The Natural History of Infectious disease II: viral and eukaryotic pathogens Flashcards
Describe viral diseases
all viruses are obligate pathogens
Describe the factors influencing the severity of the disease that a viral infection causes across hosts and species
- 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
Which viruses cause encephalitis/meningitis
- JC virus
- measles
- MC virus
- arbovirus
- rabies
Which viruses cause common cold?
- rhinoviruses
- parainfluenza virus
- respiratory syncytial virus
Which viruses cause eye infections?
- herpes simplex virus
- adenovirus
- cytomegalovirus
Which viruses cause pneumonia?
- influenza virus (A and B)
- parainfluenza virus
- respiratory syncytial virus
- adenovirus
- SARS coronavirus
Which viruses cause myelitis
- poliovirus
- HTLV-I
Which viruses cause gastroenteritis?
- adenovirus
- rotavirus
- norovirus
- astrovirus
- coronavirus
Which viruses cause pancreatitis?
coxsackie B virus
Which viruses cause STIs?
- herpes simplex type 2
- human papillomavirus
- HIV
Which viruses cause skin infections?
- varicella zoster virus
- human herpesvirus 6
- smallpox
- molluscum contagiosum
- human papillomavirus
- parvovirus B19
- rubella
- measles
- coxsackie A virus
Which viruses cause hepatitis?
hepatitis virus types A, B, C, D, E
Which viruses cause cardiovascular disease?
coxsackie B virus
Which viruses cause pharyngitis?
- adenovirus
- Epstein-Barr virus
- cytomegalovirus
Which viruses cause gingivostmatitis
herpes simplex virus 1
Describe the different types of pathogen transmission
- direct transmission
- respiratory tract (airborne)
- gastrointestinal
- sexually transmitted
- vertical transmission
- arthropod borne
Give an example of a directly transmitted pathogen
Parvo viruses (ssDNA)
Give an example of an airborne pathogen
Influenza (segmented -ve ss RNA Orthomyxovirus)
Give an example of a gastrointestinally transmitted pathogen
Polio (+ve ssRNA Picornavirus, Enterovirus)
Give an example of an STI
HIV (+ve ssRNA Retrovirus)
Give an example of a vertically transmitted pathogen
- HTLV (+ve ssRNA Retrovirus, also sexually transmitted
and through blood contamination).
Give examples of arthropod-borne pathogens
- dengue (+ve ssRNA Flavivirus),
- zika (+ve ssRNA Flavivirus, also vertically transmitted).
Describe the routes for pathogen transmission
- mouth/nose
- lungs
- skin (scratch/bite)
- urogenital tract
- anus
- capillary
- conjunctiva
Describe Variola virus
- single invariant antigenic type
- human cases are symptomatic
- no animal reservoir.
- natural infection or vaccination provides long-term sterilising immunity against disease and infection
Describe rabies
- 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
Describe Rhabdovirus
- enveloped (-ve) ssRNA genome
- 12kb single molecule, encoding 5 proteins
- bullet-shaped
Describe host neural tissue
an ‘immune privileged’ site
Describe rabies replication in the host
- 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
Describe rabies migration in the host
- 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.
Describe polio virus
- 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
Describe HIV
- sexually transmitted HIV infects cells have CD4 cell surface protein
- HIV replicates within the CD4 cell which subsequently diminish in number
Describe AIDS
- acquired immune deficiency syndrome
- result of life-threatening opportunistic infections arising from depleted immune system
Describe the progression of HIV to AIDS
- 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
Describe CD4 levels in the blood
- healthy individuals have >600 CD4 T cells/mm3 of blood
- <200 corresponds to severe depletion.
Describe the Yellow Fever transmission cycle in Africa
- 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
Describe the Yellow Fever transmission cycle in South America
- sylavtic, found in NHPs
- transmitted to Haemogogus spp. and Sabethes spp.
- found in A. aegypti in urban areas
Describe yellow fever
- 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
Which pathogens cause yellow fever?
- West Nile
- Chikungunya
- Zika
- Colorado tick fever
- dengue
- eastern and western equine encephalitis
- St. Louis encephalitis
- Japanese encephalitis
Describe the importance of parasitic diseases
- socio-economic
- medical
- biological
Describe the socio-economic importance of parasitic infections
- protozoan parasites commonly affect the poorest people;
- significant obstacle to economic and political development;
- financial loss >$12B per year in Africa for malaria alone.
Describe the medical importance of parasitic infections
– common human infections, especially in low income countries
– high burden of morbidity and mortality
Describe the biological importance of parasitic diseases?
- diverse host-pathogen interactions, e.g. immunity, physiology
- complex life-cycles and transmission patterns
- unique organelles and biochemistry
- important biochemical and evolutionary models
Describe the sites of parasitic infection in humans
- brain
- eyes
- lymph
- lungs
- liver
- intestines
- muscles
- blood
- joints
- skin
List some parasites that affect the brain
Naegleria fowleri
List some parasites that affect the lymph
Filariodidae nematodes
Describe some parasites that affect the lungs
Paragonimus westermani (lung fluke)
Describe a parasite that infects the muscles
- trichinella spiralis
Describe a parasite that colonises the blood
Brugia malayi
Describe a parasite that affects the joints
Giardia
Give some features of parasitic diseases
- complex lifestyles (sexual and asexual phases) and life cycles
- large genomes
- multiple tranmission routes
- high mortality (many offspring)
What is the effect of the large genomes of parasites?
- accommodate multiple hosts
- produce resting stages and highly resistant spores
- diverse means of locomotion and spread
Give some different parasitic transmission routes
- faecal-oral
- sexual
- vector borne (biting insects)
Give some parasitic life cycle stages
- trophozoite
- merozoite
- sporozoite
Trophozite
feeding stage of a protozoan parasite
Merozoite
daughter cell of asexual replication
Sporozoite
motile, spore-like stage
Describe Apicomplexans
- 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
Describe the apicoplast
- secondary endosymbiosis
- degenerate chloroplast (non-photosynthetic)
Describe the sporozoa of Apicomplexans
- produce sporozoites
- transmission function
Describe the apical complex
involved in attachment and invasion
Who are the Apicomplexans?
- Toxoplasma gondii (toxoplasmosis, faecal-oral)
- Cryptosporidium parvum (faecal oral)
- Eimeria (faecal-oral, highly host specific species’)
– Plasmodium (malaria, vector borne)
Describe the morphology P. falciparum Merozoite
- surface coat
- polar ring
- microneme
- rhoptry
- dense granules
- microtubules
- ribosomes
- mitochondria
- plastids
- nucleus
Describe faecal-oral transmission
common lifestyle strategy
List some faceal-orally transmitted parasites
– Giardia intestinalis
– Entamoeba histolytica
– Cryptosporidium parvum
– Eimeria spp (veterinary pathogen)
– Toxoplasma gondii (one of the routes)
What are the lifestyle challenges of faecel-oral transmission
- 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
What are the lifestyle advantages of faecel-oral transmission
- adaptation focussed on a single host type (for some)
- ease of entry into the host by ingestion
- environmental reservoir (spore stages)
Describe Giardia species
have an adhesive disc
Describe Cryptosporidium spp.
have apical organelles
Describe Toxoplasma gondii
- have moving junctions
Describe Entamoeba histolytic
- inflammatory response
- lamina propria
Describe Trypanosoma cruzi
gastric mucosal epithelium
Describe the parasitic use of invertebrate vectors
common lifestyle strategy
Describe the lifestyle challenges of invertebrate host use by parasites
– 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)
Describe the lifestyle advantages of invertebrate host use by parasites
– protection from the environment
– ease of entry by injection by vector
– dispersal by vector (e.g. wings)
– vector-based host targeting
List some species that use invertebrate host as vectors
– Plasmodium spp, mosquitoes
– Trypanosoma brucei, Tsetse flies
– Trypanosoma cruzi, Triatomid bugs
– Leishmania spp., Sand-flies
– Babesia, Ioxdidae tick
Describe malaria
- restricted by parasite and vector distribution
- 156 named Plasmodium spp four infect humans
Where is malaria restricted to?
tropical, sub tropical, low altitude
Describe the 4 human malarial species
– 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)
Describe the varying symptom severity of malaria
– parasite species
– host immune status
- host exposure
– host age (cerebral malaria commoner in children)
Describe African Trypanosomiasis
- Sleeping Sickness
- transmitted by the tsetse fly
Describe the sleeping sickness species affecting humans and animals
– Trypanosoma brucei gambiense (TbG) (98% of cases)
– Trypanosoma brucei rhodesiense (TbR) (acute form)
Trypanosoma cruzi causes
Chaga’s disease
Describe the clinics of sleeping sickness
- 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
Describe modern treatment of African sleeping sickness
In 2009 the number reported dropped below 10 000 for the first time in 50 years: 2015, 2804 cases; in 2018, 977 cases recorded.
Describe the life history of African Trypanosomiasis
- 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
Describe antigenic variability in Trypanosomes and
Plasmodium
- 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
VSG in Tsetse fly
- 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
allelic exclusion
DNA repair mechanisms allow a new VSG to be copied into a single transcribed locus
Describe fungal diseases
- few hundred species
- more common in immunocompromised patients
- plant pathogens have great economic importance
Describe mammals’ natural defences against fungal infection
higher body temperature
Describe the various potential pathologies of fungi
– 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
Describe Candida albicans
- 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)
Describe Candida albicans polymorphism
- can exist as yeast, pseudohyphae, and hyphal forms
- hyphal form causes tissue damage and allows access to the bloodstream
Describe the diseases caused by C. albicans
- oral or vaginal candidiasis (thrush)
- skin infections in newborn (nappy rash) and burns victims
Describe systemic C. albicans
- in immunocompromised patients
- affects all organs of the body
- 30-50% mortality
Describe Trichopyton rubrum
- 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
Describe ringworm
- 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
Describe the contagion of ringworm
- human-human
- animal-human
- object-human (direct and indirect contact)
Describe Cryptococcus neoformans
- 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
Describe the life history of Cryptococcus neoformans
- ‘division of labour’ in immunocompetent host
- survival and latency
- immune deficiency triggers intracellular proliferation
- lysis: extracellular proliferation
- vomocytosis: titan cell formation
Describe Aspergillus flavus
- saprophytic soil fungus
- allergies
- aflatoxicosis
Describer Aspergillus in cancer
- 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.
Describer Aspergillus flavus allergies
- develop after repeated inhalation of spores (asthma, Aspergillosis)
- rabbits and poultry especially susceptible
Describe Aspergillus Flavus aflatoxicosis
- 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
Describe fungal plant pathogens
- primarily Ascomycota and Basidiomycota.
- biotrophs
- necrotrophs
- hemibiotrophic
- Magnaporthe oryzae
- Botrytis cinerea
- Puccinia graminis
biotrophs
utilise living tissue
necrotrophs
kill tissue to extract nutrients
hemibiotrophic
- utilise living tissue
- kill tissue to extract nutrients
Describe Magnaporthe oryzae
- Rice Blast Disease.
- > 50% world’s population relies on rice as the main source
of calories - important model for research
Describe Botrytis cinerea
- Grey Mould
- pre- and post- harvest damage.
- broad host-range (200 plant species including fruit and vegetables)
Describe Puccinia graminis
- Wheat Stem Rust
- recent emergence of race UG99.
- alternative host ‘Barberry’
Describe Wheat Stem Rust
- 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
How did we tackle Wheat Stem Rust?
- introduction of wheat resistance genes
- SR31 was the most successful derived from wheat x rye hybrid derivatives
- produced in Germany in the 1930s
Describe Ug99
- 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
Describe the likely spread of Ug99
- 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
HYSPLIT
- HYbrid Single-Particle Lagrangian Integrated Trajectory
- simulates the movement of particles using meteorological data
