Transcript Toxoplasma gondii

Opportunistic protozoa
Pathogens
Disease
Sites parasitized
Toxoplasma gondii
toxoplasmosis
All cells except RBC
Cryptosporidium spp.
cryptosporidiosis
Intestinal epithelium
Isospora spp.
isosporiasis
Intestinal epithelium
microsporidia
microsporidiosis
Blastocystis hominus
blastocystosis
Intestinal epithelium
Brain, liver, kidney…
intestine
Pneumocystis jeroveci
(Pneumocystis carinii)
Pneumocystis
pneumonia (PCP)
lung
Toxoplasma gondii
(toxoplasmosis)
Introduction
• Toxoplasma gondii has very low host specificity, and it
will probably infect almost any mammal. It invades all
kinds of cells except RBC
• Cats (both domestic and wild) are the only definitive
hosts and can also be the intermediate hosts
• The disease that Toxoplasma gondii caused
(toxoplasmosis) has been found in virtually every
country of the world
• Toxoplasmosis is a significant cause of morbidity and
mortality in AIDS patients and congenitally infected
infants -- opportunistic infection for human
Morphology
• Trophozoite
– The intracellular parasites (tachyzoite速殖子) are
3x6µm, crescent shaped organisms that are enclosed
in a cell membrane to form a pseudocyst (假包囊)
measuring 10-100 µm in size
Morphology
• Pseudocyst -intracellular
tachyzoites of
Toxoplasma gondii
Morphology
• A cyst (包囊)of
Toxoplasma gondii
filled with bradyzoites;
cyst in cardiac muscle
Cyst in brain
Morphology
• A sporulated oocyst (卵囊)of Toxoplasma gondii.
• The oocyst contains two sporocysts(孢子囊), each
of which contain four crescent-shaped sporozoites
(子孢子)
• Only cats produce and pass Toxoplasma oocysts;
approximate diameter = 10 µm
Life Cycle
Life Cycle
• Two host pattern with alternation of
generations----mammal  mammal
• Toxoplasma gondii is a serious zoonotic
parasite that has almost all the warm blooded
animals as the reservior hosts (intermediate
hosts)
• Life cycle includes two phases called the
intestinal (or enteroepithelial) and
extraintestinal phases
Life Cycle
• The intestinal phase occurs in cats only and
produces "oocysts" (___ hosts)
– Schizogony – schizont merozoite asexual reproduction
– Gametogony – male & female gamete fertilize  oocyst
sexual reproduction
– Sporogony – sporocyst sporozoites asexual
reproduction
• The extraintestinal phase occurs in all infected
animals (including cats) and produces
trophozoites -- asexual reproduction (__ hosts)
– Tachyzoites – pseudocysts
– Bradyzoites -- cysts
Life Cycle
• Toxoplasmosis can be transmitted by
ingestion of oocysts (in cat feces) or
“pseudocysts" or “cysts"(in raw or
undercooked meat)
• Shedding of oocysts in faeces is most common
in kittens, but can occur in any age of cat
• Oocysts can remain infectious for several
months and are quite resistant to disinfectants,
drying and freezing. Tissue cysts are less
resistant, and are destroyed by proper cooking
of food
Pathogenesis
In general, most of the human population infected
with Toxoplasma are asymptomatic carriers
There are a number of factors which determine
whether an infected host will express disease
symptoms
–The strain of the pathogen (RH strain)
–The susceptibility of the host -- immunocompromised
–Age of the host – new born infants
–Degree of acquired immunity
Pathogenesis
The tachyzoites directly destroy host cells
Clinical features
• Although Toxoplasma infection is common
(~13% overall world prevalence), it rarely
produces symptoms in normal individuals
• Could be classified as
– Congenital toxoplasmosis
– Acquired toxoplasmosis
Congenital Toxoplasmosis
• Two types:
– Asymptomatic Congenital Toxo
• 60% of infected
• may suffer from Long Term Sequela
– Symptomatic Congenital Toxo
• 40% of infected
• more likely if mother infected in 1st/2nd Trimester
• Severe damage to fetus = stillbirth or abortion
• or may be severely affected
Asymptomatic Congenital Toxo
• Diagnosis:
– + IgM titer in serum of newborn (TORCH +)
– no overt clinical disease at birth
• Long Term Sequela:
– within 7 years of birth - children born to women with
high levels of Toxo antibody had
• 2x > frequency of deafness
• 60% more microcephaly (small head)
• 30% more Low IQ babies
Symptomatic Congenital Toxo
• 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
Acquired Toxoplasmosis
• usually asymptomatic
– majority of population was infected
• IgG titer is demonstrable for 10 yr. post-infection
• Symptoms – flu-like
– swollen neck (cervical lymphadenopathy)
– fever, malaise(不舒服)
– enlarged liver/spleen (hepatosplenomegaly)
– mimics infectious mononucleosis(单核细胞增
多症)
Toxoplasmosis in AIDS patients
• A significant OI (opportunistic Infection in AIDS)
– Toxo lymphadenopathy (swollen lymph
glands)
– Toxo encephalitis (TE) & CNS Toxo  death
– pulmonary Toxo & Toxo pneumonia
– UTIs - Toxo urinary tract infections
– disseminated Toxo
• Peritonitis(腹膜炎), chorioretinitis(脉络视网膜炎),
etc.
Immunology
• Both humoral and cell mediated immune
responses are stimulated in normal
individuals
• CMI is protective
– Th1 cytokines such as IFN-gamma, IL-12
•
Humoral response is of diagnostic value
Diagnosis
• Microscopic Examination
-Smears and Sections
– Specimens
-Blood, Sputum, CSF, bone marrow
-Tissue Biopsy
• Animal Inoculation
• Serological tests – IHA, IFA, ELISA (IgM/IgG)
• PCR & DNA probes
Positive result of IFA
Epidemiology and control
• 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
• Some countries have instituted screening
programs of pregnant women
• About 5-10% of AIDS patients complicated with
toxoplasmosis
Reasons of epidemic
• Source of oocysts ...
– domestic and wild cats, passes tons of oocysts
• Persist in environment if moist
– reservoir of infective oocysts
• Many intermediate hosts with infective
stage
– reservoir of infective tissue cysts
Epidemiology and control
• Transmission route for humans
– Infected
• by ingesting infective oocysts (in >4 day old cat
feces)
• by ingesting tachyzoites or bradyzoites in rare
meat
• by receiving blood or tissues with “-zoites”
• CONGENITALLY by transplacental tachyzoites
Epidemiology and control
• Avoid contact with cat feces
• Change cat litter daily to prevent infective
oocyst formation
• Pregnant women should avoid all contact with
cats
• Instituted screening programmes of pregnant
women
• Avoid raw or undercooked meat
• Handle uncooked meat carefully
• Wash your hands
Treatment
•
Combination Therapy
– Pyrimethamine(乙胺嘧啶) plus either
– Sulfadiazine(磺胺嘧啶) or
– Trisulfapyrimidines(三重磺胺嘧啶)
• During pregnancy,
– spiramycin(螺旋霉素) until delivery
Summary
• Toxoplasma gondii: pathogenesis, clinical
features, control
– Opportunistic infection
– What are the infective stages of toxoplasma
gondii?
– Please describe the possible consequences
of toxoplasma infection in a young lady.
• What parasitic diseases can be
transmitted by blood transfusion?
Cryptosporidium spp.
Introduction
Cryptosporidium is a
protozoan parasite in
water environment
Have a low infectious
dose necessary to
infect human as less
than 10 organisms
Potentially lethal for
immunosuppressed
individuals
A threat to the quality
of surface water
and the environment...!
Introduction
• Cryptosporidiosis:an emerging infectious
disease
– 1907 ---Tyzzer identifies the oocysts of C. muris in
mice
– 1910 --- Infection is transmitted by oocysts
– 1912 --- Description of C. parvum
– 1952 --- C. parvum causes morbidity and mortality
– 1971 --- Diarrhea in cattle is associated with C.
parvum
– 1976 --- Human cryptosporidiosis
– 1982 --- First case in AIDS patients
– 1987 --- first report in Nanjing, China
Introduction
• A complex life cycle, with multiple asexual and
sexual developmental stages
• Causal agent of acute diarrheal disease in human
(third major cause of diarrheal disease worldwide)
and animals -- zoonosis
• Cryptosporidium parvum has emerged as a very
important pathogen worldwide due to its morbidity
in AIDS patients
• Despite its significance, little is known about this
parasite biology and specific chemo- or
immunotherapies to treat cryptosporidiosis are yet
to be developed
Morphology
• Oocysts are spherical to subspherical,
measuring from 4-6  m
• Acid-fast method:against a blue-green
background, the oocysts stand out in a
bright red stain
• Four banana-shaped
red sporozoites and one
dark residual body
Life cycle
Life cycle
Clinical features
• Latent duration: 1wk -- cryptosporidiosis
• immunocompetent patients
– acute, self-limiting diarrheal illness (1-2 week
duration), and symptoms include
•
•
•
•
•
Frequent, watery diarrhea
Nausea
Vomiting
Abdominal cramps
Low-grade fever
Clinical features
• immunocompromised persons
–
–
–
–
–
–
–
Debilitating, cholera-like diarrhea (up to 20 liters/day)
Severe abdominal cramps
Malaise(不适)
Low-grade fever
Weight loss
Anorexia (厌食）
C. parvum infection has also been identified in the
biliary tract (causing thickening of the gallbladder wall)
and the respiratory system
Diagnosis
• Stool examiniation for oocysts
• Biopsy of the intestine
epithelium
• ！！Multiple stool samples
(at least 3) should be tested
before a negative diagnostic
interpretation is reported
Diagnosis
• Direct fluorescent
antibody (FA) assay
• ELISA: controls are
necessary to determine
whether the kit is
performing or not
• Molecular diagnosis
Epidemiology and control
• Transmission is usually fecal-oral,
including water-borne and food-borne
means
• The highly environmentally resistant cyst
of C. parvum allows the pathogen to
survive various drinking water filtrations
and chemical treatments such as
chlorination
Epidemiology and control
• Swimming pools and water park wave
pools have also been associated with
outbreaks of cryptosporidiosis
• Food can also be a source of transmission,
when either an infected person or an
asymptomatic carrier contaminates a food
supply
Epidemiology and control
• Special cautions must be taken by immunocompromised
persons :
–
–
–
–
With HIV/AIDS
Patients receiving treatment for cancer
Recipients of organ or bone marrow transplants
Congenital immunodeficiencies
• Avoid:
– sexual practicing involving fecal exposure
– contacting with infected adults or infected children who wear
diapers
– contacting with infected animals
– drinking or eating contaminated water or food, and exposure to
contaminated recreational water
• Drink : boiled water; filtered (1um) water or bottled water
Treatment
• No safe and effective therapy for cryptosporidial
enteritis has been successfully developed
• The urgent need of chemotherapy for persons
with AIDs has led to administration of a variety of
drugs:
– Spiramycin (螺旋霉素),Paromomycin (巴龙霉素)
– Berberine to contorl diarrhea
• All these drugs have met with different levels of success