Cryptosporidium parvum: an emerging pathogen
DR. Bimal Kumar Das, M.D.
Associate Professor
Department of Microbiology
AIIMS
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
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
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
Source:http://biology.kenyon.edu
Source: www.cdc.gov
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
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.
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)
Source:http://biology.kenyon.edu
Phase contrast photograph of sporozoite release
from the Cryptosporidium oocyst
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 plateletactivating factor which induce loss of fluid and
electrolytes
Epithelial cells are damaged
1. 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
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
Source: http://medlib.med.utah.edu
C. parvum - Cysts in stool Acid fast
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)
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)
Duodenal biopsy sample from a patient with AIDS
and cryptosporidiosis. Source:http://biology.kenyon.edu
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
Cryptosporidium oocysts ( Original image from a Japanese language site
Tentatively titled Internet Atlas of Human Parasitology)
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.
“ghosts”
Source: http://www.dpd.cdc.gov
modified acid-fast method non acid-fast oocysts “ghosts”
Source: http://www.dpd.cdc.gov
Oocysts of Cryptosporidium parvum stained with the
fluorescent stain auramine-rhodamine
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
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
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).