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Opportunistic Protozoa Opportunistic Protozoa

Toxoplasma gondiiToxoplasma gondii

PneumocystisPneumocystis cariniicarinii

CryptosporidiumCryptosporidium

2 Cancer patients; Apparatus transplant; AIDs patients

Death infection among immunodeficiency persons.

No special clinical effects among immunocompetent persons

Water: oocysts of Cryptosporidium; Food: cysts or pseudocysts of Toxoplasma gondii;

Air: Pneumocystis carinii

Characteristics

The infection sources are widely spread.

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Toxoplasma gondii 刚地弓形虫

• It will probably infect almost any mammal.

• It parasitizes in all kinds of cells except RBC.

• Man is its intermediate host --- toxoplasmosis.

• Man is its intermediate host --- toxoplasmosis.

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(1)Trophozoite

crescent shaped 4~ 7 × 2 ~4 μm

1. Morphology and life cycle

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Trophozoites from peritoneal fluid of an infected mouse;

Scanning electron microgragh of toxoplasma trophozoites

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sporocyst

sporozoite

(2) Oocyst

round or oval

11×12.5μm

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mature oocyst

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Pseudocyst ： the individuals (trophozoite) within pseudocyst termed as tachizoites

Cyst ： the trophozoite within the cyst termed as bradyzoite

In intermediate host

Schizont ： Gametocyte ：♀ ,♂

Oocyst ：

In final host

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Five forms in life cycle

The life cycle is very complex

in villus epithelium of small intestine of cat, containing 4-29 merozoites (usually 10-15)

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zygote

Gametocyte

female gametocyte

male gametocyte

oocyst

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The life cycle of Toxoplasma

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Final host

Interm

ed

ia

te h

ost

oocyst

PseudocystCyst

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（ 2 ） intermediate host ： birds, fishes and almost any blooded

animals (include man) can be as intermediate host of T. gondii , undergoing extraintestinal asexual reproduction (extraintestinal phase)

（ 3 ） definitive host ： feline in which undergoing intestinal sexual reproduction (intestinal phase) （ cat can also be intermediate host in which undergoing asexual reproduction ）

（ 1 ） Being circulation transfer Two hosts are usually needed in the life cycle with alternation of generations (asexual and sexual reproduction), but also finishing life cycle without the definitive host

Key points ：

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（ 4 ） Infective stage

Mode of infection

Parasitic site

Oocyst, cyst, pseudocyst

All kinds of cells except RBC

By mouth

By skin and mucosa

By placenta

By transfusion

By organ transplant

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No host specialityNo host speciality

No tissue specialityNo tissue speciality

Toxplasma gondii can parasite in various tissue, heart, liver, lung, brain, muscle, blood and other tissues.

But sexual reproduction must take place in villus epithelium of small intestine of feline

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2. Pathogenesis (1) Mechanism associated with the virulence of the parasite and

immunologic status of the host1 ） The virulence

Strong toxic strain, e.g.RH strain

Weak toxic strain, e.g. Beverley strain

Toxins secreted by T.g ：

① toxotoxin （弓形虫毒素）： from the ascites of infected mice,

causing death

② toxoplasmin （弓形虫素）： extracts from the parasite ，

causing abnormality ③ toxofactor （弓形虫因子）： from the supernate of the culture

medium ,causing abortion

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2 ） The immunologic status of hostIn the persons with normal immunity –most of them are suppressive infection

In immunocompromised individuals, infection results in generalized parasitemia involvement of brain, liver, lung and other organs, and often death.

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Spontaneous abortion or stillbirths Bilateral retinochoroiditis ( 双侧视网膜脉络膜炎 ) Microcephalus( 小头畸形 )or hydrocephalus( 脑积水 ) Intracerebral calcification( 大脑钙化灶 ) Neurological damage Learning difficulties Jaundice( 黄疸 ) and hepatosplenomegaly

(2)Clinical manifestation ① Congenital Toxoplasmosis

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hydrocephalus dementia

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dementia

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② Acquired toxoplasmosis

• usually multi-organs involved

e.g.

lymphadenopathy, myalgia, myocarditis, peritonitis( 腹膜炎 ),chorioretinitis( 脉络视网膜炎 ),hepatitis, pneumonia, encephalitisfever, headache,

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Photograph of fundus. Showing a heavily pigmented central choroidal lesion in a young person due to acquired toxoplasmosis. The whitish patches inside the lesion are areas where the sclera （巩膜） is exposed due to the necrosis of the retina（视网膜） . A sharply demarcated lesion, as seen in this photograph, is typical of both acquired and congenital toxoplasmosis. However, in some cases a more diffus

ed lesion may be observed.

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3. Immunology

Both humoral and cell mediated immune responses are stimulated in normal individuals

CMI is protective Th1 cytokines e.g. IFN-gamma, IL-12

Humoral response is of diagnostic value

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3 ） Cultivation

4. Diagnosis

(1) Parasitic diagnosis

1 ） Smears ： Specimens

Blood, Sputum, bone marrowcerebrospinal fluid

-Tissue Biopsy

2 ） Animal Inoculation ： inoculation to laboratory rats or mice ,for 1w, collecting liquid from the abdomen

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(2) Serological tests

　　 1 ） Dye test (DT) ---is sensitive and specific

2 ） IHA, IFA, ELISA, IEST

IGSS （免疫金银染色） ,Dot-IGSS

(3) PCR

DNA probe

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5. Epidemiology5. Epidemiology

(1) Distribution

Toxoplasma gondii is worldwide distribution

Infection rate(Ab detection)

American: 33%

Chinese: 9.8%

African: 55%

Domestic animal: 10-50%

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Worldwide cases of congenital toxoplasmosis are estimated at between 140,900 and 1,127,200, based on an estimated rate of 0.1 to 0.8% of 140.9 million live births in 1992

About 5-10% of AIDS patients complicated with toxoplasmosis

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人体弓形虫阳性率的分

布

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弓形虫感染的病例分布

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(2) Epidemic links

1 ） The source of infection--infected animals and infected persons

2 ） The routes of transmission---

• insect vector (e.g. fly and cockroach)• by meat ,milk and egg which containing the pathogens

• directly by lesion skin and mucosa

• transfusion

• by placenta• organ transplant

• contaminated water and food (with oocyst)

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3) Susceptible population

Human in all age are susceptible to Toxplasma gondii. especially the foetus, babies and old age population, the cancer patients and AIDS patients, or other immunodeficiency persons.

Many kinds of animals --- cat, pig, cattle, sheep bird, etc

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(3) Reasons of epidemic

2) Strong resistance --- Oocyst has strong resistance to acid, alkali and temperature

1 ） Several stages in life cycle are infective – Oocyst, cyst and pseudocyst

3 ） There are many hosts that are susceptible to T. gondii --- Mammalia and birds can be as the intermediate host

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6 ） Domestic and wild cats, passes tons of oocysts （ 10 milion/d/cat ）

4 ） There are many circulations in life cycle Definitive host Intermediate host Intermediate host Intermediate host

5 ） The tissue cysts alive in host’s tissue for many years

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6. Prevention and Treatment

(1) Avoid raw or undercooked meat

(2) Avoid contact with cat feces, Pregnant women should avoid all contact with cats

Avoid contaminating water and food

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(3) Combination Therapy (no effective drugs

so far)

Pyrimethamine( 乙胺嘧啶 ) Sulfadiazine( 磺胺嘧啶 ) Trisulfapyrimidines( 三重磺胺嘧啶 )

Spiramycin( 螺旋霉素） During pregnancy---spiramycin( 螺旋霉素 ) until delivery

If at the early stage of pregnancy, the pregnancy should be stopped.

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Pseudocyst -- intracellular tachyzoites of Toxoplasma gondii

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pseudocyst

Tachyzoite

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Cyst (bradyzoite, 缓殖子 ), tissue cyst

The cyst have a elastic wall. They contain several to several hundreds trophozoites which called bradyzoite. Under certain conditions, the cyst may be break, and the bradyz

oites invade a new cell and form another cyst

Cyst wall

Bradyzoite

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Cryptosporidium Cryptosporidium was recognized as Opportunistic Protozoa Opportunistic Protozoa

recognized in AIDS patients in 1976

• 50% of AIDS patients reported to CDC have Cryptosporidium  

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Cryptosporidium This parasite has been incriminated in large outbreak of diarrhea in humans in US

• associated with contamination of surface water in Lake Michigan used for drinking

• unusually wet spring resulted in river runoff containing oocysts from feces of young cattle

• one of 2 water purification plants was contaminated, and treated water showed high turbidity levels.

• numbers of cases – >2000

• cost – >300 000$ 

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Life Cycle of Cryptosporidium

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Cryptosporidium parvum

_____________ on the surface of small intestinal cells

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Oocysts of Cryptosporidium

unstained acid red stain

Oocysts from cattle feces – oocysts are 4-5 µm in diameter

Each oocyst contains 4 sporozoites that attach to surface of small intestinal cells

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Cryptosporidium MOST Cases of Cryptosporidiosis are a ZOONOSIS as human infections arise from infections in young cattle • oocysts in cattle feces typically contaminate surface water used for drinking PATHOLOGY: (1) In immunocompetent (normal) humans -   (2) In AIDS patients and immunocompromised persons -

 TREATMENT -