Protozoa as Human Parasites

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Microbiology @ Leicester: Microbiology Notes: Protozoa Updated:

October 19, 2004

 

 

Protozoa as Human Parasites

Taxonomy:

Kingdom: Protista

Phylum: Subphylum: Genera:

Sarcomastigophora Mastigophora (mastigo = whip = flagellates)

Trypanosoma, Leishmania, Giardia, Trichomonas

Sarcodina (amoebae) Entamoeba, Naegleria, Acanthamoeba

Apicomplexa Plasmodium, Toxoplasma, Cryptosporidium, Isospora

Ciliophora Balantidium

 

Ecological Niches in the Human Body:

 

1. Skin: Leishmania

2. Eye: Acanthamoeba

3. Mouth: Amoebae and flagellates (usually non-pathogenic)

4. Gut: Giardia, Entamoeba (and invasion to liver),

 

Cryptosporidium, Isospora, Balantidium

5. G.U. tract: Trichomonas

6. Bloodstream: Plasmodium, Trypanosoma

7. Spleen: Leishmania

8. Liver: Leishmania, Entamoeba

9. Muscle: Trypanosoma cruzi

10. CNS: Trypanosoma, Naegleria, Toxoplasma, Plasmodium

 

 

 

 

 

 

The Gut:

Entamoeba histolytica:

Amoebiasis - death and illness due to dysentery and liver abcess.

Worldwide distribution. Estimated 40 million develop intestinal

disease or liver abcess annually; 40,000 die from amoebiasis annually.

Human is definitive host. Simple lifecycle:

 

Ingestion of cysts in sewage contaminated water or on contaminated

fruit, vegetables etc.; excystation in distal small intestine and

colon; trophozoites feed and multiply and may invade liver via colonic

mucosa; cysts pass out with faeces.

 

Giardia lamblia:

Less harmful, but chronic damage to intestinal wall can lead to

malabsorption syndrome . Similar lifecycle, but reservoir hosts may

play role in transmission.

 

Cryptosporidium parvum:

Severe and life-threatening diarrhoea in AIDS patients. Worldwide

distribution. Zoonosis. Coccidian lifecycle:

 

Oocysts are ingested which hatch in the intestine into sporozoites.

These invade cells; 2 asexual generations, then gamete formation and

production of oocyst containing 4 sporozoites; oocysts pass out with

faeces. Danger from sewage contaminated water supplies - have been

recent outbreaks in UK. Video

Human infection seen in 1-4 % of patients with diarrhoea in developed

countries and up to 16% in less developed countries.

Most common in children; immunocompetent adults seem to be immune, but

in those who are immunodeficiency in any way, intense infections may

develop. Among AIDS patients 3- 4% prevalence reported in USA and over

50% in Africa and Haiti.

 

Isospora belli:

Coccidian - lifecycle similar to Cryptosporidium. Important in AIDS

patients, particularly common in Haitian and African AIDS patients.

 

Balantidium coli:

Ciliate; similar lifecycle to E. histolytica with transmission by

cysts. Zoonotic infection acquired from pigs. May invade and cause

ulceration of colon.

 

The Bloodstream:

Plasmodium falciparum:

(Also P.vivax, P.malariae, P.ovale - cause less severe forms of

malaria). Malaria - estimated 40% of world's population at risk; 10%

severe risk. Major killer of children in tropical Africa. Tropics and

subtropics - Africa, Asia and South America. Human is definitive host.

Transmitted by mosquitoes - Anopheles. Lifecycle:

 

Mosquito (female) inoculates sporozoites during feeding; invade first

hepatocytes in liver and then red blood cells; cycles of schizogony

inside rbc's, rupture and reinvasion, cause characteristic periodic

fever and chills; sexual stages are taken up by mosquito; formation of

oocyst in gut wall; sporogony and release of sporozoites which invade

salivary glands, ready to infect at next feed.

 

Trypanosoma brucei rhodesiense and T. b. gambiense:

African sleeping sickness - East African form of disease (Rhodesian

sleeping sickness) is acute, West African form (Gambian sleeping

sickness) is more chronic. 25,000 cases reported per year, but 55

million estimated at risk. Restricted to tropical Africa, largely

rural areas. Zoonotic infections, with both wild and domestic animals

acting as reservoir hosts of disease. Transmitted by tsetse fly

(Glossina):

 

Fly takes up trypanosomes with bloodmeal; trypanosomes multiply and

undergo developmental cycle first in gut and then salivary glands of

fly; infective forms (metacyclics) develop here and pass out in saliva

during feeding. In host, first stage is multiplication of trypanosomes

at site of bite - chancre; followed by invasion of bloodstream; waves

of parasitaemia with accompanying fever and malaise; late stage is

invasion of CNS - classical sleeping sickness syndrome.

 

Other Tissues:

Trypanosoma cruzi:

Chagas' disease - initial acute phase of several weeks, subsides into

chronic phase, which may continue for decades.

Mega syndromes: Megaoesophagus, megacolon. Heart damage: arrhythmias,

dilatation, sudden death. South America; largely disease of poverty -

poor housing. 100 million estimated at risk; 16-18 million infected.

Zoonosis - oppossums and other forest animals in northern part of

South America . Vectors are triatomine bugs:

 

Trypanosomes in bloodstream of human, taken up by bug; multiplication

in gut, infective forms passed out with faeces; infect next host by

contamination of bite or mucosal surface (Romana's sign); circulate in

blood and then invade cells, preferably muscle or glia cells;

multiplication of trypanosomes as amastigote forms and formation of

pseudocyst; cycle of rupture and release of trypanosomes to invade

bloodstream and other cells.

 

Leishmania donovani, L. tropica, L. mexicana, L. braziliensis:

Visceral and cutaneous leishmaniasis. Widespread in tropics and

subtropics. L. donovani causes visceral disease in Old and New Worlds;

L. tropica causes cutaneous leishmaniasis (oriental sore) in Old

World; L. mexicana and L. braziliensis cause muco-cutaneous

leishmaniasis in New World. Zoonotic infections - dogs and rodents

particularly important. Transmitted by sandflies - Phlebotomus, Lutzomyia:

 

Promastigotes inoculated when sandfly bites; parasites ingested by

dermal macrophages; multiply as amastigotes, which are released and

ingested by further macrophages; taken up with blood by sandfly;

parasites multiply first in gut and then migrate forward, to be

reinoculated at next bite.

 

Toxoplasma gondii:

Toxoplasmosis. Common, but only problematic in AIDS patients or to

foetus. Humans are not definitive host - domestic cat and other

felines are where full lifecycle including sexual phase takes place.

Coccidian lifecycle:

 

Infection is via cysts either through contamination with cat faeces or

ingestion of flesh containing cysts. Cysts rupture in intestine,

releasing sporozoites which penetrate gut epithelial cells; after

cycles of multiplication, tachyzoites enter circulation and infect

various nucleated cell types; finally tissue cysts are formed in brain

and muscle, which contain many slowly dividing bradyzoites and last

for years, unless new cycles of tachyzoite proliferation are

initiated, e.g. in AIDS.

 

This rather remarkable species was known as a potential parasite of

man for many years, but its true nature as a coccidian was only

discovered within the past 20 years. It was known to occur in all

warm-blooded animals - but its nature and means of transmission were a

mystery. It was known that there was a trophozoite and it was also

known that cysts formed. It was only when it was discovered that T.

gondii developed a sexual stage in the intestine of a cat, that its

true coccidian nature was revealed. It was also thought initially that

the parasite was transmitted via the eggs of the nematode worm

Toxocara cati , but it was later found that Toxoplasma could be

transmitted via the faeces of worm free cats - the faeces containing

what appeared to be oocysts - again indicating the coccidian nature of

the parasite. Cats were infected by ingesting oocysts or cysts in

tissues of paratenic hosts, such as mice, or transplacentally.

Parateny: transmission of a parasite from one host to another without

the occurrence of maturation or development of the parasite - i.e.

parasite in transit.

 

After ingestion of infective stages (oocysts or cysts) the intestinal

epithelium is invaded and there follow several series of asexual

generations during which the parasites divide by an unusual process

known as endodyogeny.

 

Endodyogeny is a budding process in which two daughter cells are

formed inside the original 'mother', which is then consumed by the

developing daughters. Starts off with appearance of two new areas of

internal membrane which will be the external membranes of the

daughters. Each membrane grows within the mother, taking in a piece of

the nucleus plus other organelles.

 

As in the 'typical' coccidian cycle asexual reproduction is followed

by macro- and microgametogenesis, fertilization takes place , the

zygote developing into a thick walled oocyst that is passed out with

the faeces. This is not infective when laid and requires 2-3 days

under appropriate conditions to sporulate, resulting in an infective

oocyst containing two sporocysts each with four sporozoites.

 

Extra-intestinal development in cats. some of the organisms formed

during intestinal asexual development pass into other tissues and

organs. First mesenteric lymph nodes are infected, followed by the

liver, lungs and other tissues. By the 6th day the trophozoites, now

known as zoites, may be found in many tissues and persist for about

two weeks after infection. By the 14th day, toxoplasma lesions begin

to subside, but after acute infections cysts commonly persist in the

brain and muscles of cats, as in other animals.

 

Intermediate (paratenic) hosts: Over 300 species of mammal and 20

species of bird have been identified as paratenic hosts. Toxoplasma

can only complete its sexual cycle in the cat. In the 'wrong' host,

when oocysts are ingested the sporozoites hatch, cross the gut wall

and invade macrophages and almost any other cell type (except

erythrocytes) and - before any immunity develops - divide rapidly by

endodyogeny until the cell is full of them. The accumulation of

organisms, bounded only by the plasmalemma of the host cell is known

as a PSEUDOCYST to distinguish it from a cyst, a term which is only

used in parasitology for a protective membrane surrounding an organism

which has, at least in part, been produced by the parasite.

 

Within a pseudocyst, zoites divide rapidly and are known as

tachyzoites (Greek tachos = speed). The host cell eventually bursts

and releases tachyzoites which invade other cells. When this

proliferative phase is slowed down by the influence of developing host

immunity and finally ends, accumulations of zoites form true cysts and

the contained zoites are known as bradyzoites as they develop slowly

(Greek brady = slow). These cysts may become quite large 60µm and can

survive for many years - even the life time of the host. It is these

latent infections that can provide problems in humans.

The prepatent period in the cat - time from ingestion of infective

material to oocyst excretion in the faeces, varies with the stage

ingested. If the oocysts are ingested it is >20 days . If it becomes

infected by eating mouse B that contains tachyzoites it takes >19

days, but if the infection is from eating mouse A where cysts

containing bradyzoites are ingested it takes 3-10 days.

 

Infection: Humans normally become infected either by direct ingestion

of oocysts from a cat or by eating raw or undercooked meat. Cooks or

butchers that handle raw meat are particularly at risk. Man and other

animals can be infected by the congenital route and acute infection in

children can cause severe clinical symptoms. Children can become

infected playing near cat litter trays etc.

 

The congenital condition can occur when a pregnant woman acquires

toxoplasmosis for the first time, usually if infected at start of

gestation period. The mother may show no symptoms but infection can

take place across the placenta and the foetus has a 45% chance of

being infected. On the infants born, about 60% will be sub-clinical,

but of the remainder 30 % suffer symptoms ranging from hydrocephalus

to intracerebral calcification, mental subnormality or some (9%) will

die. Incidence in France and Austria of congential infection is 3-4

per 1000 births. In the UK, 91 cases were reported between 1975-1980.

In adults toxoplasmosis is almost symptomless but may result in fever

and swelling. The most important factor in pathogenicity in adults is

the immune status of the infected individual. About 30% of AIDs

patients who have toxoplasma-specific antibodies suggestive of a past

infection will develop toxoplasma encephalitis in the course of their

illness - i.e. cysts develop in the brain. It is almost probable that

illness in a result of a reactivated latent infection. That is, cysts

with bradyzoites are present, but do no further damage in the immune

competent person. Once an individual become immuncompromised then the

parasite can emerge again and infect other organs etc. Prognosis for

AIDS patients with toxoplasma is not good at present and therapy has

not proved successful.

 

However, before you all rush out and abandon your cats, you should be

aware that a current 3rd year project here has found no evidence of

oocysts in cat faeces collected from local catteries - a study in

Glasgow showed that a high proportion of cats were sero-positive for

toxoplasma, but again no oocysts to match the seropositive data.

 

Trichomonas vaginalis:

Trichomoniasis - not life threatening, but unpleasantly common

infection of vagina in females, urethra in males. venereally transmitted.

 

Acanthamoeba castellanii, A. culbertsoni and other species:

Opportunistic infection. Corneal ulcers, common but not

life-threatening. Occasional death through invasion of CNS.

 

Naegleria fowleri:

Opportunistic infection. Enters via nasal passages from water;

invasion of CNS causes fatal meningoencephalitis.

 

A

 

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