Pathogenesis Flashcards
What is a pathogen
Any agent that can cause disease
Similar to parasites
One organism using resources of another in a way which is not beneficial to the host.
Differences between parasites and pathogens
Cant see virus with naked eye
Can see parasites
What are prions
Infectious proteins that make correctly folded proteins folded incorrectly
What makes a successful pathogen
Gains access to the host
Locate nutritionally compatible niches
Avoid, subvert, or circumvent the host innate and adaptive immune response
Access host and resources
Exit and spread to new host (transmission)
When does infection occur
Access host resources and replicate
Not all exposure to pathogens result in disease
What is the innate immune system
Non-specific
Rapid
What is the adaptive immune system
Highly specific
Slower
What is virulence
Measure of disease severity
Mortality - number of deaths
Morbidity - number of cases
How do you measure pathogen success
“is it still around”
Infectious dose - number of individual particles required for infection
What is the mortality rate of ebola, plague, rabies and vCJD
ebola - 90%
Others - 100%
What are virulence factors
Adhesins - Find a niche and colonise host
Capsules (S-layer) - immune evasion/survival in host
Digestive enzymes - Finding a niche, colonizing and finding host resource
Toxins - Reprogram host biology to benefit the pathogen - make you sick
Stealth mode - Absence of outer-surface structures (immune evasion)
NOT for causing disease
What number of lower respitory infections are deaths worldwide
3.2 million
How many diarrhoeal deaths
1.4 million
How many TB deaths
1.4 million deaths
How many HIV deaths
1.1 million
What percentage of deaths world wide are from pathogens
54%
Who proved germ theory
Robert Koch
Established a scientific basis linking microbes and diseases
Pioneered the use of pure cultures to understand infectious diseases
States many diseases are caused by microbes
What did Robert Koch demonstrate germ theory with
bacterium Bacillus anthracis (anthrax)
Invented petri dish (hi Adam and Meg and Aidan)
What are Koch’s postulates
To prove a specific pathogen causes a specific disease
Host + pathogen = disease
Healthy rabbit never contains anthrax
Unhealthy rabbit always has anthrax
Microbe is isolated from the diseased host and grown
Inject healthy rabbit with anthrax and it becomes unhealthy
Same strain is obtained from the new host
What are the main advances in combating disease in the last 200 years
Clean water and better diet
Improved sanitation
Less overcrowding in urban areas with better living conditions also
contribute.
What are vaccines
Chemical agents which prime the adaptive immune system to repel a pathogen
What is immunity through vaccination
After vaccination, if the subject can be exposed to the pathogen
and does NOT develop the disease, they are said to be immune.
What is IgG
Default antibody
What is IgM
5 IgG molecules
What does attenuated mean
Damaged particles
What is inactivated
Wont replicate
Who invented vaccination
Lady Montagu
Directly added pus from smallpox into open vein of patient
What did Edward Jenner discover
Cross protection - inoculated a person with cowpox and they were then protected from smallpox
Can vaccinate someone from a disease without using the disease
What is the last therapeutic option
Antibiotics
What are antibiotics
Chemicals produced by bacteria and fungi that inhibit or kill other microbes
Who invented penicillium
Alexander Fleming
Who did the first use of penicillin
Dr Cecil Paine
What did Florey and Chain discover
successfully manufactured the drug from the liquid broth in which penicillin grows.
How many lives has penicillin saved
between 80 and 200 million
What is the family of penicillins
Different types of penicillin for different usage
Injection only, orally, narrow spectrum, broad spectrum, extended spectrum and resistant to B-lactamase enzymes
What does penicillin target
Cell wall synthesis
What do antibiotics target
Cell wall synthesis
Protein synthesis
Cell membrane integrity
Nucleic acid function
Intermediary metabolism
What is a symptom
A change in body function that is felt by a patient because of a disease
“I feel a bit tired”
What is a sign
A change in the body that can be measured or observed because of disease
“temperature is high”
What is a syndrome
A specific group of signs and symptoms that accompany a disease
High temperature, Feeling tired, Cough, Confusion
What diseases can streptococcus pneumoniae cause
Pneumonia, sepsis, Meningitis
How many ways can pneumonia be caused
Bacterial, Viral and Fungal
Symptoms and signs are identical
What is the most abundant life form on the planet
Bacteria
What does the microbiota do
Help with digestion
Metabolism
Immune function
Mood
What is commensalism
One organism benefits and the other is unaffected
What is mutalism
Both organisms benefit
What is parasitism
One organism benefits at the expense of the other
What is Clostridium Difficle
Pathogen - Clostridium difficile
Disease - CDI
Classification - Spore forming, Gram-positive bacteria
Symptoms - Diarrhoea, Colonisation and inflammation of the colon
Virulence - Mortality rate of 9%
What is an opportunistic pathogen
Microbes which are not normally pathogenic but can cause infection or disease if the host is compromised
What are hospital acquired infections
These infections are acquired because of a hospital stay
Usually, patients are the cause of their own illness not the hospital
How does urbanization effect pathogenesis
More than 50% of the world live in urban areas
Higher population densities drive many potential routes of transmission
What is Vibrio cholerae
Pathogen - Vibrio cholerae
Classification - Gram - negative
Disease - Cholera
Symptoms - Large amounts of watery diarrhoea (rice water stool)
Virulence - Death through severe dehydration - Can be 1% mortality if treated quick
Transmission - Faecal-Oral route
MVF - Cholera toxin
Treatment - Oral REHYDRATION`
What was the first historical cause of epidemiology
Broad street water pumb for Vibrio cholerae
What is epidemiology
Study of where and when diseases occur to control
spread of disease
What are the principles of epidemiology
Identify first person to have the disease
‘Patient zero’
• Identify anyone who had contact with
that person
• Identify the reservoir for the pathogen
• Blocking or contain it
What are the struggles of epidemiology
Difficult for new pathogens
• Disease must first be recognised
• Many already infected by then
What is an epidemic disease
disease acquired by
many hosts in a given
area in a short time
What is an endemic disease
Disease constantly present in a population
What is a pandemic disease
Worldwide epidemic
What is - Salmonella ‘typhi’
Pathogen - Salmonella enterica serovar Typhi
Class - Gram-negative bacterium
Disease - Typhoid Fever
Symptoms - Rash (Rose Spots) - Symptoms are non-specific and extremely variable
Reservoir - Human carriers (colonised gall bladder), 1-3% of people will permanently carry the disease
Transmission - Faecal-Oral route
Virulence - Mortality rate is about 30% without treatment.
What is Polio Virus
Pathogen - Polio Virus
Class - + strand RNA virus
Disease - Polio
Symptoms - Irreversible paralysis (1/200), muscle weakness, atrophy, deformities, twisted feet or legs
Reservoir - Faecal - Oral route, usually via a contaminated water source
Treatment - Vaccine - Attenuated (weakened) virus
Why is polio virus vaccine an imperfect solution
In very rare cases, the virus can revert into a form capable of causing disease and infecting others (OPV paradox)
In extremely rare cases some
immunocompromised individuals appear to
become ‘healthy carriers’ - Excreting large
amounts of active Polio virus for long periods of
time
Polio vaccine is extremely safe to the person receiving
the vaccine – but what about everyone else
What are famous examples of healthy carrierr
Typhoid Mary - thyphoid
Birmingham man - Polio
What is Yersinia Pestis
Pathogen - Yersinia pestis
Disease - Bubonic plague, Pneumonic plague
Symptoms - Buboes (swollen lymph nodes), Pneumonia
Virulence - extremely high mortality if untreated, bubonic - 50%, pneumonic - 90-100%. Treatable if less than 24hrs since symptoms
Reservoir - Rodents, Priarie dogs - Rodent fleas, Human respiratory aerosol (pneuomonic)
What type of pathogen is Yersinia pestis
Zoonotic
What is Epizootics
Animal equivalent of an epidemic
What can pathogens infect
Any organism apart from viruses
What is Phytophthora infestans
Pathogen - Phytophthora infestans
Disease - ‘Potato Blight’, Late blight
Virulence - Approaching 100% of crops
Treatment - Fungicides and copper sulphate
Blight makes soil full of spores so the field is no longer usable
Where do potatoes originate
South America
Why is blight not a problem in South America
Wide variety of genetically different potatoes. Europe has a genetic bottleneck
What is influenza virus
Pathogen - Influenza virus
Disease - Influenza ‘flu’
Virulence - Very varied 0.01% - 50%‘newer’ strains have higher case fatality rates.
H1N1 (Hemagglutinin 1 and Neuraminidase 1)
Flu weakens the immune system so that secondary infections are common
How are new influenza viruses made
Re-assortment of genetic material
generates ‘new’ influenza virus particles
Bird virus + human virus –> Swine cell –> new reassortant virus
What is Zika Virus
Pathogen - Zika
Disease - Zika virus disease
Virulence - Extremely low, most people have no symptoms
Transmission - Mosquito (aedes)
How are new diseases identified
A disease is first identified as a geographically clustered pattern of symptoms and signs
What was the factor that identified zika
Microcephaly in babies (small skull –> small brain)
What is the Aedes mosquito a vector for
Dengue virus
Zika virus
What is epidemiological surveillance
Epidemiological surveillance is the collection, analysis
and dissemination of public health data
Takes time, can be inaccurate
Correlation based data falls
very short of ‘cause and effect’
What is the updated Zika pathogen information
Sexually transmitted (men - 6 month and women - 8 weeks)
Associated with birth defects microcephaly, Guillain–Barré syndrome
Where is Zika found
It is not limited to areas where the mosquito is found
What did epidemiological surveillance discover in the Zika virus
Set up the Zika Birth Defects Surveillance,
Zika-associated birth defect rate in the US ≈ 5%
Chances of any pregnancy having a birth defect ≈ 3%
What is Ebola
Pathogen - Ebola virus
Disease - Ebola virus disease, Ebola hemorrhagic fever
Symptoms - bleeding
Virulence - Highly virulent, 40-90% mortality
Reservoir - Unknown thought to be zoonotic
Treatment - Currently untreatable
Named after the ebola river in DRC
What is the biggest challenge to modern medicine
Antimicrobial resistance
Why is AMR such a big deal
The problem is the rate
of drug discovery has
sharply declined
The continued use of
antibiotics has driven
selection for resistant
strains
Without antibiotics
• Relatively minor infections would become life threatening
• Surgery
• Child birth
• Chemotherapy (for cancer treatment)
- ‘anyone who is immunocompromised’
• Infectious diseases would claim many more lives
- particularly the elderly and the very young
Why is AMR so complex
Each antibiotic has a different target, each bacterial pathogen has a different virulence, characteristic and survival strategies and the resistance mechanisms are varied and poorly understood
What are antibiotics
chemicals produced by bacteria and fungi that
inhibit or kill other microbes
An infectious disease state is…
when a biological conflict occurs between host and pathogen