Week 9: Infectious Disease

Question 1

What organisms/acellular molecules can become pathogenic to humans?

Answer 1

1. Prions
2. Viruses
3. Bacteria
4. Unicellular eukaryotic parasites
5. Metazoan parasites (helminths)

Question 2

What strategy do most systemic infections e.g. S. aureus and Adenovirus use to infect a large number of tissues around the body?

Answer 2

• These pathogens often manipulate immune cells in the body to facilitate their spread

Question 3

How does Toxoplasmosa cause systemic infection in humans?

Answer 3

• Humans ingest toxoplasmosa (A eukaryotic organism) from cat feces
• The parasite penetrates into intestinal cells, asexually reproduces in cells and then causes cell rupture
• This allows the parasite to spread through the body via the blood stream

Question 4

How does Candida cause systemic infections in humans?

Answer 4

• Candida albicans (a fungi) is a normal resident of the GI and genito-urinary tract systems
• Occasionally they can cause a systemic infection due to an epithelial infection invading into deeper tissues and eventually reaching the blood stream and then vital organ
• This systemic Candida infection is very rare and usually indicative of a weakened immune system

Question 5

How does Trichinella cause systemic infection in humans?

Answer 5

• Trichinella are a type of helminth
• Trichinella ca infect pigs due to the pigs ingesting the infected meat of rodents
• The Trichinella larvae in the rodent meat hatch in the intestines of the pig and move through the pigs body becoming systemic and forming cysts in striated muscle
• If humans consume pig with a systemic Trichinella infection and do not cook the meat sufficiently, they will ingest larvae that hatch and grow into adult worms in the intestine
• There are 2 stages of Trichinella infection in humans:
  1. Local- Enteral Phase:
• The symptoms during this adult phase may be minor and unoticible, potentially causing a mild gastroenteritis
  2. Systemic- Parenteral Phase:
• The symptoms depend on their number of larvae produced by the adult worms
• The body’s inflammatory response results in oedema, muscle pain, swelling and fatigue
• Fata systemic infections of Trichinosis involve the heart, lungs and CNS

Question 6

What is a local infection?

Answer 6

• A local infection involve local spread which is the multiplication of microorganisms in epithelial cells at the site of entry on the bodies surface e.g. skin, respiratory tract, GI tract
• Local spread takes place readily on fluid-covered mucosa
• Large areas can be infected within a few days with the shedding of the progeny to the exterior
• Incubation period is <1 week
• The main response to the local infection is the innate immune system including NK cells and IFN

Question 7

What are the components of mucous?

Answer 7

• Mucous is made up of 2 layers: a thinner inner layer that is sterile and an outer layer that is not sterile
• Mucous lies on mucosa (epithelial cells)
• Mucous is secreted by goblet cells and contains proteins called mucins (e.g. MUC5AC and MUC6)
• Mucins are secreted or remain as transmembrane proteins with their extracellular domain contributing to the inner mucous layer

Question 8

How does the epithelial barrier in the GI system prevent the attachment of enteric pathogens to the epithelial cells?

Answer 8

1. The contact of the enteric pathogen with the epithelial barrier stimulates the secretion of stored mucous from goblet cells
2. Engagement of the cell-surface mucins by pathogens initiates signalling and a consequence of this is that the mucin granules expand and surround the pathogens with fresh mucous containing antimicrobial molecules
3. If the pathogen binds to a cell surface mucin, the mucin extracellular domain is shed which releases the pathogen from the cell surface
4. The cell surface mucins also exclude the pathogen from the cell surface where it could bind the receptor by steric hindrance

Question 9

How do enteric pathogens overcome the mucus barrier?

Answer 9

1. Pathogens can penetrate the mucous barrier physically:
   - Through flagella mediated motility or enzymatic degradation of mucous
2. Avoidance of mucus by entering via microfold (M) cells which are not covered by a thick mucous layer
3. Secretion of toxins that can diffuse through the mucus and disrupt tight junctions between cells, block epithelial cell growth and disrupt mucous production
   - All of these methods allow the enteric pathogens to reach the epithelial cell surface where it can bind receptors

Question 10

How do pathogens spread rapidly across mucosal surfaces?

Answer 10

• In the upper respiratory tract, coughing and sneezing can platter infectious agents onto new areas of mucosa such as the sinuses and middle ear
• The gentle trickle of mucous down the throat during sleep may seed an infectious agent into the lower respiratory tract
• Particles and bacteria lining the nose and throat can cause irritation and sneezing which spreads the aerosal several meters

Question 11

What are the characteristics of a systemic infection?

Answer 11

• Much longer incubation period (>1 week)
• The pathogens spreads to multiple tissues
• The main recovery mechanism is the adaptive immune response

Question 12

What are some pathogens restricted to the surfaces of the body (cannot become systemic)?

Answer 12

1. Temperature:

E.g. 1: Rhinovirus

• Infections are restricted to the upper respiratory tract because the virus is temperature sensitive and only replicates between 32-35 degrees (not at the higher temperatures in the lower respiratory tract)
• The virus is dependent on this lower temperature because at higher temperatures (37) there is a much higher host antiviral response (enhanced IFNB) which restricts rhinovirus replication

E.g.2: Mycobacterium leprae:
- Is temperature dependent and thus is restricted to the nasal mucosa, skin ans superficial nerves

2. Site of Budding:
   - Can restrict viruses to the surface
   - Epithelial cells are highly polarised and many viruses that are restricted to the surface of the body are only able to bud off the cell surface from which they entered (the external surface)

E.g.1. Influenza Virus:
- Invades epithelial cells of the lung but only buds from the external surface so it cannot spread to deeper tissues

Question 13

Why do some pathogens become pathogenic?

Answer 13

1. Obligatory spread for multiplication:
   - Many microorganisms are obliged to spread systemically because they are unable to multiple at the site of initial infection (at the body surface)
   - These infections often spread via the blood stream and lymphatic system and multiply in blood vessels, lymph nodes and the spleen
   - After multiplying in these internal sites they can move to other tissues such as the lungs, kidneys and salivary glands where they can be shed
   - Only after spreading through the body are large numbers of the microorganism delivered back to the same surfaces where they infected and are shed to the exterior

Question 14

What host defences are there against invading systemic pathogens?

Answer 14

• After moving through the epithelium basement membrane, the microbes face the following defences:
  1. Tissue fluids containing anti-microbial substances e.g. antibodies and complement
  2. Local macrophages (histocytes): although some pathogens use them for vehicles for spread
  3. Local tissue structure: most tissues contain hydrated cell matrix which makes it difficult for bacteria to spread
  4. Lymphatic system: the lymphatic system will convey invading microorganisms to the immunologic defenses in the local lymph node

Question 15

Describe the pathogenesis and spread of the Measles Virus:

Answer 15

• Measles virus is an obligate systemic pathogen
  1. The site of entry: respiratory tract, there is little/no replication of the virus at the entry site
  2. The virus first infects macrophages and dendritic cells in the alveoli or epithelium
  3. The infected macrophages/dendritic cells migrate to lymphoid tissues
  4. The virus then infects lymphocytes within the lymphoid tissues which are released into the blood that causes systemic dissemination
  5. The virus then invades body surfaces from the blood, moving through blood vessles to reach surface epithelium
  6. The invasion of epithelial tissue occurs first in the respiratory tract and then on the skin
  7. Epithelial damage may contribute to the efficient transmission to the next host

Question 16

What is the prodromal phase of a disease?

Answer 16

• The prodromal phase of disease is an early set of symptoms that might indicate the start of the disease before the disease specific symptoms occur
  E.g. For measles the prodromal phase includes malaise, anorexia and cough

Question 17

How does measles virus spread so efficiently though populations?

Answer 17

• Measles virus does not undergo genetic drift or suppress virus-specific responses in hosts, rather is specialises in targeting naive hosts
• It is able to do this as its reproductive rate (the number of cases one case generates on average over the course of its infectious period) is very high being 15-30
• Measles virus can only establish endemic circulation if the naive population is of sufficient size
• This makes the measles vaccine very effective though

Question 18

Describe Syphilis and its spread through the body:

Answer 18

• Syphillis is an STI caused by the spirochete bacterium Treponema pallidum
• There are four stages of infection:

1. Primary syphilis:
   - local infection
   - a chancre develops at the site of first contact
2. Secondary syphilis:
   - due to systemic spread
   - occurs 4-10 weeks after primary infection
   - due to the local infection infecting macrophages and then spreading through the body
   - Symptoms include rash on the trunk and extremities, fever, sore throat and malaise
3. Latent Stage Syphilis:
   - The secondary phase of syphilis is followed by a latent phase of 3-30 years
   - It is thought that the bacteria persists in the body as it has a surface rich in lipids which are antigentically unreactive
4. Tertiary Syphilis:
   - After the bacteria have grown for years there will be lesions affecting various tissues such as the bones, skin, nervous tissue, heart and arteries
   - There are 3 forms: gummatous syphilis, neurosyphilis and cardiovascular syphlis
   - Without treatment 1/3 of people will develop tertiary syphlis which has a high mortality rate
   - Tertiary syphilis is not infectious

Question 19

How is syphilis treated?

Answer 19

• Penicillin is very active against T. pallidum bacteria
• Doxycycline can also work
• Before penicillin was avaliable malaria was used to treat syphilis as it causes high fevers that raised the body temperature high enough to kill the bacteria
• Although malaria kills 5% of those infected, untreated syphlilis is fatal

Question 20

What is a zoonoses?

Answer 20

A zoonoses is an infectious disease of animals that can be transmitted to humans

Question 21

How are zoonoses initially transmited to humans?

Answer 21

• There are 3 transmission routes:
  1. Direct contact (by wounds or inhalation)
  2. Indirect contact (via food e.g. eating filter feeding vertebrates or an environmental reservoir, including through intermediate hosts)
  3. Vector borne (by biting or mechanical transfer by arthropods)
• Once animal to human transmission has occurred it can be followed by direct human-to-human contact transmission when the pathogen adapts

Question 22

How does the rabies virus more through the body?

Answer 22

1. Virus (-ssRNA) enters human via animal bite
2. Virus replicates in muscle at site of bite
3. Virus infects nerve in PNS and moves towards the CNS by retrograde transport
4. The virus replicates in the dorsal root ganglion and travels up the spinal cord to the brain
5. The brain becomes infected
6. Virus travels from brain via nerves to other tissues such as the eye, kidneys and salivary glands

Question 23

How does the Hendra virus infect humans?

Answer 23

• The hendra virus (-ssRNA) is naturally harboured by fruit bats
• The virus is spread to intermediate hosts (horses) by the horses eating grass/feed infected with rat foetal tissue/fluids
• The virus can then spread from horses to human in close vicinity to the respiratory secretions of dying/recently dead Hendra virus infected horses
• It was a 60% mortality in horses and a 75% mortality in humans

Question 24

How does Borellia bacteria infect humans?

Answer 24

• Borellia bacteria is naturally harboured by rodents and is transmitted from rodents-rodents and rodent-other mammals via tick bites
• Once the bacteria is present in a human it cannot spread any further to other humans (no human-human transmission)

Question 25

How does Rickettsia (Epidemic Typhus) infect humans?

Answer 25

• Rickettsia is an obligate intracellular parasite that is restricted to an arthropod reservoir
• It can be transferred to vertebrates including humans via ticks
• Lice in crowded conditions can cause quasi human-human transmission

Question 26

What are examples of Zoonoses that once transmitted to humans mutated and then were able to spread by human-human transmission?

Answer 26

1. SARS and MERS Coronaviruses
2. Ebola
3. HIV
4. Pneumonic Plague

Question 27

How is Yersinia pestis transmitted in humans?

Answer 27

• Yersinia pestis is a bacteria that is a zoonotic pathogen that naturally occurs in wild rodents causing sylvatic plague (that is not severe)
• Fleas can spread infected blood from wild rodents to urban black rats and the bacteria has a high mortality rate in these urban rats
• Fleas can spread bacteria from infected urban black rats to humans- the bubonic plague
• The bubonic plague causes buboes at lymph nodes and it not transmitted from humans to other humans
• If humans infected with bubonic plague developed a systemic infection, the bacteria would replicate in the lungs and cause pneumonic plague which could then be spread from humans to humans via respiratory droplets

Question 28

Why did Bolivian Haemorrhagic fever emerge?

Answer 28

• First seen in Bolivia in 1962
• The spread to humans was caused by:
  1. Arenavirus within local bush mice caused a symptomless lifelong infection
  2. This virus was shed in urine and feces of the mice and could infect humans
  3. The emergence of the virus as a severe concern was caused by bush mice invading human dwellings due to DDT spraying to kill mosquitos resulting in geckos containing DDT that were then eaten by cats that would then die- with the loss of the cats the bush mice were able to invade human dwellings

Question 29

What percentage of the infectious organisms known to be pathogenic in humans are zoonotic in origin?

Answer 29

• 61%

- Helminths are particularly likely to be associated with zoonoses

Question 30

What are the characteristics of EID pathogens?

Answer 30

• Emerging infectious disease events are dominated by zoonoses (60%)
• The majority of these EIDs that are zoonotic originate in wildlife (70%) e.g. SARS, Ebola
• The incidence of zoonotic EIDs is increasing
• The increase in transmission of zoonoses from wildlife to humans is potentially due to encroachment of humans onto the natural habitate of many animals

Question 31

Why are Great Apes a common reservoir for human pathogens?

Answer 31

• Pathogens adapt closely to their host organism
• Therefore it is much more likely for a zoonotic pathogen to spread between closely related species rather than distant species
• Therefore the Great Apes which are closely related to humans are a large reservoir for human pathogens

E.g. 1. Malaria:
- The P. falciparum that infects humans likely originated from gorillas in a single cross species transmission

E.g.2. HIV:
- The human strain of HIV mainly originates from one clade of SIV in chimpanzees

Question 32

What % of organisms in the world are parasitic?

Answer 32

• 40% of known species are parasitic, with parasitism ubiquitous in some taxa and either absent or rare in others
• This is due to pressure on organisms to find the most favourable niche for their proliferation
• Many arthropods are parasitic
• Many more arthropods that are not parasitic transmit disease

Question 33

Give examples of the human pathogens transmitted by arthropods:

Answer 33

1. Viruses: arboviruses such as Dengue and Zika
2. Bacteria: Plague and Lyme disease
3. Unicellular eukaryotes: plasmodium
4. Metazoan parasites: guinea worm

Question 34

What adaptions occur in parasitic protists?

Answer 34

• Parasitic protists diverged and independently evolved 1.5-2 mya
• Parasites have a lot of potential for gene gain/loss
• When unicellular eukaryotes become parasitic, they tend to lose a number of genes as they rely on functions conducted by the host
  E.g. Microsporida: undergoes extreme gene loss
  E.g. Closest related non-parasitic relatives of Plasmodia have much larger kinomes (sets of protein kinases)

Question 35

What are the main types of diseases caused by Eukaryotic Parasites?

Answer 35

1. Protists:
   - Malaria, toxoplasmosis (apicomplexia)
   - Trypanosomiasis
   - Trichomoniasis, giardiasis (anerobic and others)
2. Metazoans (mainly helminths, some anthropods):
   - Scabies, Hookworm disease, Schistosomiasis
3. Fungi:
   - Candidiasis (yeast Candida)
   - Microsporidiosis (Microsporidia)

• Parasites can infect a wide variety of major tissues and organs

Question 36

How are parasitic infections transmitted?

Answer 36

• Most infections are acquired through:
  1. Ingestion of contaminated food/water (fecal/oral route and via tissue of intermediate host)
  2. Active skin penetration by the parasite
  3. Injection by blood-sucking insects
  4. Some are transmitted from mother to foetus

Question 37

How do extracellular parasitic protists evade the host immune responses?

Answer 37

1. Antigenic variation of surface antigen e.g. Trypanosomes (VSG genes) and Plasmodia (var genes)
2. Polymorphisms in dominant surface antigens
   e. g. Plasmodia
3. Degradation of complement/antibodies at the cell surface
   e. g. Amoebae and Leishmania

Question 38

How do intracellular parasitic protists evade the host immune response?

Answer 38

• Although intracellular pathogens are removed from direct contact with antibodies, complement and phagocytes, their antigens may be expressed at the surface of the host cell and be a target for CD8+ Effector Cells
• Survival within cells involves a variety of mechanisms to evade or inactivate harmful effects of intracellular enzymes and reactive oxygens e.g. survival of Leishamania in macrophages

Question 39

What is Malaria?

Answer 39

• A disease caused by a type of Apicomplexan protist parasite called Plasmodium falciform
• It is a poverty related disease
• There has been an emergence of chloroquinine resistance (the drug traditionally used to treat the disease)
• There is a lack of investment into finding a treatment

Question 40

What is the lifecycle of Plasmodium Falciparum?

Answer 40

1. An infected mosquito bites a human and spreads sporozoites in its saliva into the human host, the sporozoites are motile and will move through the dermis to vessels
2. Sporozoites move through Kupfer cells to enter into the liver and replicate
   - The first level of schizogony (asexual reproduction by fission occurs in the first host cell they setlle in where they form a schizont)
3. Merozoites then are released into the blood stream (within merosomes) and establish several cycles of asexual replication within the RBCs
4. Every 2-3 days a large proportion of infected RBCs will attach to blood vessel walls and rupture and release their merozoites
5. Some of these merozoites develop into gametocytes (which are the only type that an survive ingestion by the mosquito)
6. Mosquitos when biting an infected human must ingest both male and female gametocytes for the malarial life cycle to continue
7. In the mosquito gut, the gametocytes form zygotes and then ookinete (motile) and then eventually an oocyst (motile)
8. The oocyst forms on the outer lining of the stomach and generates the sporozoites
9. The sporozoites then infect the salivary gland of the mosquito
10. When a mosquito bites a human now- it can transmit sporozoites

Question 41

What do most anti-malarial drugs target?

Answer 41

• Prophylactic drugs can prevent the growth or merozoites in the liver and prevent the release of the first round
• Curative drugs interfere with asexual reproduction of merozoites within the RBCs
• Drugs can potentially block the transmission by stopping the progression of merozoites to gametocytes (not curative, but will block transmission)

Question 42

In detail, how to merozoites invade erythrocytes?

Answer 42

1. Attachment via a ligand-receptor interaction
2. The parasite senses the interaction and reorients its cytoskeleton so that the apical complex faces the RBC
3. The parasite then forms a tight junction with the RBC and releases the contents of its Rhops and micronemes (gland-like organelles which modify the RBC membrane)
4. The membrane invaginates and forms a vacuole around the invading plasmodium
5. The parasite moves inwards through the activity of an actinomyosin motor
6. The parasite then sheds its outer coat and fully enters the RBC
7. Completion of the parasitophorous vacuole

Question 43

How do Plasmodium parasites modify host RBCs?

Answer 43

1. Knobs: the parasite exports proteins to the surface of the RBC that form knobs and mediate the attachment of the parasite to the endothlium
2. Cytoadhesion occurs
3. Activates and hijacks the MAPK pathway

Question 44

How is the developmental fate of merozoites (to form shizont, male gametocyte or female gametocyte) determined?

Answer 44

• The merozoite is haploid and when it multiplies in the RBCs, its commitment to fate is already determined (it was determined in the schizont)

Question 45

What are the features of apicomplexan parasites?

Answer 45

1. Polar ring
2. Microneme and Rhoptry
3. Dense granules
4. Plastids called Apicoplasts which are non-photosynthetic plastids
   - The plastid has similar DNA to chloroplasts and has 4 membranes (indicating it underwent 2 successive events of endosymbiosis)

Question 46

How did Apicomplexans potentially evolve?

Answer 46

• Apicomplexans are very similar to both toxoplasmosa and colpodellas
• Colpodellas latch into larger parasites and suck out their cytoplasm
• Colpodella is a potential ancestor to intracellular apicomplexans like malaria

Question 47

What is Cryptosporidiosis?

Answer 47

• A disease caused by Cryptosporidium- another apicomplexan protozoan
• Major cause of waterborne diarrhoea
• Has a sexual cycle in the vertebrate (no insect vector)
• Major problem in immunocomprimised people

Question 48

What is Theileria?

Answer 48

• Theleria is an apicomplexan protozoan that infects cattle
• Transmitted by ticks
• It invades leukocytes and triggers proliferation of host cells in synchrony with its own replication which causes a Lymphoma-like disease
• Prevents apoptosis of its host during its proliferative phase (by interfering with NF-kB signalling)

Question 49

What are kinetoplastids?

Answer 49

• Flagellated protists, some free living, many parasitic
• Parasitic species are transmitted by insects
• Defined by the presence of the kinetoplast (a DNA-containing region of the mitochondria)
• Major parasitic kinetoplastids include:
  1. Trypanosoma brucei (african sleeping sickness)
  2. Trypanosoma cruzi (Chaga’s disease)
  3. Leishmania

Question 50

What is Trypanosoma brucei and what does it cause?

Answer 50

• Trypanosoma brucei is a kinetoplastid transmitted by Tsetse flies
• It causes Human African Sleeping Sickness
• These protists live in the blood stream and later infect the brain
• It also infects domestic lifestock causing Nagana (most wild animals are resistant)
• The lifespan of trypanosoma brucei is:

1. Tsetse flies take a blood meal and from host and inject metacyclic trypomastigotes
2. The trypomastigotes multiply by binary fission
3. The trypomastigotes remain in the blood and can be ingested by different Tsetse files that feed on the host
4. They transform into procyclic trypomastigotes which multiply in the fly

Question 51

What is the kinetoplast?

Answer 51

• The kinetoplast is a disk-shaped mass of circular DNA inside a large mitochondria that contains many copies of the mitochondrial genome
• It is made up of maxicircles and minicircles
• Maxicircles encode typical mitochondrial gene products: some of these protein coding genes are encrypted and must undergo post transcriptional modifications via RNA editing (involving the insertion and deletion of different uracil residues)
• The genetic information for editing these encrypted mRNAs is provided by gRNAs that are mostly encoded by minicircles

Question 52

What is antigenic variation?

Answer 52

• Upon infection, the parasite proliferates, and his results in an immune response against it
• This results in a drop in parasite numbers
• A small proportion of the parasites will then express a different surface glycoprotein via antigenic variation, which allows this population to proliferate (as the original adaptive immune response does not recognise this variant)
• The adaptive immune response then develops antibodies against this new variant and the parasite population decreases
• Antigenic switching occurs again

Question 53

How do Trypanosomes undertake antigenic variation?

Answer 53

• Trypanosomes have a variant surface glycoprotein (VSP) coat
• It is the VSP (not the ISP) that antibodies are developed against and bind to, thus they are switched periodically
• The genome of trypanosomes contains large, intermediate and mini chromosomes
• The minichromosomes have the VSG genes
• Recombinational switching occurs when a different VSG will replace another at the bloodstream expression site (BES)

Question 54

What is the lifespan of Trypanosoma cruzi? What does it cause?

Answer 54

1. Trypanosoma cruzi is a kinetoplast that is transmitted by the reduviid bug by its feces that it deposits on the skin when it bites the host
2. When the reduviid bug bites the human host, it deposts its feces which contain metacylic trypomastigotes in its feces
3. When the bite wound is scratched, the trypomastigotes enter the host
4. The trypomastigotes enter into cells and transform into amastigotes which divide by binary fission
5. The amastigotes are able to systemically infect the host and reach any organ
6. The amastigotes then transform into trypomastigotes and burst out of cells and into the blood stream
7. Trypomastigotes can be ingested by the reduviid bug when it takes a blood meal and will undergo development within the bug

• Trypanosoma crucei causes Chaga’s disease which can result in heart or intestinal failure

Question 55

What are Leishmaniases?

Answer 55

• Diseases caused by the parasitic prostists Leishmania
• These parasites infect various species and can affect various parts of the body (can be cutaneous, muco-cutaneous or visceral)
• They are transmitted through blood sucking sand flies

Question 56

What is the lifecycle of Leishmaniases?

Answer 56

1. Sandfly takes a blood meal and injects a promastigote into the skin
2. Promastigotes are phagocytosed by macrophages
3. Inside macrophages, promastigotes transform into amastigotes
4. Amastigotes multiply in cells (including macrophages) and infect various tissues
5. When the sandfly takes another blood meal, it ingests macrophages that are infected with amastigotes
6. Within the sand fly, the amastigotes transform into promastigotes again (flaggelated, infectious form)

Question 57

Describe the genome of Leishmania:

Answer 57

• Leishmania have chromosomes which are only encoded on one strand
• All genes are transcribed by one RNA molecule
• Translation of the splice leader (SL) allows polycistronic transcripts to be generated by moving the SL 5’ cap onto gne transcripts which allow multiple RNAs to be generated from 1 DNA sequence

Question 58

Give examples of Anaerobic Protists:

Answer 58

1. Trichomonas vaginalis:
   - Lives in vagina and male urethra and prostate
   - Common STD (only seen in humans)
   - The trophozoite form is oval and has 5 flagella and has an axostyle for tissue attachment
   - No cyst form
   - Lacks mitochondria byt obtains energy via glycolysis in cytoplasm followed by conversion of pyruvate and malate in the hydrogenosome
   - As they hydrogenosome is unique to these pathogens and other anerobes it can be targeted with metronidazole
   - Trichomonas vaginalis has adherence factors that allow it to adhere to the vaginal epithelial cells
   - The infection is frequently symptomatic in women (increases risk of HIV transmission also) but asymptomatic in men
2. Giardia lambila:
   - Intestinal pathogen
   - Common
   - Transmitted in water
   - Infection occurs by ingestion of cysts in contaminated water, food or by fecal oral route
   - The cysts burst in the intestine and form trophozoites (actively swimming form) in the intestine which divide by binary fission and then form more cysts
   - The cyst can then be passed in feces and are a source of new infections
3. Entamoeba histolytica:
   - Intestinal pathogen (but can also invade blood and liver)
   - Common
   - Transmitted in water
   - Acquired by ingestion of cysts in fecally contaminated food, water or hands
   - Trophozoites enter the intestines and multiply by binary fission and form cysts which are passed in the feces
   - In many cases the trophozoites remain confined to the intestinal lumen but in other patients they may invade the blood stream and other tissues such as the liver
   - Cysts can survive for weeks in the external environment

Question 59

What are the 3 main groups of important helminth parasites in humans?

Answer 59

1. Tapeworms (Cestoda):
   - Flattened bodies with muscular suckers and/or hooks for attachment to host
   - Have indirect life cycles
2. Flukes (Trematoda)
   e. g. Schistosoma
   - Flattened bodies with muscular suckers and/or hooks for attachment to host
   - Have indirect life cycles:
3. Cercariae are released by snails into the water and are free swimming and infectious
4. The Cercariae penterate the skin of human hosts and lose their tails and enter the blood stream where they mature into adults
5. The adult worms produce eggs that are produced in the gut and excreted by urine or feces
6. When the eggs enter water they can hatch into miracadia and infect snails
7. Within the snails they replicate and produce sporocytes from which cercariae are generated
8. Roundworms (Nematoda)
   e. g. Hookworms
   - Long cylindrical bodies that lack specialised attachment organs
   - Have direct life cycles:
9. Eggs are passed in the stool and larvae hatch
10. The larvae grow and become infectious
11. They penetrate the skin and are carried through blood to the lungs, ascend to the pharynx, are swallowed and reach the small intestine
12. The larvae mature into adult worms in the small intestine and then produce eggs that are passed in stol

Question 60

What is schnistomasisis:

Answer 60

• A disease caused by Trematoda helminths called schistosoma
• It is different to other helminth diseases as much of the pathogenesis is due to eggs and most of the pathology is caused by the host immune response
• Has 3 phases:
  1. Migratory phase: cercariae penetrate and migrate through skin
  2. Acute phase: coincident with egg release and characterised by allergic response
  3. Chonic phase: occurs in response to cumulative deposition of eggs in tissues such as the liver
• Eggs become surrounded by inflammatory cells which can cause disease such as liver fibrosis