Pathogenesis Flashcards
what is a pathogen?
- any agent that can cause disease to any organism
- one organism using the resources of a other to survive, in a way that is not beneficial to the host
what is the difference between a parasite and a pathogen?
parasite: can be seen with naked eye
pathogen: can only be seen with a high powered microscope
(worms are parasites but sometimes need microscopes to be seen)
how have different kingdoms dedicated themselves to pathogenesis?
- Bacteria e.g. Yersinia pestis = plague
- viruses e.g. poliovirus
- fungi e.g. cryptococcus = meningitis
- protozoa e.g. Plasmodium falciparum = malaria
- prions (infectious proteins) e.g. vCJD = human mad cow disease
archaea have not dedicated themselves to pathogenesis
what happens when a human is infected by a prion?
- if exposed to a prion in an unfolded conformation by ingestion, the protein will enter CNS and cause other proteins to unfold
- this causes progressive loss of brain function
what is the difference between pathogens and poisons?
poisons: don’t create more poisons after injection
- amount is constant
injection of pathogenic protein can replicate and increase in conc inside the host
what is the main criteria for a successful pathogen?
- gain access to the host
- locate a nutritionally compatible niche
- avoid, subvert or circumvent the hosts innate and adaptive immune responses
- access to host resources and replicate
- exit and spread to a new host: transmission
how does a pathogen gain entry to a host?
- portal of entry e.g. open wound, inhalation, consumption and ingestion
- open areas of body e.g. eyes, ears, nose, mouth
why do pathogens need to locate a nutritionally compatible niche?
- if they don’t locate this niche, you can be exposed to a pathogen but you will not fall ill with the disease
what two immune systems must the pathogen avoid?
- innate immune system
- non-specific, rapid, involves macrophages/neutrophils phagocytosing pathogenic material - adaptive immune system
- highly-specific, slower, involves T-cells activating B-cells to generate antibodies
what happens to the host when pathogens access host resources?
- at this point, infection has occured
- but, not all exposure to pathogens causes disease, some can be asymptomatic infection
how are pathogens transmitted?
- via air droplets, water, food, mechanical/vector
what is mechanical transmission?
- the pathogen has not had any biological interaction with the organism that transported it
- it simply sat on the organism’s surface for a means of transport from one place to another
e.g. pathogen gets on fly from one surface, fly lands on burger, now pathogen is on burger and can be ingested
what is vector transmission?
biological reaction between pathogen and vector
pathogen dedicated part of its life cycle to that particular organism
malaria:
- transmitted via mosquito bites
- mosquito extracts blood from someone infected with malaria
- malaria exits stomach of mosquito and migrates to its salivary glands
- malaria is then ejected into another host’s bloodstream when the mosquito bites the next person
what is virulence?
a measure of disease severity
- determines how successful a pathogen is
high virulence = low infectious dose can cause illness
- e.g. Shingella dysenteriae (diarrhoea disease) needs 10 cells to cause infection
low virulence = high infectious dose is needed to cause disease
- e.g. salmonella needs 1 million cells to cause infection
how is virulence measured?
- mortality
- morbidity
- infectious dose
what is mortality?
number of deaths caused from notifiable diseases
what is morbidity?
number of cases of a disease in a population
what is infectious dose?
number of individual particles/cells required for infection
what are virulence factors?
- they enable a pathogen to colonise the host, but are not responsible for causing the disease
e. g. adhesins, capsules/s-layers, digestive enzymes, toxins, stealth mode
how are adhesins virulence factors?
- anchoring role
- pathogen finds a niche and adhesins allow pathogen to adhere to certain tissues and colonise the host
how are capsules/s-layers virulence factors?
- armour role
- involved in immune evasion by avoiding phagocytosis as macrophages cannot engulf the surface
- can survive chemical attacks, so enables pathogen to survive the immune system of the host
how are digestive enzymes virulence factors?
- pathogen finds a niche, and enzymes are important in colonising and utilising host resources
how are toxins virulence factors?
- they can reprogram host biology to benefit the pathogen
- e.g. cholera toxin causes diarrhoea as a way to exit the host
what is stealth mode? how is it a virulence factor?
- stealth mode is when a pathogen has absence of outer-surface structures like proteins
- enables immune evasion by avoiding detection
- e.g. syphilis bacteria remove as many surface structures from its capsule as possible to reduce chance of identification
how is it difficult to seek reliable information on pathogenesis?
- pathogenesis is an emotive subject
- statistics are often massaged to support the writer’s perspective
- e.g outbreaks of influenza, covid and ebola
why do we study pathogenesis?
- 15% of world deaths are caused by infectious diseases
- lower respiratory infections caused 3.2 million deaths worldwide in 2015
- diarrhoeal diseases caused 1.4 million deaths
- tuberculosis caused 1.4 million deaths
- HIV/AIDS is no longer among the top 10 causes of death, after it had killed 1.1 million in 2015
how do we know what pathogens cause what disease?
Founding principle = Germ Theory
- germ theory states that many diseases are caused by microbes
- Robert Koch established a scientific bases linking microbes and diseases
- Koch’s Postulates
what is Koch’s Postulates?
- Koch pioneered the use of pure cultures to understand infectious diseases and prove how a specific pathogen caused a specific disease
- he demonstrated this using the bacterium Bacillus anthracis (anthrax) which killed cattle
what were the conclusions of Koch’s Postulates?
criteria for a microbe:
- microbe is found in call cases of the disease, but absent from healthy individuals
- microbe can be isolated from the host and grown in pure culture
- when the microbe is introduced to a healthy, susceptible host, the same disease occurs
- the same strain of microbe is obtained from the newly diseased host
host + pathogen = disease ???
how do we treat/prevent disease?
- main advances have been a better diet and access to clean water
- improved sanitation
- less overcrowding
- improved living conditions
- vaccination
- unique treatments for different pathogens
all done to reduce transmission
what are vaccines?
- chemical agents which prime the adaptive immune system to repel a pathogen
- after vaccination, if the subject is exposed to the pathogen and doesn’t develop the disease, they are immune
how was vaccination first used?
1717:
- Lady Montagu added pus from smallpox directly into the open vein of a patient
- dangerous as it is very virulent and killed patients
1796:
- Jenner inoculated a child with cowpox, who then was protected from smallpox via secondary immune response
- this was much safer and less virulent than smallpox
why did inoculation of cowpox protect people against smallpox?
- these viruses share the same antigens and produce similar immune responses
- cross-protection
how successful was the smallpox vaccine?
- smallpox is now extinct
what is a limitation of vaccines?
- they do not work against all pathogens
- but they do work against viruses particularly well
what are magic bullets?
- compound which can control pathogenic infections without harming the patient
what are antibiotics?
- chemicals produced by bacteria and fungi that inhibit/kill other microbes growing in patients
who discovered the first antibiotic?
Alexander Fleming:
- he accidentally contaminated his Staphylococcus petri dish
- he observed a zone of inhibition around the mould that formed - penicillin
how was penicillin turned into a drug?
Florey and Chain:
- they had penicillin mass-produced
challenges:
- purification: purifying penicillin caused destruction of its structure
- production on large scale
- proof that it was non-toxic
- human and animal testing
penicillin saved 80-200 million lives
what families are antibiotics divided into?
- injection-only
- oral
- narrow-spectrum
- broad-spectrum
- extended-spectrum
- resistant to beta-lactamases
what bacterial processes do antibiotics target?
- cell wall synthesis (penicillin)
- protein synthesis
- cell wall integrity (daptomycin)
- nucleic acid function
- intermediary metabolism
what is a symptom of disease?
- a change in body function that is felt by a patient due to a disease
- e.g. feeling tired
what is a sign of disease?
- a change in the body that can be measured or observed as a result of disease
- e.g. change in body temperature
what is a syndrome of disease?
- a specific group of signs and symptoms that accompany a disease
- e.g. high temperature, feeling tired, cough, confusion
how do we know what pathogens cause what disease?
some pathogens can cause multiple diseases
- e.g. Streptococcus pneumoniae is a gram positive bacteria that can cause pneumonia, sepsis and meningitis, depending on which tissue it has infected
some diseases can be caused by multiple pathogens: pneumonia
- can be caused by:
- Bacterial - S. pneumoniae, Haemophilus influenzae
- Viral: Respiratory Syncytial Virus
- Fungal: Cryptococcus neoformans (usually in immunocompromised patients)
what is pneumonia?
- a reaction of the body to colonisation, or damage to the airways, regardless of which pathogen as infected a patient
- accounting for all 16% of all deaths of children under 5 (WHO)
- the most common cause of infection-related deaths in UK and USA
- no matter what pathogen causes it, all symptoms and signs are identical
what is microbiota?
- all large multicellular organisms, like humans, are heavily populated with bacteria
- they provide benefits to our health and well-being e.g.:
- help digestion
- healthy metabolism
- immune function
- our mood and behaviour
what are the 3 different relationships between humans and microbes?
Commensalism: one organism benefits, the other is unaffected
- Although benefits of commensal organisms are still emerging – repel effect (they are friendly colonisers)
Mutualism: both organisms benefit
- E.g. E. coli enables vitamin K12 blood clotting, while we provide a warm environment
Parasitism: one organism benefits at the expense of the other (all human viruses)
what is disease?
a disease state is the product of a relationship change/conflict between host and pathogen
host pathogen
how are antibiotics limited?
- they can harm our microbiome
- microflora exist in a delicate and balanced ecosystem
Is C. difficile really a pathogen?
- If C.difficile is treated with penicillin, their spores are released and outgrow, as they are not killed by penicillin
- It took penicillin to turn C. difficile into a pathogen
what are opportunistic pathogens?
- microbes which are not normally pathogenic but can cause infection or disease in a compromised host
- e.g. in the case of sepsis blood infection, curing that patient means total annihilation of the organism in that environment
what are hospital acquired infections?
- opportunistic pathogens as a result of hospital stays
- it is often the patients themselves which are the source of their own infections e.g. C. diff and MRSA
how has urbanisation had an affect on pathogenesis?
- as of 2007, more than 50% of the world’s population now live in urban areas
- next big rise expected in Asia and Africa
- higher population densities drive many routes of transmission
- airborne route is amplified as droplets have higher chance of contacting neighbours
- increases faecal-oral and animal transmission
how was Vibrio cholerae discovered?
1854 Broad Street Pump: John Snow
- Snow produced a map with lines that indicated the locations of deaths from cholera
- the deaths were clustered around a communal water pump on broad street
- he broke the handle off the pump so people could no longer use it
- disease outbreak halted
first historical case where a disease outbreak was methodically investigated
what is epidemiology?
study of where and when diseases occur to control the spread of disease
what are the principles of epidemiology?
- identify patient zero
- identify anyone who had contact with patient zero to track spread
- identify reservoir of infection e.g. Broad Street pump
- block or contain the reservoir
- difficult for new pathogens
- disease must be first recognised
- many already infected by then
what are the 3 disease patterns?
- epidemic disease: disease acquired by many hosts in a given area in short time
- endemic disease: disease constantly present in population e.g. common cold
- pandemic disease: worldwide epidemic e.g. HIV
what is the importance of disease patterns?
- tracking and surveillance of disease is an essential tool to control disease
what is the solution when the reservoir of a disease is a human being?
isolation
what type of vaccine is the poliovirus vaccine?
- made using an attenuated (weakened) version of the live virus
what difficulties does the poliovirus present?
- in rare cases, the virus can revert to a form capable of infecting others
- in extremely rare cases, some immunocompromised people appear to become healthy carriers and can excrete large amounts of the virus for a long time
what is the Oral Poliovirus Vaccine (OPV) paradox?
- if population is treated with poliovirus vaccine, those individuals can create mass amounts of new poliovirus
- new poliovirus can sit in sewage systems and be spread in floods/natural disasters
- if people stop having the vaccine, not all the public is immune to the vast new polioviruses that have been accumulated and spread
is the polio vaccine safe?
yes for the people receiving the vaccine
no for those who are not having the vaccine
what is the Birmingham Man?
- polio carrier
- has been confirmed to have excreted live Polio for the last 30 years
what kind of pathogen is Yersinia pestis?
zoonotic pathogen which affects rodents and wild dogs
- can be equally devastating to rodent populations
- mass death in rat population before plague epidemic is seen
epizootics = animal epidemic
what caused the potato blight?
- potatoes that were carried to Britain and Spain were the ones sailors liked the look of
- this produced a tight bottle neck and reduced genetic diversity of potatoes in Europe
- large population of susceptible potatoes which die is soil is contaminated with the blight
- if potatoes are replanted in contaminated soil, the blight reoccurs
what is the geographical characteristic of pathogens?
- they share similar geographic distribution and co-evolve with their hosts
what does genetic reassortment of influenza virus lead to?
- generation of new influenza virus particles
- if once cell is infected by 2 influenza viruses, the cell produces viruses with different chromosomes from both viruses
- forms new strains
how was swine flu created?
genetic reassortment:
- bird influenza virus and human influenza virus infected a swine cell
- formed a new reassortant virus in pigs
- this new strain was reintroduced to the human population and is not vaccinated against
how are new diseases identified?
- it is first identified as a geographically clustered pattern of symptoms and signs
how was the link between Zika and microcephaly established?
2015: Dr Linden noticed an increased number of newborns with microcephaly in Brazil
- Linden alerted state health secretary about spike in microcephaly
- at same time and location in Brazil there was an outbreak of mosquito-associated diseases
Aedes mosquito was a vector for both Dengue and Zika viruses
2016: link between Zika and microcephaly was established by scientific consensus
what is epidemiological surveillance? what are its limitations?
- the collection, analysis and dissemination of public health data
Limitations:
- takes lots of time
- can be inaccurate
- correlation based data falls very short of cause and effect
what were the Zika-associated birth defects found in 2018?
- brain abnormalities
- microcephaly
- eye defects
- hearing loss
- damage to brain that affects nerves, muscles and bones (clubfoot, inflexible joints)
what is the global distribution of Zika?
- any country that has the Aedes mosquito
- can also be other countries without the mosquito due to sexual transmission (as of 2017)
what surveillance system did the CDC set up for Zika in 2018?
Zika Birth Defects Surveillance
- monitors defects potential related to Zika virus infection
what data was found about Zika virus from the Zika Birth Defects Surveillance?
- zika-associated birth defect rate in US = 5%
- chances of any pregnancy having birth defect = 3%
- correlation between zika virus infection during pregnancy and specific birth defects has a mild effect side e.g. 2.2-2.4 cases per 1000 live births
what is antimicrobial resistance (AMR)?
- bacteria can resist against antibiotics
- bacterial pathogens each have different virulence characteristics and survival strategies, and can have resistance mechanisms which are varied and poorly understood
- the continued use of antibiotics has driven selection for resistant strains
- thus, the rate of new drug discovery has sharply declined
how significant is antimicrobial resistance (AMR)?
- biggest challenge to global public health today
- without antibiotics, minor infections become deadly, surgery is impossible, child birth deaths are more likely
