which they may infect new hosts, produce
toxins, or adapt by responding to changes in
the host immunity.(e.g. influenza, HIV)
• Development of resistance by infectious
agents such as Mycobacterium tuberculosis
and Neisseria gonorrhoeae to
chemoprophylactic or chemotherapeutic
medicines.
S.Typhi Drug Resistance 1999-2006
Multidrug resistant S.typhi
Naladixic acid resistant S.typhi
87% cases from India
NARST
Sensitivity to ciprofloxacin
JAMA. 2009;302(8):859-865
FACTORS CONTRIBUTING TO
EMERGENCE OR RE-EMERGENCE OF
INFECTIOUS DISEASES (5)
• Resistance of the vectors of vector-borne
infectious diseases to pesticides.
• Immunosuppression of persons due to medical
treatments or new diseases that result in
infectious diseases caused by agents not
usually pathogenic in healthy hosts.(e.g.
leukemia patients)
FACTORS CONTRIBUTING TO
EMERGENCE OR RE-EMERGENCE OF
INFECTIOUS DISEASES (6)
• Deterioration in surveillance systems for
infectious diseases, including laboratory
support, to detect new or emerging disease
problems at an early stage (e.g. Indonesian
resistance to “scientific colonialism”)
• Illiteracy limits knowledge and
implementation of prevention strategies
• Lack of political will – corruption, other
priorities
GeoSentinel:
The Global Surveillance Network
of the ISTM and CDC
A worldwide
communications and
data collection network
of travel/tropical
medicine clinics
Geosentinel Network Map
49 clinics & 166 collaborators
49 travel/tropical medicine clinics globally (since 1996)
FACTORS CONTRIBUTING TO
EMERGENCE OR RE-EMERGENCE OF
INFECTIOUS DISEASES (7)
• Biowarfare/bioterrorism: An unfortunate
potential source of new or emerging disease
threats (e.g. anthrax and letters)
• War, civil unrest – creates refugees, food and
housing shortages, increased density of living,
etc.
• Famine causing reduced immune capacity, etc.
• Manufacturing strategies; e.g., pooling of
plasma, etc.
GLOBAL EXAMPLES OF EMERGING AND
RE-EMERGING INFECTIOUS DISEASES
AS Fauci
Direct economic impact of selected infectious disease outbreaks, 19902003
These are costly!
Heymann DL. Emerging and re-emerging infections. In Oxford Textbook of Public
Health, 5th ed, 2009, p1267.
Drug Resistant Microorganisms
Preventing Emerging Infectious Diseases: A Strategy for the 21st century. The CDC Plan, p. 26,
1998
Multidrug resistant
National Academies Press
http://www.nap.edu/books/0309071844/html/13.html
War as a factor in spread of MDR organisms
Acinetobacter isolates from FOB-Delta
New Combat Surgical/Trauma Suite
• High risk organism isolation over time during construction of medical facility
• MDR Gram negatives not isolated prior to patient introduction into facility but
high risk pathogens present
Enserink M. Old drugs losing effectiveness against flu; could statins fill gap? Science 309:177,
2005.
Recent EIDs:
Influenza
Structure of the Influenza Virus
Hemagglutinin (HA)
16 types in influenza
A
Neuraminidase (NA)
9 types in influenza A
M2
Nucleoprotein (NP)
ssRNA–highly mutable
8 segments-allows
reassortment during
double infection
M1
Polymerase (P) Proteins
Adapted from: Hayden FG et al. Clin Virol. 1997:911-42.
Viral Nomenclature
Type of Nuclear
Material
Hemagglutinin
Neuraminidase
A / Sydney / 184 / 93 (H3N2)
Virus
type
Geographic Strain Year of
origin
number isolation
Virus
subtype
CDC. Atkinson W, et al. Chapter 13: Influenza. In: Epidemiology and Prevention of Vaccine-Preventable
Diseases, 4th ed. Department of Health and Human Services, Public Health Service, 1998, 220
Antigenic Drift
Antigenic Shift
INFLUENZA PANDEMICS
IN THE 20th CENTURY
Years
1918-1919
“Spanish”
1957-58
“Asian”
1968-69
“Hong Kong”
US
Spread from
Virus Mortality Greatest Risk Asia to US
Type A 500,000 Young,
Unknown
H1N1
healthy adults
Type A
H2N2
70,000 Infants,
elderly
4-5 mo
Type A
H3N2
34,000 Infants,
elderly
2-3 mo
HHS Pandemic Influenza Plan, October 2005
Some Confirmed Instances of Avian
Influenza Infecting Humans since 1997 (*)
Year
1997
1999
2002
2003
2003
2003
2003
2004
2004
Virus
H5N1
H9N2
H7N2
H5N1
H7N7
H9N2
H7N2
H5N1
H7N3
Location
Hong Kong
Hong Kong
Virginia
Hong Kong
Netherlands
Hong Kong
New York
Thailand, Vietnam
Canada
Summary tally:
H5N1: 3
H7N2: 2
H7N3: 1
H7N7: 1
H9N2: 2
Is this virus actively
reassorting its genes
to achieve a unique
combination of
virulence and
communicability?
(*) For details see: www.cdc.gov/flu/avian/gen-info/avian-flu-humans.htm
Thanks to Eric Brenner, MD for slide.
Characteristics of H5N1
Avian Influenza
1. Highly infectious and pathogenic for
domestic poultry
2.Wild fowl, ducks asymptomatic reservoir
3.Now endemic in poultry in Southeast Asia
4.Proportion of humans with subclinical
infection unknown
5.Case fatality in humans is >50%
Novel Swine origin Influenza A
(H1N1)
• Swine flu causes respiratory disease in pigs
– high level of illness, low death rates
• Pigs can get infected by human, avian and
swine influenza virus
• Occasional human swine infection reported
• In US from December 2005 to February
2009, 12 cases of human infection with
swine flu reported
Kaplan K. How the new virus came to be. LA Times, 14 Sept, 2009; latimes.com/health
Swine Flu
Influenza A (H1N1)
• March 18 2009 – ILI outbreak reported in
Mexico
• April 15th CDC identifies H1N1 (swine flu)
• April 25th WHO declares public health
emergency
• April 27th Pandemic alert raised to phase 4
• April 29th Pandemic alert raised to phase 5
Pandemic H1N1 (Swine flu)
• Worldwide- 162,380 cases
1154 deaths
• Canada – 400+ deaths (Jan 2010)
Recent EIDs:
SARS
A Novel Virus: SARS
NEJM May 15, 2003
SARS: Summary
• In retrospect epidemic started ~ November
2002 in Southern China
• WHO issues “Global Alert” March 2002
• February 2003 very infectious patient infects
many guests at Metropole Hotel in Hong Kong
who in turn spread SARS to their own countries
• World attention remained focused on SARS
until global surveillance shows all chains of
transmission interrupted ~ July 2003
SARS in Toronto, 2003
Is there a small subset of SARS patients who
account for a disproportionate share of
transmission? MMWR May 9, 2003 / Vol. 52 / No. 18 - I
Patients No: 1, 6, 35,
130&127 seemed to be
“hypertransmitters”
Recent EIDs:
MDR and XDR TB
35 yo HIV (+) woman with
productive am cough ,low grade
fever, and weight loss over
several weeks.
On exam cachectic,
normal chest exam.
CXR
-Dx : Pulmonary tuberculosis
Tuberculosis
• Estimated 15 million Americans with latent
infections
• Minorities affected disproportionately [as is
the case with many other infectious diseases]
– 54% active M. Tuberculosis cases (1995)
reported among African American and
Hispanic populations
– An additional 17.5% among Asians
• In some U.S. sectors, morbidity rates surpass
those of poorest countries
Cases of M. Tuberculosis by
Year of Diagnosis, 1953-1999
90,000
80,000
70,000
60,000
50,000
40,000
30,000
20,000
10,000
19
53
19
55
19
57
19
59
19
61
19
63
19
65
19
67
19
69
19
71
19
73
19
75
19
77
19
79
19
81
19
83
19
85
19
87
19
89
19
91
19
93
19
95
19
97
19
99
0
Source: Centers for Disease Control and Prevention, 20001
Estimated TB incidence rate, 2006
Estimated new TB cases (all
forms) per 100 000
population
No estimate
0-24
25-49
50-99
100-299
300 or more
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
Prevalence of HIV/TB co-infection
Global incidence of tuberculosis
Still rising as a result of the growing epidemic in Africa
Incidence per 100,000 per year
600
AFR high HIV
500
400
300
AFR low HIV
Sth East Asia
200
World
West. Pacific
East. Medit.
East. Europe
Lat. America
Cent. Euro,
Est Market
100
0
1990
1995
2000
2005
2010
2015
MDR and XDR TB
Definitions
• Multidrug-resistant tuberculosis (MDRTB)
Resistance to Isoniazid and Rifampicin
• Extensively (extremely) drug-resistant
tuberculosis (XDR-TB)
MDR-TB plus resistance to a second line
injectable drug such as amykacin plus a
quinolone.
Impact of drug resistance on TB cure rates with standard
4-drug therapy
% Success
New Case Retreated
Pan-susceptible
Any resistance, not MDR
INH resistance, not MDR
RIF resistance, not MDR
M DR
85
81
82
73
52
67
56
54
53
29
Espinal, JAMA 2000; 283:2537
XDR-TB related to district hospital, Tugela
Ferry, KwaZulu-Natal South Africa 2006
Demographics of XDR TB Patients
Resistant to all drugs tested
(XDR)
Characteristics
Total (N)
53
Age: years: Median (range)
35 (20-75)
Sex: Female (%)
25 (49%)
Sputum Smear: Positive: n (%)
42 (79%)
Negative: n (%)
11 (21%)
HIV Characteristics
Characteristic
XDR TB Patients
HIV Tested: n (%)
44 (86%)
HIV positive (if tested):
Recent CD4 count: mean
median (range)
On Antiretroviral Therapy: n (%)
100%
72.7
63 (9 - 283)
15 (34%)
Mortality
• 52 of 53 (98%) XDR TB patients died
• Median survival from sputum collection 16
days (range 2-210 days)
Transmission of XDR TB
• 64% of patients hospitalized for any cause before
onset of XDR TB
• 2 healthcare workers died with confirmed XDR TB
– 4 other workers died with suspected XDR TB
• Nosocomial transmission in hospitals probable
• Transmission in community also possible since 36%
XDR TB patients with no prior hospitalizations
Summary
• New and re-emerging infectious diseases
continue to challenge public health
practitioners
• Adequate surveillance systems remain
critical in detecting and controlling these
pathogens
• Ultimate control will depend on
development of new vaccines and
antimicrobial agents and better use of our
current armamentarium
Thank you!