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Trinity Term 1 > The Natural History of Infectious disease II: viral and eukaryotic pathogens > Flashcards

The Natural History of Infectious disease II: viral and eukaryotic pathogens Flashcards

1
Q

Describe viral diseases

A

all viruses are obligate pathogens

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2
Q

Describe the factors influencing the severity of the disease that a viral infection causes across hosts and species

A
  • role of pathology in transmission
  • viral replication mechanisms
  • host factors, including age and nutritional status
  • host immune status and response
  • tissue tropism
  • acute or chronic phases of infection
  • interactions with the microbiome
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3
Q

Which viruses cause encephalitis/meningitis

A
  • JC virus
  • measles
  • MC virus
  • arbovirus
  • rabies
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4
Q

Which viruses cause common cold?

A
  • rhinoviruses
  • parainfluenza virus
  • respiratory syncytial virus
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5
Q

Which viruses cause eye infections?

A
  • herpes simplex virus
  • adenovirus
  • cytomegalovirus
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6
Q

Which viruses cause pneumonia?

A
  • influenza virus (A and B)
  • parainfluenza virus
  • respiratory syncytial virus
  • adenovirus
  • SARS coronavirus
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7
Q

Which viruses cause myelitis

A
  • poliovirus
  • HTLV-I
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8
Q

Which viruses cause gastroenteritis?

A
  • adenovirus
  • rotavirus
  • norovirus
  • astrovirus
  • coronavirus
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9
Q

Which viruses cause pancreatitis?

A

coxsackie B virus

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10
Q

Which viruses cause STIs?

A
  • herpes simplex type 2
  • human papillomavirus
  • HIV
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11
Q

Which viruses cause skin infections?

A
  • varicella zoster virus
  • human herpesvirus 6
  • smallpox
  • molluscum contagiosum
  • human papillomavirus
  • parvovirus B19
  • rubella
  • measles
  • coxsackie A virus
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12
Q

Which viruses cause hepatitis?

A

hepatitis virus types A, B, C, D, E

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13
Q

Which viruses cause cardiovascular disease?

A

coxsackie B virus

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14
Q

Which viruses cause pharyngitis?

A
  • adenovirus
  • Epstein-Barr virus
  • cytomegalovirus
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15
Q

Which viruses cause gingivostmatitis

A

herpes simplex virus 1

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16
Q

Describe the different types of pathogen transmission

A
  • direct transmission
  • respiratory tract (airborne)
  • gastrointestinal
  • sexually transmitted
  • vertical transmission
  • arthropod borne
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17
Q

Give an example of a directly transmitted pathogen

A

Parvo viruses (ssDNA)

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18
Q

Give an example of an airborne pathogen

A

Influenza (segmented -ve ss RNA Orthomyxovirus)

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19
Q

Give an example of a gastrointestinally transmitted pathogen

A

Polio (+ve ssRNA Picornavirus, Enterovirus)

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20
Q

Give an example of an STI

A

HIV (+ve ssRNA Retrovirus)

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21
Q

Give an example of a vertically transmitted pathogen

A
  • HTLV (+ve ssRNA Retrovirus, also sexually transmitted
    and through blood contamination).
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22
Q

Give examples of arthropod-borne pathogens

A
  • dengue (+ve ssRNA Flavivirus),
  • zika (+ve ssRNA Flavivirus, also vertically transmitted).
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23
Q

Describe the routes for pathogen transmission

A
  • mouth/nose
  • lungs
  • skin (scratch/bite)
  • urogenital tract
  • anus
  • capillary
  • conjunctiva
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24
Q

Describe Variola virus

A
  • single invariant antigenic type
  • human cases are symptomatic
  • no animal reservoir.
  • natural infection or vaccination provides long-term sterilising immunity against disease and infection
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25
Q

Describe rabies

A
  • zoonotic infection of humans
  • almost certainly fatal once symptoms develop
  • 40-70,000 cases annually
  • vaccination of stray dogs and education are important strategies
  • globally distributed
  • transmitted by biting
  • aggressive behaviour in the host an essential
    component of disease
  • spreads through the host in neural tissue
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26
Q

Describe Rhabdovirus

A
  • enveloped (-ve) ssRNA genome
  • 12kb single molecule, encoding 5 proteins
  • bullet-shaped
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27
Q

Describe host neural tissue

A

an ‘immune privileged’ site

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28
Q

Describe rabies replication in the host

A
  • virus particle absorbs to, and is engulfed by, a host cell
  • viral glycoprotein fuses to the endosome membrane
  • nucleocapsid is released into the host cell
  • viral RNA produced by the viral polymerase
  • forms viral mRNAs, translated by the host into viral proteins
  • nucleocapsids are assembled
  • associate with the matrix and glycoproteins
  • virions released from the host cell by budding
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29
Q

Describe rabies migration in the host

A
  • virions introduced by an animal bite
  • enriched at neuromuscular junction and/or amplified in muscle
  • virus enters neuron
  • rapid transport though the neuron to brain
  • multiplies, changing behaviour (most commonly hydrophobia and aggression) and killing the host
  • salivary glands important propagation site and exit route for the virions, completing the cycle.
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30
Q

Describe polio virus

A
  • Picorna virus with humans the only known natural host.
  • can lead to viraemia, neural involvement and poliomyelitis
  • only three serotypes;
  • no animal or environmental reservoir
  • effective and inexpensive vaccine (OPV)
  • life-long immunity against transmission
  • OPV viruses revert to virulence by mutation and recombination
  • asymptomatic transmission
  • immunocompromised vaccinees can
    excrete virulent virus for decades
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31
Q

Describe HIV

A
  • sexually transmitted HIV infects cells have CD4 cell surface protein
  • HIV replicates within the CD4 cell which subsequently diminish in number
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32
Q

Describe AIDS

A
  • acquired immune deficiency syndrome
  • result of life-threatening opportunistic infections arising from depleted immune system
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33
Q

Describe the progression of HIV to AIDS

A
  • early infection (~3 months) is symptomless; virus is dividing in lymph nodes
  • acute HIV syndrome at 3 months
  • wide dissemination of the virus
  • clinical latency
  • constitutional symptoms
  • opportunistic diseases
  • death
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34
Q

Describe CD4 levels in the blood

A
  • healthy individuals have >600 CD4 T cells/mm3 of blood
  • <200 corresponds to severe depletion.
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35
Q

Describe the Yellow Fever transmission cycle in Africa

A
  • sylavtic, found in NHPs
  • transmitted to Aedes africanus
  • intermediate in the Savanna
  • found in semi-domestic Aedes spp. and humans
  • found in A. aegypti in urban areas
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36
Q

Describe the Yellow Fever transmission cycle in South America

A
  • sylavtic, found in NHPs
  • transmitted to Haemogogus spp. and Sabethes spp.
  • found in A. aegypti in urban areas
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37
Q

Describe yellow fever

A
  • a mosquito-borne arbovirus
    – CNS pathology
    – short duration fevers
    – hemorrhagic fevers
    – polyarthritis and rash
  • caused by human environmental encroachment, including the slave trade
  • vaccines and treatments available
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38
Q

Which pathogens cause yellow fever?

A
  • West Nile
  • Chikungunya
  • Zika
  • Colorado tick fever
  • dengue
  • eastern and western equine encephalitis
  • St. Louis encephalitis
  • Japanese encephalitis
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39
Q

Describe the importance of parasitic diseases

A
  • socio-economic
  • medical
  • biological
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40
Q

Describe the socio-economic importance of parasitic infections

A
  • protozoan parasites commonly affect the poorest people;
  • significant obstacle to economic and political development;
  • financial loss >$12B per year in Africa for malaria alone.
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41
Q

Describe the medical importance of parasitic infections

A

– common human infections, especially in low income countries
– high burden of morbidity and mortality

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42
Q

Describe the biological importance of parasitic diseases?

A
  • diverse host-pathogen interactions, e.g. immunity, physiology
  • complex life-cycles and transmission patterns
  • unique organelles and biochemistry
  • important biochemical and evolutionary models
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43
Q

Describe the sites of parasitic infection in humans

A
  • brain
  • eyes
  • lymph
  • lungs
  • liver
  • intestines
  • muscles
  • blood
  • joints
  • skin
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44
Q

List some parasites that affect the brain

A

Naegleria fowleri

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45
Q

List some parasites that affect the lymph

A

Filariodidae nematodes

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46
Q

Describe some parasites that affect the lungs

A

Paragonimus westermani (lung fluke)

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47
Q

Describe a parasite that infects the muscles

A
  • trichinella spiralis
48
Q

Describe a parasite that colonises the blood

A

Brugia malayi

49
Q

Describe a parasite that affects the joints

A

Giardia

50
Q

Give some features of parasitic diseases

A
  • complex lifestyles (sexual and asexual phases) and life cycles
  • large genomes
  • multiple tranmission routes
  • high mortality (many offspring)
51
Q

What is the effect of the large genomes of parasites?

A
  • accommodate multiple hosts
  • produce resting stages and highly resistant spores
  • diverse means of locomotion and spread
52
Q

Give some different parasitic transmission routes

A
  • faecal-oral
  • sexual
  • vector borne (biting insects)
53
Q

Give some parasitic life cycle stages

A
  • trophozoite
  • merozoite
  • sporozoite
54
Q

Trophozite

A

feeding stage of a protozoan parasite

55
Q

Merozoite

A

daughter cell of asexual replication

56
Q

Sporozoite

A

motile, spore-like stage

57
Q

Describe Apicomplexans

A
  • obligate parasites of animals.
  • apicoplast
  • no flagella or cilia; move by gliding motility
  • food taken up in soluble form across the cytoplasmic
    membrane
  • sexual and asexual reproduction
  • apical complex
58
Q

Describe the apicoplast

A
  • secondary endosymbiosis
  • degenerate chloroplast (non-photosynthetic)
59
Q

Describe the sporozoa of Apicomplexans

A
  • produce sporozoites
  • transmission function
60
Q

Describe the apical complex

A

involved in attachment and invasion

61
Q

Who are the Apicomplexans?

A
  • Toxoplasma gondii (toxoplasmosis, faecal-oral)
  • Cryptosporidium parvum (faecal oral)
  • Eimeria (faecal-oral, highly host specific species’)
    – Plasmodium (malaria, vector borne)
62
Q

Describe the morphology P. falciparum Merozoite

A
  • surface coat
  • polar ring
  • microneme
  • rhoptry
  • dense granules
  • microtubules
  • ribosomes
  • mitochondria
  • plastids
  • nucleus
63
Q

Describe faecal-oral transmission

A

common lifestyle strategy

64
Q

List some faceal-orally transmitted parasites

A

– Giardia intestinalis
– Entamoeba histolytica
– Cryptosporidium parvum
– Eimeria spp (veterinary pathogen)
– Toxoplasma gondii (one of the routes)

65
Q

What are the lifestyle challenges of faecel-oral transmission

A
  • need to resist the environment, cysts or oocysts
  • high parasite losses (needs high numbers)
  • needs a way of sensing entry into the host
  • host availability
66
Q

What are the lifestyle advantages of faecel-oral transmission

A
  • adaptation focussed on a single host type (for some)
  • ease of entry into the host by ingestion
  • environmental reservoir (spore stages)
67
Q

Describe Giardia species

A

have an adhesive disc

68
Q

Describe Cryptosporidium spp.

A

have apical organelles

69
Q

Describe Toxoplasma gondii

A
  • have moving junctions
70
Q

Describe Entamoeba histolytic

A
  • inflammatory response
  • lamina propria
71
Q

Describe Trypanosoma cruzi

A

gastric mucosal epithelium

72
Q

Describe the parasitic use of invertebrate vectors

A

common lifestyle strategy

73
Q

Describe the lifestyle challenges of invertebrate host use by parasites

A

– adaptation to multiple hosts
– transferring among different hosts
– sensing the change of host
– host availability/lifespan can be problematic
– host immune responses (two of them)

74
Q

Describe the lifestyle advantages of invertebrate host use by parasites

A

– protection from the environment
– ease of entry by injection by vector
– dispersal by vector (e.g. wings)
– vector-based host targeting

75
Q

List some species that use invertebrate host as vectors

A

– Plasmodium spp, mosquitoes
– Trypanosoma brucei, Tsetse flies
– Trypanosoma cruzi, Triatomid bugs
– Leishmania spp., Sand-flies
– Babesia, Ioxdidae tick

76
Q

Describe malaria

A
  • restricted by parasite and vector distribution
  • 156 named Plasmodium spp four infect humans
77
Q

Where is malaria restricted to?

A

tropical, sub tropical, low altitude

78
Q

Describe the 4 human malarial species

A

– Plasmodium falciparum (most severe: global distribution)
– Plasmodium vivax (most prevalent: Central/South America, India, Pakistan, Asia)
– Plasmodium malariae (globally distributed)
– Plasmodium ovale (almost exclusively found in Africa)

79
Q

Describe the varying symptom severity of malaria

A

– parasite species
– host immune status
- host exposure
– host age (cerebral malaria commoner in children)

80
Q

Describe African Trypanosomiasis

A
  • Sleeping Sickness
  • transmitted by the tsetse fly
81
Q

Describe the sleeping sickness species affecting humans and animals

A

– Trypanosoma brucei gambiense (TbG) (98% of cases)
– Trypanosoma brucei rhodesiense (TbR) (acute form)

82
Q

Trypanosoma cruzi causes

A

Chaga’s disease

83
Q

Describe the clinics of sleeping sickness

A
  • haemo-lymphatic stage; fever, headaches, joint pains and itching
  • neurological or meningo-encephalic stage parasites cross the BBB to infect the CNS
  • changes of behaviour, confusion, sensory problems, poor coordination, disturbance of the sleep cycle
  • diagnosis and treatment of the disease is complex
  • usually fatal without treatment
84
Q

Describe modern treatment of African sleeping sickness

A

In 2009 the number reported dropped below 10 000 for the first time in 50 years: 2015, 2804 cases; in 2018, 977 cases recorded.

85
Q

Describe the life history of African Trypanosomiasis

A
  • tsetse fly takes blood meal: injects metacyclic trypomastigotes
  • transform into bloodstream trypomastigotes; carried to other sites
  • multiply by binary fission in (blood, lymph and spinal) fluids
  • tsetse fly takes blood meal: ingests bloodstream trypomastigotes
  • transform into procyclic trypomastigotes in tsetse fly’s midgut
  • multiply by binary fission
  • leave the midgut and transform into epimastigotes
  • multiply in the salivary gland
  • transform into metacylic trypomastigotes
86
Q

Describe antigenic variability in Trypanosomes and
Plasmodium

A
  • thousands of VSG genes available
  • only one is expressed at a any one time
  • as infection progresses, majority of parasites are periodically eliminated
  • ‘arms race’ between host and pathogen
87
Q

VSG in Tsetse fly

A
  • variant surface glycoprotein
  • mediate immune evasion in the mammalian host
  • switched on in the Tsetse fly midgut, switched off on return to the Tsetse fly
  • changing expression gives relapsing parasitaemia
  • allelic exclusion
88
Q

allelic exclusion

A

DNA repair mechanisms allow a new VSG to be copied into a single transcribed locus

89
Q

Describe fungal diseases

A
  • few hundred species
  • more common in immunocompromised patients
  • plant pathogens have great economic importance
90
Q

Describe mammals’ natural defences against fungal infection

A

higher body temperature

91
Q

Describe the various potential pathologies of fungi

A

– asthma or allergies
– rashes or infections on the skin and nails
– eye infections
– lung infections (pneumonia- symptoms similar to the flu or tuberculosis)
– bloodstream infections
– meningitis

92
Q

Describe Candida albicans

A
  • ubiquitous human commensal found as part of the mucosa or skin microbiota
  • polymorphic
  • can cause mucosal diseases
  • Candidiasis can result from a perturbed normal microbiota (antibiotic use)
93
Q

Describe Candida albicans polymorphism

A
  • can exist as yeast, pseudohyphae, and hyphal forms
  • hyphal form causes tissue damage and allows access to the bloodstream
94
Q

Describe the diseases caused by C. albicans

A
  • oral or vaginal candidiasis (thrush)
  • skin infections in newborn (nappy rash) and burns victims
95
Q

Describe systemic C. albicans

A
  • in immunocompromised patients
  • affects all organs of the body
  • 30-50% mortality
96
Q

Describe Trichopyton rubrum

A
  • superficial fungal infection
  • dermatophyte from the Ascomycota phylum
  • colonises upper layers of dead skin
  • most common cause of Athlete’s foot, fungal nail infections, jock itch, and ringworm
97
Q

Describe ringworm

A
  • most commonly caused by Tricophyton, Microsporum
    or Epidermophyton fungi
  • ring like itchy, scaly, inflamed skin with hair loss
  • highly contagious
    – laboratory diagnosis
  • infection lasts several months
98
Q

Describe the contagion of ringworm

A
  • human-human
  • animal-human
  • object-human (direct and indirect contact)
99
Q

Describe Cryptococcus neoformans

A
  • widespread opportunist pathogen of humans and animals
  • probably diverged from a common environmental saprophyte ancestor around 30–40Mya
  • common AIDS-defining illness
  • associated with reduced T-cell function, resulting in pneumonia and brain
    infections
  • ability to manipulate the human immune response to facilitate disease
100
Q

Describe the life history of Cryptococcus neoformans

A
  • ‘division of labour’ in immunocompetent host
  • survival and latency
  • immune deficiency triggers intracellular proliferation
  • lysis: extracellular proliferation
  • vomocytosis: titan cell formation
101
Q

Describe Aspergillus flavus

A
  • saprophytic soil fungus
  • allergies
  • aflatoxicosis
102
Q

Describer Aspergillus in cancer

A
  • Cancer:
    – Aflatoxin B1 is potent hepatocarcinogen upon long term
    exposure.
    – Estimated that 4.5 billion humans in low income countries chronically exposed to high doses.
    – Aflatoxin and Hepatitis viral infections act synergistically to increase liver cancer development.
103
Q

Describer Aspergillus flavus allergies

A
  • develop after repeated inhalation of spores (asthma, Aspergillosis)
  • rabbits and poultry especially susceptible
104
Q

Describe Aspergillus Flavus aflatoxicosis

A
  • aflatoxins produced as secondary metabolites when growing on stored foods (cereals, oilseeds, nuts) at 24- 35°C and high moisture content
  • toxic effects in humans and animals leads to impaired food consumption, stunted growth and immune suppression
105
Q

Describe fungal plant pathogens

A
  • primarily Ascomycota and Basidiomycota.
  • biotrophs
  • necrotrophs
  • hemibiotrophic
  • Magnaporthe oryzae
  • Botrytis cinerea
  • Puccinia graminis
106
Q

biotrophs

A

utilise living tissue

107
Q

necrotrophs

A

kill tissue to extract nutrients

108
Q

hemibiotrophic

A
  • utilise living tissue
  • kill tissue to extract nutrients
109
Q

Describe Magnaporthe oryzae

A
  • Rice Blast Disease.
  • > 50% world’s population relies on rice as the main source
    of calories
  • important model for research
110
Q

Describe Botrytis cinerea

A
  • Grey Mould
  • pre- and post- harvest damage.
  • broad host-range (200 plant species including fruit and vegetables)
111
Q

Describe Puccinia graminis

A
  • Wheat Stem Rust
  • recent emergence of race UG99.
  • alternative host ‘Barberry’
112
Q

Describe Wheat Stem Rust

A
  • ancient scourge of agriculture (Biblical records; Ancient Greece and Rome)
  • epidemics recorded over the past 150 years
  • near and far east, Europe, and the Americas
    – major famines in Asia
  • massive grain losses North America in 1903 and 1905 and 1950-54
113
Q

How did we tackle Wheat Stem Rust?

A
  • introduction of wheat resistance genes
  • SR31 was the most successful derived from wheat x rye hybrid derivatives
  • produced in Germany in the 1930s
114
Q

Describe Ug99

A
  • lineage of wheat stem rust (Puccinia graminis f.​ sp.​ tritici)
  • present several countries in Africa and the Middle East
  • can cause major crop losses
  • virulent against almost all resistance genes, including Sr31.
  • reliant on chemical controls
115
Q

Describe the likely spread of Ug99

A
  • HYSPLIT model
  • spores can travel thousands of kilometres carried by the wind.
  • bread baskets of Egypt and India/Pakistan are both threatened
  • transmission to both Asia and Australia likely
116
Q

HYSPLIT

A
  • HYbrid Single-Particle Lagrangian Integrated Trajectory
  • simulates the movement of particles using meteorological data

Trinity Term 1 (38 decks)

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