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434 Cards in this Set

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What is the pork tapeworm?
Taenia solium
What is the beef tapeworm?
Taenia saginata
What is the hydatid?
Echinococcus granulosus
What is the fish tapeworm?
Diphyllobothrium latum
What is Diphyllobothrium latum?
Fish tapeworm
What is Taenia solium?
Pork tapeworm
What is Echinococcus granulosus?
Hydatid
What is Taenia saginata?
Beef tapeworm
What are the characteristics of cestodes and tapeworms?
No free-living representatives
No gut
Depend solely on their tegument to obtain food
Hermaphroditic
Have a prominent head or scolex
Usually the adult worms parasitize the intestine
What are the lengths of pork and beef tapeworms?
Taenia Solium - Pork tapeworm - 1-7 meters long

Taenia Saginata - Beef tapeworm - 5-25 meters long
How do Taenia get their name?
Taenia - latin for ribbon
What is the geographic distribution of Taeniasis?
Worldwide, depending on dietary habits and quality of cattle and pork farming
What is the structure of the proglottid?
Structure possessing both male and female reproductive elements (testes, uterus, vas deferens, vagins, ovary and *vitellaria*)

Both male and female genital bodies exit the taenia together at a structure called the Genital Pore
Taenia Saginata - Scolex and Proglottids
Taenia Solium - Scolex and Proglottid
Life Cycle of Taenia from host to man?
Infection of cattle or pig with larval stage of T. Saginata or T. Solium, respectively.

Oncosphere in blood carried to organs, forms Cysticercus in muscles, brains, eyes and lungs.

Cysticercus in muscle is the infective stage.

Human ingests meat containing Cysticercus, releasing worm into GI tract.

Worm latches on to GI with Scolex, producing infection and releasing many eggs into the feces.
What are the features of the Taenia egg?
Hexacanth - six hooks
Taeniasis Symptoms?
GI - Abdominal discomfort, epigastric pain, vomiting. Caused by the physical presence of the worm.

Other organs (cysticercosis) - Cyst formation in brain, eye, lung and liver may cause related symptoms. Due to physical mass and inflammation.
How is diagnosis of Taeniasis made?
Symptoms
History of eating undercooked beef or pork
Recovery of Proglottids and/or Eggs in the stool
How is the diagnosis of Cysticercosis made?
CNS and/or symptoms involving other organs

History of ingesting food with T. Solium eggs (or Saginata)

Radiographic localization of cysticercal lesions in tissues
Treatment for Taeniasis?
Niclosamide - targets Oxidative Phosphorylation

**Praziquantel - Calcium agonist that leads to tetanic muscular contractions in the worm ~~> Expulsion of the worm, INCLUDING THE SCOLEX
Prevention of Taeniasis?
Veterinary inspection of Beef and Pork
Adequate cooking or freezing of meat - Cysticerci do not survive temperatures below -10 C and above 50 C.
Cysticercosis
Cysticercosis
Cysticercosis - Brain
Cysticercosis - Brain
Cysticercosis
Scolex of Taenia Saginata
Taenia Egg
Taenia Larva Cyst
Taenia Larvae release
Taenia Proglottids
Taenia Solium
Taenia
What is the smallest of the Taeniids?
Echinococcus Granulosus

3-6 mm long
What Taeenid has 3 different proglottids, and what are they?
Echinococcus Granulosus

Immature, Mature, and Gravid
Characteristics of Echinococcus Granulosus?
Smalles of the Taeniids - 3-6 mm long

3 Proglottids - Immature, Mature, and Gravid

Hydatid Disease - Liver, Brain
What is the geographic distribution of Echinococcus Granulosus?
Hydatid

Present in Asia, Europe, North, East and South Africa, Parts of Australia and South America, Canada and Alaska. Seldom in the US.

Basically everywhere.
What is the life cycle of Echinococcus Granulosus?
Life cycle takes place in 2 different hosts: Intermediate and Definitive

Intermediate host ingests eggs. Larva hatches in intestine, penetrates the intestinal lining and enters the blood stream. Larva distribute to almost any organ, but **LIVER** is most common. The larva develops into a Hydatid Cyst.

The DEFINITIVE host is infected when it ingests a Hydatid Cyst. The protoscolex attaches to the host's intestine and develops into a tapeworm. The adult tapeworm is found in the small intestine of the canine (DEFINITIVE HOST). Eggs are then released into the feces.

The eggs are ingested by an INTERMEDIATE HOST, and the cycle repeats.
What are the two hosts of Echinococcus Granulosus?
Definitive Host - Canine
Intermediate Host - Human and other warm blooded mammals
What are the Sites, Symptoms, and Pathogenesis of Echinococcus Granulosus infections?
Abdomen - Abdominal Distension, Ascites - Progressively growing cyst

Liver - Obstructive Jaundice - Growing cyst

Lung - Pulmonary Abscess, cough, chest pain - Growing cyst

CNS - Jacksonian epilepsy - Growing cyst

Lung - Fever, pruritus, urticaria, anaphylactoid reactions - Type-1 Hypersensitivity
What is the pathology of Hydatid Cysts?
Caused by Echinococcus Granulosus

***Cyst formation can take 10-20 years

Cysts are fluid filled

Cysts may reach up to the size of a soccer ball
How is the diagnosis of Echinococcus Granulosus made?
Endemicity
Symptoms
X-ray and CT scan
Serology
Skin (Casoni) Test
What is the Casoni Test?
A simple skin test used for the diagnosis of Hydatid (Echinococcus Granulosus) disease

Sterilized cyst fluid injected subdermally. Wheal response indicates positive response
What skin test is used for the diagnosis of Hydatid disease?
Casoni Test (Echinococcus Granulosus)
What is the treatment and control of Echinococcus Granulosus infections?
Surgical removal of the cyst
Injection of 20% hypertonic saline
Praziquantel
Benzimidazoles (albendazole, mebendazole) - Acts by inhibition of Glucose transport
Avoidance of treatment of infected canines
How do Benzimidazoles work?
Inhibition of glucose transport
How does Praziquantel work?
Acts as a Ca++ agonist, leading to tetanic muscular contractions of the parasite. Results in paralysis of the worm, and summary expulsion with the scolex
What is the life cycle of Hymenolepis nana?
Embryonated egg is released in feces. It is either directly ingested by humans from contaminated food, water or hands, OR the egg is ingested by an insect. Humans and rodents can then be infected by ingesting an infected insect.

Once ingested by a human, the embryonated egg hatches, and a Cysticercoid develops in the intestinal villus. Scolex forms, and the adult lives in the ileal portion of the small intestine. Eggs are released from the genital atrium of the gravid proglottids. Gravid Proglottids can also disintegrate releasing eggs that are passed in stools.

Eggs are released in the stool.
Characteristics of Hymenolepis nana?
The Dwarf Worm

Small tapeworm about 40 mm long
Adult worm has a retractable rostellum and only one row of hooks (about 20-30)
Children harbor the bulk of infections

There is very little pathology associated with this infection, unless it is very heavy.
What is the treatment for Hymenolepis nana?
Daily administration of antihelmintic, Niclosamide or Praziquantel, for 4-5 days.
What is the pathology of Hymenolepis nana?
There is little pathology associated with this infection unless it is very heavy.
How is the diagnosis of Hymenolepis nana made?
Eggs in the feces
What has 2 Bothria?
Diphyllobothrium latum (broad fish tapeworm)
What Taeniid can produce one million eggs per day?
Diphyllobothrium latum (broad fish tapeworm)
What are the features of the Diphyllobothrium latum egg?
Has an Operculum (lid) and a Knob
What is the geographic distribution of Diphyllobothrium?
Northern Europe - Diphyllobothrium Latum
North Eastern U.S. - Diphyllobothrium Ursi
Northern Canada - Diphyllobothrium Dendriticum
What is the life cycle of Diphyllobothrium Latum?
1) Unembryonated Egg passed in feces
2) Eggs EMBRYONATE in water
3) CORACIDIA hatch from eggs and are ingested by crustaceans
4) PROCERCOID larva in body cavity of crustaceans
5) Crustacean ingested by small feshwater fish, procercoid larva released and develops into PLEROCERCOID larva
6) Predator fish eats smaller infected fish
7) Human eats infected fish
8) Adult develops in small intestine, and releases UNEMBRYONATED eggs in the feces
What is the pathology of Diphyllobothriasis?
Known as "Jewish housewife's disease" because the preparers of gefillte fish or fish balls tended to taste these dishes before theyw ere fully cooked.

Non-specific symptoms - abdominal distention, flatulence, intermittent abdominal cramping, and diarrhea with onset about 10 days after consumption of raw or insufficiently cooked fish.

Anemia related to a vitamin B12 deficiency.
What is Jewish housewife's disease?
Diphyllobothriasis - associated with gefillte fish or fish balls
How is diagnosis of Diphyllobothriasis made?
Finding eggs in the patient's feces on microscopical examination
What is the treatment for Diphyllobothriasis?
Niclosamide, Praziquantel
How is the spread of Diphyllobothriasis controlled?
Cooking fish thoroughly, and freezing for at least 12 hours at -12 C or below
What are the characteristics of Entamoeba Histolytica?
Enteric Amoeba that Lyses tissues

Movement in host by extending pseudopodia

Engulf and digest bacteria and RBC

Excrete toxic products that lyse host cells.
What is the epidemoiology of Entamoeba Histolytica?
10% of all humasn are infected by Entamoeba species, and 50 million develop clinical amoebiasis annually, with 40,000-110,000 deaths

Entamoeba Histolytica is implicated in 2.8% of water-borne parasitic disease outbreaks

Amoebiasis ranks second (malaria is first) as a cause of death due to parasites
What is the source of infection of Entamoeba Histolytica?
Contaminated water is the source of infection
What are the trends of Amoebiasis cases in Mexico and the West bank/Gaza?
Mexico: 1999 - 1.5 million, 2006 - 660,000

West Bank/Gaza: 1999 - 6,500, 2003 - 10,000
What is the life cycle of Entamoeba Histolytica?
Cysts are ingested with food or water contaminated with human fecal material.

Cysts "excyst" in the small intestine, and the resulting trophozoites colonize the large intestine

Trophozoites reproduce by simple division, and they may invadethe lining of the large intestine resulting in symptoms (colitis, diarrhea, dysentary).

Cysts are then passed in feces and the cycle repeats

Upon invading the lining of the GI large intestine, trophozoites may invade the blood vessels and be transported to other organs of the body
What are the virulence factors of Entamoeba Histolytica?
Binding
Killing
Digestion
What is the important adherence molecule for Entamoeba Histolytica?
Gal-Lectin

A 260 kDa Gal/GalNAc specific lectin complex

Under reproducing conditions, this heavy complex dissociates into Heavy Subunit and Light Subunit

3 genes encoding the light subunit, lgl 1, lgl 2, lgl 3
What are Amoebapores?
A family of small amphipathic peptides capable of
insertion into bacterial or eukaryotic membranes and causing cellular lysis

They are REQUIRED for virulence
What is the role of Cystein Proteinases in Entaemoeba Histolytica?
Degradation of Human IgA
Disruption of Immune IgG
What is the Entamoeba two species hypothesis?
Proposed by Emile Brumpt - There are two morphologically indistinguishable species: Entamoeba Histolytica and Entamoeba Dispar. Only one of them (Histolytica) causes disease while the other is benign

This theory was entirely discounted and ridiculed

Recent molecular data has revived the two species hypothesis

We now know that most people are infected with the apathogenic Entamoeba Dispar
What is species is identical morphologically to E. histolytica and non-pathogenic?
Entamoeba Dispar
What are the characteristics of E. histolytic and E. dispar?
E. dispar:
In vitro culture - Xenic
ConA Agglutination - negative
Complement Resistance - negative
Zymodemes (isoenzymes) - I & III

Entamoeba histolytica:
In vitro culture - Axenic
ConA Agglutination - positive
Complement Resistance - positive
Zymodemes (isoenzymes) - II

Numerous DNA Sequence differences ~> PCR. 2.2% sequence diversity
What is the gentic evidence fo the two species hypothesis?
Species specific isoenzyme pattern
Multiple antibodies specific for either the pathogenic or apathogenic species
Numerous genes sequences showing clear differences
Repetitive DNA elements are different
Genomic organizaiton of conserved gene loci like actin is different
Ribosomal RNA (2.2% differences)
How is the diagnosis of E. histolytica made?
Examination for trophozoites in fluid feces
Examination for cysts in formed feces
Scraping and biopsies obtained through a sigmoidoscope
Liver abscess aspirates

Serology

Identification of Entamoeba histolytica / Entamoeba dispar ~> monoclonal antibodies against Entamoeba histolytica galactose adhesin

PCR
What is the treatment and prevention for E. histolytica?
Treatment:
Iodoquinol
Metronidazole

Prevention:
Better hygiene
Efficient sewage treatment and disposal
What is the drug of choise for amebiasis?
Metronidazole

For invasive amoebiasis, Metronidazole should be combined with a lumen acting drug as it is not fully effective on luminal stages
What is the treatment for invasive amoebiasis?
Metronidazole is the drug of choice, and should be combined with a lumen acting drug as it is not fully effective on luminal stages
How does Metronidazole work?
It is a prodrug which is activated by an enzyme (pyruvate ferredoxin oxioreductase) involved in the microaerobic fermentation metabolism of Entamoeba histolytica
What is the most common flagellate in the human digestive tract?
Giardia Lamblia
What are the characteristics of G. lamblia?
Giardia Lamblia
Most common flagellate in human digestive tract
Highly contagious

No mitochondria
No endoplasmic reticulum
No golgi apparatus
No lysosomes
Reproduction by simple division
Glucose as a main food source
Aerotolerant anaerobes

Classic "Smiley Face" of nucleus (eyes), median body (smile)
What is the pathology of Giardia lamblia?
Asymptomatic carriers

Diarrhea, dehydration, abdominal pain and weight loss

No blood loss associated with the diarrhea

The disease is not generally fatal

Strains of variable virulence
How is the diagnosis of G. lamblia made?
Giardia lamblia

Giardia cysts in the stool
Detection of salivary IgA antibodies to Giardia
What is the treatment for G. lamblia?
Metronidazole
What is the life cycle of G. lamblia?
Cysts ingested with contaminated water or food.

Cysts "excyst" and trophozoites colonize the small intestine.

Cysts passed in feces, and can either enter the reservoir host (beavers) or directly back to human infection
Chronic Amoebiasis - mucosal erosion and crater formation
Chronic Amoebiasis - mucosal erosion and crater formation
Echinococcus Granulosus
Echinococcus Granulosus
Echinococcus Granulosus
Echinococcus Granulosus
Echinococcus Granulosus - Cysts
Diphyllobothrium latum - Egg - Has Operculum (Lid) at top and Knob at bottom
Diphyllobothrium Latum - Egg
Diphyllobothrium latum - Proglottid
Diphyllobothrium latum
Echinococcus Granulosus - Egg
Echinococcus Granulosus - Protoscoleces (Hydatid Sand)
Echinococcus Granulosus
Entamoeba Histolytica - Cyst.jpg
Entamoeba Histolytica - Human colon mucosal damage
Entamoeba Histolytica
Giardia lamblia
Giardia lamblia
Giardia lamblia - Cyst - 12x8 micrometers
Giardia Lamblia
Hymenolepis nana (dwarf worm)
Hymenolepis nana (dwarf worm)
Trophozoite
Trophozoites start to engulf detached epithelial cells
Entamoeba Histolytica - Immature Cyst
What are the characteristics of Trematoda?
Flukes or leaf-shaped

Size - few mm to over several cm in length
Flat dorso-ventrally
Powerful muscular sucking discs for attachment and also spines and hooks as armature
Most of their anatomy is composed of reproductive structures
Most of them being HERMAPHRODITIC and having complex life cycles
They have a ***Simple Digestive Tract***
Molluscs are used as intermediate hosts for their larval forms
Targets: blood, lung, liver and intestine of people
What are the medically important trematode?
Schistosoma
Fasciola
Clonorchis
Paragonimus
What are the Schistosoma that cause infections?
Schistosoma mansonia
Schistosoma haematobium
Schistosoma japonicum (Katayama fever)
What is the distribution of Schistosoma disease?
Nearly all of Africa
Parts of southeast Asia
Parts of northwest South America

1,000,000 deaths per year
What are the characteristics of Schistosoma?
*Unusual trematodes in that the sexes are separate

They reside in the blood vessels of the definitive host
What is the life cycle of Schistosoma?
Cercaria penetrate teh skin of humans in infected waters.
Maturation occurs in liver circulation
They then grow in either the intestines or bladder, releasing eggs into the feces and urine, respectively.
Egg releases a MIRACIDIUM, which then infects the intermediate host, the ***SNAIL***

The miracidium then forms a sporocyst, and is released as a Cercaria into the water, which can reinfect humans.
What is the intermediate host of Schistosoma?
Snails
What are the proteins involved in Schistosoma Cercaria invasion of humans kin?
Group of proteins involved in calcium binding, calcium regulation, and calcium-activate functions

Two proteins (paramyosin and SPO-1) implicated in immune evasion

Protease isoforms implicated in degradation of host skin barriers
Where are the male and female Schistosoma located?
Female exists in the groove (Gynaecophoric canal) of the male

Males are shorter and wider
Females are longer and narrower
What are the features of the Schistosoma eggs?
***Presence of a SPINE
Presence of a thin transparent shell
Eggs measure between 110-175 by 45-70 micrometers
What are the sites of symptoms of Schistosomiasis, and what is their pathogenesis??
Skin - Dermatitis (swimmer's itch) - Parasitic toxic material, skin damage

GI (mansoni & japonicum) - Abdominal pain, ascites, diarrhea, bloody stool, Fever - Inflammatory response to eggs (mucosal fibrosis)

Urogenital (haematobium) - Chronic cystitis and urethritis, fever - Granulomatous fibrosis due to egg-deposits
How is the diagnosis of Schistosomiasis made?
Journey in an endemic region with bath in the local rivers or exposure to contaminated water
Identification of the eggs in feces or urine
Immunological methods
What is the treatment for Schistosomiasis?
Praziquantel (biltricide)
How does Schistosoma accomplish immune evasion?
The outer membrane of the cercaria has a lipid bilayer and a glycocalyx coat

3 hours after penetration, the outer membrane of the cercaria is replaced by a double lipid bilayer with no glycocalyx coat

Components of the host system incorporated into schistosome surface - blood group ags A, B, Lewis X & H factors, MHC antigens
How does Schistosoma mansoni evade the complement?
Produces an analog of decay accelerating factor in order to inhibit C3 convertase
What species produces an analog of decay accelerating factor in order to inhibit C3 convertase?
Schistosoma mansoni
How does the Schistosome accomplish immune deviation?
Production of a morphine-like substance that down-regulates macrophages, B-cells, T-cells, and NK cells
How does the Schistosome accomplish active molecular mimicry?
Passive transmission of genes

Virus mediate transfer - presence of HIV-1 genes in Schistotoma
What is the life cycle of Fasciola?
Unembryonated eggs are passed in feces of humans or pigs into the water

Embryonated eggs form in water

Embyonated egg hatches, releaseing Miracidia

Miracidia penetrates snail

In snail tissue: Miracidia ~> Sporocysts ~> Rediae ~> Cercariae

Cercariae released free-swimming into the water

Metacercariae on water plant ingested by humans or pigs, causing infection

Excyst in the duodenum, and adults in the small intestine, begin producing eggs
How is the diagnosis of F. buski made?
Fasciolopsis buski

Most infections are light and asymptomatic. In heavier infections, symptoms include diarrhea, abdominal pain, and fever

History of eating uncooked chestnuts in endemic area

Eggs in stool
What food is F. buksi infection associated with?
Uncooked chestnuts
What infection is associated with ingestion of uncooked chestnuts?
Fasciolopsis buski
What is the treatment and control of F. buksi?
Praziquantel is effective

Avoid eating uncooked chestnuts in endemic areas
Sanitary disposal of sewage
Elimination of snails
What is the geographic distribution of C. sinensis?
Chlonorchis sinensis

Parts of Eastern Europe
Parts of Northeast Asia
Parts of Southwest Asia and Japan
What is the life cycle of C. sinensis?
Embryonated eggs are passed in the feces

Eggs are ingested by the snail

Inside the snail: ~> Miracidia ~> Sporocysts ~> Rediae ~> Cercariae

Free-swimming cercariae encyst in the skin or flesh of fresh water fish

Metacercariae in flesh or skin of fresh water fish are ingested by human host

Excyst in duodenum, and adults in the BILIARY DUCT. Adults produce eggs, and embryonated eggs are released in the feces
What are the symptoms of C. sinensis?
Chlonorchis sinensis

Epigastric pain
Indigestion
Liver necrosis and tenderness
Liver dysfunctions related to fluke burden
Diarrhea, hepatomegaly, jaundice and ascites in heavier infections
How is the diagnosis of C. sinensis made?
Chlonorchis sinensis

Symptoms
History of eating improperly cooked fish in endemic area
Eggs in stool
What food is C. sinensis infection associated with?
Chlonorchis sinensis

Improperly cooked fish
What is the treatment and control of C. sinensis?
Chlonorchis sinensis

Praziquantel

Avoid eating improperly cooked fish in endemic areas
Sanitary disposal of sewage
Elimination of snails
What is the geographic distribution of P. Westermani
Paragonimus westermani

Small pockets in Central America
Small pockets in Western South America
Small pockets in Africa
Largest affected area in East Asia
What are the symptoms of P. westermani infection?
Paragonimus Westermani

Dry cough, pleurisy
Pulmonary pain
Blood-stained rusty brown sputum
Fluke may migrate to brain, produce eggs and cause epilepsy-like symptoms
What food is P. westermani infection associated with?
Paragonimus Westermani

Improperly cooked crab-meat
What pathogen is associated with eating improperly cooked crab meat?
Paragonimus Westermani
How is the diagnosis of P. westermani made?
Symptoms
History of eating improperly cooked crab meat in endemic areas
Eggs in sputum
What is the treatment for P. westermani?
Paragonimus Westermani

Praziquantel
Bithionol as alternative drug
Which Trematode releases its eggs in human urine?
Schistosoma hematobium
Which Trematodes release their eggs in human feces?
Schistosoma mansoni
Schistosoma japonicum
Fasciolopsis buski
Chlonorchis sinensis
What is the drug of choice for all Trematodes?
Praziquantel
Chlonorchis sinensis
Chlonorchis sinensis
Fasciolopsis buski
Paragonimus Westermani
Paragonimus Westermani
Schistosoma
Schistosoma - Emission of Cercaria
Schistosoma - Exit of Miracidium from egg
Schistosoma haemotobium - Egg
Schistosoma Japonicum - Egg
Schistosoma Mansoni - Egg
Schistosoma
What are the characteristics of T. vaginalis?
Trichomonas vaginalis

Four flagella
single nucleus
What pathogen has four flagella and a single nucleus?
Trichomonas vaginalis
How does T. vaginalis multiply?
Trichomonas vaginalis multiplies by longitudinal binary fission
How is T. vaginalis spread?
Via sexual intercourse

Trichomonas vaginalis is present in vaginal and prostatic secretions and urine. It may exist in the vagina or orifice of urethra
What is the epidemiology of T. vaginalis?
Trichomonas vaginalis has a worldwide distribution

Incidence as low as 5% in normal females and as high as 70% among prostitutes and prison inmates

U.S. about 3 million people are infected every year
What are the symptoms of T. vaginalis infection?
Trichomonas vaginalis infection is rarely symptomatic in men, although it may cause mild urethritis or occasionally prostatitis

In women, it is often asymptomatic, but heavy infections in a high pH environment may cause mild to severe vaginitis with copious foul-smelling yellowish, sometimes frothy discharge
How is T. vaginalis diagnosed?
Trichomonas vaginalis is diagnosed by Pap stain / microscopy
What is the treatment for T. vaginalis infection?
Metronidazole
What organism can live within T. vaginalis?
Mycoplasma hominis can survive intracellularly in Trichomonas vaginalis
In what organism can Mycoplasma hominis live intracellularly in
Mycoplasma hominis can survive intracellularly in Trichomonas vaginalis
What are the infective and diagnostic stages of T. vaginalis infection?
Infective - Trophozoite in vagina or orifice of urethra

Diagnostic - Trophozoite in vaginal and prostatic secretions and urine
Trichomonas infection of the cervix
Trichomonas vaginalis - Four Flagella, Single Nucleus
Trichomonas vaginalis - Four Flagella, Single Nucleus
Trichomonas Vaginalis - Pap stain and microscopy
Trichomonas vaginalis
What are the coccidia parasites?
Cryptosporidium
Isospora, Sarcocystis, Cyclospora
Toxoplasma
Plasmodium
What are the characteristics of C. parvum?
Cryptosporidium parvum

Major cause of epidemic diarrhea
Animal reservoir
Severe diarrhea and invasive infection in AIDS patients
What is the life cycle of C. parvum?
Cryptosporidium parvum

Thick-walled oocyst (sporulated) exits the host

Contamination of water and food with oocysts

Thick-walled oocyst ingested by the host

Inside host, complex sexual and asexual lifecycle takes place.

Thick-walled oocysts (sporulated) exit host in feces
How is the diagnosis of C. parvum made?
Cryptosporidium parvum

Detectionof oocysts (4-5 um) in fresh stool samples

Ziehl stain
What organism is the Ziehl stain used for?
Cryptosporidium parvum
What stain is used to detect C. parvum?
Ziehl stain
What is the treatment and control for C. parvum?
Spiramycine, and supportive therapy may be temporarily effective

Control - water quality
Cryptosporidium parvum - Oocysts
What pathogens cause the cutaneous form of Leishmaniasis?
Leishmania tropica
Leishmania major
Leishmania mexicana
What pathogens cause the mucocutaneous form of Leishmaniasis?
Leishmania braziliensis
What pathogens cause the visceral form of Leishmaniasis?
Leishmania donovani (India)
Leishmania infantum (Mediterranean form of kala azar)
What is the name for the cutaneous form of Leishmaniasis?
Oriental sore
What is Oriental sore?
The cutaneous form of Leishmaniasis
What is Kala azar?
The visceral form of Leishmaniasis
What is the geographic distribution of Leishmaniasis?
South America (mucocutaneous mainly)
Parts of Africa, Mediterranean, and Asia with all 3 types
How many cases of Leishmaniasis are there per year?
2 million new cases per year
2/3 are Cutaneous Leishmaniasis (CL)
1/3 are Visceral Leishmaniasis (VL)
What is the insect vector of Leishmaniasis?
Sand Fly

Old World
Phlebotomus sp.
Sergentomya sp.

New World
Lutzomyia sp.
Brumptomya sp.
What is the life cycle of Leishmaniasis?
The vector (a sand fly) ingests macrophages when it ingests blood.

The amastigotes are released in the vector's gut, and the parasite reproduces as promastigotes

The vertebrate host is infected with promastigotes when bitten by the vector

The promastigotes enter circulating macrophages and reproduce as asmastigotes

The macrophage dies, and the amastigotes are released, and they infect more circulating or fixed macrophages

The vector (sand fly) ingests the infected macrophages during a blood meal, repeating the cycle
What is the morphology of Leishmania?
Promastigote (leptomonad) - seen in sand fly

Amastigote (leishmania) - seen in the mammalian host (LD body - Leishman-Donovan body)
What is a Kinetoplast?
A disk-shaped mass of circular DNA inside a large mitochondria that contains many copies of the mitochondrial genome.
Where are the rRNA and structural genes located on the Kinetoplast?
The maxicircles
What is located on the maxicircles of kinetoplasts?
rRNA and structural genes like cytochrome oxidase subunits I, II, and II, cytochrome b
What is the progression and resolution of Old World CL?
CL - Cutaneous Leishmaniasis
Leishmania Major and Leishmania Tropica

Caues a moist, cutaneous, ulcer-like lesion at the site of the bite. It starts as a papule that runs an acute course of 1-3 weeks.

Natural healing of the infection over 2-12 months
What is the vector and reservoir of old world CL?
CL - Cutaneous Leishmaniasis

Transmission via sand fly
Reservoirs - gerbil, rodents, dogs
Human to human transmission possible

Direct transmission from human to human ~~> primitive form of vaccination
What is the progression and resolution of New World CL, and where and among whom is it found?
CL - Cutaneous Leishmaniasis
Leishmania mexicana

Ulcer usually heals spontaneously over a few months. When bite occurs on ear it results in chronic lesions known as chiclero's ulcer. Because cartilidge of ear is poorly vascularized, immune response is weak, and 40% of cases result in mutilation of ear.

Rural diseases that are more prevalent among males who work in forests. Found principally in Central America and Mexico where it occurs in the forest dwelling people who harvest latex from the chicle trees to be used in the manufacture of chewing gum
What is Chiclero's Ulcer?
Chronic lesions on the ear of New World Cutaneous Leishmaniasis
How is the diagnosis of CL made?
Diagnosis of cutaneous leishmaniasis is made by using scraping from the edge of the ulcer smeared on a slide, stained and examined microscopically for **amastigotes**

PCR amplification of parasite genes.

Tissue biopsies are touched to filters, and filters are hybridized with labeled probes against parasite genes
What is the treatment and control for cutaneous leishmaniasis?
Pentavalent antimonials may be used, such as Stilbophen, Pentostam, or Glucantime. Usually they are not necessary.

Local antibiotic to avoid secondary infection

Control:
1) Cover sores
2) Remove reservoirs
3) Remove vectors near habitation using insecticides
4) Screen against sandflies and use repellents
Where does mucocutaneous leishmaniasis occur?
Only in the New World
What is the progression of mucocutaneous leishmaniasis?
Begins like cutaneous leishmaniasis, and the ulcer heals spontaneously within 6-15 months. However, there is **metastatic** spread of the promastigotes from the site of the bite via the lymphatics

Leishmania brailiensis:
Metastatic lesion involves the nasal and buccal mucosa causing destruction and malformations of the cartilage and soft tissues
Death may occur from secondary infections or respiratory complications
What is the reservoir for L. braziliensis
Leishmania braziliensis - Mucocutaneous Leishmaniasis

Sloths and Anteaters
How is the diagnosis of Mucocutaneous Leishmaniasis made?
Diagnosis made by using scrapings fromt he edge of the ulcer smeared on a slide, which is stained and microscopically examined for amastigotes
What is the treatment for mucocutaneous leishmaniasis?
Treatment is usually ineffective despite intramuscular or intravenous injections of pentavalent antimonials.

Secondary bacterial infections are treated with antibiotics.

Liposomal amphotericin B 3mg/kg
What causes Kala Azar?
Leishmania donovani - found in India
What is the pathology of Kala Azar?
Leishmania donovani
This is a metastatic disease
Rarely is a lesion seen at the site of bite, and parasites are only occasionally seen in blood, but are present in the spleen and lymph nodes

Incubation period of 1-4 months

Disease is characterized by fever, anemia, splenomegaly, wasting, imbalance of serum proteins (A/G ratio is reversed) and hyperpigmentation of the skin. The death rate is VERY HIGH if left untreated.
Splenomegaly, hyperpigmentation, reversal of A/G ratio of serum proteins and endemicity in India is indicative of...?
Visceral Leishmaniasis (Kala Azar)
What is the reservoir of Visceral Leishmaniasis?
There is no reservoir
What are the symptoms of Visceral Leishmaniasis?
1-4 months: fever, chills, diarrhea, dysentery
Progressive hepatosplenomegaly
Skin hyperpigmentation

Death, if untreated
What pathogen causes the Mediterranean form of Kala Azar?
Leishmania infantum
What is the natural reservoir for Mediterranean Kala Azar?
Dogs, jackals and foxes
Humans are accidental hosts
Principally occurs in children, but unknown why this is the case
L infantum causes what?
Mediterranean form of Visceral Leishmaniasis (Kala Azar)
What is the treatment for visceral leishmaniasis?
Sodium stibogluconate or pentastam, a derivative antimony

Severe reactions including death occur in 10% of those treated

It is very expensive, and the recommended one month treatment costs around $150

Drug resistance has also developed. Up to 70% of infected patients in India are resistant to the drug.

Pentamidine isethionate has been used in antimony-resistant visceral leishmaniasis, but although the initial response is often good, the relapse rate is high and it is associated with serious side effects

Recently, new drug ***Miltefosine*** developed. Acts as a membrane signaling pathway inhibitor. Taken orally, 95% cure rate.
What new drug is in clinical trials for treatment of Leishmaniasis with promising results?
Miltefosine - A membrane signaling pathway inhibitor
Where in the host do Leishmania reside?
Inside macrophages
What are the virulence factors of Leishmania?
Trypanothione - Resistance to superoxide anion (oxidative burst)

Lipophosphoglycan (LPG) - In the insect vector, LPG:
1) Inhibits the release of midgut proteases in the fly
2) LPG mediates the attachment of promastigotes to the gut wall
In the mammalian host:
1) A direct measurement of oxidative burst in stimulated macrophages showed that LPG inhibited this activity
2) LPG inhibits the induction of the burst

gp63 - Major surface glycoprotein of L. major promastigotes. It is a GPI-anchored zinc metalloprotease.

The gp63 protein appears to mimic fibronectin. The gp63 protein can also degrade lysosomal enzymes.

The A2 gene in L. donovani and L. major
What is the A2 gene?
Leishmania donovani and Lieshmania major

A2 gene familly exists in amastigote stage in L. donovani. In L. major, only a pseudogene

A2 genes are tanden repeated with a distinct gene family termed the A2erl genes. A2rel is expressed at equal levels in the promastigote and amastigote.

L. donovani amastigotes deficient in A2 protein (asRNA, gene k.o.) are attenuated with respect to survival in visceral organs of infected mice.

L. major genetically engineered to express A2 produced higher infection levels in the spleen and liver, compared to control L. major.
Cutaneous Leishmaniasis - Amastigotes
Leishmania - Promastigotes
Leishmania donovani promastigote binding to macrophage
Macrophage filled with Leishmania Amastigotes
What is the whip worm?
Trichuris Trichiura
What is the distribution of T. Triciura? How many people are infected?
Trichuris Trichiura
Temperate and tropical areas
355 million people infected worldwide
How is T. Trichiura diagnosed and treated?
Diagnosis - presence of eggs in feces

Treatment - Adult worms sensitive to Mebendazole and Benzimidazole
What are the symptoms of Trichuris Trichiura infections?
Mild infections are generally asymptomatic
Serious infections can cause blood diarrhea, anemia, and rectal prolapse
What is the threadworm?
Enterobius Vermicularis
What is the commonest cosmopolitan worm parasite?
Enterobius Vermicularis
What are the characteristics of E. vermicularis?
The "threadworm", Oxyuris

Commonest of the cosmopolitan worm parasites in man, infecting mostly children.

Worm lays eggs which contain an infective larva ready to infect other people.
What are the clinical symptoms of E. Vermicularis infection?
Enterobius Vermicularis

Most infections are light and asymptomatic
Heavy infections - abdominal pain, anal pruritus (biting of the female during the night), pallor and dysentery

Enterobiasis can cause severe complications - skin lesions, vulvovaginitis in children, appendicitis, peritonitis, **insomnia**
How is the diagnosis of Enterobius Vermicularis made?
Nocturnal observation. The worms come to the outside of the anus during the night, and can be seen as "cottony wisps"

The "Scotch-test anal swab" utilizes a piece of tape that is pressed against the anus at night. The worms stick to the tape, which is then pressed against a microscope slide and viewed directly.
What is the treatment of Enterobius Vermicularis?
Mebendazole - single dose of 100 mg repeated at least once after an interval of 2 to 4 weeks.

Pyrantel pamoate - single dose of 10 mg/kg repeated after an interval of 2 to 4 weeks.
How rapidly does infeciton of Enterobius Vermicularis develop?
Infective larvae are already developed 5-6 hours after the laying of the eggs.
What is the life cycle of Enterobius Vermicularis?
Hands, bed clothing, bed linens, floors, drapes, kitchen counters, clothing, school rooms, desk tops, etc. are contaminated with infective eggs.

Humans are infected when the ingest eggs containing infective juveniles.

Eggs hatch in small intestine, and male and female worms migrate to the large intestine and reach sexual maturity.

Females crawl out of the anus (during night/early morning) and deposit eggs on the perianal skin.

At this point, retroinfeciton possible - eggs that remain on perianal skin long enough hatch, and juveniles will crawl back into the anus to mature.

Eggs deposited on the perianal skin become infective within six hours, and can then be spread by being deposited on virtually any surface or object.
Enterobius Vermicularis - Egg
Enterobius Vermicularis - Egg
Enterobius Vermicularis - Female
Enterobius Vermicularis
Trichuris Trichiura - Egg
Trichuris Trichiura
What are the characteristics of Nematodes?
Round worms

Nematodes have remarkable consistency of shape, normally being vermiform, long and slender with pointed ends

Sexes are usually separate

The outer surface of the nematode is not cellular but cuticular

Unlike the Cestodes and Trematodes, the Nematodes have a continuous gut with a separate mouth at one end and an anus at the other
Nematode Structures:
C - cuticle
Hy - hypodermis
n - Dorsal and Ventral nerves
Ps - pseudocoelom
ll - Lateral line
et - Excretory tubule
O - ovary
Ut - uterus
G - gut
What are the characteristics of Strongyloides stercoralis?
Dwarf worm
180-380 mm long by 14-20 mm wide
Common parasite of man in warm countries
Presence of free-living stage
Females produce eggs parthenogenetically in the upper part of the small intestine
What are the sites of symptoms of S. stercoralis infection and their pathogenesis??
Strongyloides stercoralis

Skin - Itching and red blotches - Cutaneous invasion and sub-cutaneous migration of larva

Pulmonary - Verminous pneumonia - cough, shortness of breath, wheezing, and fever

GI Tract - Mid-epigastric pain, nausea, vomiting, diarrhea/constipation, bloody dysentery - Attachment of adult worms and injury to upper intestinal mucosa

General - Weight loss and anemia (rare) - Loss of nutrients and blood
What does S. stercoralis cause in young children?
Strongyloides stercoralis

"Swollen Baby (or belly) syndrome"

Young infants develop massive Strongyloides infections.
Fatal infection unless rapid treatment is given
How is diagnosis of S. stercoralis made?
Strongyloides stercoralis larva observed in stool

Immunofluorescent antibody test
What is the treatment for Strongyloides stercoralis?
Thiabendazole or Ivermectin
What are the characteristics of the hyper-infective mode of S. stercoralis?
Strongyloides stercoralis
Patients with asymptomatic chronic infection that become immunocompromised (steroids, surgery, HIV...) develop serious infection

Fatality rate as high as 87%

Fatality caused by presence of the parasite but also by heavy bacterial infection
What is the life cycle of S. stercoralis?
Strongyloides stercoralis

Juveniles are released in host feces. Juveniles molt and either produce infective juveniles (filariform larvae) or free-living juveniles (rhabditiform larvae)

In the free-living cycle, males and females mate, producing eggs that hatch new juveniles that can become infective.

the infective juvenile penetrate the skin of the host, enter the blood stream and migrate to the lungs.

From the lungs, they enter the alveoli and are coughed up and swallowed. Juveniles then take up residence in small intestine and mature into parasitic females.

Parasitic females embed in intestinal mucosa, and release eggs which hatch in intestine into juveniles that are released in feces.
What is the definitive host of T. gondii?
Toxoplasma gondii
The cat and relatives in the family Felidae
What symptoms can toxoplasmosis cause?
Congenitally infected children may suffer impaired vision (retinitis) and mental retardation (encephalitis)

Immunosuppressed patients may have central nervous system disease (encephalitis)

Infection is usually asymptomatic in immunocompetent individuals
What is the pathogenesis of toxoplasmosis?
Number of factors that determine if infected host will express disease smptoms

Diet - if uncooked or poorly cooked meat is eaten

Immunocompromised Host - if the patient is undergoing suppressive immunotherapy as in the case of transplant patients or if the patient is suffering from HIV.

**New born infants are particularly susceptible to heavy infections
What are the characteristics of congenital toxoplasmosis?
Toxoplasma gondii can cause abortion of the fetus or can cause severe malformation at birth

Most authorities believe that if a woman is infected before she is pregnant transplacental transmission will not occur

The greatest risk of congenital toxoplasmosis occurs during the first trimester of pregnancy

The transmission rate from a maternal infection is about 45%. Of these 60% are sub-clinical infections, 30% have severe damage such as hydrocephalus, intracerebral calcification, retinochoroiditis, and mental retardation, and 9% result in death of the fetus
How is the diagnosis of toxoplasmosis made?
Serologic testing - ELISA

Pregnant women - Serological tests before or at the beginning of the pregnancy. Survey during pregnancy

Immunosuppressed patients - direct diagnosis (PCR)
What is the treatment of toxoplasmosis in immunoconversion of a pregnant woman? In immunosuppressed patients? If the fetus is affected?
Imunoconversion of a pregnant woman - Spiramycine (Rovamycine) until the childbirth

Immunosuppressed patients - PYRIMETHAMINE (inhibitor of DHFR - dihydroxyfolate reductase) + SULFADIAZINE

If the fetus is affected - PYRIMETHAMINE + SULFADIAZINE (sulfonamide) + ACID FOLINIC
How is toxoplasmosis prevented?
Avoidance of contact with cats during pregnancy

Avoidance of eating uncooked or poorly cooked meat
What is the life cycle of T. gondii?
Toxoplasma gondii

The definitive host is the cat, which releases unsporulated oocysts in its feces. The oocyst then sporulates, and can infect a human directly or an intermediary animal.

In the intermediary, pseudocysts form in tissues, which if improperly cooked can be ingested in beef, lamb, pork, etc.

The organism enters the host, and the Tachyzoites are ingested by macrophages, where they multiply. The Tachyzoites then migrate to tissues where they form pseudocysts.
Nematodes Structures
Strongyloides stercoralis - Larva
Strongyloides stercoralis - Larva
Strongyloides stercoralis
Toxoplasma gondii - Pseudocyst filled with bradyzoites
Toxoplasma gondii - Tachyzoites
What is the epidemiology of hookworms?
Distributed in the Americas, Africa, Asia, Australia, and parts of Europe.

Hookworms parasitize more then 900 million people worldwide.

Cause a daily blood loss of 7 million liters.
What are the species of hookworms?
Ancylostoma duodenale
Necator americanus
What are the characteristics of hookworms?
Hemophages - Change from white to red after a meal

Necator americanus - few, broad dull teeth at the mouth

Ancylostoma duodenale - many, sharpy pointy teeth at mouth

Male has broad fan-like tail, Female has pointy tail
What are the sites of symptoms of hookworms, and what is their pathogenesis?
Dermal - Erythema, macules, papules (ground itch) - Cutaneous invasion and sub-cutaneous migration of larva

Pulmonary - Bronchitis, pneumonitis, eosinophilia - Migration of larvae through lung, bronchi, and trachea

GI - Anorexia, epigastric pain, and GI hemorrhage - Attachment of adult worms and injury to upper intestinal mucosa

Hematologic - Iron deficiency, anemia, hypoproteinemia, edema, cardiac failure - Loss of nutrients and blood
How is the diagnosis of hookworms made?
Travel in an endemic region
Eggs in stool
What is the treatment and prevention of hookworms?
Benzimidazole: Mebendazole, Flubendazole, Albendazole
Pyrantel
To correct anemia - Iron and Vitamin B12

1) Hookworm disease is best controlled by sanitation involving proper disposal of human feces
2) Treatment of infected individuals and proper diets to correct anemia
3) Protective measures such as wearing of shoes in areas where hookworm is endemic
What is the life cycle of hookworms?
Eggs hatch in soil, and juveniles develop into infective stage.

Infective juveniles penetrate the skin, and migrate via the blood to the lungs.

Juveniles penetrate alveoli and are coughed up and swallowed.

Juveniles enter small intestine, attach to surface and mature into adult forms.

Adult hookworms attach to lining of small intestine and feed on blood. Females produce eggs that are passed in the host's feces.
Hookworm Egg
Hookworm Egg
Hookworm Egg
Hookworm Morphology - Left = Necator americanus - Right = Ancylostoma duodenale
Hookworms
What is Chagas disease?
Trypanosoma cruzi
What is the Epidemiology of Chagas disease?
Trypanosoma cruzi
Primarily South and Central America
15-20 million people are infected
Transmission associated with poor living conditions
What is the life cycle of T. cruzi?
Trypanosoma cruzi
Trypomastigote infects humans, and distributes in the body.

Amastigotes are released in the feces, and then ingested by the vector, the REDUVID bug.

Inside midgut Amastigote ~> Epimastigote, which then multiplies and becomes the Metacyclic Trypomastigote (infective stage)
What is the vector and reservoir for Chagas disease?
Trypanosoma cruzi
Vector - Reduvid Bug
Reservoir - Armadillo
How does T. cruzi replicate in the cell of the vertebrate host?
Trypanosoma cruzi
Trypomastigote attaches to membrane and initiates signaling process that results in elevation of intracellular Ca++. Lysosomes migrate to trypomastigote attachment site and fuse with membrane. As they fuse, parasite moves into cell in a tight vacuole formed by lysosomal membranes. Lysosome-derived vacuole is disrupted, releasing the parasite into the cytosol.

In cytosol, parasite differentiates into amastigotes, which replicate by binary fission, doubling time 12 h. Amastigotes differentiate back into infective trypomastigotes, which release into the blood stream upon rupture of host cell.

Bloodstream trypomastigotes can infect new cells, or be ingested by the insect vector (REDUVID bug).
What are the clinical syndromes of Chagas disease?
Asymptomatic - No symptoms at this stage which may last for many years. No trypomastigotes in the bloodstream, but antibody (IgG) against T. cruzi is present

Acute - Site of infection develops localized inflammatory reaction "Chagoma nodule". If infection is on the eye, unilateral edema and conjunctivitis develops, the "CHAGOMA/ROMANA'S sign". Trypanosomes appear in blood in about 10 days. Systemic signs 2-3 weeks after infection, of high feveres, myalgia, CNS may be affected. ***Disease more severe in children <5 years.

Chronic - 10-30% of individuals progress from the asymptomatic stage to the chronic stage. There are very low levels of parasites in the blood. The adverse effects of chronic Chagas disease include enlargement and aberrant function of the liver, spleen, heart, esophagus, and large intestine.
What is Romana's sign?
Infection of the eye by Trypanosoma cruzi that results in unilateral edema and conjunctivitis
How is the diagnosis of Chagas disease made?
Trypanosoma cruzi

Blood microscopy
Low sensitivity during the chronic stage
Xenodiagnosis (50% efficiency)
Serological detection
ELISA - Chagas kit
PCR
What is the treatment and prevention of T. cruzi?
Trypanosoma cruzi - Chagas disease

Nifurtimox - decreases duration and severity of the acute phase. But if it is taken orally for long periods, severe side effects - pain, nausea, vomiting, neurologic symptoms. No effect on chronic phase.
Benzimidazole - can suppress parasites in the acute phase. This drug is also taken orally for long periods and has many side effects.

Avoid and control the insect population.
No vaccine.
What are the antibody based molecular diagnosis kits available for Chagas disease?
Trypanosoma cruzi

1) FATALA kit - measures T. cruzi antibodies in blood using 2 recombinant proteins

2) BIO CHAGAS kit - uses cocktail recombinant T. cruzi antigens. Infection sera produces blue precipitate on strip in 60 minutes

$25 US per kit
What are the theorized targets in the THEORETICAL autoimmune mechanism of chronic Chagas disease?
Trypanosoma cruzi

B13 - cardia myson
Cruzipain - 210 kDa antigen from a skeletal muscle extract
Cha - ?
Trypanosoma cruzi
Trypanosoma cruzi
Trypanosoma cruzi - In Tissue
Epidemiology of T. spiralis
Trichinella spiralis
At one time widely distributed in Europe and US, though reduced now due to livestock maintenance.

Found in many species of carnivores and omnivores. Infection related to consumption of raw or undercooked meat, mainly pork.
Characteristics and morphology of T. spiralis?
Trichinella spiralis
1) Smallest Nematode parasite of humans
2) Although it has a single host life cycle, the host acts as both the primary and intermediate host.
3) There are no free-living stages

Morphology:
Males - 1.5 mm
Females 3.4 mm
Females (ovoviviparous) produce living young (approximately 1,500 per female over a period of 4 to 16 weeks) and then die.
Males die after mating
What is the life cycle of T. spiralis?
Trichinella spiralis

Humans are infected most often by eating improperly cooked meat products that contain infective juveniles.


Carnivores and omnivores are infected when they eat meat containing the infective juvenile stage.

Juveniles digested from muscle, and penetrate into tissues of small intestine and grow to sexual maturity.

Juvenile worms migrate to muscles of host and mature into infective stage.
What diseases does T. spiralis cause in humans?
Trichinella spiralis

Trichinosis and Trichnellosis
What are the symptoms of Trichinosis, and what is their timeline?
GI - 24-72 hours - Nausea, vomiting, abdominal pain, diarrhea, head ache

Circulation - 10-21 days - Edema, periorbital conjunctivitis, photophobia, fever, chills, sweating, muscle pain, spasm, eosinophilia

Myocardium - 10-21 days - Chest pain, tachycardia, edema, vascular thrombosis

Brain - 14-28 days - Head ache (supraorbital), vertigo, tinnitus, deafness, mental apathy, delirium, coma, loss of reflexes
How is the diagnosis of Trichinosis made?
Symptoms
Recent history of eating undercooked pork
Eosinophilia
Increased serum creatinine phosphate and lactage dehydrogenase
Serology
What is the treatment and prevention of Trichinosis?
All the nematocides are efficient against the adult stage (very short phase)

Benzimidazole should be used against L1 stage because of their bood diffusion

Prevention:
1) Cook pork thoroughly (also bear, wild pigs)
2) Cook all garbage fed to hogs
3) Proper meat handling, ordinary curing and slating of pork products will not kill encysted juveniles
4) Freezing is effective if carried out properly
Trichinella spiralis - Female
Trichinella spiralis - Infective juvenile in muscle
Trichinella spiralis - Trichinosis
What are the types of Trypanosomiasis?
African trypanosomiasis - Sleeping Sickness
Trypanosoma brucei rhodesinse
Trypanosoma brucei gambiense

American Trypanosomiasis - Chagas Disease
T. cruzi
What is the distribution of Sleeping Sickness?
African trypanosomiasis - Sleeping Sickness

Western, central and southern Africa
What is the host, vector, localization and disease of the two strains of African Sleeping Sickness?
T. brucei rhodesinse:
Host - Human, antilopes, deer
Vector - Glossina morsitans
Localization - Savannah
Disease - acute (weeks-months)

T. brucei gambiense:
Host - Human
Vector - Glossina palpalis
Localization - Rivers
Disease - Chronic (1-2 years)
What is Winterbottom's sign?
Enlarged neck lymph nodes in Trypanosoma brucei gambiense or Trypanosoma brucei rhodesinse disease
What is the life cycle of African Sleeping Sickness?
T. brucei gambiense or T. brucei rhodesinse

Infection of human by bite of TSE-TSE FLY (GLOSSINA). Trypomastigote multplies in blood, lymphnodes and spinal fluid. Trypmastigotes in blood can be re-ingested by the vector.

In the vector, multiplication occurs in midgut, then migration to salivary gland. Epimastigote stage in salivary glands, with further multiplication. Transforms to metacyclic trypomastigote in salivary glands, which are infective.
What are the forms of T. brucei?
Trypanosoma brucei

Epimastigote (crithidial form) - in the insect

Trypomastigote (trypanosomal form) - in the mammalian host
What is the pathology and immunology of T. brucei disease?
Trypanosoma brucei
Pathology:
Inflammation
Antigenic change
CNS damage by the organisms

Immunology:
Antibodies are not protective due to antigenic change
Polyclonal B cell expansion; hyper-IgM
Hypocomplementemia (CRP)
Immunosuppression
What mediates somnolence in T. brucei disease?
Somnolence - Indole Catabolites

Toxic metabolites of aromatic ring AAs (Tryptophan, tyrosine, phenylalanine)

Anaesthetic affects
Damage blood vessels
Induce temperature changes
Immunosuppression
How is the diagnosis of T. brucei made?
Trypanosoma brucei

History of travel and fly-bite
Symptoms
Blood smear and/or CSF
Anionic supper concentration
Bioassay (mouse)
Immunoassays
What is the treatment and control of T. brucei disease?
Pentamidine
Arsenical suramin (early phase, inhibits glycolytic enzymes of trypomastigote)
Melarsoprol (arsenical)
Eflornithine (difluoromethyl-ornithine, ADVANCED DISEASE)

No reliable vaccine ~> Antigenic variation

Tse-tse fly insecticides or traps with an attractant bait plus insectiside
How does antigenic variation in T. brucei occur?
Possesses a surface coat of proteins, 10 million copies of a single molecular species of antigen

VSG - Variant Surface Glycoprotein - Each trypanosome carries a large repertoire of VSG genes coding for multiple VSG variants with different primary sequence
How is the VSG ES organized?
Variable Surface Glycoprotein Expression Site

20 different ESs
Only one is active at any one time
Polycystronic transcription followed by mRNA processing
Many homologous sequences
Rich in recombination events
ESs as a whoel are homologues in sequence, further supports recombination
Many combinations to build a repertoire of different VSGs and ESAGs.
Contributes to host adaptation
How is cellular regulation in T. brucei accomplished?
Greatly unknown
Open chromatin conformaiton in the active ES, closed in the silent ones
Base J (a modified uracil) was found incorporated in the silent ESs, while absent from the active one
Base J probably represses transcription in a way similar to methylation
What is the VSG switching mechanism in T. brucei?
Gene conversion (homologous recombination) - most common

Mosaic VSG formation

VSGs are transcribed in a specialized nuclear compartment
Trypanosoma brucei
Trypanosoma brucei - trypomastigote form
Trypanosoma brucei - VSGs
Trypanosoma brucei
Epidemilogy of Malaria?
40% World population at risk
300 million develop clinical malaria
1 million die each year - mainly children
Generally limited to tropics and subtropics

P. Falciparum - Asia, africa, and south and central america
P. vivax - less temperature sensitive ~> most widespread Europe (rare), north africa, middle east, southa merica
P. ovale - rate, Central and occidental africa
P. malariae - Tropical africa, south and central america
What are the strains of malaria, and which is the most virulent form?
Plasmodium species:
P. Falciparum - most virulent
P. vivax
P. ovale
P. malariae
How is malaria transmitted?
Anophele (female mosquito) and also blood transfusion
What is the life cycle of malaria?
Mosquito ingests gametocytes, which form zygote in gut and develops into oocyst. Oocyst releases sporozites, which reach salivary gland and are infective.

Mosquito bites again, injecting sporozites into host. Sporozites first infect hepatic cells (can be dormant here), which rupture and release merozoites that infect RBCs. Reproduction in RBCs, and rupture to release gametocytes.
What are the symptoms of the three stages of malaria?
Cold Stage - Fever, shaking chills

Hot Stage - High fever, headache, nausea, vomiting, dizziness, pain, delirium

Sweating Stage - Sweating, fall in temperature, prostration
Anemia (pallor, tiredness, fatigue, shortness of breath), splenomegaly, hepatomegaly
What is cerebral malaria?
Most often seen with Plasmodium falciparum

Cerebral malaria (CM) collectively involves the clinical manifestations of P. falciparum malaria that induce changes in mental status and coma. It is an acute, widespread disease of the brain which is accompanied by fever. Mortality is 25-50%

In untreated person, CM is fatal in 24-72 hours

The histopathological hallmark of this encephalopathy is sequestration of cerebral capillaries and venules with parasitized RBCs and and non PRBCs. Ring-like lesions in brain are major characteristics. Disease risk factors include being child under 10 years of age and living in malaria-endemic area.
Possible mechanisms to explain CM?
CM - Cerebral malaria
P. falciparum erythrocyte membrane protein (PfEMP-1)

Ligands on endothelial cells, such as ICAM-1 or E-selectin

Reduction of microvascular blood flow and induces hypoxia

Expression of iNOS, oxidative stress and finally apoptosis in endothelial cells
What are the incubation periods, erythrocyte cycle (hr), liver status, and parasitemia (mm^3) of the 4 plasmodium species?
P. falciparum:
Incubation - 7-10 days
Erythrocytic cycle - 48 hours
Persistent Liver Stage - No
Parasitemia - 50k-500k, max 2.5 mil

P. vivax:
Incubation - 10-17 days
Erythrocytic cycle - 48 hours
Persistent Liver Stage - Yes
Parasitemia - 20k, max 50k

P. malariae:
Incubation - 18-40 hours
Erythrocytic cycle - 72 hours
Persistent Liver Stage - No
Parasitemia - 6k, max 20k

P. ovale:
Incubation - 10-17 days
Erythrocytic cycle - 48 hours
Persistent Liver Stage - Yes
Parasitemia - 9k, max 80k

48 hours - tertian
72 hours - quartan
How is diagnosis of malaria made?
Blood smear with Giemsa stain (methylene blue and eosin) under microscope

PCR - 1 plasmodium in 10 mL of lbood

Immune detection
What are Schuffner's dots?
Microscopically visible specs of P. vivas (malaria) under blood smear microscopy with giemsa stain
What induces gametocyte exflagellation in infected mosquitoes?
Xanthurenic acid
Additional stimulus: drop in temperature
What induces infectivity in P. falciparum containing mosquitoes?
Xanthurenic acid induces gametocyte exflagellation of plasmodium in the mosquite
Additional stimulus - drop in temperature
What are the indirect immune responses of the mosquito to plasmodium proteases?
Various proteases are secreted from the midgut epithelium. Ingested asexual erythrocytic stage parasites and **any gametocytes that have failed to transform into ookinete stage are also digested**

Two GPI-anchored proteins, P25 and P28, cover the ookinete surface and their disruption results in increased sensitivity to proeases in vitro, and reduced oocyst formation, in spite of normal ookinete numbers.
What is the cross interaction between bacteria and plasmodium in the mosquito gut?
Feeding of gram-negative bacteria with a malaria-infected meal reduces oocyst formtaion

Administration of antibiotics has a positive effect on parasite development - it kills the bacteria and therefore helping the parasite

Bacteria DECREASE plasmodium
What is the role of humans and mosquitoes in malaria transmission?
Both humans and mosquitoes are not passive.

Mosquitoes secrete proteases in the gut, and have flora bacteria that both decrease plasmodium infectivity
What are the human host defense mechanisms against malaria?
Antibodies to sporozoites can prevent invasion of hepatocytes

IFN-gamma and cytokines inhibit development of liver stage

CD8+ T-cells lyse infected hepatocytes

Abs to merozoites can prevent invasion of RBCs

Duffy antigen required for invasion of RBC.

Sickle cells provide poor environment for P. falciparum

Cytokines can destroy infected RBCs

Abs to gametocytes, gametes, ookinetes can prevent development of sporozoites
What is the development cycle of malaria?
Sporozites infect humans

Invade hepatocytes, become merozoites

Merozoites invade RBCs, become gametocytes

Gametocytes ingested by mosquito.

Inside mosquito, Gamete ~> Zygote ~> Ookinete ~> Oocyst
How does sickle cell anemia protect against malaria?
Sickling depletes cell reserves of potassium which is required for the parasite to grow
What is malaria prophylaxis?
Sleep under netting
Use mosquito repellent
Consult an updated map - Chloroquine resistant vs. sensitive malaria

Chloroquine
In chloroquine resistant areas:
Mefloquine
Doxycycline
Primaquine
What are the chemoprophylxis for malaria?
Chloroquine is the recommended chemoprophylactic for traveling to areas with plasmodia still chloroquine sensitive

In chloroquinine resistant areas:

Mefloquine - 50% resistance in Asia. OK for pregnancy. Risk of neuropsychatric side effects (1 in 10k-13k users). Begin 2 weeks before entering and continue 4 weeks after leaving.

Doxycycline - Begin 1-2 days before travel and continue for 4 weeks after.

Primaquine - Not available in Israel - G6PD (glucose-6-phosphate dehydrogenase) activity is needed. Better for P. vivax (kill hypnozoites). Best combined with cloroquine.
What chemoprophylaxis is best for P. vivax?
Primaquine
What drug is good for prevention AND treatment of P. falciparum malaria?
Malarone

2 drugs, atovaquone and proguanil.

Works by killing parasites in blood and liver. Useful for individuals who cannot tolerate or take mefloquine

Begin 1-2 days before entering malaria zone, and continue for 7 days after leaving.

***Downside - price, significantly more expensive than other antimalarials

Dose is one table daily. Not recommended for people who weigh less than 40kg.
The commonest side effects are headache, abdominal pain, and diarrhea. ***It does not have neuro-psychiatric effects of mefloquine.

Not recommended during pregnancy, nor if you are taking certain drugs. In particular, tetracyclines or a certain anti-nausea drug called metoclopramide.

DOES NOT KILL HYPNOZOITES
What are the treatments of acute malaria?
Tissue schizonticides (liver stage):
Primaquine

Blood schizonticides:
Chloroquinine sensitive Plasmodia:
Chloroquine

Chloroquine-resistant Plasmodia:
Mefloquine
Quinine
Quinidine
Pyrimethamine-sulfadoxine
Doxycycline
Halofantrine
Artemisinin
Malarone
What is hemozoin?
A digestion product of hemoglobin produced by blood eating parasites such as malaria
How does chloroquine work?
Inside the plasmodium parasite, it targets the food vacuole.

It blocks transport proteins CRT and MDR1 externally or possibly internally.

Inside the vacuole, it blocks digestion of Heme to hemozoin by targetting PfHRP2 (histidine rich protein 2)
What drug blocks digestion of heme in plasmodium?
Chloroquine
What antimalarial drug is an antifolate?
Pyrimethamine proguanil

Blocks DHFR
How does pyrimethamine proguanil prevent malaria?
Antifolate, acts by blocking DHFR
What is Artemisin?
Remedy from a nobleman's tomb. Herb wormwood used by Chinese for thousands of years in various remedies.

One use is treatment of malaria, lost until rediscovered in archeological dig in early 70s.

Inside tomb of Han nobleman, found silk scroll labeled "medical treatments for 52 diseases", containing 238 treatments including herbla recipe for treatment of malaria by soaking leaves and branches of artemisia herb in water and drinking it.

This silk scroll is now the oldest existing text on Chinese medicine.
What is Qinghaosu?
Artemisin derivative used to treat malaria
What is the geographic distribution of Ascariasis?
Central and South America, Africa, Asia and Australia

25% of the world's population is infected with this parasite
What are the characteristics of Ascaris?
Very large worms
Head has 3 jaw-like structures oriented on the circumference of the mouth that clamp down

Eggs have a bumpy shell
What is the unique identifiable feature of Ascaris eggs?
A bumpy shell
What are the characteristics of Eggs of Ascaris?
Eggs are very resistant to environmental stress
they can survive in moist soil for 3-5 years
They are resistant to cold, heat, and to antiseptic
In endemic zone until 100 eggs/g of soil
What is the life cycle of Ascaris?
Ascaris Lumbricoides and Ascaris Suum

Eggs are ingested by host and hatch in small intestine. Juveniles penetrate intestine and enter blood stream, where they travel to lungs and molt into third stage juveniles.

Third stage juveniles migrate into alveoli, and are "coughed up" and swallowed. Juveniles then complete their development in the small intestine.

Adult males and females are in the small intestine, and females produce eggs that are passed in the feces (single female can produce 200,000 eggs per day).

Juveniles in eggs mature to infective (second) stage.
What are intestinal roundworms?
Ascaris Lumbricoides and Ascaris Suum
What are the symptoms of Ascariasis?
Ascaris Lumbricoides

Pulmonary - Cough, wheezing, dyspnea, sub-sternal discomfort

Small and large intestine - Abdominal pain, distended abdomen, anorexia, weight loss, occasional vomiting and loose stool, ***Occlusion, acute (and fatal) peritonitis***
How is the diagnosis of Ascariasis made?
No direct diagnosis during invasive phase. Indirect diagnosis during invasive phase using immunological methods.

Acute phase - presence of eggs in feces
X-ray (often observed during non-specific exam)

**The worm is sensitive to anesthetics

The worm can get out in the feces or during vomiting
What is the treatment and prevention for Ascariasis?
Infection should always be treated because of risk of complications.
Benzimidazole (mebendazole)
Piperazine
Pyrantel Pamoate

Prevention - Hygiene
~Promiscuous defacation of small children around houses
~Inadequate sanitation
~Use of human night soil as fertilizer
What is the anti-inflammatory effect of Ascariasis?
Binding of WBC to endothelium selectins is inhibited by lectins secreted by the parasite.

Chemokines destroyed by parasite's proteases.

Secretion of serpins inhibits host proteases.

NO production and oxidative stress is inhibited by anti-oxidant molecules like GST.
Ascariasis - Intestinal Rupture
Ascariasis - Xray
Ascaris Lumbricoides
Ascaris Lumbricoides
Ascaris Lumbricoides - Egg - BUMPY SHELL
Ascaris Lumbricoides - Head of adult worm
Ascaris Lumbricoides - Sensitive to anesthetics.jpg
Ascaris Lumbricoides
Cerebral Malaria
Malaria - human infected cell
Plasmodium falciparum gametocyte
Plasmodium falciparum gametocyte
Plasmodium Oocysts inside mosquito
What is the Guinea worm?
Dracunculus medinensis - one of the largest nematodes known with adults reaching 50-120 cm in size
What is the epidemiology of the Guinea worm?
Dracunculus Medinensis

Distribution - Asia (India, Iran, Pakistan, Afghanistan, Turkestan, USSR), Africa (Nile Valley, Central, East), Indonesia, Fiji, Brazil

50 million people infected worldwide
What is the lifecycle of C. medinensis?
Dracunculus medinensis - Full life cycle occurs in 3-4 months

Humans are infected when ingesting water containing infected copepods

Juvenile worms exit the intestinal tract and migrate to the subcutaneous tissues. Male and females mate, and male dies.

Female worms migrate to skin (legs, ankles, feet). Females produce juveniles, and a blister forms under the skin.

Blister produces a burning sensation, and when put into water, blister bursts releasing juveniles into the water.

Juveniles are ingested by copepods and mature into infective stage, and cycle repeats.
What are the symptoms and pathogenesis of D. medinensis?
1) Rash accompanied by severe itching, nausaea, vomiting, diarrhea, and dizziness

2) A blister is formed

3) The blister breaks, liberating toxic fluids contained in the blister

4) When this area is exposed to water, the female nematode discharges numerous first stage juveniles into the water (ovoviviparous)
What is the prevention and treatment of Guinea worm?
Water treatment

Mebendazole is effective

Worm must be extracted, a few cm a day
Dracunculus medinensis
Dracunculus medinensis
Dracunculus medinensis
Dracunculus medinensis
Dracunculus medinensis
What are the three causes of Filariasis in humans?
Wuchereria bancrofti
Brugia malayi
Brugia timori
What is the epidemiology of the causative agents of Filariasis?
Wuchereria bancrofti - Eastern South America, Sub-saharan Africa, Southeast Asia and Indonesia/Polynesia
Brugia malayi - Southeast Asia and Indonesia/Polynesia
Brugia timori - small area of Indonesia/Polynesia

120 million people affected in 73 endemic countries world-wide
What is the disease process of Filariasis?
1) Entry - larva via mosquito bite
2) Larva mature to adults in lymphatics and produce microfilariae which enter blood
3) Spread of microfilariae
4) DISEASE - Lymphadenitis, Lymphangitis, elephantiasis
5) Exit - microfilariae ingested by mosquito, develop to infective stage
What are the characteristics of W. bancrofti?
White worm with a smooth cuticle and bluntly round ends
Males - 4cm x 0.1 mm
Female - 8cm x 0.2 mm (ovovivipare)
What are the four stages of W. bancrofti disease?
1) Incubation period (3 to 12 months) - no symptoms
2) Acute stage - swelling of extremities, pain, weakness of arms and legs, headache, insomnia. Fever usually not present
3) Period of recovery
4) If there is continued reinfection, the cycle repeats and elephantiasis may result
How is diagnosis of W. bancrofti made?
Diagnosis is based on history of mosquito bites in endemic areas

Clinical findings

Presence of microfilaria in blood samples COLLECTED AT NIGHT

Serology - PCR
Diagnosis of what organism requires blood samples be collected at night?
Wuchereria Bancrofti - Filariasis/Elephantiasis
What is the management of Filariasis?
Wuchereria Bancrofti
1) Antibiotics to prevent secondary infections
2) Pressure bandages to reduce swelling
3) Surgical removal of infected tissues to improve lymph flow
4) Chemotherapy (new) - Diethylcarbamazine, Ivermectine
5) Vector control (malaria, intermediate host)
What are Wolbachia?
Wolbachia are Gram-negative bacteria that form intracellular inherited infections in many invertebrates.

Wolbachia is related to rickettsial bacteria.
It is transmitted by female worms, and horizontal transmission can occur within the vector

Mating will take place only between infected males and female worms

**Tetracycline reduces the worm fertility and inhibits the growth of the worm.

LPS are responsible for the inflammatory response

Bacterial catalase MAY be involved in resistance to oxidative stress
How does tetracycline protect against Filariasis?
Tetracycline kills Wolbachia, the gram negative bacteria that reside inside Wuchereria Bancrofti

This reduces worm fertility and inhibits growth of the worm
Wolbachia in Nematodes
Wuchereria Bancrofti
Wuchereria Bancrofti
Wuchereria Bancrofti - Elephantiasis of Scrotum
Wuchereria Bancrofti - Elephantiasis of Leg
Wuchereria Bancrofti - Microfilaire - larva before stage L1
What is the "worm of the blind"?
Onchocerca Volvulus - causes human onchocerciasis

Large worms:
Males - 19-42 cm x 0.2 mm
Females: 50-60 cm x 0.4 mm
What is the epidemiology of O. volvulus?
Onchocerca Volvulus

More then 30 million people infected in Africa
In some small communities in Africa and Central America, most of the people of middle age and over are blind
What is the life cycle of O. volvulus?
Humans are infected by the BLACK FLY, when infective juveniles are injected into the human during feeding.

The infective juveniles mature into adults. The adult worms occur in "nodules" just under the skin of the human host.

Female worms produce microfilariae whicha re found in the subcutaneous tissues

Microfilariae are ingested by a black fly when it feeds
What is river blindness?
Onchocerciasis, caused by Onchocerca Volvulus
What is the vector of Onchocerca Volvulus?
The Black Fly
What disease is the Black Fly the vector for?
Onchocerca Volvulus - Onchocerciasis (river blindness)
What are the symptoms for onchocerciasis?
Formation of nodules: nodules consist mainly of collagen fibers surrounding one of several adult worms.

Dermatitis due to the presence of microfilariae in the skin - allergic responses or toxic effects after the death of the juveniles (9 months to 2 years)

Lesions of the eye ~> invasion of the cornea by microfilariae (10-15 years)
How is the diagnosis of Onchocerca Volvulus made?
History
Symptoms
Microfilaria in nodules
What is the management of O. volvulus?
Onchocerca Volvulus:
Surgery to remove nodules
Ivermectin ~> Microfilaricide
~Acts as inhibitor of GABA mediated conduction in the peripheral nervous system

Control of black flies
What drug is a Microfilaricide and how does it work?
Ivermectin - acts as an inhibitors of gamma-aminobutyric acid (GABA) mediated conduction in the peripheral nervous system
What is the new approach to treatment of onchocerciasis?
Targeting Wolbachia, the gram negative bacteria that lives within Onchocerca Volvulus.

Doxycycline therapy have shown great promise

Doxycycline interrupts microfilarial embryogenesis, dramatically decreasing or eliminating microfliaria for at least 18 months after treatment.

The drug has modest activity against adult worms, reducing numbers by approximately 50-60%
Onchocerca Volvulus
Onchocerca Volvulus
Onchocerca Volvulus - Microfilariae
Onchocerca Volvulus - Progressive Keratitis
Onchocerca Volvulus - Skin Nodules
Onchocerca Volvulus
What is the Eye worm, and what is it's distribution?
Loa Loa
Located in West Africa
What is the life cycle of Loa Loa?
3rd stage juvenile (J3) enters humans when bitten by Deerfly.

J3 ~> J4 ~> Adult in subcutaneous tissues of human

Microfilaria (J1) migrate to blood (sheathed)

Deerfly bites human, and picks up Microfilaria (J1) in mouthparts

J1 penetrates gut wall of Deerfly, migrates to fat body and develops J1 ~> J2 ~> J3

J3 migrates to mouth-parts of Deerfly, where it can infect human again
What is the vector of Loa Loa?
The Deer fly (Chrysops)
What oragnism is the Deer fly the vector for?
Loa Loa
What are the characteristics of Loa Loa?
White worm with smooth cuticle covered with irregular, small bosses, except at the head and tail.

Males are 20-34 mm x 350-430 um
Females are 20-70 mm x 425 mm

They have extreme longevity, 10-15 years
What are the symptoms associated with Loa Loa infection?
Adults have a tendency to wander through the subcutaneous connective tissue, creating a Calabar swelling

Adults also migrate through the conjunctiva and cornea
What is a Calabar swelling?
Red itching swellings beneath the skin caused by Loa Loa present in the subcutaneous connective tissue
How is the diagnosis of Loa Loa disease made?
Travel in endemic region
Worm under the skin or in the eye
Presence of microfilaire in the blood
Serology
What is the management of Loa Loa disease?
Surgical removal of the swellings

Chemotherapy: Diethyl Carbamazine - Induces a rapid destruction of the microfilariae ~> allergy

Ivermectine

Control of Deer flies
Loa Loa - Adult Worm
Loa Loa - Calabar Swellings
Loa Loa - Eye
Loa Loa - Microfilariae
What is the Whip Worm?
Trichuris trichiura