Opportunistic protozoa

1
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 Intestinal epithelium Brain, liver, kidney
Blastocystis hominus blastocystosis intestine
Pneumocystis jeroveci (Pneumocystis carinii) Pneumocystis pneumonia (PCP) lung
2
Toxoplasma gondii(toxoplasmosis)
3
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

4
Morphology

• Trophozoite
• The intracellular parasites (tachyzoite???) are
  3x6µm, crescent shaped organisms that are
  enclosed in a cell membrane to form a pseudocyst
  (???) measuring 10-100 µm in size

5
Morphology

• Pseudocyst -- intracellular tachyzoites of
  Toxoplasma gondii

6
(No Transcript)
7
Morphology

• A cyst (??)of Toxoplasma gondii filled with
  bradyzoites

cyst in cardiac muscle
8
Cyst in brain
9
Morphology

• A sporulated oocyst (??)of Toxoplasma gondii. 
• The oocyst contains two sporocysts(???), each of
  which contain four crescent-shaped sporozoites
  (???)
• Only cats produce and pass Toxoplasma oocysts
  approximate diameter 10 µm

10
Life Cycle
11
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

12
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

13
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

14
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

15
Pathogenesis

• The tachyzoites directly destroy host cells

16
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

17
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

18
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 gt frequency of deafness
• 60 more microcephaly (small head)
• 30 more Low IQ babies

19
Symptomatic Congenital Toxo

• Spontaneous abortion or stillbirths
• Bilateral retinochoroiditis (?????????)
• Microcephalus(????)or hydrocephalus(???)
• Intracerebral calcification(?????)
• Neurological Damage
• Learning Difficulties
• Jaundice(??) and hepatosplenomegaly

20
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(???)
• enlarged liver/spleen (hepatosplenomegaly)
• mimics infectious mononucleosis(???????)

21
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(???), chorioretinitis(??????), etc.

22
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

23
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

24
Positive result of IFA
25
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

26
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

27
Epidemiology and control

• Transmission route for humans
• Infected
• by ingesting infective oocysts (in gt4 day old cat
  feces)
• by ingesting tachyzoites or bradyzoites in rare
  meat
• by receiving blood or tissues with -zoites
• CONGENITALLY by transplacental tachyzoites

28
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

29
Treatment

• Combination Therapy
• Pyrimethamine(????) plus either
• Sulfadiazine(????) or
• Trisulfapyrimidines(??????)
• During pregnancy,
• spiramycin(????) until delivery

30
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?

31
Cryptosporidium spp.
32
Introduction
A threat to the quality of surface water and the
environment...!

• 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

33
Introduction

• Cryptosporidiosisan 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

34
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

35
Morphology

• Oocysts are spherical to subspherical, measuring
  from 4-6 ? m
• Acid-fast methodagainst a blue-green background,
  the oocysts stand out in a bright red stain
• Four banana-shaped
• red sporozoites and one
• dark residual body

36
Life cycle
37
Life cycle
38
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

39
Clinical features

• immunocompromised persons
• Debilitating, cholera-like diarrhea (up to 20
  liters/day)
• Severe abdominal cramps
• Malaise(??)
• Low-grade fever
• Weight loss
• Anorexia (??)
• C. parvum infection has also been identified in
  the biliary tract (causing thickening of the
  gallbladder wall) and the respiratory system

40
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

41
Diagnosis

• Direct fluorescent antibody (FA) assay
• ELISA controls are necessary to determine
  whether the kit is performing or not
• Molecular diagnosis

42
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

43
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

44
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

45
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 (????),Paromomycin (????)
• Berberine to contorl diarrhea
• All these drugs have met with different levels of
  success