micr 420 emerging and re-emerging infectious diseases lecture 9: cryptosporidium, schistosoma dr....
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MICR 420
Emerging and Re-EmergingInfectious Diseases
Lecture 9:Cryptosporidium, Schistosoma
Dr. Nancy McQueen & Dr. Edith Porter
Cryptosporidium
Cryptosporidium Protozoa
Apicomplexa Sporozoa
Currently 20 species recognized
Reservoir Mammals, birds, reptiles
Waterborne infection Affects primarily
intestinal tract
Oocysts Sporozoites
Water
Sporozoites
Invade intestinal epithelial cell
Life Cycle of Cryptosporidium
http://www.dpd.cdc.gov/dpdx/HTML/Cryptosporidiosis.htm
Cryptosporidiosis: Pathogenesis
Formation of a unique intracellular compartment in the apical region of the host cell
Involves rearrangement of the host cell cytoskeleton in intestinal epithelial cell
Incorporates host cell actin and alpha-actinin into a host-parasite junctional complex
Cryptosporidiosis: Disease Infectious dose ~ 10 oocysts
Autoinfection Incubation time 2 – 10 days Massive diarrhea
Malnourished children and immunocompromised Up to 25 bowel movements
Millions of oocysts are shed Up to 17 liters fluid loss/day Accompanied by fever
Last about for 1-2 weeks Life threatening for immunocomprised patients
Some may not develop symptoms Genetic association with certain MHC II types
Cryptosporidiosis: Diagnosis
Modified acid fast stain from stool sample (Kinyoun)
ELISA testing for Cryptosporidium antigen in stool samples
IFA Molecular (PCR)
60-kDa glycoprotein gene (gp60)
http://www.stanford.edu/class/humbio103/ParaSites2006/Cryptosporidiosis/Images/acid-fast%20crypto%20(2).jpg
5 m
http://www.dpd.cdc.gov/dpdx/HTML/Cryptosporidiosis.htm
Cryptosporidiosis: Therapy
Nitazoxanide in otherwise healthy patients Nitrothiazole benzamide Blocks anaerobic metabolism Inhibition of the ferredoxine reductase Is effective if immune system is functional Also used in worm infections, some anaerobic
bacterial infections Symptomatic Improve immune system
Anti-retroviral therapy for AIDS patients
Cryptosporidiosis: Prevention
Problem: resistance to common disinfectants Requires special water treatment in municipal
systems Routine chlorine does not inactivate oocysts Small size allows penetration through routine filter
Home filtration Reverse osmosis 1 micron filters
Threats by Cryptosporidium 1993 Milwaukee outbreak
Contamination of the municipal water system C. parvum
100 deaths and 400,000 illnesses Critical Biological Agent for Public Health
Preparedness Category B Some potential for large-scale dissemination, but generally
cause less-severe illness than those in Category A Could be used to contaminate food or water sources, and
many of them are relatively easy to obtain. Difficult to detect, high dose in fecal movements and
low infectious dose
The worms crawls in,
the worms crawl out,
in your belly,
and out your snout.ANONYMOUS
Overview
Schistosoma Helminths Morphology Life cycles Vector Pathogenesis Diseases Diagnosis Therapy Prevention Threats
Helminths: Classification
Phylum: Platyhelminthes (flatworms) Class: Cestodes
(tapeworms) Class: Trematodes
(flukes) E.g., Schistosoma
Phylum: Nematodes (roundworms) E.g., Filaria
Animalia Multicellular Organs and biological
systems* Circulatory Nervous Reproductive
Hermaphrodites Dioecious
Digestive Excretory
* Depending on species some systems may be lacking or rudimentary
Trematodes Flukes Oral sucker: food uptake
Incomplete digestive tract Ventral Sucker: Attachment Mostly hermaphroditic
(monoecious)
"Copyright Dennis Kunkel Microscopy, Inc. (www.denniskunkel.com)"
Schistosoma
Schistosoma japonicum Schistosoma mansoni Schistosoma haematobium
Adults Females size 7 to 20 mm Males slightly smaller
Schistosoma: Life Cycle (1) Infection from contaminated fresh
water in which certain types of snails that carry schistosomes are living
Schistosoma can penetrate the skin
Within several weeks, worms grow inside the blood vessels of the body and produce eggs.
Some of these eggs travel to the bladder or intestines and are passed in the urine or stool
Schistosoma eggs gain access to fresh water when infected people urinate or defecate in the water. Eggs
Miracidia
Sporocysts
Cercariae
Adults
Snail
Human
Schistosoma: Life Cycle (2)
Developmental Stages of Schistosoma
Cercariapenetrating skin
Adult male and femaleworms
Egg Miracidia
Borowski et al. 2008, Trends in Parasitology Vol.24 No.11
The Apical Complex (ac) of Cryptosporidia
Secretory organelles multiple micronemes (mn)
Selection of host cells Gliding motility
single rhoptry (r) Parasitrophus vacuole
formation dense granules (dg)
Modification of host cell
Zoite pellicle (p) Cryptosporidium receptors
involved in host-cell invasion
Borowski et al. 2008, Trends in Parasitology Vol.24 No.11
(a) Ingested oocysts adhere to ileal mucus via surface lectins.(b) Oocysts excyst and release four sporozoites. (c) Sporozoites express mucin-like surface receptors, which mediate attachment to the ileal mucus lining. (d) Sporozoites discharge enzymes to degrade intestinal mucus. The penetration of mucus is thus
facilitated. (e) Sporozoites penetrate the mucus lining and establish host-cell contact via specific receptor–ligand
interactions.
Sporozoites of C. parvum have to penetrate intestinal mucus to establish host-cell contact
Borowski et al. 2008, Trends in Parasitology Vol.24 No.11
Schistosoma and Affected Organs
S. japonicum
S. mansoni
S. haematobium
superior mesenteric veins of small intestine
superior mesenteric veins draining of large intestine
venous plexus of bladder
Schistosoma: Virulence Factors
Tegument Unique double membrane structure dynamic host-interactive layer involved in nutrition, immune evasion
and modulation, excretion, osmoregulation, sensory reception and signal transduction
single syncytium that covers the entire body Soluble hypersensitivity antigen released by miracidia within
the eggs. Local inflammation
Glycan rich surface Antioxidant enzymes Elastase-like IgE protease Excretory/secretory (ES) molecules from cercariae down-
regulate the host's immune response Bind host defense molecules on their surface
S. mansoni eggs in liver
Schistosoma: Diseases Bilharzia Often asymptomatic Acute schistosomiasis (Katayama's fever)
May occur weeks after the initial infection S. mansoni and S. japonicum Fever, cough, abdominal pain, diarrhea, hepatospenomegaly, and
eosinophilia Occasionally central nervous system lesions occur
granulomatous lesions around ectopic eggs Brain, spinal cord
Chronic infection Granulomatous reactions and fibrosis in the affected organs Colonic polyposis with bloody diarrhea (Schistosoma mansoni mostly) Portal hypertension with hematemesis and splenomegaly (S. mansoni, S.
japonicum) Cystitis and ureteritis (S. haematobium) with hematuria, which can progress
to bladder cancer;
Schistosoma and Cancer
General: Chronic inflammation with chronic phagocytes at the
inflammatory site Release reactive oxygen radicals and reactive nitrogen
radicals Chronic inflammation leads to repeated cycles of cell
damage and compensatory cell proliferation Promoting neoplasia
Schistosoma specific Adult schistosomes liberate carcinogenic amines in urine Increased beta-glucuronidase levels originating from
miracidia enclosed in the eggs
Khurana S et al. (2005) Indian J Med Microbiol. 2005 Apr;23(2):74-9.
Squamous Bladder Cancer Induced by Schistosoma
Normal epithelium Squamous bladder cancer
Schistosoma: Diagnosis
Microscopy Antibody detection
ELISA and immunoblot Schistosomal adult microsomal antigen indicative only of schistosome infection at some
time cannot be correlated with clinical status, worm
burden, egg production, or prognosis
Schistosoma: Identification of Eggs
S. mansoni S. japonicum
Spine
S. haematobium
In Feces In Urine
Schistosoma: Therapy
Praziquantel for all species
Schistosoma: Prevention No vaccine Avoid wading, swimming or other fresh-water
contact in endemic countries Avoid untreated piped water coming directly from
canals, lakes, rivers, streams or springs that may contain cercariae
Heating bathing water to 50°C (122°F) for 5 minutes or filtering water with fine-mesh filters
Allow bathing water to stand for 2 days because cercariae rarely remain infective longer than 24 h
Schistosoma: Epidemiology
200 million people infected world wide in over 70 countries
50% endemic among the local population in high infested areas
South America Caribbean Africa Middle East Far East
Depends on species
Schistosoma: Endemic Areas
Threats by Schistosoma
Mainly threat to population in endemic areas and to travelers
Resistance against praziquantel
Resources
The Microbial Challenge, by Krasner, ASM Press, Washington DC, 2002. Brock Biology of Microorganisms, by Madigan and Martinko, Pearson Prentice Hall,
Upper Saddle River, NJ, 11th ed, 2006. Microbiology: An Introduction, by Tortora, Funke and Case; Pearson Prentice Hall;
9th ed, 2007. www.asnom.org/.../nodule_oncho.jpg http://www.icp.ucl.ac.be/~opperd/parasites/images/man.jpg http://www.the-travel-doctor.com/filari9.gif http://www.payer.de/entwicklung/entw2029.gif http://emu.arsusda.gov/typesof/images/onchyo.jpg http://www.denniskunkel.com/product_info.php?products_id=1089 http://www.denniskunkel.com/product_info.php?products_id=592 http://www.cdc.gov/ncidod/dpd/parasites/schistosomiasis/default.htm http://www2.ncid.cdc.gov/travel/yb/utils/ybGet.asp?section=dis&obj=schisto.htm http://education.vetmed.vt.edu/curriculum/VM8054/Labs/Lab4/IMAGES/SIMPL
%20COLM%202%20GALL.JPG http://www.pathguy.com/lectures/bladder_cis.jpg http://www.dpd.cdc.gov/dpdx/HTML/ImageLibrary/Schistosomiasis_il.htm Bayne 2009, Molecular & Biochemical Parasitology 165 (2009) 8–18