Professional Documents
Culture Documents
Group Members:
M. Adil Nawaz
Muhammad Aslam
AmanUllah Khan
Historical Perspective and
Bacterial Pathogenesis
M. Adil Nawaz
Background
• Bacteria are found everywhere: from geothermal vents in the ocean
depths to the coldest arctic ice, to every person’s skin.
• Majority of microorganisms play beneficial or benign roles.
• Microbes that inhabit humans play important roles, including helping
the body digest food and producing vitamins B and K.
• Besides their beneficial role it may cause systemic infection, infectious
diseases and outbreaks within the society.
• Some harm humans and have disrupted society over the millennia.
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Historical Perspective
• Even before microorganisms were seen, some investigators suspected
their existence and responsibility for disease
• the Roman philosopher Lucretius (about 98–55 B.C.) and the physician
Girolamo Fracastoro (1478–1553) suggested that disease was caused
by invisible living creatures.
• Microbial diseases undoubtedly played a major role in historical
events such as the decline of the Roman Empire.
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Historical Perspective
• 11 Century Leprosy- it grew into a pandemic in the Europe resulting in
sores and deformities.
• In 1347, plague or black death struck Europe with brutal force, killing 1/3
of the population (about 25 million people) within four years.
• Over the next 80 years, the disease struck again and again, eventually
wiping out 75% of the European population.
• The Great Plague of London 1665-bubonic plague led to the death of 20%
of London’s population.
• First Cholera Pandemic 1817- Small intestine infection originated in Russia
and spread to India, Spain, Africa, Indonesia, China, Japan, Italy, killed
millions.
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Historical Perspective
• In ancient times the spoilage of enemy’s water source was the key to
inflict damages upon them.
• Many water borne outbreaks pose serious thread to public health.
• Historical accounts show that besides pandemics and epidemics
bacteria are also a major source of lab associated infections.
• Bacterial food borne outbreaks spread across different societies and
were thoroughly investigated.
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Bacterial Pathogenesis
Pathogenicity:
The ability of a microbe to cause a disease
Virulence:
The degree of pathogenicity in a microorganism.
Primary Infection:
An infection that develops in a healthy individuals.
Secondary Infection:
An infection that develops in an individual who is already infected with
a different pathogen.
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Bacterial Pathogenesis
• There are only about 5% of bacterial species that are pathogenic.
• Tuberculosis, bacterial pneumonia, typhus, plague, diphtheria,
typhoid, cholera, dysentery were major causes of disease and
premature death in Europe and the United States.
• Bacterial pathogenesis in the form of lab acquired infection comprises
about 42.5% of infections.
• These infections are major source of health burden as well as has
huge economic impact.
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Bacterial Mechanism of Pathogenicity
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Host Pathogen Interaction
• There are many variables to take into account in a host-pathogen
interaction, which is a dynamic relationship that is constantly
changing.
• The virulence of the pathogen is important, but so is the number of
microbes that gained entry to the host, the location of entry, the
overall health of the host, and the state of the host’s defenses.
• Exposure to a pathogen does not ensure that disease will occur, since
a host might be able to fight off the infection before disease
signs/symptoms develop.
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Bacterial Pathogenicity
Upon encountering a human host, a bacterial pathogen may illicit
several host responses and use a variety of mechanisms to evade
the host defences.
• Capsules that act to “frustrate” phagocytosis
• Lipopolysaccharide (LPS) and cell wall components which can
cause septic shock,
• Toxins that can serve to damage host cells and aid invasion,
• Adhesins which facilitate binding of the pathogen to host surfaces.
Once adhered to a host surface, a bacterial pathogen may further
invade host tissues.
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The Balance Between Microorganism
Activity and Host Immunity
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Route of Infection and Some
Bacterial Pathogen of Interest
Muhammad Aslam
Route of Infection
“Disease usually results from inconclusive negotiations for symbiosis, an
overstepping of the line by one side or the other, a biological misinterpretation
of borders”. —Lewis Thomas
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Important Factors
• Properties of an agent are:
Pathogenicity
Route of Transmission
Agent Stability
Infectious dose
Concentration
Prophylactic treatment
• Host: Immune status, previous disease, occupation etc.
• Environment: Temp, humidity, crowding,
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Mode of Transmission
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Bacterial Pathogen of Interest
1. Plague:
• The plague, caused by the bacterium Yersinia pestis and also known
as "the Black Death“.
• In some countries, such as Britain, the feudal system collapsed.
• Worldwide, upto 3000 cases of plague are reported to the WHO each
year.
• It is transmitted through flea, which are usually present on the bodies
of rodents.
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1. Plague
• Once in the human body, the bacteria
multiply in the blood and lymph.
• An important factor in the virulence of Y. pestis is its ability to survive
and proliferate inside phagocytic cells rather than being killed by
them.
• In 50 to 70% of the untreated cases, death follows in 3 to 5 days from
toxic conditions.
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2. Tuberculosis
• To this day, TB has been responsible for
the deaths of one billion people.
• At its peak in the 1800s, tuberculosis is estimated to have killed one in
seven of all people who had ever lived.
• Recent data collected in Europe in 2017 found 55,337 reported cases
of TB that year.
• At a global level, 1.3 million people died of TB in the same year.
• It is one of the major public health problems in Pakistan.
• Pakistan ranks fifth amongst TB high-burden countries worldwide.
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2. Tuberculosis
• Pakistan is also estimated to have the fifth highest prevalence of
multidrug-resistant TB (MDR-TB) globally.
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2. Tuberculosis
No History of
History of
All Patients treatment
Drug Resistant to treatment p-value
N = 1270 N = 803
N=467
Isoniazid + Rifampicin
18.6% 8.2% 36.4% <0.05
(MDR%
Rifampicin 22.8% 9.9% 44.9% <0.05
Isoniazid 23.3% 10.2% 45.6% <0.05
Streptomycin 24.4% 10.8% 47.5% <0.05
Ethambutol 12.7% 5.6% 24.8% <0.05
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Dr. Rizwan Iqbal PHRC KEMU Lahore
3. Anthrax
• Its spores can remain viable in soil and animal products for decades.
• Skin infection comprises most of the cases. Without treatment the risk of
death from skin anthrax is 24%.
• For intestinal anthrax it is 25-75%.
• One reason this form of anthrax is so difficult to treat is that the
symptoms appear after B. anthracis has already multiplied and started to
produce large amounts of the tripartite exotoxin.
• The medial lethal inhalation dose for humans has been estimated to be
about 8,000 spores.
• 2001 USA outbreak and investigation.
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4. Vibrio
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4. Vibrio
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5. Emerging and Re-emerging Infectious
Diseases
• In developed countries, people were lulled into believing that
microbial threats were a thing of the past.
• However, this trend ended in 1982 and
death rate has since risen.
• Staphylococcus bacteria with resistance to
methicillin and vancomycin.
• A new strain of tuberculosis that is
resistant to many drugs.
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5. Emerging and Re-emerging Infectious
Diseases
• Many factors characteristic of the modern world undoubtedly favor
the development and spread of these microorganisms and their
diseases.
• Nobel laureate Joshua Lederberg
stated,
AmanUllah Khan
Biosafety
• The containment principles, technologies and practices that are
implemented to prevent the unintentional exposure to biological
agents and toxins or their accidental release.
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Four Controls in Biosafety
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Four Controls of Biosafety
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Biological Risk Groups
Risk Group 1
No or low individual and community risk
Unlikely to cause human or animal disease
Do not cause disease in healty adult humans
Work is done with define and characterize microorganisn
• Example: E. coli.
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Biological Risk Groups
• Risk Group 2
Moderate individual risk, low community risk
Can cause disease but unlikely to be a serious hazard
Lab exposures may cause serious infection
but effective treatment and preventative measures are available
and risk of spread of infection is limited
• Example: Salmonella.
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Biological Risk Group
Risk Group 3
High individual risk low community risk
Usually causes serious human or animal disease but does not ordinarily
spread.
Effective treatment and preventative measures are available.
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Risk Assessment Pathway
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Laboratory Biosafety Containment Levels
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Sterilization and Disinfection
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Different Methods
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Laboratory Biosecurity
Muhammad Aslam
Laboratory Biosecurity
• The term “biosecurity” has multiple definitions. In the animal industry, the
term biosecurity relates to the protection of an animal colony from
microbial contamination.
• “Biosecurity” refers to the protection of microbial agents from loss, theft,
diversion or intentional misuse.
• Laboratories with good biosafety programs already fulfill many of the basic
requirements for security of biological materials.
• Security assessments and additional security measures should be
considered when:
select agents,
other agents of high public health and agriculture concern
or agents of high commercial value such as patented vaccine candidates
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The Biological and Toxins Weapon
Convention
• Convention on the prohibition of the development, production and
stockpiling of bacteriological (Biological) and toxin weapons and their
destruction.
• Signed at London, Moscow and Washington on 10 April 1972. Entered
into force on 26 March 1975.
• Pakistan signed on 10-04-72 and ratified 25-09-74
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Action to be taken by State Parties
Legislation and other measures:
• Information and texts of specific legislation enacted or other measures taken by State’s Parties to
assure domestic compliance with the Convention is to be provided to the United Nations
Department of Disarmament Affairs
Confidence building-measures:
• Submission of complete and timely declarations to the United Nations Department of Disarmament
Affairs.
• Action required by State’s Parties annually by 15 April .
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UNSCR 1540 and Biosecurity
• Urges States to take preventative measures to mitigate the threat of WMD
proliferation by non-state actors
• UNSCR 1540 requires States to Establish and enforce legal barriers to
acquisition of WMD by terrorists and states
• Submit reports to the 1540 Committee on efforts to comply
• Paragraph 3 is the key provision that supports biosecurity“Take and enforce
effective measures to establish domestic controls to prevent the proliferation of . . .
biological weapons . . .; including by establishing appropriate controls over related
materials”
• Develop and maintain appropriate effective measures to account for and secure such items in
production, use, storage or transport
• Develop and maintain appropriate effective physical protection measures.
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Component of Biosecurity
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Common Components
Biosafety and biosecurity programs share common components.
• Both are based upon risk assessment and management methodology
• Personnel expertise and responsibility
• Control and accountability for research materials
• Microorganisms and culture stocks
• Access control elements
• Material transfer documentation
• Training; emergency planning
• Program management.
But, in some cases, biosecurity practices may conflict with biosafety
practices.
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Laboratory Biosecurity Supports Laboratory
Biosafety
• Laboratory biosecurity supports the laboratory biosafety agenda of
preventing disease in people, animals, and plants and minimizing the
risk of worker injury
• Safe and secure laboratories help ensure the containment of
hazardous infectious substances in laboratories
• Maintain citizens’ confidence in the activities of the bioscience
research community
• Increase transparency to investors in the biomedical and
biotechnology industries
• Protect valuable research and commercial assets
• Reduce the risks of crime and bioterrorism
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Biosecurity Risk Assessment
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Summary
• There is long history of bacterial pathogens which altered the history
and posed risk to the community.
• Different virulence factors and toxins are key in causing a disease in a
host.
• Every bacteria that enters the host may not necessarily cause disease.
• Many bacterial pathogens which are largely public health concern in
developing and developed countries.
• Robust biosafety measures along with biosecurity plan is necessary for
safe and secure lab worker, community, environment and pathogen of
interest itself.
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