parasites

key points to remember

• Who is affected?

• How do we know they are infected?

• What happens when infected?

• How can we treat?

• How can we prevent?

can answer by knowing the life cycle of the parasite

host parasite relationships

symbiosis

• organism 1: essential

• organism 2: essential

mutualism:

• organism 1: benefit

• organism 2: benefit

commensalism:

• organism 1: benefit

• organism 2: no benefit

disease (or parasitic)

• organism 1: benefit

• organism 2: harm

some can be a commensulate or cause disease. the development od disease depends on the hosts immune system

host-parasite relationships: reproduction

genetics:

• asexual: direct replication

• sexual: exchange if genetic material

protozoans:

• all are asexual, some are sexual

metazoans:

• some are asexual, all are sexual

definitive host

SEXUAL; a host that harbours adult or sexual stage

intermediate host

ASEXUAL; a host that harbours juvenile or asexual stages

reservoir host

NON-HUMAN; a non-human host that harbours same stages as humans; serves as reservoir for the parasite

incidental host

DEAD-END; a host that is not the normal part of the life cycle (i.e. transmission will not continue)

host vs vector

must be a living organism

Host:

• Where does the parasite live? (as an adult or juvenile)

• (Definitive, Intermediate, Reservoir, Incidental)

vector

• How does the parasite move from one host to another?

• Biological, Mechanical

eg

• Biological vector of MALARIA: Female Anopheles mosquito

versus

• Mechanical vector of Entamoeba histolytica: housefly

• No development or growth of E. histolytica in houseflies, just passively carried.

How do parasites infect (get into the body)

• Skin (intact or broken)

• Gut

• Lungs

• Eyes, nose, mouth

• Vagina

• Any external surface/barrier

how do parasites cause disease?

Overall Pathological Mechanisms:

a. Toxic parasite products

b. Mechanical tissue damage

c. Immunopathology

d. Immune evasion

Remember that they can cause disease through more than one of these mechanisms

Trypanosoma brucei: life cycle

1. tsete fly take blood meal

2. injected metacyclic trypomastigites transform into bloodstream trypomastigotes whihc are carried to otehr sites

3. trypomastigites multiply by binary fission in various bodily fluids

4. diagnositic stage: circulating trypomastigotes in blood duringa cute phase

   1. usually undetectable in latent stage

5. tsete fly eats blood from infected person

6. bloodstream trypomastigotes transform into procyclic trypomastigites in vector midgut. multiply by binary fissin.

7. procyclic trypomastigites leva emidgyr abd transform into epimastigotes

8. multiply in salivary gland, transform into metacyclc trypomastigotes, ready to infect

two variants, west and east

trypanosoma brucei: epidemeology

• Targeted by WHO for elimination by 2020.

• 92% of infections are West (T. brucei gambiense).

• 1998: ~40 000 cases reported but estimated 300,000 undiagnosed.

• 2009: first time below 10,000.

• 2021: 750

• 61% of cases in D.R. of Congo

trypanosoma brucei: symptoms at both stages

Hemolymphatic stage

• Nodule or chancre at bite site

• Fever

• Enlarged lymph nodes

CNS stage

• Vacant expression

• Sleeping in day

• Insomnia

• Seizures

• Coma

• Death

T. brucei gambiense transition takes month (west)

T. brucei rhodesiense transition takes weeks (east)

trypanosoma brucei: diagnosis

• Lymph Node Aspiration for Diagnosis of Trypanosomiasis

• Lumbar Puncture for Diagnosis of

• wrights stain: can see parasite, distinct shape

trypanosoma brucei: disease

• African Trypanosomiasis

• african sleeping sickness

pathological mechanism of trypanosoma brucei

Antigenic variation

• T. brucei expresses ONE protein on its surface.

• Variable surface glycoprotein (VSG)

• It can switch this protein so that it evades immune recognition.

therefore cannot produce a vaccine for it

trypanosoma brucei treatment

• Fexinidazole (oral)

(CNS for T.b.g.)

• NECT or fexinidazole

trypanosoma cruzi: life cycle

1. triatomine bug takes blood meal

2. metacyclic trypomastogites penetrate various cells at bite wound site. inside cells transfomr into amastigotes

3. amastigites multiply by binary fission on cells of infected tissues

4. intracellular amastigites transform into trypomastigotes then burst out of cell and into bloodstream

   1. can infect ourher cells and transform amastigotes in new infection sites. can result in clinical manifestations

5. triatoamine bug take sblood meal

6. epimastigites in midgut, multiply

7. metacyclic trypamastigites in hindgut

8. metacyclic tryomastigites in hindgut can be transferred when bug takes blood meal as bug defecates into wound when eating

trypanosoma cruzei: disease

chagas disease:

• spread by reduviid bugs (kissing bugs) that defecate into wound when eating

trypanosoma cruzei: epidemeology

endemic to south america, present in west europe, north america (current estimate is at 280,000 in the US), nz/aus, japan

8 million infected

transmission of trypanosoma cruzi

• vector

• congenital

• blood bank

• oral (rare)

bites at night, comes out of walls of mud huts, can help rpevent by using different building materials, bed nets

trypanosoma cruzi parasitemia

acute phase:

• ten days, polyclonal lymphocyte proliferation

indeterminate and chronic phase

• month-years

• parasitemia detectable by xenodiagnosis or PCR

• immunosuppression

trypanosoma cruzi: Romaña’s Sign

Acute stage:

• parasites in blood

• fever

• swelling at site of entrance (Romaña’s sign)

trypanosoma cruzi: chronic manifestation

(20-30% develop 10-20 years after infection)

• mega heart (Chagasic Megacardia, can develop Apical

Aneurysm)

• mega colon (Chagasic Megacolon)

• mega oesophogus

trypanosoma cruzi: diagnosis

acute:

• blood smear, distinct C shape, can see kinetoplast and flagellum

• can used lymph node aspiration and smear to see Amastigotes and Trypomastigotes, but may also be difficult in chronic phase

chronic

• Serology (antibodies)

• PCR

• xenodiagnosis (feed uninfected bugs on infected persons blood, wait and see if bugs become infected)

Diagnosis of chronic Chagas disease is made after consideration of the patient’s clinical findings, as well as by the likelihood of being infected, such as having lived in a country where Chagas disease is common

Chagas Disease: A Silent Emergency

due to antigenic variation, (can change surface coating/very confusing surface coating) difficult to mount immune response, therefore vaccine doesn't work

 

Prevention is important, method is bite of bug, therefore if bug come from mud wall, thacthed walls, can provide diffirent housing, pesticides. If come from blood bank, can throw out blood to prevent furtehr infection

 

Treatments best for acute phase, not so good for chronic as parasite has expanded into tissues, hard to get.

Treatments have such sugnificant side effects that once 50yrs old, have to weigh benefits of treatment side effect and parasite side effects

Treatment does not fix damage, only prevent more damage

trypanosoma cruzi: treatment

• Nifurtimox

• Benznidazole

no vaccine due to antigenic variation

trypanosomes

t. brucei has less people at risk as less people infected, hopefully eridicated in next 5 years

Both treated by dangerous drugs that must balance risk of drug with risk if parasite before treating, though t. brucei have new oral drug that is better

Trichomonas vaginalis: life cycle

imple life ccycle: doesn't infect into any cells, transmitted from person to person via sexual intercourse

• Survives mostly on mucosal surfaces, divides by binary fission, no sexual reproductio

• multiplies by longitudinal binary fission

trichomonas vaginalis epidemeology

can be found everywhere in the world, all age groups, women and men: though tehre are preferential places for parasite

is sexually transmitted

Trichomonas vaginalis trophozoites

females:

• (10-50% asymptomatic)

• vaginitis

• discharge

• irritation, pain

• long term…

mostly diagnosed in female, mostly because while 10-50% are asymptomatic, the rest are symptomatic

• Suffer from vaginitis: discharge, irriation, pain

Long term: by having immune response trying to cntrol infection may have long term conseuqence ot fertility and reproduction

males:

• mostly

asymptomatic

trichomonas vaginalis: disease

vaginitis

trichomonas vaginalis diagnosis

giemsa stain of vaginal smear

trichomonas vaginalis: treatment

 treat with metronidazole,

• prevent with protective sex, notfiing partner etc

Giardia lamblia: disease

giardia

Giardia lamblia: lifestyle

 primarily faecal-oral, live in faecal are trophozoites but cannot survie in environemnt. Cyst can exits for longer

 

Both trophozoite and cyst are infective, but since cyst exits for longer, more common infection method

 

Doe not infect cell, but stays outsid ein gut

Giardia lamblia: scanning electron micrograph

has tear drop shape, multiple flagella and suction disc to stick to villi of small

when tehre is a lot there, immune system has large reaction, chaniges physiology, intestine wall

Giardia lamblia: epidemeology

world wide:

spread:

• water-bourne

• food less common

• person-person in early childhood centres

usually srpead through contanimated water (cysts) but also human to human, normally early childhood centres (creshe)

nz has higher incidence of giardiasis than other developed countries, though to be due to high farming, but actually was person to person spread. 

• Improving hygeine, handwashing, nappy handling in early chidl hood centres were where coming from

giardia lamblia: clinical picture

infected:

• asymptomatic (2/3 cases)

can be commensle, can live and benefit wothout harmt o host (2/3 cases asymtptomatic)

• symptomatic (no IgA)

Symptomatic people are so as don’t secreted IgA into gut, tehrefore cannot manage parasite, cause explosion of parasites

giardia lamblia: clinical picture symptoms

• malabsorbtion

• diarrhea

sudden, explosive, greasy, smelly (1-2 weeks later)

• gas & cramping

symptoms can resolve in 1-4 weeks

Giardia lamblia trophozoites diagnosis

usually diagnose thru faecal smaer.

• Has flagella, 2 nuclei, ready to undergo cell division

can also see with trichrome stain: teardrop shape

• Vets use snap test, to test giardia in faeces, is rapid test

Giardia lamblia: treatment

symptoms will resolve with time but treat to help symptoms

• metronidazole

prevention is easy with hygeine measures to ensure no transmission of cysts in faeces, trophozoite

Entamoeba histolytica

 

  does not have flagellum, is amoeba so amorphic

Two life cycle stages: trophozoitic (free living form tjhat can divide) or cyst (when want to exist outside host)

 

Can be passed thru faeces and reinfect

Entamoeba histolytica trophozoites: blood smear

 red dots are red blood cells, as e. histolytica likes ot eat blood

Entamoeba histolytica: epidemeology

world wide spread, but much more common in tropical areas,

Generally spread thru food

• causes ~50,000 deaths/year

entamoeba histolytica disease

amoebic colitis

“Shirt button” lesions of amoebic colitis

it doesn’t infect cells but damages intestion linig (shirt button lesions)

Damages cells directly from outside to destroy epithelial layer because wants to cause bleeding to eat

tehrefore symptoms:

• If symptomatic, can have bloody diarrhoea, complications incl haemorrhage, or tissue abcesses in liver, brain, lungs(caused by immuen system trying to kill parasite)

•  can have low level of infection and be asymptomiatic, immune system can overcome it

Flask-like ulcers of amoebic colon disease

 entamoeba are in bottom of ulcer causing problems

E. histolytica trophozoites invading colon mucosa (recognition)

  can be recognised by eye looking nuclei (one of diagnostic features for this)

entamoeba histolytica: abscess

common in liver, lung, sometime brain

•   lots of this is immune driven by also release digestive enzymes to eat and create abcess

Entamoeba histolytica diagnosis

can see cyst in faecal smears

see trophozoite in trichrome stain

entamoeba histolytic treatment

treatment also with metronidazole 

Prevention is by hygeince, esp with preparation of fruit

Sporozoa (Apicomplexa)

 apicomplexa so called for very special organelle that allows them to infect into cells

 Go thru sexual phase and asexual in one hsot

sporogony (sexual)

• gametocyte—> gamete→ zygote→ oocyst→sporozoite

schizogony (asexual)

• sporozoite→ trophozoite → schizont→merozoite

Cryptosporidium lifecycle

asexual and sexual stages in the same host

 is ingested then lives in gut, in humans goes thru both asexual and sexual stages

Exits body, gets into water

Usually transmissiion thru contanimated water

Cryptosporidium Sporozoites

(released from cysts by trypsin/bile/37 C)

  when oocyst is ingested, brekas open and sphorcyte come out, is ifectius stage can infect epitehlium cells

Cryptosporidium in Colon Biopsy

form ring/butthole shape

Cryptosporidium EM

epithelial cell attachment

Cryptosporidium epidemeology

 found world-wide

associated with water,  not only drinking but recreational (water reservoirs, swimming pools)

•   common caue of diarrhoea outbreak

Is zoonotic: aniamls are soruce that infects humans, very little host specificity

• nz has higher incidence than other developed coutnries (highly zoonotic: due to animal contanminatin of drinking water)

Cryptosporidium treatment and symptoms

Immunocompetent:

• benign, self-limiting diarrhear explosive onset, very watery (5-14 days)

• no need to treat

Immunocompromised:

• unremitting, persistent diarrhea, abdominal pain, weight loss, mortality

• cannot control parasite, must treat

Cryptosporidium diagnosis

Diagnosis is faecal smear

Prevention again is hygiene, more so at organisational level to ensure water sources are clean

Toxoplasma gondii life cycle

 cat is definitive host:sexual stage

Cat has oocysts in faeces if ingested by pretty much any other animal, becomes infectied

 

When infected, forms cysts.

Because infected into cells, can get anywhere (brain, etc) but preferes muscle

 

Cat get from eating tissue cysts in animal it eats

 

Cat only gets cysts in gut where forms oocysts

Toxoplasma gondii transmission

 transmission can be congenital (mother to child),

blood trnasfusions,

ingestion of oocysts (faecal-oral)

infected meats

toxoplasma gondii: epidemeology

exist world wide prevalence os ~30%, but some areas much higher

 

Most common protozoan parasite in the wolrd (~30%)

Toxoplasma sporogony in cat intestine

can become infected very ealry in life and remain infected for life

• Difficult to show demonstration of parasite for diagnosis, so use serology instead

 hard to find parasite itself as live in tissue, so use serology to look to see if antibodies present

• In france, most common transmission from raw meat

• Central america most common from cats and climate allow oocysts to survive longer

Toxoplasma gondii: immunity

 presents differently for imme adn non-immune host.

 in non-immune host

• After first infection, is continued infection as parasite hidden away, but enough immunity to control parasite, enough so that if reexposed, can kill parasite

immune host

• control of infection

• extracelkular parasites killed

in immunicomprimised host

• If immunocomprise,d cannot control parasite anymore. Issue with controlling parasite already in body

• If mother is non-immune host, foetus can become infected and can cause significant damage and cause birth defects

  If mother immune, imunitu protects foetus.

 

HIV+ Person: Toxoplasma Encephalitis

common for cysts to be in brain,

• in HIV+ person is immunocomprimised: where cyst become activated in brain, cause encephalitis

• cyst may be able to alter nuerology, dopamine levels in brain

Toxoplasma gondii diagnosis

diagnosis:

• serology, look for antibodies as evidence of immune response/exsposure

 

Prevention: cooking meat fully so cysts are killed

• Control cats so that cat do not get infecting (keep from eating wild birds, rats etc)

• Wash hands esp if dealing with cats

 

Treatment: if needed

• Use pyrimethamine, often reserved for cases when essential to clear parasite because not suffiencent immunological control

Plasmodium spp disease

malaria

Plasmodium spp risk

3 leading cause of death - half of worlds population is at trisk at becoing infected

• If put all cancers together, are 3rd

Plasmodium spp life cycle

mozzie: host and vector, responsible for transmitted disease

• Life cycle cycles through humans and mozzie

human stage

• human stages important for how disease manifest and can be control - vaccine etc

key stages of Plasmodium spp life cycle

• 1st: starts when mozzie eat blood and inject sphorzoyte into blood, whhc then goes ot target liver, infect liver cells then goes to blood and reproduction

in liver, transforms to trophozoite, then replciates forms schizont, which ruptures and infects blood

• One sphrozoite takes six days to replciate enough to go from 1--> 40,000, and go into blood

infects red blood cell, multiplies and becomes schizont, ruptures and infects more blood cells. This cycle can continue indefinetly

• Depedning on species, take 36-48 hrs, goes from 1 parasite to 8-24

at some point, once infect blood cel, triggers to become gametocyte, which is triggered to become distinctly female or male

• Picked up by mozzie, undergoes sexual reproduction in mozzie

• Asexual phase in humans

plasmodium sporozoites

thin, small parasite, infect liver cell

Plasmodium falciparum early trophozoites (rings)

 trophozoite, often called ring stage: chromotin dot (with dna), has darker ring around it

• Diagnostic for this form

• take over red blood cells, multiply inside forming schizont, which later bursts and releases parasites

plasmodium spp. transmission

transmitted only by female anopheles mosquito that eats blood and support development of parasite

plasmodium spp. epidemeology

 primarily in tropical regions (must have particular mozzie and support life cycle)

• half the world at risk

  • ~300 million cases/yr

  • 4 species of Plasmodium that cause disease in humans

• >400,000 deaths (2018)

  • 67% of deaths in children <5 y.o.

Plasmodium species characteristics

P. falciparum

• causes the most deaths

• high drug resistance;

• 90% of countries with malaria

P. vivax and ovale

• relapses are common (within 2-4 years)

• more common in Asia than Africa

• p. Vivax and p. ovale act very similar so can be grouped together, but look distinct under microscope

P. malariae

• uncommon

Malaria deaths over time (1980-2010)

 in this period, rapid development of drug resistance. Had one drug thsat worked for long time, but not anymore

2005 new drug was developed, decreased number of deaths

Endemic versus epidemic areas

when people get and how often different for different areas, not evenly spread

Hyperendemic:

• occurs year round

• in hyperendemic areas immune system develops partial immunity allows for control to some extentm as get older less likely to die from it. People without partialm immunity are children or people who come from other places who don’t have immunity

Hypoendemic:

• get episodes/epidemics, periods of higher incidence (may be relating to seasons, when is standing water so mozzie can breed and trnasmit parasite

• In hypoendemic area,s may not develop any immunity, mortality in all age groups

plasmodium spp. presentation

how presents I human depends on stage of life cycle

major symptoms:

• fever followed by chills (97%)

• headache (94%)

relapsing fever

• P. vivax/ovale = 48 hours

• P. malariae = 72 hours

• P. falciparum = 36-48 hours

uncomplicated vs complicated malaria sysmtoms

uncomplicated

• symptoms

• eventual recovery

• partial immunity

complicated

• specially with P. falciparum

• serious organ failure

• cerebral malaria (coma, loss of consciousness, seizures)

Distinguishing Features of Malaria Species

P/ falciparum

• ring stage

multiple rings in red blood cells, “headphones”

• female gametocyte

• male gametocyte

banana shaped gametocytes

plasmodium falciparum. pathological mechanisms

red blood cell (RBC) becomes “sticky” (Pf)

• RBC stick together and form “rosettes”

• RBC bind blood vessel wall; sequestration

antigenic variation (Pf esp.)

• RBC have P. falciparum erythrocyte membrane protein-1 (PfEMP-1) on surface.

• PfEMP-1 has antigenic variation

fever (all species)

• When infected RBC rupture to release merozoite, “toxins” are released.

• Induces TNF-𝝰 which causes fever.

Distribution of Drug Resistant P. falciparum

worldwide across teh equator

• drug resistance big problem 1980s-2000s

  Ranges of drugs were used but over time resistantance developed to oral drugs

previous treatments

• chloroquine

• primaquine

• mefloquine

• doxycycline

• atovaquone and proguanii

malaria and coartem

• Coartum was dual acting, so parasite couldn't circumbvent - combination therapy

Combines artemether with lumefantrine

• Provide orally avaliable dose that very efficent at parasite destruction

• 6 tablet 2x per day, 3 days, clear parasites

thought to decrease in death by new combination therapys that clear parasite and less likely to induce drug resistence

malarial prevention

preventation also becoming more common.

bed nets

insect cotnrol

• More prevalent biting at dusk-night, bet nets for sleep is good

prophylaxis

• Prophalayix reserved more for travellers coming in

malaria vaccine

had to find which stage to target (mosquito, RBC, liver)

• vaccine look at not prevent infeciton, but reduce severe disease

• pilot studies in malawi, ghana, kenya

  Reduction in severe disease, prevent further deatsh of children

dracunculus

• causes dracunculiasis or Guinea worm infection

• from ingestion of infected cyclops (tiny crustacean) in water

trichinella spiralis

• causes trichinosis

• source: ingestion of uncooked carnivore or pork meat

wucheria bancrofti

• causes lymphatic filariasis (elephantiasis)

• transmitted by mosquito

Wuchereria bancrofti life cycle

mozzie=both vector and host

When eats blood, injects larvae into blood stream

Larvae mature into adutls that live in lymphatics

Adults produce progeny (live microfilarae worms) into blood

 

Picked up by mozzie, develop in mozzie into different larval stages, put back into host when eat blood

 

Human=definitive host

Mozzie=intermediate host

lymphatic filariasis: life cycle diagram

• larvae

• adults

• microfilariae(MF)

 microfilarae: very small, during daytime go to ahng out in lung. At nigth, go into peripheral circulation where mozzie can pick it up

• Adults always in lymphatics

• Important for manifestation and diagnosis of disease

distribution of lymphatic filariasis

 only some places, depend s of where mozzie ar einfected and transmitting

• Mostly in southeast asis and africa, not much elsewhere

worldwide: 51 million infected (863 million at risk)

• W. bancrofti causes 90% of cases

Wucheria bancrofti sympotoms

manifestiations of disease depend on life stage, where is located.

Microfilare in blood at night, cause night fever, chills, sweats fur to immune response

• muscle pain, swollen lymph nodes (bc activated immune system)

wucheria bancrofti diagnosis

Diagnosis is looking at microfilarium in blood smear (must do at night, as thats when are found in blood)

distinct sheathed microfilarium in peripheral blood

• looks like a worm

Cause adutls in lymphatics, very hard to get

• but Can also use serology

lymphatic filariasis: elephantiasis symptoms

 adult worm cause lymphatic filariasis: leads to elephantantiasis

• Obstruct fluid flow as are located in lymphatics, causes edema, typically in lower extremities

Over longer period of time, elephantiasis occurs

lymphatic filariasis: preventing secondary infections

adults inlymphatics supress immune cells, immuen cells cannot control parasites

• As a result, in lower extremities, if have barrier break and bacteria infection, immune cells cannot control, causes significant issue.

Overtime get clearnace of infections, but overtime get thickinging of skin, scarring

wucheria bancrofti treatment

diethyl carbamazine (DEC)

WHO strategy to stop spread (as biting only occurs at night, can sue bed nets to prevent transmission

• aim to stop spread

• alleviate suffering

• over corse of 2000-2018, dramatic reduction in prevalence in central/equatorial africa and south east asia

Dracunculus mediensis life cycle

one of easiest infections to prevent

 

Two key host: human as definitive host (Also others but focus on huma)

Copepod are intermediate host

Become infected by drinking water cotaining these tin infected crustatceans

• When ingested, larvae can escape through gut and spend year migrating until get to lower extremities

• For most nematodes, females much larger than males (make fertilise female, then die shortly after)

Female migrate to feet etc, extend through skin and release larvae into water.

• Year long cycle

• Travel is not nessarily through blood

Dracunculus mediensis transmission

 must be contact between human foot and water for release 

• Tends to occur during rainy period typically aligned with harvest season etc

Large economic burden as people have sores on lower extremitites during thos time

drancunculiasis prevalence

• 4 cases to July 2024

• 14 cases in 2021

these cases in very specific areas, likely due to civil unrest that mean has remained

• CDC believe will be eradicated very soon