Download International Symposium on One Health and INDOHUN Annual

International Symposium on One Health
and INDOHUN Annual Meeting
Perspective and Factors Contributing to Emerging
and Re-emerging Pandemics
Saul Tzipori, DVM, PhD, DSc, FRCVS
Department of Infectious Disease and Global Health
Solo, October 22, 2014
GLOBAL EXAMPLES OF EMERGING AND
RE-EMERGING INFECTIOUS DISEASES
AS Fauci
Examples of Pathogens Emerged* or Recognized in humans for the first
YEAR
MICROBE
DISEASE
1973 (1968)
Rotavirus
Major cause of infantile diarrhea globally
1976 (1907)
Cryptosporidium hominis
Acute and chronic diarrhea
1997*
Ebola virus
Ebola hemorrhagic fever
~1970
Enterovirus 71 (C)
Hand, Foot, Mouth Disease (death from
CNS)
1983*
HIV
AIDS
1984*
E. Coli O157:H7 (enterohemorrhagic)
Hemorrhagic colitis & HUS
1985
Enterocytozoon bieneusi (microsporidiosis)
Chronic diarrhea and wasting in HIV/AIDS
1992*
Vibrio cholerae O139
New strain associated with epidemic cholera
1994*
Hendra virus
Respiratory and CNS disease (horses/&
humans)
1995*
Human herpes virus-8
Associated with Kaposi sarcoma in AIDS
patients
1997*
Avian Influenza [Type A (H5N1)]
Influenza
1999
Nipah virus
Influenza-like symptoms (deaths from CNS)
2003*
SARS coronavirus
SARS - Severe Acute Respiratory Syndrome
2005*
Clostridium difficile (highly virulent strains)
Pseudomembranous colitis
2011*
Swine influenza [H1N1]
influenza
2012*
MERS
Middle East Respiratory Syndrome
Emerging Infectious Diseases Newly
Recognized Diseases
 Marburg
 Legionnaires' Disease
 Toxic Shock Syndrome
 Lyme Disease
 Campylobacteriosis
 Vibrio vulnificus Infections
 Helicobacter Infections (Ulcers)
 Bartonella Infections (Cat Scratch)
 Opportunistic Molds
The Threat of Zoonotic Disease is Not New
Beyond HIV/AIDS, SAR, MERS, Ebola, Avian flu, Nipah virus, etc
Malaria - Plasmodium falciparum - Probably birds
Malaria - Plasmodium vivax - Asian macaques
Sleeping sickness - Trypanosoma brucei subsp.. - Wild ruminants
Diphtheria - Corynebacterium diphtheriae - Domestic herbivores
Hepatitis Hepatitis B virus - Apes
Respiratory Infections Human coronavirus OC43 - Bovine
Influenza Influenza A virus - Wildfowl
Measles - virus - Sheep/goats
Plague - Yersinia pestis - Rodents
Dengue fever virus - Old World primates
Yellow fever virus - African primates
Smallpox - Variola virus - Ruminants (camels)
Mumps virus - Mammals (pigs)
(Source: Adapted from Wolfe et al. (2007)
Some Profound Events in Infectious Diseases in
Human History
Bubonic Plague in 16th-17th Europe leading to reforms in
sanitation.
Smallpox was a major killer of young and the unimmunized
leading to development of vaccination.
Group A Streptococcal infection in 1840 initiated
chlorinated lime solution in hand washing
Spanish flu pandemic of Influenza in 1918 (HIN1), and the
impact of globalization
HIV/AIDS appeared in 1981 initiated a worldwide pandemic,
and introduced massive anti retroviral therapy
Factors Contributing to Emergence or
Reemergence of zoonotic Infectious Diseases
Microbial evolution
Urbanization
Large population migration
Rapid long distance transportation of people and material
Natural disasters (earth quakes, Tsunamis, floods)
Intrusion into new uninhabited lands
Climatic changes
Decreased vaccination
Increased number of Immunosuppressed individuals
Increased antimicrobial resistance due to overuse
Factor contributing to the spread of
emerging new zoonotic diseases
The origins of newly emerging diseases
have been found to strongly correlate with
specific:
1) Geographic areas,
2) Animal hosts,
3) Microbial agents,
4) High risk populations.
Southeast Asia
Cambodia
China
Indonesia
Laos
Malaysia
Philippines
Thailand
Vietnam
Amazon
Bolivia
Brazil
Colombia
Ecuador
Mexico
Peru
Congo region
Angola
Burundi
Cameroon
CAR
Congo
DR Congo
Eq. Guinea
Gabon
Rwanda
Tanzania
Uganda
South Asia
Bangladesh
India
Nepal
Credit: USAID, EcoHealth Alliance
The Rise of Zoonotic Diseases
The emergence of the H5N1, SARS and H1N1, H9N7 and MERS
viruses are examples of an accelerated dynamic pace that has
given rise to a new and increasingly deadly zoonotic diseases.
• Of these new zoonotic diseases, ¾ were caused by pathogens
originating in wildlife
•–SARS, emerged in Guangdong Province, China;
•–Nipah virus in Perak State, Malaysia; and
•–HIV in Central Africa.
•--MERS in the middle East
• Domestic animals are the other major source of zoonotic
pathogens responsible for ~20% of all new zoonotic diseases.
• RNA viruses e.g. highly pathogenic H5NI Influenza virus,
because of their high rates of mutation and higher capacity to
adapt to new hosts
2. Hot Animal Species
Approx. 50,000 vertebrate species are potential reservoirs for
viruses, bacteria, and others that could potentially infect humans.
However, not all animal hosts are equal in their potential for
ability to transfer microbial agents to humans because: Very few
of these species will ever have direct or even indirect contact
with people.
W. Ian Lipkin (2009): Microbe Hunting in the 21st Century: PNAS:vol106(1 )
Hot Species: Rodents, Bats, Avian, and Primates
Animal-to-human and animal-to-domestic animal interactions
provide ideal setting for pathogens to evolve as humans pathogens
The numbers of species for these transfers appear limited:
 Rodents - have proved highly adaptive in their ability to spread
pathogens to humans - Hanta virus through their feces and
urine;
 Bats - have infected people with Nipah virus directly through
contaminated feces and indirectly by infecting pigs who are
later consumed by humans.
 Primates - infected by bats with Ebola and Marburg viruses)
have been the source of human infections when consumed as
bush meat.
 Avian species – are responsible for the emergence of many
avian Influenza strains)
“High-Risk” Microbial Agents Targets for
Surveillance (Predict)
Target families of pathogens that have demonstrated
capacity to “infect”, “spread”, and “kill”. Examples of
families that are capable of acquiring human-to-human
transmission, are therefore pose special risks to humans:
 RNA viruses, such as:
 retroviruses (HIV/AIDS),
 influenza A viruses,
 Coronaviruses (SARS, MERS), and
 Filoviruses (Ebola and Marburg)
4. Populations Targets for Surveillance
People and populations with high levels of exposure
(directly and indirectly) to wild animals:
hunters, butchers of wild game,
bush meat traders and consumers
settlements abutting wildlife areas
Farmers
domestic animals
loggers, miners, road builders etc.
“Risk-Based” Surveillance - Conclusions
The relationship between risky:
1. geographic “hot spots”;
2. animal hosts;
3. microbial agents; and
4. At-risk populations demonstrate that the emergence
of new zoonotic diseases strongly correlates with:
• socio-economic,
• environmental,
• genetic,
• biological, and
• ecological factors.
You can do a lot of damage with just seven genes
• Ebola is a simple and subtle virus.
• The stringy virus consists of a genome wrapped
up in two layers of proteins
• This long thin string contains the polymerase,
nucleoproteins and is studded with a
glycoproteins (proteins with sugar stuck to them
make them less immunogenic)
• Inside the infected cell the polymerase makes
massive copies of the genome
You can do a lot of damage with just seven
genes
(The Economist Oct 18th 2014)
•
•
•
•
•
•
Viral Pathogenesis
The virus makes cells produce more glycoprotein than it
needs.
The surplus is secreted into the bloodstream. Antibodies
which would otherwise attack the virus stick to this decoy
protein instead.
Immune cells carry the virus in the bloodstream to infect
the liver, the spleen and lymph nodes.
Symptoms may manifest from 1 to weeks.
Eventually the virus triggers an s a cytokine storm.
Blood-vessel walls become leaky, blood pressure and
core temperature drop, organs fail and the body goes into
shock.
Various combinations of those and other symptoms kill
about 70% of those who get ill
Uniqueness of this outbreak
Earlier outbreaks were often in isolated places with few
opportunities for transmission of the virus between a wild
animal and a human to set off such outbreaks.
The west African outbreak has broken through the
barriers of isolation and into the general population, both
in the countryside and the cities, and it was up and
running before public-health personnel fully realized the
magnitude.
There is no reason to expect it to subside of its own
accord, nor to expect it to come under control in the
absence of a far larger effort to stop it
The Current Status
• On Oct. 15th the WHO released its latest update.
• The outbreak has now seen 8,997 confirmed,
probable and suspected cases of Ebola.
• All but 24 of those have been in Guinea (16% of
the total), Sierra Leone (36%) and Liberia (47%).
• The current death toll is 4,493. These numbers
are underestimates; many cases, in some places
probably most, go unreported.
Emerging Diseases
Hendra virus
Nipah virus
Nipah Virus Infection
Human patient symptoms:
 “Flu-like” illness
 Fever
 Headache
 Vomiting
 Muscle pain
 Neurologic: dizziness, weakness, disorientation
 Severe: encephalitis, respiratory distress
 545 cases, 316 deaths (58%)
 No cure – only supportive intensive care
Nipah Beyond Malaysia
2001 - present
 Outbreaks in India and
Bangladesh
 No swine involvement
 Humans consumed
infected date palm sap
 Human to human
transmission
Emergence of SARS Severe Acute Respiratory Syndrome
November 2002
 Severe pneumonia-like illness in Guangdong China
 Not reported to World Health Organization
 Vague reports of a flu outbreak
Global Spread of SARS
February 2003
 Business traveler dies of undiagnosed respiratory illness in
Hanoi, Vietnam
 Within weeks SARS cases reported across Asia
March 2003
 First case appears in Canada
 Cases reported across the United States
April 2003
 China began reporting on SARS outbreak
Epidemic through mid 2004
 29 countries
 Nearly 8500 cases and 900 deaths worldwide
(A) Genome structures of SARS-CoV and MERS-CoV.
Coleman C M , and Frieman M B J. Virol. 2014;88:52095212
Unique Attributes that make control of Influenza difficult
 Mutate rapidly: This allows quick changes in surface antigens, the target
of the immune system, resulting in
 antigenic changes/variation:
 Antigenic drift: The gradual occurrence of spontaneous point mutation
(change in a single RNA base)
 Antigenic shift: rare but result in either the H (hemagglutination), or
the N (neuraminidase) often resulting from interspecies transmission.
E.g. avian H1N1 flu infecting humans (1918, 1997) leading to “bird flu”.
Two avian flu viruses (H5N1; H7N9), have caused fatal disease in
humans, but transmission from human to human (so far only from bird
to human) has not occurred!
 Genetic reassortment: when two flu viruses from different animal
species infect the same host/cell therein, mixing the 8 RNA segments of
the two. The new hybrid virus now has proteins from two different
sources which the immune system does not recognize.
Çç√ç√ç
Influenza
 From 2003-2013 (February) Indonesia has reported the greatest number of
human cases of Avian Influenza (H5N1)
(http://gamapserver.who.int/mapLibrary/Files/Maps/2003_AvianInfluenza_GlobalMap_01Feb13.png)
33
The Principle of One Health (OH)
Hotspots are where there is:
a) intensive livestock
production;
b) recent, rapid demographic
changes;
c) encroachment on wildlife
habitat
Human
Environment
Daszak P, A Call for “Smart Surveillance”: A Lesson Learned from H1N1.
EcoHealth, September 16, 2009
Animal
Emergence is a “Rare” Event
While the risk of new zoonotic diseases is increasing,
their emergences is a rare events occurring at
unpredictable times and places.
The biggest obstacles to early detection of these
diseases is the lack of sufficient, sensitive surveillance
capacity geared toward rapid and reliable detection of
highly unusual pathogens