Infectious diseases 17/10/22

Question 1

What is an infectious disease?

Answer 1

Causes pathological effect.
Caused by an infectious agent.
Can be passed between people easily.

Question 2

What is the microbiome?

Answer 2

All the genomes from microorganisms in an environment.

Question 3

What is the microbiota?

Answer 3

All the microorganisms in an environment.

Question 4

How many microorganisms are there in and on us?

Answer 4

There are 38 trillion cells.

Question 5

What are the different microorganisms?

Answer 5

Bacteria - single celled prokaryote.

Virus - non-cellular or living + survive in host.

Fungi - eukaryote.

Protozoa - single celled eukaryote.

Prions - protein that can make other proteins fold abnormally.

Helminths - parasitic worms that are large non microbial.

Arthropods - eukaryotic invertebrate animals such as insects.

Archaea - single celled prokaryotes and have no infectious agent identified.

Question 6

What is commensal?

Answer 6

Relationship where one benefits and the other is unaffected.

Question 7

What is mutualistic?

Answer 7

Both benefit.

Question 8

What are the different types of pathogens?

Answer 8

Opportunistic - when conditions alter and permit infection (thrush)
Obligate - always cause disease (colds)

Question 9

What is an infection?

Answer 9

An infection is when there is damage to tissues or cells leading to symptomatic disease.

Question 10

What is a causative agent?

Answer 10

Microscopic microorganism or microbes that causes infection.

The etiological agent is a substances that contain the infectious microorganism.

Question 11

Who invented the microscope?

Answer 11

Robert Hooke in 1664.

Question 12

Who discovered the germ theory?

Answer 12

Robert Koch, 1843-1910. German microbiologist.

Germ theory of disease - certain diseases caused by single species of bacteria. Discovered Bacillus anthracis as causing Anthrax in mice in 1876. Developed precursor of Ziehl-Neelson stain to view Mycobacterium tuberculosis to observed in lung tissue (mycolic acids in cell wall structure). Developed solid media with glass plates to culture and isolate single species/strains.

Question 13

What is the historical context of infectious disease?

Answer 13

Not always possible to culture microorganism to obtain pure species (e.g., Treponema palladium which causes syphilis, bejel, and yaws).

Not always a suitable animal model of disease available (e.g., Epstein Barr Virus mice with reconstituted human immune system components (HIS mice)).

Some infections may be polymicrobial, or have additive effects (e.g., V. Cholera. Some infectious agents may be present but not cause disease).

Question 14

What was the discovery of helicobacter pylori?

Answer 14

• Gram negative corkscrew shaped bacilli
• No animal model
• Had been thought that gastric ulcers were caused by lifestyle factors
• In 1982, Barry Marshall deliberately infected himself with H. pylori before and after gastric biopsy for evidence of cause of acute gastric illness.
• Barry Marshall and Robin Warren – 2005, Nobel Prize in Physiology or Medicine
• Colonizes human stomach 90% of duodenal ulcers and 70-80% of gastric ulcer

Question 15

What are the routes of transmission?

Answer 15

Aerosol - by inhalation of air droplets containing microorganism

Oral - by ingestion of contaminated food or water

Direct contact - contact with infected individual tissues or bodily fluids, via entry sites, e.g., eyes/mouth/nose or wound (e.g., bite/scratch)

Fomite transmission - contaminated surfaces of inanimate objects e.g cages/door handles/medical equipment

Vector-borne - by other living organisms e.g., mosquitoes, ticks

Zoonotic - originating from other animal species through routes above

Question 16

What is bacillus anthracis?

Answer 16

First described by Robert Koch in 1864.

Gram positive bacilli
Endospore forming
In the environment (soils, water, contaminated animal products e.g., wool, hides, or hair).

Depending on transmission route:

Cutaneous anthrax - contamination of wound with spores from environment or contaminated animal products

Inhalation anthrax - breathing in of spores from contaminated animal products such as workers in wool mills, tanneries

Gastrointestinal anthrax - spores with meat from an animal infected with anthrax

Injection anthrax - resulting from contaminated needle, this is the least common form of anthrax

Question 17

What are the differences in bacillus anthracis depending on where the bacilli is located in the body?

Answer 17

Cutaneous anthrax:
1 - 6 days from exposure
Swelling, skin ulcer with black centre
20% fatality rate if untreated
100% survival with treatment

Inhalation anthrax:
1 week - 2 months
Fever and chills, sweating, headache, body aches, cough, chest discomfort, shortness of breath, nausea, vomiting, stomach pains, extreme tiredness
100% fatality rate if untreated
55% survive with treatment

Gastrointestinal anthrax:
Diarrhoea or bloody diarrhoea, stomach pain, swelling of abdomen, headache, fainting, flushing (red face) and red eyes
If untreated >50% fatality rate
If treated 60% survival

Question 18

What is influenza syndrome?

Answer 18

Causative agent - Influenza virus

Segmented –ve sense ssRNA genome
Pleomorphic nucleocapsid

Signs and symptoms:
* Fever
* Cough
* Sore throat
* Congestion
* Muscle/body aches
* Fatigue
* Vomiting and diarrhoea

Acute:
Contagious via airborne transmission/indirect contact. Respiratory tract infection, symptoms felt throughout body. Epidemics occur seasonally, typically low fatality, pandemics more deadly less frequent. Genome structure means it is highly changeable, infect multiple species (humans, pigs, birds). Concerns for avian flu led to new pandemic H1N1 & H5N1

Question 19

What are the phases of infectious disease?

Answer 19

Phases of an infectious disease:
* Duration of infectious disease
* Location of infectious disease
* Timing of infectious disease
* Stages in infection

Question 20

What are the phases of infectious disease?

Answer 20

Incubation period - time between infection and the appearance of signs and symptoms
Prodromal phase - mild, non-specific symptoms that signal onset of some diseases
Clinical phase - a person experiences typical signs and symptoms of disease
Decline phase - subsidence of symptoms
Recovery phase - symptoms have disappeared, tissues heal, and the body regains strength

Question 21

What is the duration of infectious disease?

Answer 21

Acute – develops and progresses quickly
Chronic – develops slowly and less severe but long lasting
Latent – characterised by no symptoms between outbreak and illness

Question 22

What are the locations of infectious disease?

Answer 22

Local – confined to a specific area of the body
Systemic – infects across multiple body sites and across tissues

Question 23

What are the timings of infectious diseases?

Answer 23

Primary – initial infection in a previously healthy person
Secondary – infection that occurs in a person weakened by a primary infection

Question 24

What is an example of an acute infection?

Answer 24

Ebola - ebola virus,
Single - ve sense ssRNA
Helical nucleocapsid
Direct contact, bodily fluids,
Symptoms onset ~5-9 days
Ebola haemorrhagic fever
* Early – fever, fatigue
* Later – vomiting, diarrhoea, rash, haemorrhaging, bleeding or bruising
Fatality rate, 50% (95%)
FDA approved 2020, Inmazeb, three monoclonal antibodies and Ebanga, single monoclonal antibody 2019 Vaccine rVSV-ZEBOV (recombinant vesicular stomatitis virus–Zaire Ebola virus), glycoprotein.

Question 25

What is an example of chronic infection?

Answer 25

Human Papilloma virus (HPV)
dsDNA genome, icosahedral capsid (L1 and L2 proteins)
Direct contact
No symptoms, resolution in majority of cases
Genital warts, oropharyngeal cancers
Vaccine - assembled L1 capsids, no genome
Modelling to suggest by 2120 > 60 million deaths
averted in low-, low-middle income countries

Question 26

What is an example of a latent infection?

Answer 26

Herpes simplex virus type 1 (HSV-1)
Herpes simplex virus type 2 (HSV-2)

dsDNA genome, icosahedral capsid
HSV1 oral-oral, HSV2 Sexually Transmitted Infection. Lifelong infection, antivirals to treat symptoms (zoxnic)

3.7 billion people under age 50 globally HSV-1
491 million people aged 15-49 (13%) HSV-2

Blisters/ulcers at site of infection, reoccur sporadically. Spread to central nervous system, state of quiescence in neuron nucleus
Rare but instances of HSV-caused encephalitis
Vaccines being developed

Question 27

What is an example of a site of location infectious disease?

Answer 27

MRSA
1/3 people carry Staphylococcus aureus in their nose, 2/100 Methicillin resistant S. aureus

Local - site of infection on skin cutaneous abscess:
* red
* swollen
* painful
* warm to the touch
* pus
* fever

Systematic - bacteraemia
20,000 MRSA bloodstream infections and 20,000 associated deaths occurred in the United States in 2017

Question 28

What is an example of a primary timing infectious disease?

Answer 28

Human Immunodeficiency virus (HIV),
+vs ssRNA genome, enveloped capsid
Direct contact, bodily fluids
Flu like illness 2-6 weeks after infection (80%)
* fever
* sore throat
* body rash
T cell infection and decrease in CD4+ cells
Development of Acquired Immunodeficiency Syndrome (AIDS)

Question 29

What is an example of a secondary timing infectious disease?

Answer 29

Opportunistic infections:
Mycobacterium tuberculosis
Toxoplasma gondii – protist
PML JC virus (JCV) polyomavirus (50-90%)
Cytomegalovirus
Cryptococcus neoformans or, C. gattii - fungus

Question 30

What are the steps in infection?

Answer 30

-Entry and Attachment to body
-Colonisation
-Local or general spread through the body
-Replication required for multiplication
-Exit (shedding from body)

Overcome innate immune response and invasion into tissues and cells. Access and obtain necessary nutrients/cellular machinery for replication and evade immune response. Leave site or sites for onward transmission.

Question 31

How do infectious agents cause disease?

Answer 31

Production of poisons such as toxins and enzymes that destroy cells and tissues (e.g., often produced by bacteria).

Direct invasion and destruction of host cells (e.g., viruses, some bacteria).

Triggering responses from the host’s immune system leading to disease signs and symptoms (e.g., fever/sneezing/vomiting triggered by the immune system to rid the body of the pathogen).

Question 32

What are shared pathological sites?

Answer 32

Some pathological effects of disease may be caused by more than one causative agent.
* Respiratory infections
* Bloodstream infections
* Encephalitis (inflammation of the brain)
* Meningitis (inflammation of the lining around brain and spinal cord)
* Endocarditis (infection of the heart)
* Gastrointestinal disease
* Skin and soft tissue infection

Question 33

What caused the Spanish flu?

Answer 33

Influenza pandemic
1918 Pandemic “Spanish Flu”

Added factors:
* Overcrowding of soldiers
* Global movement of personal fighting in the war
* Return of troops home

Resolution to outbreak:
* Public education campaigns
* Break transmission, e.g., mask wearing cover coughs/sneezes/no spitting
* Multiple waves

Question 34

What treatments were developed for influzena?

Answer 34

Antivirals - approved for seasonal flu by US Food and Drug Administration

Tamiflu - 1999
Relenza - 2006
Rapivab - 2014
Xofluza - 2018

Vaccine development 1930s. Led from first identification of virus in 1930s.

Question 35

What are the treatments of infectious diseases?

Answer 35

Antimicrobial drugs
Antibiotics - only work against some bacteria, and do not work against viruses or other agents, target bacteria-specific structures/functions in the prokaryote cell, resistance of bacteria increasing globally (AMR), CDC identified 18 infectious agents that are of concern. - $4.6 billion annually.

Antivirals - work against some viruses, block parts of viral replication, e.g., nucleotide incorporation.

Antifungals - challenging to develop due to eukaryotic nature of cells targeting/parasitic life cycles.

Question 36

What are the preventions of infectious diseases?

Answer 36

Vaccines - vaccines consist of either attenuated (weakened), inactivated or dead (killed) or components of the microorganism, work by stimulating the body’s immune system to fight off future infection, vaccination programmes successfully eradicated smallpox, global led campaigns to tackle polio
Good hygiene and sanitation
Protection against vectors (e.g., mosquitoes/ticks)
Isolation or quarantine of patients

Question 37

What is the diagnosis of infectious diseases?

Answer 37

Laboratory culture and isolation (identification, biochemical tests)
Microscopy (Gram stain, other stains, immunohistochemistry)
Nucleic acid amplification tests (NAAT) - polymerase chain reaction PCR (qPCR), isothermal amplification
Enzyme-linked immunosorbent assay (ELISA)
Latex agglutination (LA) assay)
Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF MS)
WGS

Question 38

What is the epidemiology of infectious diseases?

Answer 38

This is the science that examines patterns causes and effects of disease (not just infectious disease) on the health of a given population.

The focus is to control and reduce incidence of disease via identification of factors that:
* Cause disease
* Transmission of disease
* Help prevent/reduce future disease

Question 39

How is the epidemiology broken down?

Answer 39

• Disease aetiology (causing agent)
• Outbreak investigation
• Disease screening and surveillance
• Comparisons of treatment or effects (– clinical trials)

Question 40

What are emerging infectious diseases?

Answer 40

Emerging diseases are those that have recently appeared within a population, or incidence in increasing rapidly.

Things that can cause re-emergence:
Acquisition of resistance of antimicrobial drugs, e.g., MDR Neisseria gonorrhoeae—ceftriaxone last resort
Vaccine or preventative measures ineffectual (e.g., measles)
Appearance of a previously unknown agent
Spread of an infectious agent to a new host
Spread of an infectious agent to new locations

Question 41

What are Koch’s postulates?

Answer 41

The agent must be cultured as a single nucleotide.
The agent must be present in all cases of the disease.
The agent must be inoculated into a health, non-disease state model and cause disease.
The agent must be recovered and shown to be the same after disease occurrence.

Question 42

What does the pathology of infectious disease not result from?

Answer 42

Damage caused by host tissues by pathogen route of entry.

Question 43

What is a transient microorganisms?

Answer 43

Microorganisms that are only temporarily found in the body.