Cryptosporidium parvum: an emerging pathogen

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Cryptosporidium parvum an emerging
pathogen DR. Bimal Kumar Das, M.D. Associate
Professor Department of Microbiology AIIMS
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• Cryptosporidium parvum an emerging pathogen
• Cryptosporidium is a coccidian protozoan
  parasite( Sporozoa)
• Associated with diarrea in 1976 in a 3-year-old
  girl in EM of tthe intestinal epithelium
• Increasing population of immunocompromised
  persons and waterborne outbreaks of
  cryptosporidiosis
• Little is known about the pathogenesis of the
  parasite
• Cryptosporidium can infect several different
  hosts, can survive most environments for long
  periods

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Currently identified species Currently identified species
Cryptosporidium species Origin of isolate
C. parvum Human, Bovine
C. wrairi Guinea pigs
C. muris Bovine, Murine
C. meleagridis Domestic Turkeys
C. baileyi Chickens
C. serpentis Snakes
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• Life Cycle
• Complex monoxenous life cycle--completing its
  entire cycle within a single host with both
  sexual and asexual cycles, and there are six
  distinct developmental stages
• Excystation of the orally ingested oocyst in the
  small bowel with release of the four sporozoites
• Invasion of intestinal epithelial cells
  initiation of the asexual intracellular
  multiplication stage
• Differentiation of microgametes and macrogametes
• Fertilization initiating sexual replication
  Development of oocysts
• The formation of new, infectious sporozoites
  within the oocyst, which is then excreted in the
  stool

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Sourcehttp//biology.kenyon.edu
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Source www.cdc.gov
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Clinical manifestations In immunocompetent
patients Cryptosporidiosis is an acute, yet
self-limiting diarrheal illness (1-2 week
duration), and symptoms include (Juranek,
1995) Frequent, watery diarrhea Nausea
Vomiting Abdominal cramps Low-grade fever
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For immunocompromised persons Illness is much
more severe (Juranek, 1995) 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.
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Epidemiology Infection by C. parvum has been
reported in six continents In patients aged 3
days to 95 years old Transmission is usually
fecal-oral, often through water contaminated by
livestock mammal feces Person to person
transmission through feco-oral route Cattle
farmers, Veterinarians who come in contact with
farm animals Infants and younger children in
day-care centers 50 infective dose (ID50) of
C. parvum is only 132 oocysts ( Resistant to
chlorine treatment)
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Sourcehttp//biology.kenyon.edu
Phase contrast photograph of sporozoite release
from the Cryptosporidium oocyst
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Pathogenesis Upon oocyst excystation, four
sporozoites are released which adhere their
apical ends to the surface of the intestinal
mucosa A sporozoite-specific lectin adherence
factor has been identified Following attachment
cytokines are released from Epithelial cells
which activates macrophages Activated
macrophages release histamine, serotonin,
adenosine, prostaglandins, leukotrienes, and
platelet-activating factor which induce loss of
fluid and electrolytes
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• Epithelial cells are damaged
• Cell death is a direct result of parasite
  invasion, multiplication, and extrusion or
• 2. Cell damage could occur through T
  cell-mediated inflammation, producing villus
  atrophy and crypt hyperplasia
• Either model produces distortion of villus
  architecture results in nutrient malabsorption
  and diarrhea

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Detection and Diagnosis Staining methods were
then developed to detect and identify the oocysts
directly from stool samples. The modified
acid-fast stain is traditionally used to most
reliably and specifically detect the presence of
cryptosporidial oocysts ELISA or IFA, has
recently been described in diagnosis of
cryptosporidiosis PCR (Polymerase Chain
Reaction) has been used for C. parvum
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Source http//medlib.med.utah.edu
C. parvum - Cysts in stool Acid fast
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A scanning electron micrograph of a broken
meront of Cryptosporidium showing the merozoites
within. 
(From Gardiner et al., 1988,An Atlas of
Protozoan Parasites in Animal Tissues, USDA
Agriculture Handbook No.651)
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A scanning electron micrograph of Cryptosporidium
lining the intestinal tract. (From Gardiner et
al., 1988,An Atlas of Protozoan Parasites in
Animal Tissues, USDA Agriculture Handbook No.651)
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Duodenal biopsy sample from a patient with AIDS
and cryptosporidiosis. Sourcehttp//biology.keny
on.edu
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Source http//www.dpd.cdc.gov
Cryptosporidium parvum Oocysts of
Cryptosporidium parvum, in wet mount. The
oocysts are rounded, 4.2 µm - 5.4 µm in
diameter.  Sporozoites are visible inside the
oocysts
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Cryptosporidium oocysts ( Original image from a
Japanese language site Tentatively titled
Internet Atlas of Human Parasitology)
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Source http//www.dpd.cdc.gov
Oocysts of Cryptosporidium parvum stained by the
modified acid-fast method.  Against a blue-green
background, the oocysts stand out in a bright
red stain.  Sporozoites are visible inside the
two oocysts to the right.
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ghosts
Source http//www.dpd.cdc.gov
modified acid-fast method non acid-fast oocysts
ghosts  
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Source http//www.dpd.cdc.gov
Oocysts of Cryptosporidium parvum stained with
the fluorescent stain auramine-rhodamine
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Giardia cyst
C. parvum
Source http//www.dpd.cdc.gov
Oocysts of C. parvum (upper left) and cysts of
Giardia intestinalis (lower right) labeled with
immunofluorescent antibodies
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Treatment No safe and effective therapy for
cryptosporidial enteritis has been successfully
developed. Since cryptosporidiosis is a
self-limiting illness in immunocompetent
individuals, general, supportive care is the only
treatment for the illness. Oral or intravenous
rehydration and replacement of electrolytes may
be necessary
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Treatment Possibilities Encouraging results
following use of paromomycin (an aminoglycoside
antibiotic) have been reported. There is also
preliminary evidence to suggest that paromomycin
when used at 4 doses of 1.5 -2.0g/day has led to
symptom improvement, and even eradication of the
parasite. Although Azithromycin and Lactobin-R
(bovine colostrum immunoglobulin concentrate)
have had some experimental success, no
therapeutic agent has been clearly identified as
effective (Martins Guerrant, 1994).